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Johnson, G. Allan

Overview:

Dr. Johnson is the Charles E. Putman University Professor of Radiology, Professor of Physics, and Biomedical Engineering, and Director of the Duke Center for In Vivo Microscopy (CIVM). The CIVM is an NIH/NIBIB national Biomedical Technology Resource Center with a mission to develop novel technologies for preclinical imaging (basic sciences) and apply the technologies to critical biomedical questions. Dr. Johnson was one of the first researchers to bring Paul Lauterbur's vision of magnetic resonance (MR) microscopy to practice as described in his paper, "Nuclear magnetic resonance imaging at microscopic resolution" (J Magn Reson 68:129-137, 1986). Dr. Johnson is involved in both the engineering physics required to extend the resolution of MR imaging and in a broad range of applications in the basic sciences.

Positions:

Charles E. Putman University Professor of Radiology

Radiology
School of Medicine

Professor of Radiology

Radiology
School of Medicine

Professor in the Department of Physics

Physics
Trinity College of Arts & Sciences

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

Ph.D. 1974

Ph.D. — Duke University

News:

Grants:

Training in Medical Imaging

Administered By
Biomedical Engineering
AwardedBy
National Institutes of Health
Role
Mentor
Start Date
July 15, 2003
End Date
August 31, 2019

Quantitative MR Microscopy of Phenotypic Biomarkers in Alzheimer's Disease

Administered By
Radiology
AwardedBy
National Institutes of Health
Role
Mentor
Start Date
December 01, 2013
End Date
November 30, 2018

Integrated Center For In Vivo Microscopy

Administered By
Radiology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
September 01, 2003
End Date
June 30, 2018

Waxholm Space for Rodent Neuroinformatics

Administered By
Radiology
AwardedBy
University of Pennsylvania
Role
Principal Investigator
Start Date
September 01, 2016
End Date
August 31, 2017

Medical Scientist Training Program

Administered By
School of Medicine
AwardedBy
National Institutes of Health
Role
Mentor
Start Date
July 01, 1997
End Date
June 30, 2017

Serial Block Face Scanning Electron Microscope

Administered By
Pathology
AwardedBy
National Institutes of Health
Role
Major User
Start Date
June 01, 2016
End Date
May 31, 2017

Ultra-resolution imaging of brain circuitry and its development in mental health

Administered By
Duke-UNC Center for Brain Imaging and Analysis
AwardedBy
National Institutes of Health
Role
Co Investigator
Start Date
May 03, 2013
End Date
June 30, 2016

MRI Corticography (MRCoG): Micro-scale Human Cortical Imaging

Administered By
Duke-UNC Center for Brain Imaging and Analysis
AwardedBy
University of California - Berkeley
Role
Collaborator
Start Date
September 26, 2014
End Date
May 31, 2016

Whole brain multimodal microscopy of an apoptosis reporter mouse

Administered By
Psychiatry & Behavioral Sciences, Translational Neuroscience
AwardedBy
National Institutes of Health
Role
Collaborator
Start Date
September 01, 2012
End Date
August 31, 2014

Time-Resolved 129Xe Ventilation-Perfusion MRI in Rat Models of Acute Lung Injury

Administered By
Radiology
AwardedBy
National Institutes of Health
Role
Co-Mentor
Start Date
August 01, 2012
End Date
June 30, 2014

Agilent Direct Drive 9.4T MRS/MRI Console

Administered By
Radiology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
May 15, 2012
End Date
November 14, 2013

Cross-disciplinary Training in Medical Physics

Administered By
Radiology
AwardedBy
National Institutes of Health
Role
Mentor
Start Date
July 01, 2007
End Date
June 30, 2013

Regulation of mitochondrial biogenesis by heme oxygenase-1

Administered By
Medicine, Pulmonary, Allergy, and Critical Care Medicine
AwardedBy
National Institutes of Health
Role
Collaborator
Start Date
July 14, 2008
End Date
April 30, 2013

Small Animal Imaging Resource Program

Administered By
Radiology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
August 30, 2001
End Date
February 29, 2012

The Role of PTEN in Endothelial Biology

Administered By
Medicine, Cardiology
AwardedBy
National Institutes of Health
Role
Consultant
Start Date
February 15, 2008
End Date
January 31, 2012

The Duke University Molecular Imaging Center

Administered By
Radiology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
August 30, 2001
End Date
December 31, 2006

Functional Assessment of Pulmonary Toxicity with MRM

Administered By
Radiology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
September 30, 1996
End Date
August 31, 2006

Supp. to P41 - A Mouse Brain Imaging Research Network

Administered By
Radiology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
September 01, 2001
End Date
August 31, 2003

Integrated Center for InVivo Microscopy

Administered By
Radiology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
September 30, 1998
End Date
August 31, 2003

Developmental Correlates: Membrane/Contractile Protein

Administered By
Pediatrics, Cardiology
AwardedBy
National Institutes of Health
Role
Collaborator
Start Date
December 01, 1997
End Date
April 30, 2001

Small Animal Imaging in the Basic Sciences Workshop

Administered By
Radiology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
February 01, 1999
End Date
August 31, 1999

In Vivo Microscopy Of Environmental Lung Disease

Administered By
Radiology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
September 01, 1997
End Date
August 31, 1999

In Vivo Microscopy Of Enviromental Lung Disease

Administered By
Radiology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
September 30, 1996
End Date
August 31, 1999

Integrated Center For In Vivo Microscopy

Administered By
Radiology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
September 01, 1990
End Date
September 29, 1998

(97-0184) Effects of Spatial Inhomogeneity on Nonlinear Pattern Forming Systems

Administered By
Physics
AwardedBy
National Science Foundation
Role
Co-Principal Investigator
Start Date
September 15, 1997
End Date
August 31, 1998

(96-0628) Experimental and Analytical Investigations of Flows in Porous Media

Administered By
Physics
AwardedBy
National Science Foundation
Role
Co-Principal Investigator
Start Date
March 15, 1994
End Date
August 31, 1997

An Integrated Center For In Vivo Microscopy

Administered By
Radiology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
September 01, 1990
End Date
September 29, 1996

(93-0422) Experimental and Analytical Investigation of Flows in Porous Media

Administered By
Physics
AwardedBy
National Science Foundation
Role
Co-Principal Investigator
Start Date
March 15, 1994
End Date
August 31, 1996

(95-0607) Experimental and Analytical Investigations of Flows in Porous Media

Administered By
Physics
AwardedBy
National Science Foundation
Role
Co-Principal Investigator
Start Date
March 15, 1994
End Date
August 31, 1996

(93-0469) Experimental and Analytical Investigations of Flows in Porous Media

Administered By
Physics
AwardedBy
Department of Energy
Role
Co-Principal Investigator
Start Date
August 15, 1990
End Date
August 14, 1996

In Vivo Assay Of Environmental Toxins With Mr Microscopy

Administered By
Radiology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
July 01, 1993
End Date
June 30, 1995

In Vivo Assay Of Environmental Toxins With Mri

Administered By
Radiology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
July 01, 1992
End Date
June 30, 1994

(90-0292) Analytical and Experimental Study of Instabilities in Buoyancy-driven Convection in Porous Media

Administered By
Mechanical Engineering and Materials Science
AwardedBy
National Science Foundation
Role
Co-Principal Investigator
Start Date
July 15, 1990
End Date
May 31, 1993

An Integrated Image Processing/Analysis Network

Administered By
Radiology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
February 01, 1988
End Date
February 01, 1990

Nuclear Magnetic Resonance (Nmr) Imaging Facility

Administered By
Radiology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
August 01, 1986
End Date
September 01, 1989

Nuclear Magnetic Resonance Imaging Facility For Small Anim

Administered By
Radiology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
July 01, 1984
End Date
July 01, 1986
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Publications:

MRI tools for assessment of microstructure and nephron function of the kidney.

MRI can provide excellent detail of renal structure and function. Recently, novel MR contrast mechanisms and imaging tools have been developed to evaluate microscopic kidney structures including the tubules and glomeruli. Quantitative MRI can assess local tubular function and is able to determine the concentrating mechanism of the kidney noninvasively in real time. Measuring single nephron function is now a near possibility. In parallel to advancing imaging techniques for kidney microstructure is a need to carefully understand the relationship between the local source of MRI contrast and the underlying physiological change. The development of these imaging markers can impact the accurate diagnosis and treatment of kidney disease. This study reviews the novel tools to examine kidney microstructure and local function and demonstrates the application of these methods in renal pathophysiology.

Authors
Xie, L; Bennett, KM; Liu, C; Johnson, GA; Zhang, JL; Lee, VS
MLA Citation
Xie, L, Bennett, KM, Liu, C, Johnson, GA, Zhang, JL, and Lee, VS. "MRI tools for assessment of microstructure and nephron function of the kidney." American journal of physiology. Renal physiology 311.6 (December 2016): F1109-F1124.
Website
http://hdl.handle.net/10161/13039
PMID
27630064
Source
epmc
Published In
American Journal of Physiology: Renal Physiology
Volume
311
Issue
6
Publish Date
2016
Start Page
F1109
End Page
F1124
DOI
10.1152/ajprenal.00134.2016

Imaging whole-brain cytoarchitecture of mouse with MRI-based quantitative susceptibility mapping.

The proper microstructural arrangement of complex neural structures is essential for establishing the functional circuitry of the brain. We present an MRI method to resolve tissue microstructure and infer brain cytoarchitecture by mapping the magnetic susceptibility in the brain at high resolution. This is possible because of the heterogeneous magnetic susceptibility created by varying concentrations of lipids, proteins and irons from the cell membrane to cytoplasm. We demonstrate magnetic susceptibility maps at a nominal resolution of 10-μm isotropic, approaching the average cell size of a mouse brain. The maps reveal many detailed structures including the retina cell layers, olfactory sensory neurons, barrel cortex, cortical layers, axonal fibers in white and gray matter. Olfactory glomerulus density is calculated and structural connectivity is traced in the optic nerve, striatal neurons, and brainstem nerves. The method is robust and can be readily applied on MRI scanners at or above 7T.

Authors
Wei, H; Xie, L; Dibb, R; Li, W; Decker, K; Zhang, Y; Johnson, GA; Liu, C
MLA Citation
Wei, H, Xie, L, Dibb, R, Li, W, Decker, K, Zhang, Y, Johnson, GA, and Liu, C. "Imaging whole-brain cytoarchitecture of mouse with MRI-based quantitative susceptibility mapping." NeuroImage 137 (August 2016): 107-115.
PMID
27181764
Source
epmc
Published In
NeuroImage
Volume
137
Publish Date
2016
Start Page
107
End Page
115
DOI
10.1016/j.neuroimage.2016.05.033

Digital Subtracted Angiography of Small Animals

Authors
Spiliopoulos, D; Kagadis, GC; Karnabatidis, D; Johnson, GA; Badea, CT
MLA Citation
Spiliopoulos, D, Kagadis, GC, Karnabatidis, D, Johnson, GA, and Badea, CT. "Digital Subtracted Angiography of Small Animals (Accepted)." Handbook of Small Animal Imaging: Preclinical Imaging, Therapy, and Applications. Ed. GC Kagadis, NL Ford, GK Loudos, and D Karnabatidis. Taylor & Francis Books, Inc., CRC Press, March 3, 2016. 67-75. (Chapter)
Source
manual
Publish Date
2016
Start Page
67
End Page
75

Adult rat cortical thickness changes across age and following adolescent intermittent ethanol treatment.

Human studies have established that adolescence is a period of brain maturation that parallels the development of adult behaviors. However, little is known regarding cortical development in the adult rat brain. We used magnetic resonance imaging (MRI) and histology to assess the impact of age on adult Wistar rat cortical thickness on postnatal day (P)80 and P220 as well as the effect of adolescent binge ethanol exposure on adult (P80) cortical thickness. MRI revealed changes in cortical thickness between P80 and P220 that differ across cortical region. The adult P220 rat prefrontal cortex increased in thickness whereas cortical thinning occurred in both the cingulate and parietal cortices relative to young adult P80 rats. Histological analysis confirmed the age-related cortical thinning. In the second series of experiments, an animal model of adolescent intermittent ethanol (AIE; 5.0 g/kg, intragastrically, 20 percent ethanol w/v, 2 days on/2 days off from P25 to P55) was used to assess the effects of alcohol on cortical thickness in young adult (P80) rats. MRI revealed that AIE resulted in region-specific cortical changes. A small region within the prefrontal cortex was significantly thinner whereas medial cortical regions were significantly thicker in young adult (P80) AIE-treated rats. The observed increase in cortical thickness was confirmed by histology. Thus, the rat cerebral cortex continues to undergo cortical thickness changes into adulthood, and adolescent alcohol exposure alters the young adult cortex that could contribute to brain dysfunction in adulthood.

Authors
Vetreno, RP; Yaxley, R; Paniagua, B; Johnson, GA; Crews, FT
MLA Citation
Vetreno, RP, Yaxley, R, Paniagua, B, Johnson, GA, and Crews, FT. "Adult rat cortical thickness changes across age and following adolescent intermittent ethanol treatment." Addiction biology (February 2016).
PMID
26833865
Source
epmc
Published In
Addiction Biology
Publish Date
2016
DOI
10.1111/adb.12364

Image-processing pipelines: Applications in magnetic resonance histology

© 2016 SPIE.Image processing has become ubiquitous in imaging research - so ubiquitous that it is easy to loose track of how diverse this processing has become. The Duke Center for In Vivo Microscopy has pioneered the development of Magnetic Resonance Histology (MRH), which generates large multidimensional data sets that can easily reach into the tens of gigabytes. A series of dedicated image-processing workstations and associated software have been assembled to optimize each step of acquisition, reconstruction, post-processing, registration, visualization, and dissemination. This talk will describe the image-processing pipelines from acquisition to dissemination that have become critical to our everyday work.

Authors
Johnson, GA; Anderson, RJ; Cook, JJ; Long, C; Badea, A
MLA Citation
Johnson, GA, Anderson, RJ, Cook, JJ, Long, C, and Badea, A. "Image-processing pipelines: Applications in magnetic resonance histology." January 1, 2016.
Source
scopus
Published In
Proceedings of SPIE
Volume
9784
Publish Date
2016
DOI
10.1117/12.2203525

Tumor location, but not H3.3K27M, significantly influences the blood-brain-barrier permeability in a genetic mouse model of pediatric high-grade glioma.

Pediatric high-grade gliomas (pHGGs) occur with strikingly different frequencies in infratentorial and supratentorial regions. Although histologically these malignancies appear similar, they represent distinct diseases. Recent genomic studies have identified histone K27M H3.3/H3.1 mutations in the majority of brainstem pHGGs; these mutations are rarely encountered in pHGGs that arise in the cerebral cortex. Previous research in brainstem pHGGs suggests a restricted permeability of the blood-brain-barrier (BBB). In this work, we use dynamic contrast-enhanced (DCE) MRI to evaluate BBB permeability in a genetic mouse model of pHGG as a function of location (cortex vs. brainstem, n = 8 mice/group) and histone mutation (mutant H3.3K27M vs. wild-type H3.3, n = 8 mice/group). The pHGG models are induced either in the brainstem or the cerebral cortex and are driven by PDGF signaling and p53 loss with either H3.3K27M or wild-type H3.3. T2-weighted MRI was used to determine tumor location/extent followed by 4D DCE-MRI for estimating the rate constant (K (trans) ) for tracer exchange across the barrier. BBB permeability was 67 % higher in cortical pHGGs relative to brainstem pHGGs (t test, p = 0.012) but was not significantly affected by the expression of mutant H3.3K27M versus wild-type H3.3 (t-test, p = 0.78). Although mice became symptomatic at approximately the same time, the mean volume of cortical tumors was 3.6 times higher than the mean volume of brainstem tumors. The difference between the mean volume of gliomas with wild-type and mutant H3.3 was insignificant. Mean K (trans) was significantly correlated to glioma volume. These results present a possible explanation for the poor response of brainstem pHGGs to systemic therapy. Our findings illustrate a potential role played by the microenvironment in shaping tumor growth and BBB permeability.

Authors
Subashi, E; Cordero, FJ; Halvorson, KG; Qi, Y; Nouls, JC; Becher, OJ; Johnson, GA
MLA Citation
Subashi, E, Cordero, FJ, Halvorson, KG, Qi, Y, Nouls, JC, Becher, OJ, and Johnson, GA. "Tumor location, but not H3.3K27M, significantly influences the blood-brain-barrier permeability in a genetic mouse model of pediatric high-grade glioma." Journal of neuro-oncology 126.2 (January 2016): 243-251.
PMID
26511492
Source
epmc
Published In
Journal of Neuro-Oncology
Volume
126
Issue
2
Publish Date
2016
Start Page
243
End Page
251
DOI
10.1007/s11060-015-1969-9

Dynamic contrast-enhanced quantitative susceptibility mapping with ultrashort echo time MRI for evaluating renal function.

Dynamic contrast-enhanced (DCE) MRI can provide key insight into renal function. DCE MRI is typically achieved through an injection of a gadolinium (Gd)-based contrast agent, which has desirable T1 quenching and tracer kinetics. However, significant T2* blooming effects and signal voids can arise when Gd becomes very concentrated, especially in the renal medulla and pelvis. One MRI sequence designed to alleviate T2* effects is the ultrashort echo time (UTE) sequence. In the present study, we observed T2* blooming in the inner medulla of the mouse kidney, despite using UTE at an echo time of 20 microseconds and a low dose of 0.03 mmol/kg Gd. We applied quantitative susceptibility mapping (QSM) and resolved the signal void into a positive susceptibility signal. The susceptibility values [in parts per million (ppm)] were converted into molar concentrations of Gd using a calibration curve. We determined the concentrating mechanism (referred to as the concentrating index) as a ratio of maximum Gd concentration in the inner medulla to the renal artery. The concentrating index was assessed longitudinally over a 17-wk course (3, 5, 7, 9, 13, 17 wk of age). We conclude that the UTE-based DCE method is limited in resolving extreme T2* content caused by the kidney's strong concentrating mechanism. QSM was able to resolve and confirm the source of the blooming effect to be the large positive susceptibility of concentrated Gd. UTE with QSM can complement traditional magnitude UTE and offer a powerful tool to study renal pathophysiology.

Authors
Xie, L; Layton, AT; Wang, N; Larson, PEZ; Zhang, JL; Lee, VS; Liu, C; Johnson, GA
MLA Citation
Xie, L, Layton, AT, Wang, N, Larson, PEZ, Zhang, JL, Lee, VS, Liu, C, and Johnson, GA. "Dynamic contrast-enhanced quantitative susceptibility mapping with ultrashort echo time MRI for evaluating renal function." American journal of physiology. Renal physiology 310.2 (January 2016): F174-F182.
PMID
26447222
Source
epmc
Published In
American Journal of Physiology: Renal Physiology
Volume
310
Issue
2
Publish Date
2016
Start Page
F174
End Page
F182
DOI
10.1152/ajprenal.00351.2015

A Diffusion MRI Tractography Connectome of the Mouse Brain and Comparison with Neuronal Tracer Data.

Interest in structural brain connectivity has grown with the understanding that abnormal neural connections may play a role in neurologic and psychiatric diseases. Small animal connectivity mapping techniques are particularly important for identifying aberrant connectivity in disease models. Diffusion magnetic resonance imaging tractography can provide nondestructive, 3D, brain-wide connectivity maps, but has historically been limited by low spatial resolution, low signal-to-noise ratio, and the difficulty in estimating multiple fiber orientations within a single image voxel. Small animal diffusion tractography can be substantially improved through the combination of ex vivo MRI with exogenous contrast agents, advanced diffusion acquisition and reconstruction techniques, and probabilistic fiber tracking. Here, we present a comprehensive, probabilistic tractography connectome of the mouse brain at microscopic resolution, and a comparison of these data with a neuronal tracer-based connectivity data from the Allen Brain Atlas. This work serves as a reference database for future tractography studies in the mouse brain, and demonstrates the fundamental differences between tractography and neuronal tracer data.

Authors
Calabrese, E; Badea, A; Cofer, G; Qi, Y; Johnson, GA
MLA Citation
Calabrese, E, Badea, A, Cofer, G, Qi, Y, and Johnson, GA. "A Diffusion MRI Tractography Connectome of the Mouse Brain and Comparison with Neuronal Tracer Data." Cerebral cortex (New York, N.Y. : 1991) 25.11 (November 2015): 4628-4637.
Website
http://hdl.handle.net/10161/10325
PMID
26048951
Source
epmc
Published In
Cerebral Cortex
Volume
25
Issue
11
Publish Date
2015
Start Page
4628
End Page
4637
DOI
10.1093/cercor/bhv121

Postmortem Diffusion MRI of the Human Brainstem and Thalamus for Deep Brain Stimulator Electrode Localization

Authors
Calabrese, E; Hickey, P; Hulette, C; Zhang, J; Parente, B; Lad, SP; Johnson, GA
MLA Citation
Calabrese, E, Hickey, P, Hulette, C, Zhang, J, Parente, B, Lad, SP, and Johnson, GA. "Postmortem Diffusion MRI of the Human Brainstem and Thalamus for Deep Brain Stimulator Electrode Localization." September 2015.
Source
wos-lite
Published In
Movement Disorders
Volume
30
Issue
10
Publish Date
2015
Start Page
E6
End Page
E6

A diffusion tensor MRI atlas of the postmortem rhesus macaque brain.

The rhesus macaque (Macaca mulatta) is the most widely used nonhuman primate for modeling the structure and function of the brain. Brain atlases, and particularly those based on magnetic resonance imaging (MRI), have become important tools for understanding normal brain structure, and for identifying structural abnormalities resulting from disease states, exposures, and/or aging. Diffusion tensor imaging (DTI)-based MRI brain atlases are widely used in both human and macaque brain imaging studies because of the unique contrasts, quantitative diffusion metrics, and diffusion tractography that they can provide. Previous MRI and DTI atlases of the rhesus brain have been limited by low contrast and/or low spatial resolution imaging. Here we present a microscopic resolution MRI/DTI atlas of the rhesus brain based on 10 postmortem brain specimens. The atlas includes both structural MRI and DTI image data, a detailed three-dimensional segmentation of 241 anatomic structures, diffusion tractography, cortical thickness estimates, and maps of anatomic variability among atlas specimens. This atlas incorporates many useful features from previous work, including anatomic label nomenclature and ontology, data orientation, and stereotaxic reference frame, and further extends prior analyses with the inclusion of high-resolution multi-contrast image data.

Authors
Calabrese, E; Badea, A; Coe, CL; Lubach, GR; Shi, Y; Styner, MA; Johnson, GA
MLA Citation
Calabrese, E, Badea, A, Coe, CL, Lubach, GR, Shi, Y, Styner, MA, and Johnson, GA. "A diffusion tensor MRI atlas of the postmortem rhesus macaque brain." NeuroImage 117 (August 2015): 408-416.
PMID
26037056
Source
epmc
Published In
NeuroImage
Volume
117
Publish Date
2015
Start Page
408
End Page
416
DOI
10.1016/j.neuroimage.2015.05.072

Postmortem diffusion MRI of the human brainstem and thalamus for deep brain stimulator electrode localization.

Deep brain stimulation (DBS) is an established surgical therapy for medically refractory tremor disorders including essential tremor (ET) and is currently under investigation for use in a variety of other neurologic and psychiatric disorders. There is growing evidence that the anti-tremor effects of DBS for ET are directly related to modulation of the dentatorubrothalamic tract (DRT), a white matter pathway that connects the cerebellum, red nucleus, and ventral intermediate nucleus of the thalamus. Emerging white matter targets for DBS, like the DRT, will require improved three-dimensional (3D) reference maps of deep brain anatomy and structural connectivity for accurate electrode targeting. High-resolution diffusion MRI of postmortem brain specimens can provide detailed volumetric images of important deep brain nuclei and 3D reconstructions of white matter pathways with probabilistic tractography techniques. We present a high spatial and angular resolution diffusion MRI template of the postmortem human brainstem and thalamus with 3D reconstructions of the nuclei and white matter tracts involved in ET circuitry. We demonstrate registration of these data to in vivo, clinical images from patients receiving DBS therapy, and correlate electrode proximity to tractography of the DRT with improvement of ET symptoms.

Authors
Calabrese, E; Hickey, P; Hulette, C; Zhang, J; Parente, B; Lad, SP; Johnson, GA
MLA Citation
Calabrese, E, Hickey, P, Hulette, C, Zhang, J, Parente, B, Lad, SP, and Johnson, GA. "Postmortem diffusion MRI of the human brainstem and thalamus for deep brain stimulator electrode localization." Human brain mapping 36.8 (August 2015): 3167-3178.
PMID
26043869
Source
epmc
Published In
Human Brain Mapping
Volume
36
Issue
8
Publish Date
2015
Start Page
3167
End Page
3178
DOI
10.1002/hbm.22836

Magnetic resonance histology.

Authors
Johnson, GA
MLA Citation
Johnson, GA. "Magnetic resonance histology." Journal of magnetic resonance imaging : JMRI 42.1 (July 2015): 1-2.
PMID
25297922
Source
epmc
Published In
Journal of Magnetic Resonance Imaging
Volume
42
Issue
1
Publish Date
2015
Start Page
1
End Page
2
DOI
10.1002/jmri.24774

Localization of Metal Electrodes in the Intact Rat Brain Using Registration of 3D Microcomputed Tomography Images to a Magnetic Resonance Histology Atlas.

Simultaneous neural recordings taken from multiple areas of the rodent brain are garnering growing interest due to the insight they can provide about spatially distributed neural circuitry. The promise of such recordings has inspired great progress in methods for surgically implanting large numbers of metal electrodes into intact rodent brains. However, methods for localizing the precise location of these electrodes have remained severely lacking. Traditional histological techniques that require slicing and staining of physical brain tissue are cumbersome, and become increasingly impractical as the number of implanted electrodes increases. Here we solve these problems by describing a method that registers 3-D computerized tomography (CT) images of intact rat brains implanted with metal electrode bundles to a Magnetic Resonance Imaging Histology (MRH) Atlas. Our method allows accurate visualization of each electrode bundle's trajectory and location without removing the electrodes from the brain or surgically implanting external markers. In addition, unlike physical brain slices, once the 3D images of the electrode bundles and the MRH atlas are registered, it is possible to verify electrode placements from many angles by "re-slicing" the images along different planes of view. Further, our method can be fully automated and easily scaled to applications with large numbers of specimens. Our digital imaging approach to efficiently localizing metal electrodes offers a substantial addition to currently available methods, which, in turn, may help accelerate the rate at which insights are gleaned from rodent network neuroscience.

Authors
Borg, JS; Vu, M-A; Badea, C; Badea, A; Johnson, GA; Dzirasa, K
MLA Citation
Borg, JS, Vu, M-A, Badea, C, Badea, A, Johnson, GA, and Dzirasa, K. "Localization of Metal Electrodes in the Intact Rat Brain Using Registration of 3D Microcomputed Tomography Images to a Magnetic Resonance Histology Atlas." eNeuro 2.4 (July 2015).
Website
http://hdl.handle.net/10161/10327
PMID
26322331
Source
epmc
Published In
eNeuro
Volume
2
Issue
4
Publish Date
2015

An MRI/DTI Atlas of the Rat Brain

MRI/DTI Atlas of the Rat Brain offers two major enhancements when compared with earlier attempts to make MRI/DTI rat brain atlases. First, the spatial resolution at 25μm is considerably higher than previous data published. Secondly, the comprehensive set of MRI/DTI contrasts provided has enabled the authors to identify more than 80% of structures identified in The Rat Brain in Stereotaxic Coordinates.

Authors
Paxinos, G; Watson, C; Calabrese, E; Badea, A; Johnson, G
MLA Citation
Paxinos, G, Watson, C, Calabrese, E, Badea, A, and Johnson, G. An MRI/DTI Atlas of the Rat Brain. Elsevier, Academic Press, May 28, 2015.
Source
manual
Publish Date
2015

4D MRI of polycystic kidneys from rapamycin-treated Glis3-deficient mice.

Polycystic kidney disease (PKD) is a life-threatening disease that leads to a grotesque enlargement of the kidney and significant loss of function. Several imaging studies with MRI have demonstrated that cyst size in polycystic kidneys can determine disease severity and progression. In the present study, we found that, although kidney volume and cyst volume decreased with drug treatment, renal function did not improve with treatment. Here, we applied dynamic contrast-enhanced MRI to study PKD in a Glis3 (GLI-similar 3)-deficient mouse model. Cysts from this model have a wide range of sizes and develop at an early age. To capture this crucial stage and assess cysts in detail, we imaged during early development (3-17 weeks) and applied high spatiotemporal resolution MRI (125 × 125 × 125 cubic microns every 7.7 s). A drug treatment with rapamycin (also known as sirolimus) was applied to determine whether disease progression could be halted. The effect and synergy (interaction) of aging and treatment were evaluated using an analysis of variance (ANOVA). Structural measurements, including kidney volume, cyst volume and cyst-to-kidney volume ratio, changed significantly with age. Drug treatment significantly decreased these metrics. Functional measurements of time-to-peak (TTP) mean and TTP variance were determined. TTP mean did not change with age, whereas TTP variance increased with age. Treatment with rapamycin generally did not affect these functional metrics. Synergistic effects of treatment and age were not found for any measurements. Together, the size and volume ratio of cysts decreased with drug treatment, whereas renal function remained the same. The quantification of renal structure and function with MRI can comprehensively assess the pathophysiology of PKD and response to treatment.

Authors
Xie, L; Qi, Y; Subashi, E; Liao, G; Miller-DeGraff, L; Jetten, AM; Johnson, GA
MLA Citation
Xie, L, Qi, Y, Subashi, E, Liao, G, Miller-DeGraff, L, Jetten, AM, and Johnson, GA. "4D MRI of polycystic kidneys from rapamycin-treated Glis3-deficient mice." NMR in biomedicine 28.5 (May 2015): 546-554.
PMID
25810360
Source
epmc
Published In
Nmr in Biomedicine
Volume
28
Issue
5
Publish Date
2015
Start Page
546
End Page
554
DOI
10.1002/nbm.3281

Dynamic contrast-enhanced MR microscopy identifies regions of therapeutic response in a preclinical model of colorectal adenocarcinoma.

A typical dynamic contrast-enhanced (DCE)-MRI study often compares the derived pharmacokinetic parameters on manually selected tumor regions or over the entire tumor volume. These measurements include domains where the interpretation of the biomarkers may be unclear (such as in necrotic areas). Here, the authors describe a technique for increasing the sensitivity and specificity of DCE-MRI by identifying tumor regions with a variable response to therapy.Two cohorts (n = 8/group) of nu/nu mice with LS-174T implanted in the mammary fat pad were imaged at five time points over four weeks. The treatment/control group received bevacizumab/saline at a dose of 5 mg/kg or 5 ml/kg twice weekly; imaging experiments were performed weekly. MR images were acquired at an isotropic resolution of 156 μm(3)(2.4 nl) and with a sampling rate of 9.9 s. The histogram of the time-to-peak (TTP) was used to identify two (fast- and slow-enhancing) regions based on a threshold of TTP = 1000 s. The regions were correlated with histology, and the effect of therapy was locally examined.Tumors in the treatment group had a significantly longer doubling time. The regions defined by thresholding the TTP histogram identified two distinct domains correlating significantly with tumor permeability and microvessel density. In the fast-enhancing region, the mean permeability constant (K(trans)) was significantly lower in the treatment group at day 9; in the slow-enhancing region, K(trans) was not different between the control and treatment groups. At day 9, the relative volume of the fast-enhancing region was significantly lower in the treatment group, while that of the slow-enhancing region was significantly higher.Two regions with distinct kinetic parameters were identified based on the histogram of TTP. The effect of bevacizumab, as measured by a decrease in K(trans), was confined to one of these regions. High spatiotemporal resolution MR studies may contribute unique insights into the response of the tumor microenvironment to therapy.

Authors
Subashi, E; Qi, Y; Johnson, GA
MLA Citation
Subashi, E, Qi, Y, and Johnson, GA. "Dynamic contrast-enhanced MR microscopy identifies regions of therapeutic response in a preclinical model of colorectal adenocarcinoma." Medical physics 42.5 (May 2015): 2482-2488.
PMID
25979041
Source
epmc
Published In
Medical physics
Volume
42
Issue
5
Publish Date
2015
Start Page
2482
End Page
2488
DOI
10.1118/1.4917525

Susceptibility tensor imaging of the kidney and its microstructural underpinnings.

The purpose of this study was to determine whether susceptibility tensor imaging (STI) could overcome limitations of current techniques to detect tubules throughout the kidney.Normal mouse kidneys (n = 4) were imaged at 9.4T using a three-dimensional gradient multi-echo sequence (55-micron isotropic resolution). Phase images from 12 orientations were obtained to compute the susceptibility tensor. Diffusion tensor imaging (DTI) with 12 encoding directions was compared with STI. Tractography was performed to visualize and track the course of tubules with DTI and STI. Confocal microscopy was used to identify which tubular segments of the nephron were detected by DTI and STI.Diffusion anisotropy was limited to the inner medulla of the kidney. DTI did not find a significant number of coherent tubular tracks in the outer medulla or cortex. With STI, we found strong susceptibility anisotropy and many tracks in the inner and outer medulla and in limited areas of the cortex.STI was able to track tubules throughout the kidney, whereas DTI was limited to the inner medulla. STI provides a novel contrast mechanism related to local tubule microstructure and may offer a powerful method to study the nephron.

Authors
Xie, L; Dibb, R; Cofer, GP; Li, W; Nicholls, PJ; Johnson, GA; Liu, C
MLA Citation
Xie, L, Dibb, R, Cofer, GP, Li, W, Nicholls, PJ, Johnson, GA, and Liu, C. "Susceptibility tensor imaging of the kidney and its microstructural underpinnings." Magnetic resonance in medicine 73.3 (March 2015): 1270-1281.
PMID
24700637
Source
epmc
Published In
Magnetic Resonance in Medicine
Volume
73
Issue
3
Publish Date
2015
Start Page
1270
End Page
1281
DOI
10.1002/mrm.25219

Susceptibility tensor imaging of the kidney and its microstructural underpinnings

© 2014 Wiley Periodicals, Inc.Purpose: The purpose of this study was to determine whether susceptibility tensor imaging (STI) could overcome limitations of current techniques to detect tubules throughout the kidney. Methods: Normal mouse kidneys (n=4) were imaged at 9.4T using a three-dimensional gradient multi-echo sequence (55-micron isotropic resolution). Phase images from 12 orientations were obtained to compute the susceptibility tensor. Diffusion tensor imaging (DTI) with 12 encoding directions was compared with STI. Tractography was performed to visualize and track the course of tubules with DTI and STI. Confocal microscopy was used to identify which tubular segments of the nephron were detected by DTI and STI. Results: Diffusion anisotropy was limited to the inner medulla of the kidney. DTI did not find a significant number of coherent tubular tracks in the outer medulla or cortex. With STI, we found strong susceptibility anisotropy and many tracks in the inner and outer medulla and in limited areas of the cortex. Conclusion: STI was able to track tubules throughout the kidney, whereas DTI was limited to the inner medulla. STI provides a novel contrast mechanism related to local tubule microstructure and may offer a powerful method to study the nephron.

Authors
Xie, L; Dibb, R; Cofer, GP; Li, W; Nicholls, PJ; Johnson, GA; Liu, C
MLA Citation
Xie, L, Dibb, R, Cofer, GP, Li, W, Nicholls, PJ, Johnson, GA, and Liu, C. "Susceptibility tensor imaging of the kidney and its microstructural underpinnings." Magnetic Resonance in Medicine 73.3 (January 1, 2015): 1270-1281.
Source
scopus
Published In
Magnetic Resonance in Medicine
Volume
73
Issue
3
Publish Date
2015
Start Page
1270
End Page
1281
DOI
10.1002/mrm.25219

Addendum to “Waxholm Space atlas of the Sprague Dawley rat brain” [NeuroImage 97 (2014) 374-386].

The main focus of our original article was to describe the anatomical delineations constituting the first version of the WHS Sprague Dawley atlas, apply the Waxholm Space coordinate system, and publish the associated MRI/DTI template and segmentation volume in their original format. To increase usability of the dataset, we have recently shared an updated version of the volumetric image material (v1.01). The aims of this addendum are to inform about the improvements in the updated dataset, in particular related to navigation in the WHS coordinate system, and provide guidance for transforming coordinates acquired in the first version of the atlas.

Authors
Papp, EA; Leergaard, TB; Calabrese, E; Johnson, GA; Bjaalie, JG
MLA Citation
Papp, EA, Leergaard, TB, Calabrese, E, Johnson, GA, and Bjaalie, JG. "Addendum to “Waxholm Space atlas of the Sprague Dawley rat brain” [NeuroImage 97 (2014) 374-386]." NeuroImage 105 (January 2015): 561-562. (addendum)
PMID
25635280
Source
epmc
Published In
NeuroImage
Volume
105
Publish Date
2015
Start Page
561
End Page
562

Investigating the tradeoffs between spatial resolution and diffusion sampling for brain mapping with diffusion tractography: time well spent?

Interest in mapping white matter pathways in the brain has peaked with the recognition that altered brain connectivity may contribute to a variety of neurologic and psychiatric diseases. Diffusion tractography has emerged as a popular method for postmortem brain mapping initiatives, including the ex-vivo component of the human connectome project, yet it remains unclear to what extent computer-generated tracks fully reflect the actual underlying anatomy. Of particular concern is the fact that diffusion tractography results vary widely depending on the choice of acquisition protocol. The two major acquisition variables that consume scan time, spatial resolution, and diffusion sampling, can each have profound effects on the resulting tractography. In this analysis, we determined the effects of the temporal tradeoff between spatial resolution and diffusion sampling on tractography in the ex-vivo rhesus macaque brain, a close primate model for the human brain. We used the wealth of autoradiography-based connectivity data available for the rhesus macaque brain to assess the anatomic accuracy of six time-matched diffusion acquisition protocols with varying balance between spatial and diffusion sampling. We show that tractography results vary greatly, even when the subject and the total acquisition time are held constant. Further, we found that focusing on either spatial resolution or diffusion sampling at the expense of the other is counterproductive. A balanced consideration of both sampling domains produces the most anatomically accurate and consistent results.

Authors
Calabrese, E; Badea, A; Coe, CL; Lubach, GR; Styner, MA; Johnson, GA
MLA Citation
Calabrese, E, Badea, A, Coe, CL, Lubach, GR, Styner, MA, and Johnson, GA. "Investigating the tradeoffs between spatial resolution and diffusion sampling for brain mapping with diffusion tractography: time well spent?." Human brain mapping 35.11 (November 2014): 5667-5685.
PMID
25044786
Source
epmc
Published In
Human Brain Mapping
Volume
35
Issue
11
Publish Date
2014
Start Page
5667
End Page
5685
DOI
10.1002/hbm.22578

Prenatal alcohol exposure reduces magnetic susceptibility contrast and anisotropy in the white matter of mouse brains.

Prenatal alcohol exposure can result in long-term cognitive and behavioral deficits. Fetal alcohol spectrum disorder (FASD) refers to a range of permanent birth defects caused by prenatal alcohol exposure, and is the most common neurodevelopmental disorder in the US. Studies by autopsy and conventional structural MRI indicate that the midline structures of the brain are particularly vulnerable to prenatal alcohol exposure. Diffusion tensor imaging (DTI) has shown that abnormalities in brain white matter especially the corpus callosum are very common in FASD. Quantitative susceptibility mapping (QSM) is a novel technique that measures tissue's magnetic property. Such magnetic property is affected by tissue microstructure and molecular composition including that of myelin in the white matter. In this work, we studied three major white matter fiber bundles of a mouse model of FASD and compared it to control mice using both QSM and DTI. QSM revealed clear and significant abnormalities in anterior commissure, corpus callosum, and hippocampal commissure, which were likely due to reduced myelination. Our data also suggested that QSM may be even more sensitive than DTI for examining changes due to prenatal alcohol exposure. Although this is a preclinical study, the technique of QSM is readily translatable to human brain.

Authors
Cao, W; Li, W; Han, H; O'Leary-Moore, SK; Sulik, KK; Allan Johnson, G; Liu, C
MLA Citation
Cao, W, Li, W, Han, H, O'Leary-Moore, SK, Sulik, KK, Allan Johnson, G, and Liu, C. "Prenatal alcohol exposure reduces magnetic susceptibility contrast and anisotropy in the white matter of mouse brains." NeuroImage 102 Pt 2 (November 2014): 748-755.
PMID
25175539
Source
epmc
Published In
NeuroImage
Volume
102 Pt 2
Publish Date
2014
Start Page
748
End Page
755
DOI
10.1016/j.neuroimage.2014.08.035

A high-resolution cardiovascular magnetic resonance diffusion tensor map from ex-vivo C57BL/6 murine hearts.

The complex cardiac fiber structural organization and spatial arrangement of cardiomyocytes in laminar sheetlets contributes greatly to cardiac functional and contractile ejection patterns. This study presents the first comprehensive, ultra-high resolution, fully quantitative statistical tensor map of the fixed murine heart at isotropic resolution of 43 μm using diffusion tensor (DT) cardiovascular magnetic resonance (CMR).Imaging was completed in approximately 12 hours using a six-directional encoding scheme, in five ex vivo healthy C57BL/6 mouse hearts. The tensor map constructed from this data provides an average description of the murine fiber architecture visualized with fiber tractography, and its population variability, using the latest advances in image tensor analysis and statistics.Results show that non-normalized cardiac tensor maps are associated with mean fractional anisotropy of 0.25 ± 0.07 and mean diffusivity of 8.9 ± 1.6 × 10⁻⁴mm²/s. Moreover, average mid-ventricular helical angle distributions ranged between -41 ± 3° and +52 ± 5° and were highly correlated with transmural depth, in agreement with prior published results in humans and canines. Calculated variabilities of local myocyte orientations were 2.0° and 1.4°. Laminar sheet orientation variability was found to be less stable at 2.6°. Despite such variations, the murine heart seems to be highly structured, particularly when compared to canines and humans.This tensor map has the potential to yield an accurate mean representation and identification of common or unique features of the cardiac myocyte architecture, to establish a baseline standard reference of DTI indices, and to improve detection of biomarkers, especially in pathological states or post-transgenetic modifications.

Authors
Angeli, S; Befera, N; Peyrat, J-M; Calabrese, E; Johnson, GA; Constantinides, C
MLA Citation
Angeli, S, Befera, N, Peyrat, J-M, Calabrese, E, Johnson, GA, and Constantinides, C. "A high-resolution cardiovascular magnetic resonance diffusion tensor map from ex-vivo C57BL/6 murine hearts." Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance 16 (October 16, 2014): 77-.
PMID
25323636
Source
epmc
Published In
Journal of Cardiovascular Magnetic Resonance
Volume
16
Publish Date
2014
Start Page
77
DOI
10.1186/s12968-014-0077-x

Four-dimensional MRI of renal function in the developing mouse.

The major roles of filtration, metabolism and high blood flow make the kidney highly vulnerable to drug-induced toxicity and other renal injuries. A method to follow kidney function is essential for the early screening of toxicity and malformations. In this study, we acquired high spatiotemporal resolution (four dimensional) datasets of normal mice to follow changes in kidney structure and function during development. The data were acquired with dynamic contrast-enhanced MRI (via keyhole imaging) and a cryogenic surface coil, allowing us to obtain a full three-dimensional image (isotropic resolution, 125 microns) every 7.7 s over a 50-min scan. This time course permitted the demonstration of both contrast enhancement and clearance. Functional changes were measured over a 17-week course (at 3, 5, 7, 9, 13 and 17 weeks). The time dimension of the MRI dataset was processed to produce unique image contrasts to segment the four regions of the kidney: cortex (CO), outer stripe (OS) of the outer medulla (OM), inner stripe (IS) of the OM and inner medulla (IM). Local volumes, time-to-peak (TTP) values and decay constants (DC) were measured in each renal region. These metrics increased significantly with age, with the exception of DC values in the IS and OS. These data will serve as a foundation for studies of normal renal physiology and future studies of renal diseases that require early detection and intervention.

Authors
Xie, L; Subashi, E; Qi, Y; Knepper, MA; Johnson, GA
MLA Citation
Xie, L, Subashi, E, Qi, Y, Knepper, MA, and Johnson, GA. "Four-dimensional MRI of renal function in the developing mouse." NMR in biomedicine 27.9 (September 2014): 1094-1102.
PMID
25066408
Source
epmc
Published In
Nmr in Biomedicine
Volume
27
Issue
9
Publish Date
2014
Start Page
1094
End Page
1102
DOI
10.1002/nbm.3162

Magnetic resonance histology—Applications in toxicology

Authors
Johnson, GA; Badea, A; Calabrese, E; Liu, C; Xie, L
MLA Citation
Johnson, GA, Badea, A, Calabrese, E, Liu, C, and Xie, L. "Magnetic resonance histology—Applications in toxicology." September 2014.
Source
crossref
Published In
Toxicology Letters
Volume
229
Publish Date
2014
Start Page
S31
End Page
S32
DOI
10.1016/j.toxlet.2014.06.148

Waxholm Space atlas of the Sprague Dawley rat brain.

Three-dimensional digital brain atlases represent an important new generation of neuroinformatics tools for understanding complex brain anatomy, assigning location to experimental data, and planning of experiments. We have acquired a microscopic resolution isotropic MRI and DTI atlasing template for the Sprague Dawley rat brain with 39 μm isotropic voxels for the MRI volume and 78 μm isotropic voxels for the DTI. Building on this template, we have delineated 76 major anatomical structures in the brain. Delineation criteria are provided for each structure. We have applied a spatial reference system based on internal brain landmarks according to the Waxholm Space standard, previously developed for the mouse brain, and furthermore connected this spatial reference system to the widely used stereotaxic coordinate system by identifying cranial sutures and related stereotaxic landmarks in the template using contrast given by the active staining technique applied to the tissue. With the release of the present atlasing template and anatomical delineations, we provide a new tool for spatial orientation analysis of neuroanatomical location, and planning and guidance of experimental procedures in the rat brain. The use of Waxholm Space and related infrastructures will connect the atlas to interoperable resources and services for multi-level data integration and analysis across reference spaces.

Authors
Papp, EA; Leergaard, TB; Calabrese, E; Johnson, GA; Bjaalie, JG
MLA Citation
Papp, EA, Leergaard, TB, Calabrese, E, Johnson, GA, and Bjaalie, JG. "Waxholm Space atlas of the Sprague Dawley rat brain." NeuroImage 97 (August 2014): 374-386.
PMID
24726336
Source
epmc
Published In
NeuroImage
Volume
97
Publish Date
2014
Start Page
374
End Page
386
DOI
10.1016/j.neuroimage.2014.04.001

Diffusion tensor imaging reveals white matter injury in a rat model of repetitive blast-induced traumatic brain injury.

Blast-induced traumatic brain injury (bTBI) is one of the most common combat-related injuries seen in U.S. military personnel, yet relatively little is known about the underlying mechanisms of injury. In particular, the effects of the primary blast pressure wave are poorly understood. Animal models have proven invaluable for the study of primary bTBI, because it rarely occurs in isolation in human subjects. Even less is known about the effects of repeated primary blast wave exposure, but existing data suggest cumulative increases in brain damage with a second blast. MRI and, in particular, diffusion tensor imaging (DTI), have become important tools for assessing bTBI in both clinical and preclinical settings. Computational statistical methods such as voxelwise analysis have shown promise in localizing and quantifying bTBI throughout the brain. In this study, we use voxelwise analysis of DTI to quantify white matter injury in a rat model of repetitive primary blast exposure. Our results show a significant increase in microstructural damage with a second blast exposure, suggesting that primary bTBI may sensitize the brain to subsequent injury.

Authors
Calabrese, E; Du, F; Garman, RH; Johnson, GA; Riccio, C; Tong, LC; Long, JB
MLA Citation
Calabrese, E, Du, F, Garman, RH, Johnson, GA, Riccio, C, Tong, LC, and Long, JB. "Diffusion tensor imaging reveals white matter injury in a rat model of repetitive blast-induced traumatic brain injury." Journal of neurotrauma 31.10 (May 2014): 938-950.
PMID
24392843
Source
epmc
Published In
Journal of Neurotrauma
Volume
31
Issue
10
Publish Date
2014
Start Page
938
End Page
950
DOI
10.1089/neu.2013.3144

Quantitative mapping of trimethyltin injury in the rat brain using magnetic resonance histology.

The growing exposure to chemicals in our environment and the increasing concern over their impact on health have elevated the need for new methods for surveying the detrimental effects of these compounds. Today's gold standard for assessing the effects of toxicants on the brain is based on hematoxylin and eosin (H&E)-stained histology, sometimes accompanied by special stains or immunohistochemistry for neural processes and myelin. This approach is time-consuming and is usually limited to a fraction of the total brain volume. We demonstrate that magnetic resonance histology (MRH) can be used for quantitatively assessing the effects of central nervous system toxicants in rat models. We show that subtle and sparse changes to brain structure can be detected using magnetic resonance histology, and correspond to some of the locations in which lesions are found by traditional pathological examination. We report for the first time diffusion tensor image-based detection of changes in white matter regions, including fimbria and corpus callosum, in the brains of rats exposed to 8 mg/kg and 12 mg/kg trimethyltin. Besides detecting brain-wide changes, magnetic resonance histology provides a quantitative assessment of dose-dependent effects. These effects can be found in different magnetic resonance contrast mechanisms, providing multivariate biomarkers for the same spatial location. In this study, deformation-based morphometry detected areas where previous studies have detected cell loss, while voxel-wise analyses of diffusion tensor parameters revealed microstructural changes due to such things as cellular swelling, apoptosis, and inflammation. Magnetic resonance histology brings a valuable addition to pathology with the ability to generate brain-wide quantitative parametric maps for markers of toxic insults in the rodent brain.

Authors
Johnson, GA; Calabrese, E; Little, PB; Hedlund, L; Qi, Y; Badea, A
MLA Citation
Johnson, GA, Calabrese, E, Little, PB, Hedlund, L, Qi, Y, and Badea, A. "Quantitative mapping of trimethyltin injury in the rat brain using magnetic resonance histology." Neurotoxicology 42 (May 2014): 12-23.
Website
http://hdl.handle.net/10161/10329
PMID
24631313
Source
epmc
Published In
NeuroToxicology
Volume
42
Publish Date
2014
Start Page
12
End Page
23
DOI
10.1016/j.neuro.2014.02.009

Comparison of 4D-microSPECT and microCT for murine cardiac function.

PURPOSE: The objective of this study was to compare a new generation of four-dimensional micro-single photon emission computed tomography (microSPECT) with microCT for the quantitative in vivo assessment of murine cardiac function. PROCEDURES: Four-dimensional isotropic cardiac images were acquired from anesthetized normal C57BL/6 mice with either microSPECT (n = 6) or microCT (n = 6). One additional mouse with myocardial infarction (MI) was scanned with both modalities. Prior to imaging, mice were injected with either technetium tetrofosmin for microSPECT or a liposomal blood pool contrast agent for microCT. Segmentation of the left ventricle (LV) was performed using Vitrea (Vital Images) software, to derive global and regional function. RESULTS: Measures of global LV function between microSPECT and microCT groups were comparable (e.g., ejection fraction = 71 ± 6 % microSPECT and 68 ± 4 % microCT). Regional functional indices (wall motion, wall thickening, regional ejection fraction) were also similar for the two modalities. In the mouse with MI, microSPECT identified a large perfusion defect that was not evident with microCT. CONCLUSIONS: Despite lower spatial resolution, microSPECT was comparable to microCT in the quantitative evaluation of cardiac function. MicroSPECT offers an advantage over microCT in the ability to evaluate simultaneously myocardial radiotracer distribution and function, simultaneously. MicroSPECT should be considered as an alternative to microCT and magnetic resonance for preclinical cardiac imaging in the mouse.

Authors
Befera, NT; Badea, CT; Johnson, GA
MLA Citation
Befera, NT, Badea, CT, and Johnson, GA. "Comparison of 4D-microSPECT and microCT for murine cardiac function." Mol Imaging Biol 16.2 (April 2014): 235-245.
PMID
24037175
Source
pubmed
Published In
Molecular Imaging and Biology
Volume
16
Issue
2
Publish Date
2014
Start Page
235
End Page
245
DOI
10.1007/s11307-013-0686-z

Quantitative magnetic susceptibility of the developing mouse brain reveals microstructural changes in the white matter.

Cerebral development involves a complex cascade of events which are difficult to visualize and quantify in vivo. In this study we combine information from Diffusion Tensor Imaging (DTI) and Quantitative Susceptibility Mapping (QSM) to analyze developing mouse brains at five stages up to 56days postnatal. Susceptibility maps were calculated using frequency shifts in gradient echo MR images acquired at 9.4T. The mean apparent magnetic susceptibility and magnetic susceptibility anisotropy of major white matter tracts were evaluated as a function of age. During the first two weeks, susceptibility of white matter appeared paramagnetic relative to surrounding gray matter; it then gradually became more diamagnetic. While diffusion anisotropy was already apparent and high at postnatal day 2, susceptibility anisotropy only became significant during the third week. This mismatch indicated different microstructural underpinnings for diffusion anisotropy and susceptibility anisotropy. Histological exams were also performed to evaluate myelin and iron content. It is confirmed that the main source of susceptibility contrast in WM is the myelin content. The ability to quantify the magnetic properties of white matter will provide valuable information on the architecture of the brain during development and potentially a more specific indicator for myelin degenerative diseases.

Authors
Argyridis, I; Li, W; Johnson, GA; Liu, C
MLA Citation
Argyridis, I, Li, W, Johnson, GA, and Liu, C. "Quantitative magnetic susceptibility of the developing mouse brain reveals microstructural changes in the white matter." Neuroimage 88 (March 2014): 134-142.
PMID
24269576
Source
pubmed
Published In
NeuroImage
Volume
88
Publish Date
2014
Start Page
134
End Page
142
DOI
10.1016/j.neuroimage.2013.11.026

Assessing cardiac injury in mice with dual energy-microCT, 4D-microCT, and microSPECT imaging after partial heart irradiation.

To develop a mouse model of cardiac injury after partial heart irradiation (PHI) and to test whether dual energy (DE)-microCT and 4-dimensional (4D)-microCT can be used to assess cardiac injury after PHI to complement myocardial perfusion imaging using micro-single photon emission computed tomography (SPECT).To study cardiac injury from tangent field irradiation in mice, we used a small-field biological irradiator to deliver a single dose of 12 Gy x-rays to approximately one-third of the left ventricle (LV) of Tie2Cre; p53(FL/+) and Tie2Cre; p53(FL/-) mice, where 1 or both alleles of p53 are deleted in endothelial cells. Four and 8 weeks after irradiation, mice were injected with gold and iodinated nanoparticle-based contrast agents, and imaged with DE-microCT and 4D-microCT to evaluate myocardial vascular permeability and cardiac function, respectively. Additionally, the same mice were imaged with microSPECT to assess myocardial perfusion.After PHI with tangent fields, DE-microCT scans showed a time-dependent increase in accumulation of gold nanoparticles (AuNp) in the myocardium of Tie2Cre; p53(FL/-) mice. In Tie2Cre; p53(FL/-) mice, extravasation of AuNp was observed within the irradiated LV, whereas in the myocardium of Tie2Cre; p53(FL/+) mice, AuNp were restricted to blood vessels. In addition, data from DE-microCT and microSPECT showed a linear correlation (R(2) = 0.97) between the fraction of the LV that accumulated AuNp and the fraction of LV with a perfusion defect. Furthermore, 4D-microCT scans demonstrated that PHI caused a markedly decreased ejection fraction, and higher end-diastolic and end-systolic volumes, to develop in Tie2Cre; p53(FL/-) mice, which were associated with compensatory cardiac hypertrophy of the heart that was not irradiated.Our results show that DE-microCT and 4D-microCT with nanoparticle-based contrast agents are novel imaging approaches complementary to microSPECT for noninvasive assessment of the change in myocardial vascular permeability and cardiac function of mice in whom myocardial injury develops after PHI.

Authors
Lee, C-L; Min, H; Befera, N; Clark, D; Qi, Y; Das, S; Johnson, GA; Badea, CT; Kirsch, DG
MLA Citation
Lee, C-L, Min, H, Befera, N, Clark, D, Qi, Y, Das, S, Johnson, GA, Badea, CT, and Kirsch, DG. "Assessing cardiac injury in mice with dual energy-microCT, 4D-microCT, and microSPECT imaging after partial heart irradiation." International journal of radiation oncology, biology, physics 88.3 (March 2014): 686-693.
Website
http://hdl.handle.net/10161/12625
PMID
24521682
Source
epmc
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
88
Issue
3
Publish Date
2014
Start Page
686
End Page
693
DOI
10.1016/j.ijrobp.2013.11.238

Anatomical and functional imaging of myocardial infarction in mice using micro-CT and eXIA 160 contrast agent.

Noninvasive small animal imaging techniques are essential for evaluation of cardiac disease and potential therapeutics. A novel preclinical iodinated contrast agent called eXIA 160 has recently been developed, which has been evaluated for micro-CT cardiac imaging. eXIA 160 creates strong contrast between blood and tissue immediately after its injection and is subsequently taken up by the myocardium and other metabolically active tissues over time. We focus on these properties of eXIA and show its use in imaging myocardial infarction in mice. Five C57BL/6 mice were imaged ~2 weeks after left anterior descending coronary artery ligation. Six C57BL/6 mice were used as controls. Immediately after injection of eXIA 160, an enhancement difference between blood and myocardium of ~340 HU enabled cardiac function estimation via 4D micro-CT scanning with retrospective gating. Four hours post-injection, the healthy perfused myocardium had a contrast difference of ~140 HU relative to blood while the infarcted myocardium showed no enhancement. These differences allowed quantification of infarct size via dual-energy micro-CT. In vivo micro-SPECT imaging and ex vivo triphenyl tetrazolium chloride (TTC) staining provided validation for the micro-CT findings. Root mean squared error of infarct measurements was 2.7% between micro-CT and SPECT, and 4.7% between micro-CT and TTC. Thus, micro-CT with eXIA 160 can be used to provide both morphological and functional data for preclinical studies evaluating myocardial infarction and potential therapies. Further studies are warranted to study the potential use of eXIA 160 as a CT molecular imaging tool for other metabolically active tissues in the mouse.

Authors
Ashton, JR; Befera, N; Clark, D; Qi, Y; Mao, L; Rockman, HA; Johnson, GA; Badea, CT
MLA Citation
Ashton, JR, Befera, N, Clark, D, Qi, Y, Mao, L, Rockman, HA, Johnson, GA, and Badea, CT. "Anatomical and functional imaging of myocardial infarction in mice using micro-CT and eXIA 160 contrast agent." Contrast media & molecular imaging 9.2 (March 2014): 161-168.
PMID
24523061
Source
epmc
Published In
Contrast Media & Molecular Imaging
Volume
9
Issue
2
Publish Date
2014
Start Page
161
End Page
168
DOI
10.1002/cmmi.1557

An analysis of the uncertainty and bias in DCE-MRI measurements using the spoiled gradient-recalled echo pulse sequence.

The pharmacokinetic parameters derived from dynamic contrast-enhanced (DCE) MRI have been used in more than 100 phase I trials and investigator led studies. A comparison of the absolute values of these quantities requires an estimation of their respective probability distribution function (PDF). The statistical variation of the DCE-MRI measurement is analyzed by considering the fundamental sources of error in the MR signal intensity acquired with the spoiled gradient-echo (SPGR) pulse sequence.The variance in the SPGR signal intensity arises from quadrature detection and excitation flip angle inconsistency. The noise power was measured in 11 phantoms of contrast agent concentration in the range [0-1] mM (in steps of 0.1 mM) and in onein vivo acquisition of a tumor-bearing mouse. The distribution of the flip angle was determined in a uniform 10 mM CuSO4 phantom using the spin echo double angle method. The PDF of a wide range of T1 values measured with the varying flip angle (VFA) technique was estimated through numerical simulations of the SPGR equation. The resultant uncertainty in contrast agent concentration was incorporated in the most common model of tracer exchange kinetics and the PDF of the derived pharmacokinetic parameters was studied numerically.The VFA method is an unbiased technique for measuringT1 only in the absence of bias in excitation flip angle. The time-dependent concentration of the contrast agent measured in vivo is within the theoretically predicted uncertainty. The uncertainty in measuring K(trans) with SPGR pulse sequences is of the same order, but always higher than, the uncertainty in measuring the pre-injection longitudinal relaxation time (T10). The lowest achievable bias/uncertainty in estimating this parameter is approximately 20%-70% higher than the bias/uncertainty in the measurement of the pre-injection T1 map. The fractional volume parameters derived from the extended Tofts model were found to be extremely sensitive to the variance in signal intensity. The SNR of the pre-injection T1 map indicates the limiting precision with which K(trans) can be calculated.Current small-animal imaging systems and pulse sequences robust to motion artifacts have the capacity for reproducible quantitative acquisitions with DCE-MRI. In these circumstances, it is feasible to achieve a level of precision limited only by physiologic variability.

Authors
Subashi, E; Choudhury, KR; Johnson, GA
MLA Citation
Subashi, E, Choudhury, KR, and Johnson, GA. "An analysis of the uncertainty and bias in DCE-MRI measurements using the spoiled gradient-recalled echo pulse sequence." Medical physics 41.3 (March 2014): 032301-.
PMID
24593738
Source
epmc
Published In
Medical physics
Volume
41
Issue
3
Publish Date
2014
Start Page
032301
DOI
10.1118/1.4865790

Comparison of 4D-MicroSPECT and MicroCT for murine cardiac function

Purpose: The objective of this study was to compare a new generation of four-dimensional micro-single photon emission computed tomography (microSPECT) with microCT for the quantitative in vivo assessment of murine cardiac function. Procedures: Four-dimensional isotropic cardiac images were acquired from anesthetized normal C57BL/6 mice with either microSPECT (n = 6) or microCT (n = 6). One additional mouse with myocardial infarction (MI) was scanned with both modalities. Prior to imaging, mice were injected with either technetium tetrofosmin for microSPECT or a liposomal blood pool contrast agent for microCT. Segmentation of the left ventricle (LV) was performed using Vitrea (Vital Images) software, to derive global and regional function. Results: Measures of global LV function between microSPECT and microCT groups were comparable (e.g., ejection fraction = 71 ± 6 % microSPECT and 68 ± 4 % microCT). Regional functional indices (wall motion, wall thickening, regional ejection fraction) were also similar for the two modalities. In the mouse with MI, microSPECT identified a large perfusion defect that was not evident with microCT. Conclusions: Despite lower spatial resolution, microSPECT was comparable to microCT in the quantitative evaluation of cardiac function. MicroSPECT offers an advantage over microCT in the ability to evaluate simultaneously myocardial radiotracer distribution and function, simultaneously. MicroSPECT should be considered as an alternative to microCT and magnetic resonance for preclinical cardiac imaging in the mouse. © 2013 World Molecular Imaging Society.

Authors
Befera, NT; Badea, CT; Johnson, GA
MLA Citation
Befera, NT, Badea, CT, and Johnson, GA. "Comparison of 4D-MicroSPECT and MicroCT for murine cardiac function." Molecular Imaging and Biology 16.2 (January 1, 2014): 235-245.
Source
scopus
Published In
Molecular Imaging and Biology
Volume
16
Issue
2
Publish Date
2014
Start Page
235
End Page
245
DOI
10.1007/s11307-013-0686-z

A multi-resolution approach to retrospectively-gated cardiac micro-CT reconstruction

In preclinical research, micro-CT is commonly used to provide anatomical information; however, there is significant interest in using this technology to obtain functional information in cardiac studies. The fastest acquisition in 4D cardiac micro-CT imaging is achieved via retrospective gating, resulting in irregular angular projections after binning the projections into phases of the cardiac cycle. Under these conditions, analytical reconstruction algorithms, such as filtered back projection, suffer from streaking artifacts. Here, we propose a novel, multi-resolution, iterative reconstruction algorithm inspired by robust principal component analysis which prevents the introduction of streaking artifacts, while attempting to recover the highest temporal resolution supported by the projection data. The algorithm achieves these results through a unique combination of the split Bregman method and joint bilateral filtration. We illustrate the algorithm’s performance using a contrast-enhanced, 2D slice through the MOBY mouse phantom and realistic projection acquisition and reconstruction parameters. Our results indicate that the algorithm is robust to under sampling levels of only 34 projections per cardiac phase and, therefore, has high potential in reducing both acquisition times and radiation dose. Another potential advantage of the multi-resolution scheme is the natural division of the reconstruction problem into a large number of independent sub-problems which can be solved in parallel. In future work, we will investigate the performance of this algorithm with retrospectively-gated, cardiac micro-CT data. © 2014 SPIE.

Authors
Clark, DP; Johnson, GA; Badea, CT
MLA Citation
Clark, DP, Johnson, GA, and Badea, CT. "A multi-resolution approach to retrospectively-gated cardiac micro-CT reconstruction." January 1, 2014.
Source
scopus
Published In
Proceedings of SPIE
Volume
9033
Publish Date
2014
DOI
10.1117/12.2043044

Robust material decomposition for spectral CT

There is ongoing interest in extending CT from anatomical to functional imaging. Recent successes with dual energy CT, the introduction of energy discriminating x-ray detectors, and novel, target-specific, nanoparticle contrast agents enable functional imaging capabilities via spectral CT. However, many challenges related to radiation dose, photon flux, and sensitivity still must be overcome. Here, we introduce a post-reconstruction algorithm called spectral diffusion that performs a robust material decomposition of spectral CT data in the presence of photon noise to address these challenges. Specifically, we use spectrally joint, piece-wise constant kernel regression and the split Bregman method to iteratively solve for a material decomposition which is gradient sparse, quantitatively accurate, and minimally biased relative to the source data. Spectral diffusion integrates structural information from multiple spectral channels and their corresponding material decompositions within the framework of diffusion-like denoising algorithms. Using a 3D, digital bar phantom and a material sensitivity matrix calibrated for use with a polychromatic x-ray source, we quantify the limits of detectability (CNR = 5) afforded by spectral diffusion in the triple-energy material decomposition of iodine (3.1 mg/mL), gold (0.9 mg/mL), and gadolinium (2.9 mg/mL) concentrations. © 2014 SPIE.

Authors
Clark, DP; Johnson, GA; Badea, CT
MLA Citation
Clark, DP, Johnson, GA, and Badea, CT. "Robust material decomposition for spectral CT." January 1, 2014.
Source
scopus
Published In
Proceedings of SPIE
Volume
9038
Publish Date
2014
DOI
10.1117/12.2042546

Dual-energy micro-CT imaging of pulmonary airway obstruction: Correlation with micro-SPECT

To match recent clinical dual energy (DE) CT studies focusing on the lung, similar developments for DE micro-CT of the rodent lung are required. Our group has been actively engaged in designing pulmonary gating techniques for micro- CT, and has also introduced the first DE micro-CT imaging method of the rodent lung. The aim of this study was to assess the feasibility of DE micro-CT imaging for the evaluation of airway obstruction in mice, and to compare the method with micro single photon emission computed tomography (micro-SPECT) using technetium-99m labeled macroaggregated albumin (99mTc-MAA). The results suggest that the induced pulmonary airway obstruction causes either atelectasis, or air-trapping similar to asthma or chronic bronchitis. Atelectasis could only be detected at early time points in DE micro-CT images, and is associated with a large increase in blood fraction and decrease in air fraction. Air trapping had an opposite effect with larger air fraction and decreased blood fraction shown by DE micro-CT. The decrease in perfusion to the hypoventilated lung (hypoxic vasoconstriction) is also seen in micro-SPECT. The proposed DE micro-CT technique for imaging localized airway obstruction performed well in our evaluation, and provides a higher resolution compared to micro-SPECT. Both DE micro-CT and micro-SPECT provide critical, quantitative lung biomarkers for image-based anatomical and functional information in the small animal. The methods are readily linked to clinical methods allowing direct comparison of preclinical and clinical results. © 2014 SPIE.

Authors
Badea, CT; Befera, N; Clark, D; Qi, Y; Johnson, GA
MLA Citation
Badea, CT, Befera, N, Clark, D, Qi, Y, and Johnson, GA. "Dual-energy micro-CT imaging of pulmonary airway obstruction: Correlation with micro-SPECT." January 1, 2014.
Source
scopus
Published In
Proceedings of SPIE
Volume
9038
Publish Date
2014
DOI
10.1117/12.2043094

Four-dimensional MRI of renal function in the developing mouse

The major roles of filtration, metabolism and high blood flow make the kidney highly vulnerable to drug-induced toxicity and other renal injuries. A method to follow kidney function is essential for the early screening of toxicity and malformations. In this study, we acquired high spatiotemporal resolution (four dimensional) datasets of normal mice to follow changes in kidney structure and function during development. The data were acquired with dynamic contrast-enhanced MRI (via keyhole imaging) and a cryogenic surface coil, allowing us to obtain a full three-dimensional image (isotropic resolution, 125microns) every 7.7s over a 50-min scan. This time course permitted the demonstration of both contrast enhancement and clearance. Functional changes were measured over a 17-week course (at 3, 5, 7, 9, 13 and 17weeks). The time dimension of the MRI dataset was processed to produce unique image contrasts to segment the four regions of the kidney: cortex (CO), outer stripe (OS) of the outer medulla (OM), inner stripe (IS) of the OM and inner medulla (IM). Local volumes, time-to-peak (TTP) values and decay constants (DC) were measured in each renal region. These metrics increased significantly with age, with the exception of DC values in the IS and OS. These data will serve as a foundation for studies of normal renal physiology and future studies of renal diseases that require early detection and intervention. © 2014 John Wiley & Sons, Ltd.

Authors
Xie, L; Subashi, E; Qi, Y; Knepper, MA; Johnson, GA
MLA Citation
Xie, L, Subashi, E, Qi, Y, Knepper, MA, and Johnson, GA. "Four-dimensional MRI of renal function in the developing mouse." NMR in Biomedicine 27.9 (January 1, 2014): 1094-1102.
Source
scopus
Published In
Nmr in Biomedicine
Volume
27
Issue
9
Publish Date
2014
Start Page
1094
End Page
1102
DOI
10.1002/nbm.3162

Helical dual source cone-beam micro-CT

© 2014 IEEE.While helical scanning is well established in the clinical arena, most micro-CT scanners use circular cone beam trajectories and approximate reconstructions based on a filtered backprojection (FBP) algorithm. This may be sufficient for some applications, but in studies of larger animals, such as rats, the size of the detector can constrain the field of view and extend scan time. To address this problem, we have designed and implemented helical scanning and reconstruction procedures for an in-house-developed dual source cone-beam micro-CT system. The reconstruction uses a simultaneous algebraic reconstruction technique combined with total variation regularization (SART-TV). We implemented this algorithm on a graphics processing unit (GPU) to reduce run time. The results demonstrate the speed and accuracy of the GPU-based SART-TV algorithm. The helical scan enables the reconstruction of volumes with extended field of view for whole body micro-CT imaging of large rodents.

Authors
Johnston, SM; Johnson, GA; Badea, CT
MLA Citation
Johnston, SM, Johnson, GA, and Badea, CT. "Helical dual source cone-beam micro-CT." January 1, 2014.
Source
scopus
Published In
2014 IEEE 11th International Symposium on Biomedical Imaging, ISBI 2014
Publish Date
2014
Start Page
177
End Page
180

Characterization of subtle brain abnormalities in a mouse model of Hedgehog pathway antagonist-induced cleft lip and palate.

Subtle behavioral and cognitive deficits have been documented in patient cohorts with orofacial clefts (OFCs). Recent neuroimaging studies argue that these traits are associated with structural brain abnormalities but have been limited to adolescent and adult populations where brain plasticity during infancy and childhood may be a confounding factor. Here, we employed high resolution magnetic resonance microscopy to examine primary brain morphology in a mouse model of OFCs. Transient in utero exposure to the Hedgehog (Hh) signaling pathway antagonist cyclopamine resulted in a spectrum of facial dysmorphology, including unilateral and bilateral cleft lip and palate, cleft of the secondary palate only, and a non-cleft phenotype marked by midfacial hypoplasia. Relative to controls, cyclopamine-exposed fetuses exhibited volumetric differences in several brain regions, including hypoplasia of the pituitary gland and olfactory bulbs, hyperplasia of the forebrain septal region, and expansion of the third ventricle. However, in affected fetuses the corpus callosum was intact and normal division of the forebrain was observed. This argues that temporally-specific Hh signaling perturbation can result in typical appearing OFCs in the absence of holoprosencephaly--a condition classically associated with Hh pathway inhibition and frequently co-occurring with OFCs. Supporting the premise that some forms of OFCs co-occur with subtle brain malformations, these results provide a possible ontological basis for traits identified in clinical populations. They also argue in favor of future investigations into genetic and/or environmental modulation of the Hh pathway in the etiopathogenesis of orofacial clefting.

Authors
Lipinski, RJ; Holloway, HT; O'Leary-Moore, SK; Ament, JJ; Pecevich, SJ; Cofer, GP; Budin, F; Everson, JL; Johnson, GA; Sulik, KK
MLA Citation
Lipinski, RJ, Holloway, HT, O'Leary-Moore, SK, Ament, JJ, Pecevich, SJ, Cofer, GP, Budin, F, Everson, JL, Johnson, GA, and Sulik, KK. "Characterization of subtle brain abnormalities in a mouse model of Hedgehog pathway antagonist-induced cleft lip and palate." PloS one 9.7 (January 2014): e102603-.
Website
http://hdl.handle.net/10161/11679
PMID
25047453
Source
epmc
Published In
PloS one
Volume
9
Issue
7
Publish Date
2014
Start Page
e102603
DOI
10.1371/journal.pone.0102603

Magnetic resonance imaging of graded skeletal muscle injury in live rats.

Increasing number of stretch-shortening contractions (SSCs) results in increased muscle injury.Fischer Hybrid rats were acutely exposed to an increasing number of SSCs in vivo using a custom-designed dynamometer. Magnetic resonance imaging (MRI) imaging was conducted 72 hours after exposure when rats were infused with Prohance and imaged using a 7T rodent MRI system (GE Epic 12.0). Images were acquired in the transverse plane with typically 60 total slices acquired covering the entire length of the hind legs. Rats were euthanized after MRI, the lower limbs removed, and tibialis anterior muscles were prepared for histology and quantified stereology.Stereological analyses showed myofiber degeneration, and cellular infiltrates significantly increased following 70 and 150 SSC exposure compared to controls. MRI images revealed that the percent affected area significantly increased with exposure in all SSC groups in a graded fashion. Signal intensity also significantly increased with increasing SSC repetitions.These results suggest that contrast-enhanced MRI has the sensitivity to differentiate specific degrees of skeletal muscle strain injury, and imaging data are specifically representative of cellular histopathology quantified via stereological analyses.

Authors
Cutlip, RG; Hollander, MS; Johnson, GA; Johnson, BW; Friend, SA; Baker, BA
MLA Citation
Cutlip, RG, Hollander, MS, Johnson, GA, Johnson, BW, Friend, SA, and Baker, BA. "Magnetic resonance imaging of graded skeletal muscle injury in live rats." Environmental health insights 8.Suppl 1 (January 2014): 31-39.
Website
http://hdl.handle.net/10161/10309
PMID
25525369
Source
epmc
Published In
Environmental Health Insights
Volume
8
Issue
Suppl 1
Publish Date
2014
Start Page
31
End Page
39
DOI
10.4137/ehi.s15255

Semi-automated 3D segmentation of major tracts in the rat brain: Comparing DTI with standard histological methods

Researchers working with rodent models of neurological disease often require an accurate map of the anatomical organization of the white matter of the rodent brain. With the increasing popularity of small animal MRI techniques, including diffusion tensor imaging (DTI), there is considerable interest in rapid segmentation methods of neurological structures for quantitative comparisons. DTI-derived tractography allows simple and rapid segmentation of major white matter tracts, but the anatomic accuracy of these computer-generated fibers is open to question and has not been rigorously evaluated in the rat brain. In this study, we examine the anatomic accuracy of tractography-based segmentation in the adult rat brain. We analysed 12 major white matter pathways using semi-automated tractography-based segmentation alongside manual segmentation of Gallyas silver-stained histology sections. We applied four fiber-tracking algorithms to the DTI data-two integration methods and two deflection methods. In many cases, tractography-based segmentation closely matched histology-based segmentation; however different tractography algorithms produced dramatically different results. Results suggest that certain white matter pathways are more amenable to tractography-based segmentation than others. We believe that these data will help researchers decide whether it is appropriate to use tractography-based segmentation of white matter structures for quantitative DTI-based analysis of neurologic disease models. © 2013 Springer-Verlag.

Authors
Gyengesi, E; Calabrese, E; Sherrier, MC; Johnson, GA; Paxinos, G; Watson, C
MLA Citation
Gyengesi, E, Calabrese, E, Sherrier, MC, Johnson, GA, Paxinos, G, and Watson, C. "Semi-automated 3D segmentation of major tracts in the rat brain: Comparing DTI with standard histological methods." Brain Structure and Function 219.2 (2014): 539-550.
Source
scival
Published In
Brain Structure and Function
Volume
219
Issue
2
Publish Date
2014
Start Page
539
End Page
550
DOI
10.1007/s00429-013-0516-8

Quantitative susceptibility mapping of kidney inflammation and fibrosis in type 1 angiotensin receptor-deficient mice

Disruption of the regulatory role of the kidneys leads to diverse renal pathologies; one major hallmark is inflammation and fibrosis. Conventional magnitude MRI has been used to study renal pathologies; however, the quantification or even detection of focal lesions caused by inflammation and fibrosis is challenging. We propose that quantitative susceptibility mapping (QSM) may be particularly sensitive for the identification of inflammation and fibrosis. In this study, we applied QSM in a mouse model deficient for angiotensin receptor type 1 (AT1). This model is known for graded pathologies, including focal interstitial fibrosis, cortical inflammation, glomerulocysts and inner medullary hypoplasia. We acquired high-resolution MRI on kidneys from AT1-deficient mice that were perfusion fixed with contrast agent. Two MR sequences were used (three-dimensional spin echo and gradient echo) to produce three image contrasts: T1, T2 (magnitude) and QSM. T1 and T2 (magnitude) images were acquired to segment major renal structures and to provide landmarks for the focal lesions of inflammation and fibrosis in the three-dimensional space. The volumes of major renal structures were measured to determine the relationship of the volumes to the degree of renal abnormalities and magnetic susceptibility values. Focal lesions were segmented from QSM images and were found to be closely associated with the major vessels. Susceptibilities were relatively more paramagnetic in wild-type mice: 1.46±0.36 in the cortex, 2.14±0.94 in the outer medulla and 2.10±2.80 in the inner medulla (10-2ppm). Susceptibilities were more diamagnetic in knockout mice: -7.68±4.22 in the cortex, -11.46±2.13 in the outer medulla and -7.57±5.58 in the inner medulla (10-2ppm). This result was consistent with the increase in diamagnetic content, e.g. proteins and lipids, associated with inflammation and fibrosis. Focal lesions were validated with conventional histology. QSM was very sensitive in detecting pathology caused by small focal inflammation and fibrosis. QSM offers a new MR contrast mechanism to study this common disease marker in the kidney. © 2013 John Wiley & Sons, Ltd.

Authors
Xie, L; Sparks, MA; Li, W; Qi, Y; Liu, C; Coffman, TM; Johnson, GA
MLA Citation
Xie, L, Sparks, MA, Li, W, Qi, Y, Liu, C, Coffman, TM, and Johnson, GA. "Quantitative susceptibility mapping of kidney inflammation and fibrosis in type 1 angiotensin receptor-deficient mice." NMR in Biomedicine 26.12 (December 1, 2013): 1853-1863.
Source
scopus
Published In
Nmr in Biomedicine
Volume
26
Issue
12
Publish Date
2013
Start Page
1853
End Page
1863
DOI
10.1002/nbm.3039

Quantitative susceptibility mapping of kidney inflammation and fibrosis in type 1 angiotensin receptor-deficient mice.

Disruption of the regulatory role of the kidneys leads to diverse renal pathologies; one major hallmark is inflammation and fibrosis. Conventional magnitude MRI has been used to study renal pathologies; however, the quantification or even detection of focal lesions caused by inflammation and fibrosis is challenging. We propose that quantitative susceptibility mapping (QSM) may be particularly sensitive for the identification of inflammation and fibrosis. In this study, we applied QSM in a mouse model deficient for angiotensin receptor type 1 (AT1). This model is known for graded pathologies, including focal interstitial fibrosis, cortical inflammation, glomerulocysts and inner medullary hypoplasia. We acquired high-resolution MRI on kidneys from AT1-deficient mice that were perfusion fixed with contrast agent. Two MR sequences were used (three-dimensional spin echo and gradient echo) to produce three image contrasts: T1, T2* (magnitude) and QSM. T1 and T2* (magnitude) images were acquired to segment major renal structures and to provide landmarks for the focal lesions of inflammation and fibrosis in the three-dimensional space. The volumes of major renal structures were measured to determine the relationship of the volumes to the degree of renal abnormalities and magnetic susceptibility values. Focal lesions were segmented from QSM images and were found to be closely associated with the major vessels. Susceptibilities were relatively more paramagnetic in wild-type mice: 1.46 ± 0.36 in the cortex, 2.14 ± 0.94 in the outer medulla and 2.10 ± 2.80 in the inner medulla (10(-2) ppm). Susceptibilities were more diamagnetic in knockout mice: -7.68 ± 4.22 in the cortex, -11.46 ± 2.13 in the outer medulla and -7.57 ± 5.58 in the inner medulla (10(-2) ppm). This result was consistent with the increase in diamagnetic content, e.g. proteins and lipids, associated with inflammation and fibrosis. Focal lesions were validated with conventional histology. QSM was very sensitive in detecting pathology caused by small focal inflammation and fibrosis. QSM offers a new MR contrast mechanism to study this common disease marker in the kidney.

Authors
Xie, L; Sparks, MA; Li, W; Qi, Y; Liu, C; Coffman, TM; Johnson, GA
MLA Citation
Xie, L, Sparks, MA, Li, W, Qi, Y, Liu, C, Coffman, TM, and Johnson, GA. "Quantitative susceptibility mapping of kidney inflammation and fibrosis in type 1 angiotensin receptor-deficient mice." NMR Biomed 26.12 (December 2013): 1853-1863.
PMID
24154952
Source
pubmed
Published In
Nmr in Biomedicine
Volume
26
Issue
12
Publish Date
2013
Start Page
1853
End Page
1863
DOI
10.1002/nbm.3039

Diffusion tensor magnetic resonance histology reveals microstructural changes in the developing rat brain.

The postnatal period is a remarkably dynamic phase of brain growth and development characterized by large-scale macrostructural changes, as well as dramatic microstructural changes, including myelination and cortical layering. This crucial period of neurodevelopment is uniquely susceptible to a wide variety of insults that may lead to neurologic disease. MRI is an important tool for studying both normal and abnormal neurodevelopmental changes, and quantitative imaging strategies like diffusion tensor imaging (DTI) allow visualization of many of the complex microstructural changes that occur during postnatal life. Diffusion tensor magnetic resonance histology (DT-MRH) provides particularly unique insight into cytoarchitectural changes in the developing brain. In this study, we used DT-MRH to track microstructural changes in the rat brain throughout normal postnatal neurodevelopment. We provide examples of diffusion tensor parameter changes in both white matter and gray matter structures, and correlate these changes with changes in cytoarchitecture. Finally, we provide a comprehensive database of image sets as a foundation for future studies using DT-MRH to characterize abnormal neurodevelopment in rodent models of neurodevelopmental disease.

Authors
Calabrese, E; Johnson, GA
MLA Citation
Calabrese, E, and Johnson, GA. "Diffusion tensor magnetic resonance histology reveals microstructural changes in the developing rat brain." Neuroimage 79 (October 1, 2013): 329-339.
PMID
23648962
Source
pubmed
Published In
NeuroImage
Volume
79
Publish Date
2013
Start Page
329
End Page
339
DOI
10.1016/j.neuroimage.2013.04.101

Magnetic resonance histology: cool images- but who cares?

Authors
Johnson, GA; Badea, A; Calabrese, E; Liu, C; Xie, L
MLA Citation
Johnson, GA, Badea, A, Calabrese, E, Liu, C, and Xie, L. "Magnetic resonance histology: cool images- but who cares?." TOXICOLOGY LETTERS 221 (August 28, 2013): S50-S50.
Source
wos-lite
Published In
Toxicology Letters
Volume
221
Publish Date
2013
Start Page
S50
End Page
S50
DOI
10.1016/j.toxlet.2013.06.183

HIGH-RESOLUTION NEUROIMAGING REVEALS A RANGE OF CORPUS CALLOSUM INSULT INDUCED BY ETHANOL ON GESTATIONAL DAY 7 INMICE

Authors
O'Leary-Moore, SK; Budin, F; Paniagua, B; Oguz, I; Johnson, GA; Sulik, KK
MLA Citation
O'Leary-Moore, SK, Budin, F, Paniagua, B, Oguz, I, Johnson, GA, and Sulik, KK. "HIGH-RESOLUTION NEUROIMAGING REVEALS A RANGE OF CORPUS CALLOSUM INSULT INDUCED BY ETHANOL ON GESTATIONAL DAY 7 INMICE." ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH 37 (June 2013): 167A-167A.
Source
wos-lite
Published In
Alcoholism: Clinical and Experimental Research
Volume
37
Publish Date
2013
Start Page
167A
End Page
167A

A quantitative magnetic resonance histology atlas of postnatal rat brain development with regional estimates of growth and variability.

There has been growing interest in the role of postnatal brain development in the etiology of several neurologic diseases. The rat has long been recognized as a powerful model system for studying neuropathology and the safety of pharmacologic treatments. However, the complex spatiotemporal changes that occur during rat neurodevelopment remain to be elucidated. This work establishes the first magnetic resonance histology (MRH) atlas of the developing rat brain, with an emphasis on quantitation. The atlas comprises five specimens at each of nine time points, imaged with eight distinct MR contrasts and segmented into 26 developmentally defined brain regions. The atlas was used to establish a timeline of morphometric changes and variability throughout neurodevelopment and represents a quantitative database of rat neurodevelopment for characterizing rat models of human neurologic disease.

Authors
Calabrese, E; Badea, A; Watson, C; Johnson, GA
MLA Citation
Calabrese, E, Badea, A, Watson, C, and Johnson, GA. "A quantitative magnetic resonance histology atlas of postnatal rat brain development with regional estimates of growth and variability." Neuroimage 71 (May 1, 2013): 196-206.
PMID
23353030
Source
pubmed
Published In
NeuroImage
Volume
71
Publish Date
2013
Start Page
196
End Page
206
DOI
10.1016/j.neuroimage.2013.01.017

Dual-energy micro-computed tomography imaging of radiation-induced vascular changes in primary mouse sarcomas.

PURPOSE: To evaluate the effects of radiation therapy on primary tumor vasculature using dual-energy (DE) micro-computed tomography (micro-CT). METHODS AND MATERIALS: Primary sarcomas were generated with mutant Kras and p53. Unirradiated tumors were compared with tumors irradiated with 20 Gy. A liposomal-iodinated contrast agent was administered 1 day after treatment, and mice were imaged immediately after injection (day 1) and 3 days later (day 4) with DE micro-CT. CT-derived tumor sizes were used to assess tumor growth. After DE decomposition, iodine maps were used to assess tumor fractional blood volume (FBV) at day 1 and tumor vascular permeability at day 4. For comparison, tumor vascularity and vascular permeability were also evaluated histologically by use of CD31 immunofluorescence and fluorescently-labeled dextrans. RESULTS: Radiation treatment significantly decreased tumor growth from day 1 to day 4 (P<.05). There was a positive correlation between CT measurement of tumor FBV on day 1 and extravasated iodine on day 4 with microvascular density (MVD) on day 4 (R(2)=0.53) and dextran accumulation (R(2)=0.63) on day 4, respectively. Despite no change in MVD measured by histology, tumor FBV significantly increased after irradiation as measured by DE micro-CT (0.070 vs 0.091, P<.05). Both dextran and liposomal-iodine accumulation in tumors increased significantly after irradiation, with dextran fractional area increasing 5.2-fold and liposomal-iodine concentration increasing 4.0-fold. CONCLUSIONS: DE micro-CT is an effective tool for noninvasive assessment of vascular changes in primary tumors. Tumor blood volume and vascular permeability increased after a single therapeutic dose of radiation treatment.

Authors
Moding, EJ; Clark, DP; Qi, Y; Li, Y; Ma, Y; Ghaghada, K; Johnson, GA; Kirsch, DG; Badea, CT
MLA Citation
Moding, EJ, Clark, DP, Qi, Y, Li, Y, Ma, Y, Ghaghada, K, Johnson, GA, Kirsch, DG, and Badea, CT. "Dual-energy micro-computed tomography imaging of radiation-induced vascular changes in primary mouse sarcomas." Int J Radiat Oncol Biol Phys 85.5 (April 1, 2013): 1353-1359.
PMID
23122984
Source
pubmed
Published In
International Journal of Radiation: Oncology - Biology - Physics
Volume
85
Issue
5
Publish Date
2013
Start Page
1353
End Page
1359
DOI
10.1016/j.ijrobp.2012.09.027

The utility of micro-CT and MRI in the assessment of longitudinal growth of liver metastases in a preclinical model of colon carcinoma.

RATIONALE AND OBJECTIVES: Liver is a common site for distal metastases in colon and rectal cancer. Numerous clinical studies have analyzed the relative merits of different imaging modalities for detection of liver metastases. Several exciting new therapies are being investigated in preclinical models. But, technical challenges in preclinical imaging make it difficult to translate conclusions from clinical studies to the preclinical environment. This study addresses the technical challenges of preclinical magnetic resonance imaging (MRI) and micro-computed tomography (CT) to enable comparison of state-of-the-art methods for following metastatic liver disease. MATERIALS AND METHODS: We optimized two promising preclinical protocols to enable a parallel longitudinal study tracking metastatic human colon carcinoma growth in a mouse model: T2-weighted MRI using two-shot PROPELLER (Periodically Rotated Overlapping ParallEL Lines with Enhanced Reconstruction) and contrast-enhanced micro-CT using a liposomal contrast agent. Both methods were tailored for high throughput with attention to animal support and anesthesia to limit biological stress. RESULTS AND CONCLUSIONS: Each modality has its strengths. Micro-CT permitted more rapid acquisition (<10 minutes) with the highest spatial resolution (88-micron isotropic resolution). But detection of metastatic lesions requires the use of a blood pool contrast agent, which could introduce a confound in the evaluation of new therapies. MRI was slower (30 minutes) and had lower anisotropic spatial resolution. But MRI eliminates the need for a contrast agent and the contrast-to-noise between tumor and normal parenchyma was higher, making earlier detection of small lesions possible. Both methods supported a relatively high-throughput, longitudinal study of the development of metastatic lesions.

Authors
Pandit, P; Johnston, SM; Qi, Y; Story, J; Nelson, R; Johnson, GA
MLA Citation
Pandit, P, Johnston, SM, Qi, Y, Story, J, Nelson, R, and Johnson, GA. "The utility of micro-CT and MRI in the assessment of longitudinal growth of liver metastases in a preclinical model of colon carcinoma." Acad Radiol 20.4 (April 2013): 430-439.
PMID
23498983
Source
pubmed
Published In
Academic Radiology
Volume
20
Issue
4
Publish Date
2013
Start Page
430
End Page
439
DOI
10.1016/j.acra.2012.09.030

An ontology-based segmentation scheme for tracking postnatal changes in the developing rodent brain with MRI.

The postnatal period of neurodevelopment has been implicated in a number of brain disorders including autism and schizophrenia. Rodent models have proven to be invaluable in advancing our understanding of the human brain, and will almost certainly play a pivotal role in future studies on postnatal neurodevelopment. The growing field of magnetic resonance microscopy has the potential to revolutionize our understanding of neurodevelopment, if it can be successfully and appropriately assimilated into the vast body of existing neuroscience research. In this study, we demonstrate the utility of a developmental neuro-ontology designed specifically for tracking regional changes in MR biomarkers throughout postnatal neurodevelopment. Using this ontological classification as a segmentation guide, we track regional changes in brain volume in rats between postnatal day zero and postnatal day 80 and demonstrate differential growth rates in axial versus paraxial brain regions. Both the ontology and the associated label volumes are provided as a foundation for future MR-based studies of postnatal neurodevelopment in normal and disease states.

Authors
Calabrese, E; Johnson, GA; Watson, C
MLA Citation
Calabrese, E, Johnson, GA, and Watson, C. "An ontology-based segmentation scheme for tracking postnatal changes in the developing rodent brain with MRI." Neuroimage 67 (February 15, 2013): 375-384.
PMID
23246176
Source
pubmed
Published In
NeuroImage
Volume
67
Publish Date
2013
Start Page
375
End Page
384
DOI
10.1016/j.neuroimage.2012.11.037

A comparison of radial keyhole strategies for high spatial and temporal resolution 4D contrast-enhanced MRI in small animal tumor models.

PURPOSE: Dynamic contrast-enhanced (DCE) MRI has been widely used as a quantitative imaging method for monitoring tumor response to therapy. The simultaneous challenges of increasing temporal and spatial resolution in a setting where the signal from the much smaller voxel is weaker have made this MR technique difficult to implement in small-animal imaging. Existing protocols employed in preclinical DCE-MRI acquire a limited number of slices resulting in potentially lost information in the third dimension. This study describes and compares a family of four-dimensional (3D spatial + time), projection acquisition, radial keyhole-sampling strategies that support high spatial and temporal resolution. METHODS: The 4D method is based on a RF-spoiled, steady-state, gradient-recalled sequence with minimal echo time. An interleaved 3D radial trajectory with a quasi-uniform distribution of points in k-space was used for sampling temporally resolved datasets. These volumes were reconstructed with three different k-space filters encompassing a range of possible radial keyhole strategies. The effect of k-space filtering on spatial and temporal resolution was studied in a 5 mM CuSO(4) phantom consisting of a meshgrid with 350-μm spacing and in 12 tumors from three cell lines (HT-29, LoVo, MX-1) and a primary mouse sarcoma model (three tumors∕group). The time-to-peak signal intensity was used to assess the effect of the reconstruction filters on temporal resolution. As a measure of heterogeneity in the third dimension, the authors analyzed the spatial distribution of the rate of transport (K(trans)) of the contrast agent across the endothelium barrier for several different types of tumors. RESULTS: Four-dimensional radial keyhole imaging does not degrade the system spatial resolution. Phantom studies indicate there is a maximum 40% decrease in signal-to-noise ratio as compared to a fully sampled dataset. T1 measurements obtained with the interleaved radial technique do not differ significantly from those made with a conventional Cartesian spin-echo sequence. A bin-by-bin comparison of the distribution of the time-to-peak parameter shows that 4D radial keyhole reconstruction does not cause significant temporal blurring when a temporal resolution of 9.9 s is used for the subsamples of the keyhole data. In vivo studies reveal substantial tumor heterogeneity in the third spatial dimension that may be missed with lower resolution imaging protocols. CONCLUSIONS: Volumetric keyhole imaging with projection acquisition provides a means to increase spatiotemporal resolution and coverage over that provided by existing 2D Cartesian protocols. Furthermore, there is no difference in temporal resolution between the higher spatial resolution keyhole reconstruction and the undersampled projection data. The technique allows one to measure complex heterogeneity of kinetic parameters with isotropic, microscopic spatial resolution.

Authors
Subashi, E; Moding, EJ; Cofer, GP; MacFall, JR; Kirsch, DG; Qi, Y; Johnson, GA
MLA Citation
Subashi, E, Moding, EJ, Cofer, GP, MacFall, JR, Kirsch, DG, Qi, Y, and Johnson, GA. "A comparison of radial keyhole strategies for high spatial and temporal resolution 4D contrast-enhanced MRI in small animal tumor models." Med Phys 40.2 (February 2013): 022304-.
PMID
23387766
Source
pubmed
Volume
40
Issue
2
Publish Date
2013
Start Page
022304
DOI
10.1118/1.4774050

A LabVIEW Platform for Preclinical Imaging Using Digital Subtraction Angiography and Micro-CT.

CT and digital subtraction angiography (DSA) are ubiquitous in the clinic. Their preclinical equivalents are valuable imaging methods for studying disease models and treatment. We have developed a dual source/detector X-ray imaging system that we have used for both micro-CT and DSA studies in rodents. The control of such a complex imaging system requires substantial software development for which we use the graphical language LabVIEW (National Instruments, Austin, TX, USA). This paper focuses on a LabVIEW platform that we have developed to enable anatomical and functional imaging with micro-CT and DSA. Our LabVIEW applications integrate and control all the elements of our system including a dual source/detector X-ray system, a mechanical ventilator, a physiological monitor, and a power microinjector for the vascular delivery of X-ray contrast agents. Various applications allow cardiac- and respiratory-gated acquisitions for both DSA and micro-CT studies. Our results illustrate the application of DSA for cardiopulmonary studies and vascular imaging of the liver and coronary arteries. We also show how DSA can be used for functional imaging of the kidney. Finally, the power of 4D micro-CT imaging using both prospective and retrospective gating is shown for cardiac imaging.

Authors
Badea, CT; Hedlund, LW; Johnson, GA
MLA Citation
Badea, CT, Hedlund, LW, and Johnson, GA. "A LabVIEW Platform for Preclinical Imaging Using Digital Subtraction Angiography and Micro-CT." Journal of medical engineering 2013 (January 2013): 581617-.
Website
http://hdl.handle.net/10161/11992
PMID
27006920
Source
epmc
Published In
Journal of Medical Engineering
Volume
2013
Publish Date
2013
Start Page
581617
DOI
10.1155/2013/581617

Magnetic resonance microscopy.

MRI, one of the major clinical imaging modalities, has gained an important role in studying small animal models, e.g., rats and mice. But imaging rodents comes with challenges, since the image resolution needs to be ~ 3000-times higher to resolve anatomical details at a level comparable to clinical imaging. A resolution on the order of 100 microns or less redefines MR imaging as MR microscopy. We discuss in this chapter the basic components of the MR imaging chain, with a particular emphasis on small animal imaging demands: from hardware design to basic physical principles of MR image formation, and contrast mechanisms. We discuss special considerations of animal preparation for imaging, and staining methods to enhance contrast. Attention is given to factors that increase sensitivity, including exogenous contrast agents, high performance radiofrequency detectors, and advanced MR encoding sequences. Among these, diffusion tensor imaging and tractography add novel information on white matter tracts, helping to better understand important aspects of development and neurodegeneration. These developments open avenues for efficient phenotyping of small animal models, in vivo - to include anatomical as well as functional estimates, or ex-vivo - with exquisite anatomical detail. The need for higher resolution results in larger image arrays that need to be processed efficiently. We discuss image-processing approaches for quantitative characterization of animal cohorts, and building population atlases. High throughput is essential for these methods to become practical. We discuss current trends for increasing detector performance, the use of cryoprobes, as well as strategies for imaging multiple animals at the same time. Ultimately, the development of highly specific probes, with the possibility to be used in multimodal imaging, will offer new insights into histology. MRM, alone or in combination with other imaging modalities, will increase the knowledge of fundamental biological processes, help understanding the genetic basis of human diseases, and test pharmacological interventions.

Authors
Badea, A; Johnson, GA
MLA Citation
Badea, A, and Johnson, GA. "Magnetic resonance microscopy." Stud Health Technol Inform 185 (2013): 153-184. (Review)
PMID
23542935
Source
pubmed
Published In
Studies in health technology and informatics
Volume
185
Publish Date
2013
Start Page
153
End Page
184

Dual-energy micro-computed tomography imaging of radiation-induced vascular changes in primary mouse sarcomas

Purpose: To evaluate the effects of radiation therapy on primary tumor vasculature using dual-energy (DE) micro-computed tomography (micro-CT). Methods and Materials: Primary sarcomas were generated with mutant Kras and p53. Unirradiated tumors were compared with tumors irradiated with 20 Gy. A liposomal-iodinated contrast agent was administered 1 day after treatment, and mice were imaged immediately after injection (day 1) and 3 days later (day 4) with DE micro-CT. CT-derived tumor sizes were used to assess tumor growth. After DE decomposition, iodine maps were used to assess tumor fractional blood volume (FBV) at day 1 and tumor vascular permeability at day 4. For comparison, tumor vascularity and vascular permeability were also evaluated histologically by use of CD31 immunofluorescence and fluorescently-labeled dextrans. Results: Radiation treatment significantly decreased tumor growth from day 1 to day 4 (P<.05). There was a positive correlation between CT measurement of tumor FBV on day 1 and extravasated iodine on day 4 with microvascular density (MVD) on day 4 (R2=0.53) and dextran accumulation (R2=0.63) on day 4, respectively. Despite no change in MVD measured by histology, tumor FBV significantly increased after irradiation as measured by DE micro-CT (0.070 vs 0.091, P<.05). Both dextran and liposomal-iodine accumulation in tumors increased significantly after irradiation, with dextran fractional area increasing 5.2-fold and liposomal-iodine concentration increasing 4.0-fold. Conclusions: DE micro-CT is an effective tool for noninvasive assessment of vascular changes in primary tumors. Tumor blood volume and vascular permeability increased after a single therapeutic dose of radiation treatment. © 2013 Elsevier Inc.

Authors
Moding, EJ; Clark, DP; Qi, Y; Li, Y; Ma, Y; Ghaghada, K; Johnson, GA; Kirsch, DG; Badea, CT
MLA Citation
Moding, EJ, Clark, DP, Qi, Y, Li, Y, Ma, Y, Ghaghada, K, Johnson, GA, Kirsch, DG, and Badea, CT. "Dual-energy micro-computed tomography imaging of radiation-induced vascular changes in primary mouse sarcomas." International Journal of Radiation Oncology Biology Physics 85.5 (2013): 1353-1359.
Source
scival
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
85
Issue
5
Publish Date
2013
Start Page
1353
End Page
1359
DOI
10.1016/j.ijrobp.2012.09.027

Semi-automated 3D segmentation of major tracts in the rat brain: comparing DTI with standard histological methods

Researchers working with rodent models of neurological disease often require an accurate map of the anatomical organization of the white matter of the rodent brain. With the increasing popularity of small animal MRI techniques, including diffusion tensor imaging (DTI), there is considerable interest in rapid segmentation methods of neurological structures for quantitative comparisons. DTI-derived tractography allows simple and rapid segmentation of major white matter tracts, but the anatomic accuracy of these computer-generated fibers is open to question and has not been rigorously evaluated in the rat brain. In this study, we examine the anatomic accuracy of tractography-based segmentation in the adult rat brain. We analysed 12 major white matter pathways using semi-automated tractography-based segmentation alongside manual segmentation of Gallyas silver-stained histology sections. We applied four fiber-tracking algorithms to the DTI data-two integration methods and two deflection methods. In many cases, tractography-based segmentation closely matched histology-based segmentation; however different tractography algorithms produced dramatically different results. Results suggest that certain white matter pathways are more amenable to tractography-based segmentation than others. We believe that these data will help researchers decide whether it is appropriate to use tractography-based segmentation of white matter structures for quantitative DTI-based analysis of neurologic disease models. © 2013 Springer-Verlag Berlin Heidelberg.

Authors
Gyengesi, E; Calabrese, E; Sherrier, MC; Johnson, GA; Paxinos, G; Watson, C
MLA Citation
Gyengesi, E, Calabrese, E, Sherrier, MC, Johnson, GA, Paxinos, G, and Watson, C. "Semi-automated 3D segmentation of major tracts in the rat brain: comparing DTI with standard histological methods." Brain Structure and Function (2013): 1-12.
PMID
23455647
Source
scival
Published In
Brain Structure and Function
Publish Date
2013
Start Page
1
End Page
12
DOI
10.1007/s00429-013-0516-8

Dual-energy computed tomography imaging of atherosclerotic plaques in a mouse model using a liposomal-iodine nanoparticle contrast agent

Background-The accumulation of macrophages in inflamed atherosclerotic plaques has long been recognized. In an attempt to develop an imaging agent for detection of vulnerable plaques, we evaluated the feasibility of a liposomaliodine nanoparticle contrast agent for computed tomography imaging of macrophage-rich atherosclerotic plaques in a mouse model. Methods and Results-Liposomal-iodine formulations varying in particle size and polyethylene glycol coating were fabricated and shown to stably encapsulate the iodine compound. In vitro uptake studies using optical and computed tomography imaging in the RAW 264.7 macrophage cell line identified the formulation that promoted maximal uptake. Dual-energy computed tomography imaging using this formulation in apolipoprotein E-deficient (ApoE-/-) mice (n=8) and control C57BL/6 mice (n=6) followed by spectral decomposition of the dual-energy images enabled imaging of the liposomes localized in the plaque. Imaging cytometry confirmed the presence of liposomes in the plaque and their colocalization with a small fraction (≈2%) of the macrophages in the plaque. Conclusions-The results demonstrate the feasibility of imaging macrophage-rich atherosclerotic plaques using a liposomaliodine nanoparticle contrast agent and dual-energy computed tomography. © 2013 American Heart Association, Inc.

Authors
Bhavane, R; Badea, C; Ghaghada, KB; Clark, D; Vela, D; Moturu, A; Annapragada, A; Johnson, GA; Willerson, JT; Annapragada, A
MLA Citation
Bhavane, R, Badea, C, Ghaghada, KB, Clark, D, Vela, D, Moturu, A, Annapragada, A, Johnson, GA, Willerson, JT, and Annapragada, A. "Dual-energy computed tomography imaging of atherosclerotic plaques in a mouse model using a liposomal-iodine nanoparticle contrast agent." Circulation: Cardiovascular Imaging 6.2 (2013): 285-294.
PMID
23349231
Source
scival
Published In
Circulation: Cardiovascular Imaging
Volume
6
Issue
2
Publish Date
2013
Start Page
285
End Page
294
DOI
10.1161/CIRCIMAGING.112.000119

Constructing a 4D murine cardiac micro-CT atlas for automated segmentation and phenotyping applications

A number of investigators have demonstrated the potential of preclinical micro-CT in characterizing cardiovascular disease in mouse models. One major hurdle to advancing this approach is the extensive user interaction required to derive quantitative metrics from these 4D image arrays (space + time). In this work, we present: (1) a method for constructing an average anatomic cardiac atlas of the mouse based on 4D micro-CT images, (2) a fully automated approach for segmenting newly acquired cardiac data sets using the atlas, and (3) a quantitative characterization of atlasbased segmentation accuracy and consistency. Employing the deformable registration toolkit, ANTs, the construction of minimal deformation fields, and a novel adaptation of joint bilateral filtration, our atlas construction scheme was used to integrate 6, C57BL/6 cardiac micro-CT data sets, reducing the noise standard deviation from ~70 HU in the individual data sets to ~21 HU in the atlas data set. Using the segmentation tools in Atropos and our atlas-based segmentation, we were able to propagate manual labels to 5, C57BL/6 data sets not used in atlas construction. Average Dice coefficients and volume accuracies (respectively) over phases 1 (ventricular diastole), 3, and 5 (ventricular systole) of these 5 data sets were as follows: left ventricle, 0.96, 0.96; right ventricle, 0.89, 0.92; left atrium, 0.88, 0.89; right atrium, 0.86, 0.92; myocardium, 0.90, 0.94. Once the atlas was constructed and segmented, execution of the proposed automated segmentation scheme took ~6.5 hours per data set, versus more than 50 hours required for a manual segmentation. © 2013 SPIE.

Authors
Clark, D; Badea, A; Johnson, GA; Badea, CT
MLA Citation
Clark, D, Badea, A, Johnson, GA, and Badea, CT. "Constructing a 4D murine cardiac micro-CT atlas for automated segmentation and phenotyping applications." Progress in Biomedical Optics and Imaging - Proceedings of SPIE 8669 (2013).
Source
scival
Published In
Proceedings of SPIE
Volume
8669
Publish Date
2013
DOI
10.1117/12.2007043

The effect of scatter correction on dual energy micro-CT

Dual energy (DE) CT imaging is expected to play a major role in the diagnostic arena as it provides a quantitative decomposition of basis materials, opening the door for new clinical applications without significantly increasing dose to the patient. DE-CT provides a particularly unique opportunity in preclinical CT where new elemental contrast agents are providing novel approaches for quantitative tissue characterization. We have implemented DE-CT imaging with a preclinical dual source micro-CT scanner. With this configuration, both forward and cross-scatter can substantially degrade image quality. This work investigated the effect of scatter correction on the accuracy of post-reconstruction iodine and calcium decomposition. Scatter has been estimated using a lead beam stop technique. Our approach involves noise reduction in the scatter corrected images using bilateral filtering. The scatter correction has been quantitatively evaluated using phantom experiments and in vivo cancer imaging. As shown by our measurements, the dual source scanning is affected more by the cross-scatter from the high energy to the low energy imaging chain. The scatter correction reduced the presence of cupping artifacts and increased both the accuracy and precision of dual energy decompositions of calcium and iodine. On average, the root mean square errors in retrieving true iodine and calcium concentrations via dual energy were reduced by 32%. As a result of scatter corrections, we expect more accurate quantification of important vascular biomarkers such as fractional blood volume and vascular permeability in preclinical cancer studies. © 2013 SPIE.

Authors
Clark, D; Johnston, SM; Johnson, GA; Badea, CT
MLA Citation
Clark, D, Johnston, SM, Johnson, GA, and Badea, CT. "The effect of scatter correction on dual energy micro-CT." 2013.
Source
scival
Published In
Proceedings of SPIE
Volume
8668
Publish Date
2013
DOI
10.1117/12.2006904

Altered diffusion tensor imaging measurements in aged transgenic Huntington disease rats

Rodent models of Huntington disease (HD) are valuable tools for investigating HD pathophysiology and evaluating new therapeutic approaches. Non-invasive characterization of HD-related phenotype changes is important for monitoring progression of pathological processes and possible effects of interventions. The first transgenic rat model for HD exhibits progressive late-onset affective, cognitive, and motor impairments, as well as neuropathological features reflecting observations from HD patients. In this report, we contribute to the anatomical phenotyping of this model by comparing high-resolution ex vivo DTI measurements obtained in aged transgenic HD rats and wild-type controls. By region of interest analysis supplemented by voxel-based statistics, we find little evidence of atrophy in basal ganglia regions, but demonstrate altered DTI measurements in the dorsal and ventral striatum, globus pallidus, entopeduncular nucleus, substantia nigra, and hippocampus. These changes are largely compatible with DTI findings in preclinical and clinical HD patients. We confirm earlier reports that HD rats express a moderate neuropathological phenotype, and provide evidence of altered DTI measures in specific HD-related brain regions, in the absence of pronounced morphometric changes. © 2012 The Author(s).

Authors
Antonsen, BT; Jiang, Y; Veraart, J; Qu, H; Nguyen, HP; Sijbers, J; Hörsten, SV; Johnson, GA; Leergaard, TB
MLA Citation
Antonsen, BT, Jiang, Y, Veraart, J, Qu, H, Nguyen, HP, Sijbers, J, Hörsten, SV, Johnson, GA, and Leergaard, TB. "Altered diffusion tensor imaging measurements in aged transgenic Huntington disease rats." Brain Structure and Function 218.3 (2013): 767-778.
Source
scival
Published In
Brain Structure and Function
Volume
218
Issue
3
Publish Date
2013
Start Page
767
End Page
778
DOI
10.1007/s00429-012-0427-0

Magnetic resonance microscopy-based analyses of the neuroanatomical effects of gestational day 9 ethanol exposure in mice

Animal model-based studies have shown that ethanol exposure during early gestation induces developmental stage-specific abnormalities of the face and brain. The exposure time-dependent variability in ethanol's teratogenic outcomes is expected to contribute significantly to the wide spectrum of effects observed in humans with fetal alcohol spectrum disorder (FASD). The work presented here employs a mouse FASD model and magnetic resonance microscopy (MRM; high resolution magnetic resonance imaging) in studies designed to further our understanding of the developmental stage-specific defects of the brain that are induced by ethanol. At neurulation stages, i.e. at the beginning of gestational day (GD) 9 and again 4. hours later, time-mated C57Bl/6J dams were intraperitoneally administered 2.9. g/kg ethanol or vehicle. Ethanol-exposed fetuses were collected on GD 17, processed for MRM analysis, and results compared to comparably staged controls. Linear and volume measurements as well as shape changes for numerous individual brain regions were determined. GD 9 ethanol exposure resulted in significantly increased septal region width, reduction of cerebellar volume, and enlargement of all of the ventricles. Additionally, the results of shape analyses showed that many areas of the ethanol-exposed brains including the cerebral cortex, hippocampus and right striatum were significantly misshapen. These data demonstrate that ethanol can induce dysmorphology that may not be obvious based on volumetric analyses alone, highlight the asymmetric aspects of ethanol-induced defects, and add to our understanding of ethanol's developmental stage-dependent neuroteratogenesis.© 2013 Elsevier Inc.

Authors
Parnell, SE; Holloway, HT; O'Leary-Moore, SK; Dehart, DB; Paniaqua, B; Oguz, I; Budin, F; Styner, MA; Johnson, GA; Sulik, KK
MLA Citation
Parnell, SE, Holloway, HT, O'Leary-Moore, SK, Dehart, DB, Paniaqua, B, Oguz, I, Budin, F, Styner, MA, Johnson, GA, and Sulik, KK. "Magnetic resonance microscopy-based analyses of the neuroanatomical effects of gestational day 9 ethanol exposure in mice." Neurotoxicology and Teratology 39 (2013): 77-83.
PMID
23911654
Source
scival
Published In
Neurotoxicology and Teratology
Volume
39
Publish Date
2013
Start Page
77
End Page
83
DOI
10.1016/j.ntt.2013.07.009

Quantitative mouse brain phenotyping based on single and multispectral MR protocols.

Sophisticated image analysis methods have been developed for the human brain, but such tools still need to be adapted and optimized for quantitative small animal imaging. We propose a framework for quantitative anatomical phenotyping in mouse models of neurological and psychiatric conditions. The framework encompasses an atlas space, image acquisition protocols, and software tools to register images into this space. We show that a suite of segmentation tools (Avants, Epstein et al., 2008) designed for human neuroimaging can be incorporated into a pipeline for segmenting mouse brain images acquired with multispectral magnetic resonance imaging (MR) protocols. We present a flexible approach for segmenting such hyperimages, optimizing registration, and identifying optimal combinations of image channels for particular structures. Brain imaging with T1, T2* and T2 contrasts yielded accuracy in the range of 83% for hippocampus and caudate putamen (Hc and CPu), but only 54% in white matter tracts, and 44% for the ventricles. The addition of diffusion tensor parameter images improved accuracy for large gray matter structures (by >5%), white matter (10%), and ventricles (15%). The use of Markov random field segmentation further improved overall accuracy in the C57BL/6 strain by 6%; so Dice coefficients for Hc and CPu reached 93%, for white matter 79%, for ventricles 68%, and for substantia nigra 80%. We demonstrate the segmentation pipeline for the widely used C57BL/6 strain, and two test strains (BXD29, APP/TTA). This approach appears promising for characterizing temporal changes in mouse models of human neurological and psychiatric conditions, and may provide anatomical constraints for other preclinical imaging, e.g. fMRI and molecular imaging. This is the first demonstration that multiple MR imaging modalities combined with multivariate segmentation methods lead to significant improvements in anatomical segmentation in the mouse brain.

Authors
Badea, A; Gewalt, S; Avants, BB; Cook, JJ; Johnson, GA
MLA Citation
Badea, A, Gewalt, S, Avants, BB, Cook, JJ, and Johnson, GA. "Quantitative mouse brain phenotyping based on single and multispectral MR protocols." Neuroimage 63.3 (November 15, 2012): 1633-1645.
PMID
22836174
Source
pubmed
Published In
NeuroImage
Volume
63
Issue
3
Publish Date
2012
Start Page
1633
End Page
1645
DOI
10.1016/j.neuroimage.2012.07.021

Registration-based segmentation of murine 4D cardiac micro-CT data using symmetric normalization.

Micro-CT can play an important role in preclinical studies of cardiovascular disease because of its high spatial and temporal resolution. Quantitative analysis of 4D cardiac images requires segmentation of the cardiac chambers at each time point, an extremely time consuming process if done manually. To improve throughput this study proposes a pipeline for registration-based segmentation and functional analysis of 4D cardiac micro-CT data in the mouse. Following optimization and validation using simulations, the pipeline was applied to in vivo cardiac micro-CT data corresponding to ten cardiac phases acquired in C57BL/6 mice (n = 5). After edge-preserving smoothing with a novel adaptation of 4D bilateral filtration, one phase within each cardiac sequence was manually segmented. Deformable registration was used to propagate these labels to all other cardiac phases for segmentation. The volumes of each cardiac chamber were calculated and used to derive stroke volume, ejection fraction, cardiac output, and cardiac index. Dice coefficients and volume accuracies were used to compare manual segmentations of two additional phases with their corresponding propagated labels. Both measures were, on average, >0.90 for the left ventricle and >0.80 for the myocardium, the right ventricle, and the right atrium, consistent with trends in inter- and intra-segmenter variability. Segmentation of the left atrium was less reliable. On average, the functional metrics of interest were underestimated by 6.76% or more due to systematic label propagation errors around atrioventricular valves; however, execution of the pipeline was 80% faster than performing analogous manual segmentation of each phase.

Authors
Clark, D; Badea, A; Liu, Y; Johnson, GA; Badea, CT
MLA Citation
Clark, D, Badea, A, Liu, Y, Johnson, GA, and Badea, CT. "Registration-based segmentation of murine 4D cardiac micro-CT data using symmetric normalization." Phys Med Biol 57.19 (October 7, 2012): 6125-6145.
PMID
22971564
Source
pubmed
Published In
Physics in Medicine and Biology
Volume
57
Issue
19
Publish Date
2012
Start Page
6125
End Page
6145
DOI
10.1088/0031-9155/57/19/6125

A multidimensional magnetic resonance histology atlas of the Wistar rat brain.

We have produced a multidimensional atlas of the adult Wistar rat brain based on magnetic resonance histology (MRH). This MR atlas has been carefully aligned with the widely used Paxinos-Watson atlas based on optical sections to allow comparisons between histochemical and immuno-marker data, and the use of the Paxinos-Watson abbreviation set. Our MR atlas attempts to make a seamless connection with the advantageous features of the Paxinos-Watson atlas, and to extend the utility of the data through the unique capabilities of MR histology: a) ability to view the brain in the skull with limited distortion from shrinkage or sectioning; b) isotropic spatial resolution, which permits sectioning along any arbitrary axis without loss of detail; c) three-dimensional (3D) images preserving spatial relationships; and d) widely varied contrast dependent on the unique properties of water protons. 3D diffusion tensor images (DTI) at what we believe to be the highest resolution ever attained in the rat provide unique insight into white matter structures and connectivity. The 3D isotropic data allow registration of multiple data sets into a common reference space to provide average atlases not possible with conventional histology. The resulting multidimensional atlas that combines Paxinos-Watson with multidimensional MRH images from multiple specimens provides a new, comprehensive view of the neuroanatomy of the rat and offers a collaborative platform for future rat brain studies.

Authors
Johnson, GA; Calabrese, E; Badea, A; Paxinos, G; Watson, C
MLA Citation
Johnson, GA, Calabrese, E, Badea, A, Paxinos, G, and Watson, C. "A multidimensional magnetic resonance histology atlas of the Wistar rat brain." Neuroimage 62.3 (September 2012): 1848-1856.
PMID
22634863
Source
pubmed
Published In
NeuroImage
Volume
62
Issue
3
Publish Date
2012
Start Page
1848
End Page
1856
DOI
10.1016/j.neuroimage.2012.05.041

Temporal and spectral imaging with micro-CT.

PURPOSE: Micro-CT is widely used for small animal imaging in preclinical studies of cardiopulmonary disease, but further development is needed to improve spatial resolution, temporal resolution, and material contrast. We present a technique for visualizing the changing distribution of iodine in the cardiac cycle with dual source micro-CT. METHODS: The approach entails a retrospectively gated dual energy scan with optimized filters and voltages, and a series of computational operations to reconstruct the data. Projection interpolation and five-dimensional bilateral filtration (three spatial dimensions + time + energy) are used to reduce noise and artifacts associated with retrospective gating. We reconstruct separate volumes corresponding to different cardiac phases and apply a linear transformation to decompose these volumes into components representing concentrations of water and iodine. Since the resulting material images are still compromised by noise, we improve their quality in an iterative process that minimizes the discrepancy between the original acquired projections and the projections predicted by the reconstructed volumes. The values in the voxels of each of the reconstructed volumes represent the coefficients of linear combinations of basis functions over time and energy. We have implemented the reconstruction algorithm on a graphics processing unit (GPU) with CUDA. We tested the utility of the technique in simulations and applied the technique in an in vivo scan of a C57BL∕6 mouse injected with blood pool contrast agent at a dose of 0.01 ml∕g body weight. Postreconstruction, at each cardiac phase in the iodine images, we segmented the left ventricle and computed its volume. Using the maximum and minimum volumes in the left ventricle, we calculated the stroke volume, the ejection fraction, and the cardiac output. RESULTS: Our proposed method produces five-dimensional volumetric images that distinguish different materials at different points in time, and can be used to segment regions containing iodinated blood and compute measures of cardiac function. CONCLUSIONS: We believe this combined spectral and temporal imaging technique will be useful for future studies of cardiopulmonary disease in small animals.

Authors
Johnston, SM; Johnson, GA; Badea, CT
MLA Citation
Johnston, SM, Johnson, GA, and Badea, CT. "Temporal and spectral imaging with micro-CT." Med Phys 39.8 (August 2012): 4943-4958.
PMID
22894420
Source
pubmed
Published In
Medical physics
Volume
39
Issue
8
Publish Date
2012
Start Page
4943
End Page
4958
DOI
10.1118/1.4736809

Magnetic resonance histology of age-related nephropathy in the Sprague Dawley rat.

Magnetic resonance histology (MRH) has become a valuable tool in evaluating drug-induced toxicity in preclinical models. However, its application in renal injury has been limited. This study tested the hypothesis that MRH could detect image-based biomarkers of chronic disease, inflammation, or age-related degeneration in the kidney, laying the foundation for more extensive use in evaluating drug toxicity. We examined the entire intact kidney in a spontaneous model of chronic progressive nephropathy. Kidneys from male Sprague Dawley rats were imaged at 8 weeks (n = 4) and 52 weeks (n =4) on a 9.4 T system dedicated to MR microscopy. Several potential contrast mechanisms were explored to optimize the scanning protocols. Full coverage of the entire kidney was achieved with isotropic spatial resolution at 31 microns (voxel volume = 30 pL) using a gradient recalled echo sequence. Isotropic spatial resolution of 15 microns (voxel volume < 4 pL) was achieved in a biopsy core specimen. Qualitative age-related structural changes, such as renal cortical microvasculature, tubular dilation, interstitial fibrosis, and glomerular architecture, were apparent. The nondestructive 3D images allowed measurement of quantitative differences of kidney volume, pelvis volume, main vessel volume, glomerular size, as well as thickness of the cortex, outer medulla, and inner medulla.

Authors
Xie, L; Cianciolo, RE; Hulette, B; Lee, HW; Qi, Y; Cofer, G; Johnson, GA
MLA Citation
Xie, L, Cianciolo, RE, Hulette, B, Lee, HW, Qi, Y, Cofer, G, and Johnson, GA. "Magnetic resonance histology of age-related nephropathy in the Sprague Dawley rat." Toxicol Pathol 40.5 (July 2012): 764-778.
PMID
22504322
Source
pubmed
Published In
Toxicologic Pathology (Sage)
Volume
40
Issue
5
Publish Date
2012
Start Page
764
End Page
778
DOI
10.1177/0192623312441408

EFFECTS OF CHRONIC EARLY GESTATIONAL ETHANOL EXPOSURE ON THE DEVELOPING BRAIN: A MAGNETIC RESONANCE MICROSCOPY STUDY

Authors
Parnell, SE; Holloway, HT; Paniagua, B; Oguz, I; Styner, MA; Johnson, GA; Sulik, KK
MLA Citation
Parnell, SE, Holloway, HT, Paniagua, B, Oguz, I, Styner, MA, Johnson, GA, and Sulik, KK. "EFFECTS OF CHRONIC EARLY GESTATIONAL ETHANOL EXPOSURE ON THE DEVELOPING BRAIN: A MAGNETIC RESONANCE MICROSCOPY STUDY." June 2012.
Source
wos-lite
Published In
Alcoholism: Clinical and Experimental Research
Volume
36
Publish Date
2012
Start Page
279A
End Page
279A

DIFFUSION TENSOR IMAGING (DTI)-BASED ANALYSIS OF FIBER TRACT ABNORMALITIES IN A MOUSE MODEL OF PRENATAL ALCOHOL EXPOSURE

Authors
O'Leary-Moore, SK; Johnson, GA; Calabrese, E; Budin, F; Oguz, I; Styner, MA; Parnell, SE; Sulik, KK
MLA Citation
O'Leary-Moore, SK, Johnson, GA, Calabrese, E, Budin, F, Oguz, I, Styner, MA, Parnell, SE, and Sulik, KK. "DIFFUSION TENSOR IMAGING (DTI)-BASED ANALYSIS OF FIBER TRACT ABNORMALITIES IN A MOUSE MODEL OF PRENATAL ALCOHOL EXPOSURE." ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH 36 (June 2012): 312A-312A.
Source
wos-lite
Published In
Alcoholism: Clinical and Experimental Research
Volume
36
Publish Date
2012
Start Page
312A
End Page
312A

Morphological studies of the murine heart based on probabilistic and statistical atlases.

This study directly compares morphological features of the mouse heart in its end-relaxed state based on constructed morphometric maps and atlases using principal component analysis in C57BL/6J (n=8) and DBA (n=5) mice. In probabilistic atlases, a gradient probability exists for both strains in longitudinal locations from base to apex. Based on the statistical atlases, differences in size (49.8%), apical direction (15.6%), basal ventricular blood pool size (13.2%), and papillary muscle shape and position (17.2%) account for the most significant modes of shape variability for the left ventricle of the C57BL/6J mice. For DBA mice, differences in left ventricular size and direction (67.4%), basal size (15.7%), and position of papillary muscles (16.8%) account for significant variability.

Authors
Perperidis, D; Bucholz, E; Johnson, GA; Constantinides, C
MLA Citation
Perperidis, D, Bucholz, E, Johnson, GA, and Constantinides, C. "Morphological studies of the murine heart based on probabilistic and statistical atlases." Comput Med Imaging Graph 36.2 (March 2012): 119-129.
PMID
21820867
Source
pubmed
Published In
Computerized Medical Imaging and Graphics
Volume
36
Issue
2
Publish Date
2012
Start Page
119
End Page
129
DOI
10.1016/j.compmedimag.2011.07.001

3D fiber tractography with susceptibility tensor imaging.

Gradient-echo MRI has revealed anisotropic magnetic susceptibility in the brain white matter. This magnetic susceptibility anisotropy can be measured and characterized with susceptibility tensor imaging (STI). In this study, a method of fiber tractography based on STI is proposed and demonstrated in the mouse brain. STI experiments of perfusion-fixed mouse brains were conducted at 7.0T. The magnetic susceptibility tensor was calculated for each voxel with regularization and decomposed into its eigensystem. The major eigenvector is found to be aligned with the underlying fiber orientation. Following the orientation of the major eigenvector, we are able to map distinctive fiber pathways in 3D. As a comparison, diffusion tensor imaging (DTI) and DTI fiber tractography were also conducted on the same specimens. The relationship between STI and DTI fiber tracts was explored with similarities and differences identified. It is anticipated that the proposed method of STI tractography may provide a new way to study white matter fiber architecture. As STI tractography is based on physical principles that are fundamentally different from DTI, it may also be valuable for the ongoing validation of DTI tractography.

Authors
Liu, C; Li, W; Wu, B; Jiang, Y; Johnson, GA
MLA Citation
Liu, C, Li, W, Wu, B, Jiang, Y, and Johnson, GA. "3D fiber tractography with susceptibility tensor imaging." Neuroimage 59.2 (January 16, 2012): 1290-1298.
PMID
21867759
Source
pubmed
Published In
NeuroImage
Volume
59
Issue
2
Publish Date
2012
Start Page
1290
End Page
1298
DOI
10.1016/j.neuroimage.2011.07.096

4D micro-CT using fast prospective gating.

Micro-CT is currently used in preclinical studies to provide anatomical information. But, there is also significant interest in using this technology to obtain functional information. We report here a new sampling strategy for 4D micro-CT for functional cardiac and pulmonary imaging. Rapid scanning of free-breathing mice is achieved with fast prospective gating (FPG) implemented on a field programmable gate array. The method entails on-the-fly computation of delays from the R peaks of the ECG signals or the peaks of the respiratory signals for the triggering pulses. Projection images are acquired for all cardiac or respiratory phases at each angle before rotating to the next angle. FPG can deliver the faster scan time of retrospective gating (RG) with the regular angular distribution of conventional prospective gating for cardiac or respiratory gating. Simultaneous cardio-respiratory gating is also possible with FPG in a hybrid retrospective/prospective approach. We have performed phantom experiments to validate the new sampling protocol and compared the results from FPG and RG in cardiac imaging of a mouse. Additionally, we have evaluated the utility of incorporating respiratory information in 4D cardiac micro-CT studies with FPG. A dual-source micro-CT system was used for image acquisition with pulsed x-ray exposures (80 kVp, 100 mA, 10 ms). The cardiac micro-CT protocol involves the use of a liposomal blood pool contrast agent containing 123 mg I ml(-1) delivered via a tail vein catheter in a dose of 0.01 ml g(-1) body weight. The phantom experiment demonstrates that FPG can distinguish the successive phases of phantom motion with minimal motion blur, and the animal study demonstrates that respiratory FPG can distinguish inspiration and expiration. 4D cardiac micro-CT imaging with FPG provides image quality superior to RG at an isotropic voxel size of 88 μm and 10 ms temporal resolution. The acquisition time for either sampling approach is less than 5 min. The radiation dose associated with the proposed method is in the range of a typical micro-CT dose (256 mGy for the cardiac study). Ignoring respiration does not significantly affect anatomic information in cardiac studies. FPG can deliver short scan times with low-dose 4D micro-CT imaging without sacrificing image quality. FPG can be applied in high-throughput longitudinal studies in a wide range of applications, including drug safety and cardiopulmonary phenotyping.

Authors
Guo, X; Johnston, SM; Qi, Y; Johnson, GA; Badea, CT
MLA Citation
Guo, X, Johnston, SM, Qi, Y, Johnson, GA, and Badea, CT. "4D micro-CT using fast prospective gating." Phys Med Biol 57.1 (January 7, 2012): 257-271.
PMID
22156062
Source
pubmed
Published In
Physics in Medicine and Biology
Volume
57
Issue
1
Publish Date
2012
Start Page
257
End Page
271
DOI
10.1088/0031-9155/57/1/257

Plants, seeds, roots, and soils as applications of magnetic resonance microscopy

© 2012 John Wiley & Sons, Ltd.High-resolution magnetic resonance microscopy is discussed as a useful tool in the study of plant structure and physiology. In contrast to animals, plants have a relatively homogenous distribution of water throughout the tissues. High quality images highlighting both structural and physiological differences can be acquired of plant specimens, however, based on traditional MR parameters of T1, T2 and susceptibility effects from air filled spaces. Typical in plane resolutions of 5-40μm3 can be acquired, showing significant contrasts between tissues. Additionally, MR microscopy offers the ability to visualize and study plant roots in situ, without removal from the soil substrate. Applications of MR microscopy to plants includes studies of developmental anatomy, physiological changes with maturation, environmental physiology, pathologies, and the study of intact roots in soil.

Authors
Macfall, JS; Johnson, GA
MLA Citation
Macfall, JS, and Johnson, GA. "Plants, seeds, roots, and soils as applications of magnetic resonance microscopy." eMagRes 1.1 (January 1, 2012): 147-154.
Source
scopus
Volume
1
Issue
1
Publish Date
2012
Start Page
147
End Page
154
DOI
10.1002/9780470034590.emrstm0396

Computed tomography imaging of primary lung cancer in mice using a liposomal-iodinated contrast agent.

PURPOSE: To investigate the utility of a liposomal-iodinated nanoparticle contrast agent and computed tomography (CT) imaging for characterization of primary nodules in genetically engineered mouse models of non-small cell lung cancer. METHODS: Primary lung cancers with mutations in K-ras alone (Kras(LA1)) or in combination with p53 (LSL-Kras(G12D);p53(FL/FL)) were generated. A liposomal-iodine contrast agent containing 120 mg Iodine/mL was administered systemically at a dose of 16 µl/gm body weight. Longitudinal micro-CT imaging with cardio-respiratory gating was performed pre-contrast and at 0 hr, day 3, and day 7 post-contrast administration. CT-derived nodule sizes were used to assess tumor growth. Signal attenuation was measured in individual nodules to study dynamic enhancement of lung nodules. RESULTS: A good correlation was seen between volume and diameter-based assessment of nodules (R(2)>0.8) for both lung cancer models. The LSL-Kras(G12D);p53(FL/FL) model showed rapid growth as demonstrated by systemically higher volume changes compared to the lung nodules in Kras(LA1) mice (p<0.05). Early phase imaging using the nanoparticle contrast agent enabled visualization of nodule blood supply. Delayed-phase imaging demonstrated significant differential signal enhancement in the lung nodules of LSL-Kras(G12D);p53(FL/FL) mice compared to nodules in Kras(LA1) mice (p<0.05) indicating higher uptake and accumulation of the nanoparticle contrast agent in rapidly growing nodules. CONCLUSIONS: The nanoparticle iodinated contrast agent enabled visualization of blood supply to the nodules during the early-phase imaging. Delayed-phase imaging enabled characterization of slow growing and rapidly growing nodules based on signal enhancement. The use of this agent could facilitate early detection and diagnosis of pulmonary lesions as well as have implications on treatment response and monitoring.

Authors
Badea, CT; Athreya, KK; Espinosa, G; Clark, D; Ghafoori, AP; Li, Y; Kirsch, DG; Johnson, GA; Annapragada, A; Ghaghada, KB
MLA Citation
Badea, CT, Athreya, KK, Espinosa, G, Clark, D, Ghafoori, AP, Li, Y, Kirsch, DG, Johnson, GA, Annapragada, A, and Ghaghada, KB. "Computed tomography imaging of primary lung cancer in mice using a liposomal-iodinated contrast agent." PLoS One 7.4 (2012): e34496-.
PMID
22485175
Source
pubmed
Published In
PloS one
Volume
7
Issue
4
Publish Date
2012
Start Page
e34496
DOI
10.1371/journal.pone.0034496

Magnetic resonance microscopy.

Authors
Badea, A; Johnson, GA
MLA Citation
Badea, A, and Johnson, GA. "Magnetic resonance microscopy." Anal Cell Pathol (Amst) 35.4 (2012): 205-227. (Review)
Website
http://hdl.handle.net/10161/11678
PMID
22142643
Source
pubmed
Published In
Analytical Cellular Pathology
Volume
35
Issue
4
Publish Date
2012
Start Page
205
End Page
227
DOI
10.3233/ACP-2011-0050

Denoising of 4D cardiac micro-CT data using median-centric bilateral filtration

Bilateral filtration has proven an effective tool for denoising CT data. The classic filter uses Gaussian domain and range weighting functions in 2D. More recently, other distributions have yielded more accurate results in specific applications, and the bilateral filtration framework has been extended to higher dimensions. In this study, brute-force optimization is employed to evaluate the use of several alternative distributions for both domain and range weighting: Andrew's Sine Wave, El Fallah Ford, Gaussian, Flat, Lorentzian, Huber's Minimax, Tukey's Bi-weight, and Cosine. Two variations on the classic bilateral filter, which use median filtration to reduce bias in range weights, are also investigated: median-centric and hybrid bilateral filtration. Using the 4D MOBY mouse phantom reconstructed with noise (stdev. ∼ 65 HU), hybrid bilateral filtration, a combination of the classic and median-centric filters, with Flat domain and range weighting is shown to provide optimal denoising results (PSNRs: 31.69, classic; 31.58 median-centric; 32.25, hybrid). To validate these phantom studies, the optimal filters are also applied to in vivo, 4D cardiac micro-CT data acquired in the mouse. In a constant region of the left ventricle, hybrid bilateral filtration with Flat domain and range weighting is shown to provide optimal smoothing (stdev: original, 72.2 HU; classic, 20.3 HU; median-centric, 24.1 HU; hybrid, 15.9 HU). While the optimal results were obtained using 4D filtration, the 3D hybrid filter is ultimately recommended for denoising 4D cardiac micro-CT data, because it is more computationally tractable and less prone to artifacts (MOBY PSNR: 32.05; left ventricle stdev: 20.5 HU). © 2012 SPIE.

Authors
Clark, D; Johnson, GA; Badea, CT
MLA Citation
Clark, D, Johnson, GA, and Badea, CT. "Denoising of 4D cardiac micro-CT data using median-centric bilateral filtration." 2012.
PMID
24386540
Source
scival
Published In
Proceedings of SPIE
Volume
8314
Publish Date
2012
DOI
10.1117/12.911478

Investigations on X-ray luminescence CT for small animal imaging.

X-ray Luminescence CT (XLCT) is a hybrid imaging modality combining x-ray and optical imaging in which x-ray luminescent nanophosphors (NPs) are used as emissive imaging probes. NPs are easily excited using common CT energy x-ray beams, and the NP luminescence is efficiently collected using sensitive light based detection systems. XLCT can be recognized as a close analog to fluorescence diffuse optical tomography (FDOT). However, XLCT has remarkable advantages over FDOT due to the substantial excitation penetration depths provided by x-rays relative to laser light sources, long term photo-stability of NPs, and the ability to tune NP emission within the NIR spectral window. Since XCLT uses an x-ray pencil beam excitation, the emitted light can be measured and back-projected along the x-ray path during reconstruction, where the size of the X-ray pencil beam determines the resolution for XLCT. In addition, no background signal competes with NP luminescence (i.e., no auto fluorescence) in XLCT. Currently, no small animal XLCT system has been proposed or tested. This paper investigates an XLCT system built and integrated with a dual source micro-CT system. Two novel sampling paradigms that result in more efficient scanning are proposed and tested via simulations. Our preliminary experimental results in phantoms indicate that a basic CT-like reconstruction is able to recover a map of the NP locations and differences in NP concentrations. With the proposed dual source system and faster scanning approaches, XLCT has the potential to revolutionize molecular imaging in preclinical studies.

Authors
Badea, CT; Stanton, IN; Johnston, SM; Johnson, GA; Therien, MJ
MLA Citation
Badea, CT, Stanton, IN, Johnston, SM, Johnson, GA, and Therien, MJ. "Investigations on X-ray luminescence CT for small animal imaging." United States. 2012.
PMID
23227300
Source
pubmed
Published In
Proceedings of SPIE - The International Society for Optical Engineering
Volume
8313
Publish Date
2012
Start Page
83130T

A comparison of sampling strategies for dual energy micro-CT

Micro-CT has become a powerful tool for small animal research. Many micro-CT applications require exogenous contrast agents, which are most commonly based on iodine. Despite advancements in contrast agents, single-energy micro-CT is sometimes limited in the separation of two different materials that share similar grayscale intensity values as in the case of bone and iodine. Dual energy micro-CT offers a solution to this separation problem, while eliminating the need for pre-injection scanning. Various dual energy micro-CT sampling strategies are possible, including 1) single source sequential scanning, 2) simultaneous dual source acquisition, or 3) single source with kVp switching. But, no commercial micro-CT system exists in which all these sampling strategies have been implemented. This study reports on the implementation and comparison of these scanning techniques on the same small animal imaging system. Furthermore, we propose a new sampling strategy that combines dual source and kVp switching. Post-sampling and reconstruction, a simple two-material dual energy decomposition was applied to differentiate iodine from bone. The results indicate the time differences and the potential problems associated with each sampling strategy. Dual source scanning allows for the fastest acquisition, but is prone to errors in decomposition associated with scattering and imperfect geometric alignment of the two imaging chains. KVp switching prevents these types of artifacts, but requires more time for sampling. The novel combination between the dual source and kVp switching has the potential to reduce sampling time and provide better decomposition performance. © 2012 Copyright Society of Photo-Optical Instrumentation Engineers (SPIE).

Authors
Guo, X; Johnston, SM; Johnson, GA; Badea, CT
MLA Citation
Guo, X, Johnston, SM, Johnson, GA, and Badea, CT. "A comparison of sampling strategies for dual energy micro-CT." 2012.
Source
scival
Published In
Proceedings of SPIE
Volume
8313
Publish Date
2012
DOI
10.1117/12.911548

Ethanol-induced face-brain dysmorphology patterns are correlative and exposure-stage dependent

Prenatal ethanol exposure is the leading preventable cause of congenital mental disability. Whereas a diagnosis of fetal alcohol syndrome (FAS) requires identification of a specific pattern of craniofacial dysmorphology, most individuals with behavioral and neurological sequelae of heavy prenatal ethanol exposure do not exhibit these defining facial characteristics. Here, a novel integration of MRI and dense surface modeling-based shape analysis was applied to characterize concurrent face-brain phenotypes in C57Bl/6J fetuses exposed to ethanol on gestational day (GD)7 or GD8.5. The facial phenotype resulting from ethanol exposure depended upon stage of insult and was predictive of unique patterns of corresponding brain abnormalities. Ethanol exposure on GD7 produced a constellation of dysmorphic facial features characteristic of human FAS, including severe midfacial hypoplasia, shortening of the palpebral fissures, an elongated upper lip, and deficient philtrum. In contrast, ethanol exposure on GD8.5 caused mild midfacial hypoplasia and palpebral fissure shortening, a shortened upper lip, and a preserved philtrum. These distinct, stage-specific facial phenotypes were associated with unique volumetric and shape abnormalities of the septal region, pituitary, and olfactory bulbs. By demonstrating that early prenatal ethanol exposure can cause more than one temporally-specific pattern of defects, these findings illustrate the need for an expansion of current diagnostic criteria to better capture the full range of facial and brain dysmorphology in fetal alcohol spectrum disorders. © 2012 Lipinski et al.

Authors
Lipinski, RJ; Hammond, P; O'Leary-Moore, SK; Ament, JJ; Pecevich, SJ; Jiang, Y; Budin, F; Parnell, SE; Suttie, M; Godin, EA; Everson, JL; Dehart, DB; Oguz, I; Holloway, HT; Styner, MA; Johnson, GA; Sulik, KK
MLA Citation
Lipinski, RJ, Hammond, P, O'Leary-Moore, SK, Ament, JJ, Pecevich, SJ, Jiang, Y, Budin, F, Parnell, SE, Suttie, M, Godin, EA, Everson, JL, Dehart, DB, Oguz, I, Holloway, HT, Styner, MA, Johnson, GA, and Sulik, KK. "Ethanol-induced face-brain dysmorphology patterns are correlative and exposure-stage dependent." PLoS ONE 7.8 (2012).
PMID
22937012
Source
scival
Published In
PloS one
Volume
7
Issue
8
Publish Date
2012
DOI
10.1371/journal.pone.0043067

Functional neuroimaging using ultrasonic blood-brain barrier disruption and manganese-enhanced MRI

Although mice are the dominant model system for studying the genetic and molecular underpinnings of neuroscience, functional neuroimaging in mice remains technically challenging. One approach, Activation-Induced Manganese-enhanced MRI (AIM MRI), has been used successfully to map neuronal activity in rodents 1-5. In AIM MRI, Mn 2+ acts a calcium analog and accumulates in depolarized neurons 6,7. Because Mn 2+ shortens the T 1 tissue property, regions of elevated neuronal activity will enhance in MRI. Furthermore, Mn 2+ clears slowly from the activated regions; therefore, stimulation can be performed outside the magnet prior to imaging, enabling greater experimental flexibility. However, because Mn 2+ does not readily cross the blood-brain barrier (BBB), the need to open the BBB has limited the use of AIM MRI, especially in mice. One tool for opening the BBB is ultrasound. Though potentially damaging, if ultrasound is administered in combination with gas-filled microbubbles (i.e., ultrasound contrast agents), the acoustic pressure required for BBB opening is considerably lower. This combination of ultrasound and microbubbles can be used to reliably open the BBB without causing tissue damage 8-11. Here, a method is presented for performing AIM MRI by using microbubbles and ultrasound to open the BBB. After an intravenous injection of perflutren microbubbles, an unfocused pulsed ultrasound beam is applied to the shaved mouse head for 3 minutes. For simplicity, we refer to this technique of BBB Opening with Microbubbles and UltraSound as BOMUS 12. Using BOMUS to open the BBB throughout both cerebral hemispheres, manganese is administered to the whole mouse brain. After experimental stimulation of the lightly sedated mice, AIM MRI is used to map the neuronal response. To demonstrate this approach, herein BOMUS and AIM MRI are used to map unilateral mechanical stimulation of the vibrissae in lightly sedated mice 13. Because BOMUS can open the BBB throughout both hemispheres, the unstimulated side of the brain is used to control for nonspecific background stimulation. The resultant 3D activation map agrees well with published representations of the vibrissae regions of the barrel field cortex 14. The ultrasonic opening of the BBB is fast, noninvasive, and reversible; and thus this approach is suitable for high-throughput and/or longitudinal studies in awake mice.

Authors
Howles, GP; Qi, Y; Rosenzweig, SJ; Nightingale, KR; Johnson, GA
MLA Citation
Howles, GP, Qi, Y, Rosenzweig, SJ, Nightingale, KR, and Johnson, GA. "Functional neuroimaging using ultrasonic blood-brain barrier disruption and manganese-enhanced MRI." Journal of Visualized Experiments 65 (2012).
PMID
22825127
Source
scival
Published In
Journal of Visualized Experiments
Issue
65
Publish Date
2012
DOI
10.3791/4055

Altered diffusion tensor imaging measurements in aged transgenic Huntington disease rats

Rodent models of Huntington disease (HD) are valuable tools for investigating HD pathophysiology and evaluating new therapeutic approaches. Non-invasive characterization of HD-related phenotype changes is important for monitoring progression of pathological processes and possible effects of interventions. The first transgenic rat model for HD exhibits progressive late-onset affective, cognitive, and motor impairments, as well as neuropathological features reflecting observations from HD patients. In this report, we contribute to the anatomical phenotyping of this model by comparing high-resolution ex vivo DTI measurements obtained in aged transgenic HD rats and wild-type controls. By region of interest analysis supplemented by voxel-based statistics, we find little evidence of atrophy in basal ganglia regions, but demonstrate altered DTI measurements in the dorsal and ventral striatum, globus pallidus, entopeduncular nucleus, substantia nigra, and hippocampus. These changes are largely compatible with DTI findings in preclinical and clinical HD patients. We confirm earlier reports that HD rats express a moderate neuropathological phenotype, and provide evidence of altered DTI measures in specific HD-related brain regions, in the absence of pronounced morphometric changes. © 2012 The Author(s).

Authors
Antonsen, BT; Jiang, Y; Veraart, J; Qu, H; Nguyen, HP; Sijbers, J; Hörsten, SV; Johnson, GA; Leergaard, TB
MLA Citation
Antonsen, BT, Jiang, Y, Veraart, J, Qu, H, Nguyen, HP, Sijbers, J, Hörsten, SV, Johnson, GA, and Leergaard, TB. "Altered diffusion tensor imaging measurements in aged transgenic Huntington disease rats." Brain Structure and Function (2012): 1-12.
Website
http://hdl.handle.net/10161/13090
PMID
22618438
Source
scival
Published In
Brain Structure and Function
Publish Date
2012
Start Page
1
End Page
12
DOI
10.1007/s00429-012-0427-0

Functional neuroimaging using ultrasonic blood-brain barrier disruption and manganese-enhanced MRI.

Although mice are the dominant model system for studying the genetic and molecular underpinnings of neuroscience, functional neuroimaging in mice remains technically challenging. One approach, Activation-Induced Manganese-enhanced MRI (AIM MRI), has been used successfully to map neuronal activity in rodents. In AIM MRI, Mn(2+) acts a calcium analog and accumulates in depolarized neurons. Because Mn(2+) shortens the T1 tissue property, regions of elevated neuronal activity will enhance in MRI. Furthermore, Mn(2+) clears slowly from the activated regions; therefore, stimulation can be performed outside the magnet prior to imaging, enabling greater experimental flexibility. However, because Mn(2+) does not readily cross the blood-brain barrier (BBB), the need to open the BBB has limited the use of AIM MRI, especially in mice. One tool for opening the BBB is ultrasound. Though potentially damaging, if ultrasound is administered in combination with gas-filled microbubbles (i.e., ultrasound contrast agents), the acoustic pressure required for BBB opening is considerably lower. This combination of ultrasound and microbubbles can be used to reliably open the BBB without causing tissue damage. Here, a method is presented for performing AIM MRI by using microbubbles and ultrasound to open the BBB. After an intravenous injection of perflutren microbubbles, an unfocused pulsed ultrasound beam is applied to the shaved mouse head for 3 minutes. For simplicity, we refer to this technique of BBB Opening with Microbubbles and UltraSound as BOMUS. Using BOMUS to open the BBB throughout both cerebral hemispheres, manganese is administered to the whole mouse brain. After experimental stimulation of the lightly sedated mice, AIM MRI is used to map the neuronal response. To demonstrate this approach, herein BOMUS and AIM MRI are used to map unilateral mechanical stimulation of the vibrissae in lightly sedated mice. Because BOMUS can open the BBB throughout both hemispheres, the unstimulated side of the brain is used to control for nonspecific background stimulation. The resultant 3D activation map agrees well with published representations of the vibrissae regions of the barrel field cortex. The ultrasonic opening of the BBB is fast, noninvasive, and reversible; and thus this approach is suitable for high-throughput and/or longitudinal studies in awake mice.

Authors
Howles, GP; Qi, Y; Rosenzweig, SJ; Nightingale, KR; Johnson, GA
MLA Citation
Howles, GP, Qi, Y, Rosenzweig, SJ, Nightingale, KR, and Johnson, GA. "Functional neuroimaging using ultrasonic blood-brain barrier disruption and manganese-enhanced MRI." Journal of visualized experiments : JoVE 65 (2012): e4055-.
Source
scival
Published In
Journal of Visualized Experiments
Issue
65
Publish Date
2012
Start Page
e4055
DOI
10.3791/4055

Population-averaged diffusion tensor imaging atlas of the Sprague Dawley rat brain.

Rats are widely used in experimental neurobiological research, and rat brain atlases are important resources for identifying brain regions in the context of experimental microsurgery, tissue sampling, and neuroimaging, as well as comparison of findings across experiments. Currently, most available rat brain atlases are constructed from histological material derived from single specimens, and provide two-dimensional or three-dimensional (3D) outlines of diverse brain regions and fiber tracts. Important limitations of such atlases are that they represent individual specimens, and that finer details of tissue architecture are lacking. Access to more detailed 3D brain atlases representative of a population of animals is needed. Diffusion tensor imaging (DTI) is a unique neuroimaging modality that provides sensitive information about orientation structure in tissues, and is widely applied in basic and clinical neuroscience investigations. To facilitate analysis and assignment of location in rat brain neuroimaging investigations, we have developed a population-averaged three-dimensional DTI atlas of the normal adult Sprague Dawley rat brain. The atlas is constructed from high resolution ex vivo DTI images, which were nonlinearly warped into a population-averaged in vivo brain template. The atlas currently comprises a selection of manually delineated brain regions, the caudate-putamen complex, globus pallidus, entopeduncular nucleus, substantia nigra, external capsule, corpus callosum, internal capsule, cerebral peduncle, fimbria of the hippocampus, fornix, anterior commisure, optic tract, and stria terminalis. The atlas is freely distributed and potentially useful for several purposes, including automated and manual delineation of rat brain structural and functional imaging data.

Authors
Veraart, J; Leergaard, TB; Antonsen, BT; Van Hecke, W; Blockx, I; Jeurissen, B; Jiang, Y; Van der Linden, A; Johnson, GA; Verhoye, M; Sijbers, J
MLA Citation
Veraart, J, Leergaard, TB, Antonsen, BT, Van Hecke, W, Blockx, I, Jeurissen, B, Jiang, Y, Van der Linden, A, Johnson, GA, Verhoye, M, and Sijbers, J. "Population-averaged diffusion tensor imaging atlas of the Sprague Dawley rat brain." Neuroimage 58.4 (October 15, 2011): 975-983.
PMID
21749925
Source
pubmed
Published In
NeuroImage
Volume
58
Issue
4
Publish Date
2011
Start Page
975
End Page
983
DOI
10.1016/j.neuroimage.2011.06.063

High-resolution reconstruction of fluorescent inclusions in mouse thorax using anatomically guided sampling and parallel Monte Carlo computing.

We present a method for high-resolution reconstruction of fluorescent images of the mouse thorax. It features an anatomically guided sampling method to retrospectively eliminate problematic data and a parallel Monte Carlo software package to compute the Jacobian matrix for the inverse problem. The proposed method was capable of resolving microliter-sized femtomole amount of quantum dot inclusions closely located in the middle of the mouse thorax. The reconstruction was verified against co-registered micro-CT data. Using the proposed method, the new system achieved significantly higher resolution and sensitivity compared to our previous system consisting of the same hardware. This method can be applied to any system utilizing similar imaging principles to improve imaging performance.

Authors
Zhang, X; Badea, C; Hood, G; Wetzel, A; Qi, Y; Stiles, J; Johnson, GA
MLA Citation
Zhang, X, Badea, C, Hood, G, Wetzel, A, Qi, Y, Stiles, J, and Johnson, GA. "High-resolution reconstruction of fluorescent inclusions in mouse thorax using anatomically guided sampling and parallel Monte Carlo computing." Biomed Opt Express 2.9 (September 1, 2011): 2449-2460.
Website
http://hdl.handle.net/10161/11254
PMID
21991539
Source
pubmed
Published In
Biomedical Optics Express
Volume
2
Issue
9
Publish Date
2011
Start Page
2449
End Page
2460
DOI
10.1364/BOE.2.002449

Phenylephrine-modulated cardiopulmonary blood flow measured with use of X-ray digital subtraction angiography.

INTRODUCTION: Cardiopulmonary blood flow is an important indicator of organ function. Limitations in measuring blood flow in live rodents suggest that rapid physiological changes may be overlooked. For instance, relative measurements limit imaging to whole organs or large sections without adequately visualizing vasculature. Additionally, current methods use small samples and invasive techniques that often require killing animals, limiting sampling speed, or both. A recently developed high spatial- and temporal-resolution X-ray digital subtraction angiography (DSA) system visualizes vasculature and measures blood flow in rodents. This study was the first to use this system to measure changes in cardiopulmonary blood flow in rats after administering the vasoconstrictor phenylephrine. METHODS: Cardiopulmonary blood flow and vascular anatomy were assessed in 11 rats before, during, and after recovery from phenylephrine. After acquiring DSA images at 12 time points, a calibrated non-parametric deconvolution technique using singular value decomposition (SVD) was applied to calculate quantitative aortic blood flow in absolute metrics (mL/min). Trans-pulmonary transit time was calculated as the time interval between maximum signal enhancement in the pulmonary trunk and aorta. Pulmonary blood volume was calculated based on the central volume principle. Statistical analysis compared differences in trans-pulmonary blood volume and pressure, and aortic diameter using paired t-tests on baseline, peak, and late-recovery time points. RESULTS: Phenylephrine had dramatic qualitative and quantitative effects on vascular anatomy and blood flow. Major vessels distended significantly (aorta, ~1.2-times baseline) and mean arterial blood pressure increased ~2 times. Pulmonary blood volume, flow, pressure, and aortic diameter were not significantly different between baseline and late recovery, but differences were significant between baseline and peak, as well as peak and recovery time points. DISCUSSION: The DSA system with calibrated SVD technique acquired blood flow measurements every 30s with a high level of regional specificity, thus providing a new option for in vivo functional assessment in small animals.

Authors
Lin, M; Qi, Y; Chen, AF; Badea, CT; Johnson, GA
MLA Citation
Lin, M, Qi, Y, Chen, AF, Badea, CT, and Johnson, GA. "Phenylephrine-modulated cardiopulmonary blood flow measured with use of X-ray digital subtraction angiography." J Pharmacol Toxicol Methods 64.2 (September 2011): 180-186.
PMID
21846505
Source
pubmed
Published In
Journal of Pharmacological and Toxicological Methods
Volume
64
Issue
2
Publish Date
2011
Start Page
180
End Page
186
DOI
10.1016/j.vascn.2011.08.001

In vivo imaging of rat coronary arteries using bi-plane digital subtraction angiography.

INTRODUCTION: X-ray based digital subtraction angiography (DSA) is a common clinical imaging method for vascular morphology and function. Coronary artery characterization is one of its most important applications. We show that bi-plane DSA of rat coronary arteries can provide a powerful imaging tool for translational safety assessment in drug discovery. METHODS: A novel, dual tube/detector system, constructed explicitly for preclinical imaging, supports image acquisition at 10 frames/s with 88-micron spatial resolution. Ventilation, x-ray exposure, and contrast injection are all precisely synchronized using a biological sequence controller implemented as a LabVIEW application. A set of experiments were performed to test and optimize the sampling and image quality. We applied the DSA imaging protocol to record changes in the visualization of coronaries and myocardial perfusion induced by a vasodilator drug, nitroprusside. The drug was infused into a tail vein catheter using a peristaltic infusion pump at a rate of 0.07 mL/h for 3 min (dose: 0.0875 mg). Multiple DSA sequences were acquired before, during, and up to 25 min after drug infusion. Perfusion maps of the heart were generated in MATLAB to compare the drug effects over time. RESULTS: The best trade-off between the injection time, pressure, and image quality was achieved at 60 PSI, with the injection of 150 ms occurring early in diastole (60 ms delay) and resulting in the delivery of 113 μL of contrast agent. DSA images clearly show the main branches of the coronary arteries in an intact, beating heart. The drug test demonstrated that DSA can detect relative changes in coronary circulation via perfusion maps. CONCLUSIONS: The methodology for DSA imaging of rat coronary arteries can serve as a template for future translational studies to assist in safety evaluation of new pharmaceuticals. Although x-ray imaging involves radiation, the associated dose (0.4 Gy) is not a major limitation.

Authors
Badea, CT; Hedlund, LW; Qi, Y; Berridge, B; Johnson, GA
MLA Citation
Badea, CT, Hedlund, LW, Qi, Y, Berridge, B, and Johnson, GA. "In vivo imaging of rat coronary arteries using bi-plane digital subtraction angiography." J Pharmacol Toxicol Methods 64.2 (September 2011): 151-157.
PMID
21683146
Source
pubmed
Published In
Journal of Pharmacological and Toxicological Methods
Volume
64
Issue
2
Publish Date
2011
Start Page
151
End Page
157
DOI
10.1016/j.vascn.2011.05.008

4D micro-CT for cardiac and perfusion applications with view under sampling.

Micro-CT is commonly used in preclinical studies to provide anatomical information. There is growing interest in obtaining functional measurements from 4D micro-CT. We report here strategies for 4D micro-CT with a focus on two applications: (i) cardiac imaging based on retrospective gating and (ii) pulmonary perfusion using multiple contrast injections/rotations paradigm. A dual source micro-CT system is used for image acquisition with a sampling rate of 20 projections per second. The cardiac micro-CT protocol involves the use of a liposomal blood pool contrast agent. Fast scanning of free breathing mice is achieved using retrospective gating. The ECG and respiratory signals are used to sort projections into ten cardiac phases. The pulmonary perfusion protocol uses a conventional contrast agent (Isovue 370) delivered by a micro-injector in four injections separated by 2 min intervals to allow for clearance. Each injection is synchronized with the rotation of the animal, and each of the four rotations is started with an angular offset of 22.5 from the starting angle of the previous rotation. Both cardiac and perfusion protocols result in an irregular angular distribution of projections that causes significant streaking artifacts in reconstructions when using traditional filtered backprojection (FBP) algorithms. The reconstruction involves the use of the point spread function of the micro-CT system for each time point, and the analysis of the distribution of the reconstructed data in the Fourier domain. This enables us to correct for angular inconsistencies via deconvolution and identify regions where data is missing. The missing regions are filled with data from a high quality but temporally averaged prior image reconstructed with all available projections. Simulations indicate that deconvolution successfully removes the streaking artifacts while preserving temporal information. 4D cardiac micro-CT in a mouse was performed with adequate image quality at isotropic voxel size of 88 µm and 10 ms temporal resolution. 4D pulmonary perfusion images were obtained in a mouse at 176 µm and 687 ms temporal resolution. Compared with FBP reconstruction, the streak reduction ratio is 70% and the contrast to noise ratio is 2.5 times greater in the deconvolved images. The radiation dose associated with the proposed methods is in the range of a typical micro-CT dose (0.17 Gy for the cardiac study and 0.21 Gy for the perfusion study). The low dose 4D micro-CT imaging presented here can be applied in high-throughput longitudinal studies in a wide range of applications, including drug safety and cardiopulmonary phenotyping.

Authors
Badea, CT; Johnston, SM; Qi, Y; Johnson, GA
MLA Citation
Badea, CT, Johnston, SM, Qi, Y, and Johnson, GA. "4D micro-CT for cardiac and perfusion applications with view under sampling." Phys Med Biol 56.11 (June 7, 2011): 3351-3369.
PMID
21558587
Source
pubmed
Published In
Physics in Medicine and Biology
Volume
56
Issue
11
Publish Date
2011
Start Page
3351
End Page
3369
DOI
10.1088/0031-9155/56/11/011

High-field (9.4 T) MRI of brain dysmyelination by quantitative mapping of magnetic susceptibility.

The multilayered myelin sheath wrapping around nerve axons is essential for proper functioning of the central nervous system. Abnormal myelination leads to a wide range of neurological diseases and developmental disorders. Non-invasive imaging of myelin content is of great clinical importance. The present work demonstrated that loss of myelin in the central nervous system of the shiverer mouse results in a dramatic reduction of magnetic susceptibility in white matter axons. The reduction resulted in a near extinction of susceptibility contrast between gray and white matter. Quantitative magnetic susceptibility imaging and diffusion tensor imaging were conducted on a group of control and shiverer mice at 9.4 T. We measured the resonance frequency distribution of the whole brain for each mouse. Magnetic susceptibility maps were computed and compared between the two groups. It was shown that the susceptibility contrast between gray and white matter was reduced by 96% in the shiverer compared to the controls. Diffusion measurements further confirmed intact fiber pathways in the shiverer mice, ruling out the possibility of axonal injury and its potential contribution to the altered susceptibility. As an autosomal recessive mutation, shiverer is characterized by an almost total lack of central nervous system myelin. Our data provide new evidences indicating that myelin is the predominant source of susceptibility differences between deep gray and white matter observed in magnetic resonance imaging. More importantly, the present study suggests that quantitative magnetic susceptibility is a potential endogenous biomarker for myelination.

Authors
Liu, C; Li, W; Johnson, GA; Wu, B
MLA Citation
Liu, C, Li, W, Johnson, GA, and Wu, B. "High-field (9.4 T) MRI of brain dysmyelination by quantitative mapping of magnetic susceptibility." Neuroimage 56.3 (June 1, 2011): 930-938.
PMID
21320606
Source
pubmed
Published In
NeuroImage
Volume
56
Issue
3
Publish Date
2011
Start Page
930
End Page
938
DOI
10.1016/j.neuroimage.2011.02.024

Microscopic diffusion tensor atlas of the mouse brain.

Eight diffusion tensor imaging (DTI) datasets of normal adult C57BL/6J mouse brains were acquired with an isotropic Nyquist limited resolution of 43 μm (voxel volume ~80 pl). Each specimen was scanned with a b0 image and 6 diffusion-weighted images. T1- and T2*-weighted data were acquired with each specimen to aid nonlinear registration of the data to a common reference space (called "Waxholm Space"). We identified 80 different discrete landmarks in Waxholm Space to provide the gold standard for measuring the registration quality. The accuracy of the registration was established by measuring displacement of the 80 landmarks in each registered brain from the same landmarks in the reference brain. The accuracy was better than 130 μm for 95% of the landmarks (overall landmark displacement is 65±40 μm, n=640). Mean and coefficient of variation atlases of DTI indices were generated with potential application for both voxel-based and region of interest-based analysis. To examine consistency of DTI data among individual subjects in this study and difference in diffusion indices between separate brain structures within each subject, averaged values of DTI indices (axial diffusivity, radial diffusivity, fractional anisotropy, and angular deviation of the primary eigenvector) were computed in 9 white matter structures in each brain. The variation of the DTI indices across the population was very small, e.g., ~5% for axial diffusivity for each white matter structure, enabling confident differentiation of differences in these structures within each subject. ANOVA tests indicated that the current protocol is able to provide consistent DTI data of individual brains (p>0.25), and distinguish difference of diffusion indices between white matter structures (p<0.001). Power analysis was also performed to provide an estimate of the number of specimens required to detect a 10% change of the DTI indices in each white matter structure. The data provide a critical addition to Waxholm Space, the International Neuroinformatics Coordinating Facility (www.incf.org) online comprehensive atlas of the mouse brain.

Authors
Jiang, Y; Johnson, GA
MLA Citation
Jiang, Y, and Johnson, GA. "Microscopic diffusion tensor atlas of the mouse brain." Neuroimage 56.3 (June 1, 2011): 1235-1243.
PMID
21419226
Source
pubmed
Published In
NeuroImage
Volume
56
Issue
3
Publish Date
2011
Start Page
1235
End Page
1243
DOI
10.1016/j.neuroimage.2011.03.031

MAGNETIC RESONANCE MICROSCOPY-BASED 3D FACE-BRAIN CORRELATIONS IN AN FASD MOUSE MODEL

Authors
Lipinski, RJ; Hammond, P; Ament, JJ; Pecevich, SJ; Jiang, Y; Dehart, DB; Johnson, GA; Sulik, KK
MLA Citation
Lipinski, RJ, Hammond, P, Ament, JJ, Pecevich, SJ, Jiang, Y, Dehart, DB, Johnson, GA, and Sulik, KK. "MAGNETIC RESONANCE MICROSCOPY-BASED 3D FACE-BRAIN CORRELATIONS IN AN FASD MOUSE MODEL." June 2011.
Source
wos-lite
Published In
Alcoholism: Clinical and Experimental Research
Volume
35
Issue
6
Publish Date
2011
Start Page
266A
End Page
266A

Magnetic resonance and diffusion tensor imaging of pre- and postnatal brains in a mouse Fetal Alcohol Spectrum Disorders model

Authors
Sulik, KK; O'Leary-Moore, SK; Parnell, SE; Lipinski, RJ; Pecevich, S; Holloway, HT; Ament, J; Oguz, I; Budin, F; Jiang, Y; Dehart, DB; Styner, MA; Johnson, GA
MLA Citation
Sulik, KK, O'Leary-Moore, SK, Parnell, SE, Lipinski, RJ, Pecevich, S, Holloway, HT, Ament, J, Oguz, I, Budin, F, Jiang, Y, Dehart, DB, Styner, MA, and Johnson, GA. "Magnetic resonance and diffusion tensor imaging of pre- and postnatal brains in a mouse Fetal Alcohol Spectrum Disorders model." May 2011.
Source
wos-lite
Published In
Alcohol
Volume
45
Issue
3
Publish Date
2011
Start Page
282
End Page
282

BETA-ARRESTINS REGULATE SIGNALING BY BONE MORPHOGENETIC PROTEIN TYPE II RECEPTOR IN PULMONARY ARTERIAL HYPERTENSION

Authors
Rajagopal, S; Kovacs, J; Badea, C; Johnson, GA; Rockman, HA; Piantadosi, CA; Lefkowitz, RJ
MLA Citation
Rajagopal, S, Kovacs, J, Badea, C, Johnson, GA, Rockman, HA, Piantadosi, CA, and Lefkowitz, RJ. "BETA-ARRESTINS REGULATE SIGNALING BY BONE MORPHOGENETIC PROTEIN TYPE II RECEPTOR IN PULMONARY ARTERIAL HYPERTENSION." JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 57.14 (April 5, 2011): E2046-E2046.
Source
wos-lite
Published In
JACC - Journal of the American College of Cardiology
Volume
57
Issue
14
Publish Date
2011
Start Page
E2046
End Page
E2046

A symmetrical Waxholm canonical mouse brain for NeuroMaps.

NeuroMaps (2010) is a Web-based application that enables investigators to map data from macaque studies to a canonical atlas of the macaque brain. It currently serves as an image processor enabling them to create figures suitable for publication, presentation and archival purposes. Eventually it will enable investigators studying any of several species to analyze the overlap between their data and multimodality data mapped by others. The purpose of the current project was to incorporate the Waxholm canonical mouse brain (Harwylycz, 2009) into NeuroMaps. An enhanced gradient echo (T2*) magnetic resonance image (MRI) of the Waxholm canonical brain (Johnson et al., 2010) was warped to bring the irregular biological midplane of the MRI into line with the mathematically flat midsagittal plane of the Waxholm space. The left hemisphere was deleted and the right hemisphere reflected to produce a symmetrical 3D MR image. The symmetrical T2* image was imported into NeuroMaps. The map executing this warp was applied to four other voxellated volumes based on the same canonical specimen and maintained at the Center for In-Vitro Microscopy (CIVM): a T2-weighted MRI, a T1-weighted MRI, a segmented image and an image reconstructed from Nissl-stained histological sections of the specimen. Symmetric versions of those images were returned to the CIVM repository where they are made available to other laboratories. Utility of the symmetric atlas was demonstrated by mapping and comparing a number of cortical areas as illustrated in three conventional mouse brain atlases. The symmetric Waxholm mouse brain atlas is now accessible in NeuroMaps where investigators can map image data to standard templates over the Web and process them for publication, presentation and archival purposes: http://braininfo.rprc.washington.edu/MapViewData.aspx.

Authors
Bowden, DM; Johnson, GA; Zaborsky, L; Green, WDK; Moore, E; Badea, A; Dubach, MF; Bookstein, FL
MLA Citation
Bowden, DM, Johnson, GA, Zaborsky, L, Green, WDK, Moore, E, Badea, A, Dubach, MF, and Bookstein, FL. "A symmetrical Waxholm canonical mouse brain for NeuroMaps." J Neurosci Methods 195.2 (February 15, 2011): 170-175.
PMID
21163300
Source
pubmed
Published In
Journal of Neuroscience Methods
Volume
195
Issue
2
Publish Date
2011
Start Page
170
End Page
175
DOI
10.1016/j.jneumeth.2010.11.028

Digital atlasing and standardization in the mouse brain.

Authors
Hawrylycz, M; Baldock, RA; Burger, A; Hashikawa, T; Johnson, GA; Martone, M; Ng, L; Lau, C; Larson, SD; Nissanov, J; Puelles, L; Ruffins, S; Verbeek, F; Zaslavsky, I; Boline, J
MLA Citation
Hawrylycz, M, Baldock, RA, Burger, A, Hashikawa, T, Johnson, GA, Martone, M, Ng, L, Lau, C, Larson, SD, Nissanov, J, Puelles, L, Ruffins, S, Verbeek, F, Zaslavsky, I, and Boline, J. "Digital atlasing and standardization in the mouse brain. (Published online)" PLoS Comput Biol 7.2 (February 3, 2011): e1001065-.
PMID
21304938
Source
pubmed
Published In
PLoS computational biology
Volume
7
Issue
2
Publish Date
2011
Start Page
e1001065
DOI
10.1371/journal.pcbi.1001065

Reduction of artifacts in T2 -weighted PROPELLER in high-field preclinical imaging.

A simple technique is implemented for correction of artifacts arising from nonuniform T(2) -weighting of k-space data in fast spin echo-based PROPELLER (periodically rotated overlapping parallel lines with enhanced reconstruction). An additional blade with no phase-encoding gradients is acquired to generate the scaling factor used for the correction. Results from simulations and phantom experiments, as well as in vivo experiments in free-breathing mice, demonstrate the advantages of the proposed method. This technique is developed specifically for high-field imaging applications where T(2) decay is rapid.

Authors
Pandit, P; Qi, Y; King, KF; Johnson, GA
MLA Citation
Pandit, P, Qi, Y, King, KF, and Johnson, GA. "Reduction of artifacts in T2 -weighted PROPELLER in high-field preclinical imaging." Magn Reson Med 65.2 (February 2011): 538-543.
PMID
20928875
Source
pubmed
Published In
Magnetic Resonance in Medicine
Volume
65
Issue
2
Publish Date
2011
Start Page
538
End Page
543
DOI
10.1002/mrm.22624

Quantitative neuromorphometry using magnetic resonance histology.

Magnetic resonance imaging (MRI), now common in the clinical domain, has been adapted for use by the neuropathologist by increasing the spatial resolution over 100,000 times what is common in human clinical imaging. This increase in spatial resolution has been accomplished through a variety of technical advances-higher magnetic fields, more sensitive receivers, and clever encoding methods. Magnetic resonance histology (MRH), that is, the application of MRI to study tissue specimens, now makes three-dimensional imaging of the fixed brain in the cranium routine. Active staining (perfusion fixation with a paramagnetic contrast agent) has allowed us to reduce the scan time by more than 8 times over earlier methods. The result is a three-dimensional isotropic image array that can be viewed along any direction without loss of spatial resolution. Homologous slices can be chosen interactively. Since the tissue is still fully hydrated in the cranium, tissue shrinkage and distortion are virtually eliminated. Volume measurements of neural structures can be made with a high degree of precision and accuracy. MRH will not replace more traditional methods, but it promises enormous value in choosing particular areas and times for more traditional sectioning and assessment.

Authors
Johnson, GA; Badea, A; Jiang, Y
MLA Citation
Johnson, GA, Badea, A, and Jiang, Y. "Quantitative neuromorphometry using magnetic resonance histology." Toxicol Pathol 39.1 (January 2011): 85-91.
PMID
21119052
Source
pubmed
Published In
Toxicologic Pathology (Sage)
Volume
39
Issue
1
Publish Date
2011
Start Page
85
End Page
91
DOI
10.1177/0192623310389622

Evaluation of tumor microenvironment in an animal model using a nanoparticle contrast agent in computed tomography imaging.

Non-invasive longitudinal imaging of tumor vasculature could provide new insights into the development of solid tumors, facilitating efficient delivery of therapeutics. In this study, we report three-dimensional imaging and characterization of tumor vascular architecture using a nanoparticle contrast agent and high-resolution computed tomography (CT) imaging.Five Balb/c mice implanted with 4T1/Luc syngeneic breast tumors cells were used for the study. The nanoparticle contrast agent was systemically administered and longitudinal CT imaging was performed pre-contrast and at serial time points post-contrast, for up to 7 days for studying the characteristics of tumor-associated blood vessels. Gene expression of tumor angiogenic biomarkers was measured using quantitative real-time polymerase chain reaction.Early-phase imaging demonstrated the presence of co-opted and newly developed tumor vessels. The co-opted vessels demonstrated wall-permeability and "leakiness" characteristics evident by an increase in extravascular nanoparticle-based signal enhancement visible well beyond the margins of tumor. Diameters of tumor-associated vessels were larger than the contralateral normal vessels. Delayed-phase imaging also demonstrated significant accumulation of nanoparticle contrast agent both within and in areas surrounding the tumor. A heterogeneous pattern of signal enhancement was observed both within and among individual tumors. Gene-expression profiling demonstrated significant variability in several angiogenic biomarkers both within and among individual tumors.The nanoparticle contrast agent and high-resolution CT imaging facilitated visualization of co-opted and newly developed tumors vessels as well as imaging of nanoparticle accumulation within tumors. The use of this agent could provide novel insights into tumor vascular biology and could have implications on the monitoring of tumor status.

Authors
Ghaghada, KB; Badea, CT; Karumbaiah, L; Fettig, N; Bellamkonda, RV; Johnson, GA; Annapragada, A
MLA Citation
Ghaghada, KB, Badea, CT, Karumbaiah, L, Fettig, N, Bellamkonda, RV, Johnson, GA, and Annapragada, A. "Evaluation of tumor microenvironment in an animal model using a nanoparticle contrast agent in computed tomography imaging." Academic radiology 18.1 (January 2011): 20-30.
PMID
21145026
Source
epmc
Published In
Academic Radiology
Volume
18
Issue
1
Publish Date
2011
Start Page
20
End Page
30
DOI
10.1016/j.acra.2010.09.003

Micro-CT imaging assessment of dobutamine-induced cardiac stress in rats.

INTRODUCTION: Dobutamine (DOB) stress in animal models of heart disease has been imaged so far using echocardiography and magnetic resonance imaging. The purpose of this study was to assess normal response to DOB stress in rats using anatomical and functional data using micro-computed tomography (CT). METHODS: Ten normal adult male rats were first injected with a liposomal-based blood pool contrast agent and next infused with DOB via a tail vein catheter. Using prospective gating, 5 pairs of systole/diastole micro-CT images were acquired (a) pre-infusion baseline; (b) at heart rate plateau during infusion of 10 μg/kg/min DOB; (c) at post-DOB infusion baseline; (d) at heart rate plateau during infusion of 30 μg/kg/min DOB; and (e) after post-infusion return to baseline. Heart rate, peripheral and breathing distensions were monitored by oximetry. Micro-CT images with 88-μm isotropic voxels were segmented to obtain cardiac function based on volumetric measurements of the left ventricle. RESULTS: DOB stress increased heart rate and cardiac output with both doses. Ejection fraction increased above baseline by an average of 35.9% with the first DOB dose and 18.4% with the second dose. No change was observed in the relative peripheral arterial pressures associated with the significant increases in cardiac output. DISCUSSION: Micro-CT proved to be a robust imaging method able to provide isotropic data on cardiac morphology and function. Micro-CT has the advantage of being faster and more cost-effective than MR and is able to provide higher accuracy than echocardiography. The impact of such an enabling technology can be enormous in evaluating cardiotoxic effects of various test drugs.

Authors
Badea, CT; Hedlund, LW; Cook, J; Berridge, BR; Johnson, GA
MLA Citation
Badea, CT, Hedlund, LW, Cook, J, Berridge, BR, and Johnson, GA. "Micro-CT imaging assessment of dobutamine-induced cardiac stress in rats." J Pharmacol Toxicol Methods 63.1 (January 2011): 24-29.
PMID
20399875
Source
pubmed
Published In
Journal of Pharmacological and Toxicological Methods
Volume
63
Issue
1
Publish Date
2011
Start Page
24
End Page
29
DOI
10.1016/j.vascn.2010.04.002

Continuing Education Course #1: Non-Invasive Imaging as a Problem-Solving Tool and Translational Biomarker Strategy in Toxicologic Pathology

Authors
Peterson, RA; Gabrielson, KL; Johnson, GA; Pomper, MG; Coatney, RW; Winkelmann, CT
MLA Citation
Peterson, RA, Gabrielson, KL, Johnson, GA, Pomper, MG, Coatney, RW, and Winkelmann, CT. "Continuing Education Course #1: Non-Invasive Imaging as a Problem-Solving Tool and Translational Biomarker Strategy in Toxicologic Pathology." TOXICOLOGIC PATHOLOGY 39.1 (January 2011): 267-272.
PMID
21147931
Source
wos-lite
Published In
Toxicologic Pathology (Sage)
Volume
39
Issue
1
Publish Date
2011
Start Page
267
End Page
272
DOI
10.1177/0192623310390392

Dual-energy micro-CT imaging for differentiation of iodine- and gold-based nanoparticles

Spectral CT imaging is expected to play a major role in the diagnostic arena as it provides material decomposition on an elemental basis. One fascinating possibility is the ability to discriminate multiple contrast agents targeting different biological sites. We investigate the feasibility of dual energy micro-CT for discrimination of iodine (I) and gold (Au) contrast agents when simultaneously present in the body. Simulations and experiments were performed to measure the CT enhancement for I and Au over a range of voltages from 40-to-150 kVp using a dual source micro-CT system. The selected voltages for dual energy micro-CT imaging of Au and I were 40 kVp and 80 kVp. On a massconcentration basis, the relative average enhancement of Au to I was 2.75 at 40 kVp and 1.58 at 80 kVp. We have demonstrated the method in a preclinical model of colon cancer to differentiate vascular architecture and extravasation. The concentration maps of Au and I allow quantitative measure of the bio-distribution of both agents. In conclusion, dual energy micro-CT can be used to discriminate probes containing I and Au with immediate impact in pre-clinical research. © 2011 SPIE.

Authors
Badea, CT; Johnston, SM; Qi, Y; Ghaghada, K; Johnson, GA
MLA Citation
Badea, CT, Johnston, SM, Qi, Y, Ghaghada, K, and Johnson, GA. "Dual-energy micro-CT imaging for differentiation of iodine- and gold-based nanoparticles." 2011.
Source
scival
Published In
Proceedings of SPIE
Volume
7961
Publish Date
2011
DOI
10.1117/12.878043

Continuing education course #3: current practices and future trends in neuropathology assessment for developmental neurotoxicity testing.

The continuing education course on Developmental Neurotoxicity Testing (DNT) was designed to communicate current practices for DNT neuropathology, describe promising innovations in quantitative analysis and noninvasive imaging, and facilitate a discussion among experienced neuropathologists and regulatory scientists regarding suitable DNT practices. Conventional DNT neuropathology endpoints are qualitative histopathology and morphometric endpoints of particularly vulnerable sites (e.g., cerebral, cerebellar, or hippocampal thickness). Novel imaging and stereology measurements hold promise for automated analysis of factors that cannot be effectively examined in routinely processed specimens (e.g., cell numbers, fiber tract integrity). The panel recommended that dedicated DNT neuropathology data sets be acquired on a minimum of 8 sections (for qualitative assessment) or 3 sections (for quantitative linear and stereological analyses) using a small battery of stains to examine neurons and myelin. Where guidelines permit discretion, immersion fixation is acceptable for younger animals (postnatal day 22 or earlier), and peripheral nerves may be embedded in paraffin. Frequent concerns regarding DNT data sets include false-negative outcomes due to processing difficulties (e.g., lack of concordance among sections from different animals) and insensitive analytical endpoints (e.g., qualitative evaluation) as well as false-positive results arising from overinterpretation or misreading by inexperienced pathologists.

Authors
Bolon, B; Garman, RH; Gundersen, HJG; Johnson, GA; Kaufmann, W; Krinke, G; Little, PB; Makris, SL; Mellon, RD; Sulik, KK; Jensen, K
MLA Citation
Bolon, B, Garman, RH, Gundersen, HJG, Johnson, GA, Kaufmann, W, Krinke, G, Little, PB, Makris, SL, Mellon, RD, Sulik, KK, and Jensen, K. "Continuing education course #3: current practices and future trends in neuropathology assessment for developmental neurotoxicity testing." Toxicologic pathology 39.1 (2011): 289-293.
PMID
21075916
Source
scival
Published In
Toxicologic Pathology (Sage)
Volume
39
Issue
1
Publish Date
2011
Start Page
289
End Page
293
DOI
10.1177/0192623310386247

GPU-based iterative reconstruction with total variation minimization for micro-CT

Dynamic imaging with micro-CT often produces poorly-distributed sets of projections, and reconstructions of this data with filtered backprojection algorithms (FBP) may be affected by artifacts. Iterative reconstruction algorithms and total variation (TV) denoising are promising alternatives to FBP, but may require running times that are frustratingly long. This obstacle can be overcome by implementing reconstruction algorithms on graphics processing units (GPU). This paper presents an implementation of a family of iterative reconstruction algorithms with TV denoising on a GPU, and a series of tests to optimize and compare the ability of different algorithms to reduce artifacts. The mathematical and computational details of the implementation are explored. The performance, measured by the accuracy of the reconstruction versus the running time, is assessed in simulations with a virtual phantom and in an in vivo scan of a mouse. We conclude that the simultaneous algebraic reconstruction technique with TV minimization (SART-TV) is a time-effective reconstruction algorithm for producing reconstructions with fewer artifacts than FBP. © 2010 SPIE.

Authors
Johnston, SM; Johnson, GA; Badea, CT
MLA Citation
Johnston, SM, Johnson, GA, and Badea, CT. "GPU-based iterative reconstruction with total variation minimization for micro-CT." December 1, 2010.
Source
scopus
Published In
Proceedings of SPIE
Volume
7622
Issue
PART 2
Publish Date
2010
DOI
10.1117/12.844368

Waxholm space: an image-based reference for coordinating mouse brain research.

We describe an atlas of the C57BL/6 mouse brain based on MRI and conventional Nissl histology. Magnetic resonance microscopy was performed on a total of 14 specimens that were actively stained to enhance tissue contrast. Images were acquired with three different MR protocols yielding contrast dependent on spin lattice relaxation (T1), spin spin relaxation (T2), and magnetic susceptibility (T2*). Spatial resolution was 21.5 mum (isotropic). Conventional histology (Nissl) was performed on a limited set of these same specimens and the Nissl images were registered (3D-to-3D) to the MR data. Probabilistic atlases for 37 structures are provided, along with average atlases. The availability of three different MR protocols, the Nissl data, and the labels provides a rich set of options for registration of other atlases to the same coordinate system, thus facilitating data-sharing. All the data is available for download via the web.

Authors
Johnson, GA; Badea, A; Brandenburg, J; Cofer, G; Fubara, B; Liu, S; Nissanov, J
MLA Citation
Johnson, GA, Badea, A, Brandenburg, J, Cofer, G, Fubara, B, Liu, S, and Nissanov, J. "Waxholm space: an image-based reference for coordinating mouse brain research." Neuroimage 53.2 (November 1, 2010): 365-372.
PMID
20600960
Source
pubmed
Published In
NeuroImage
Volume
53
Issue
2
Publish Date
2010
Start Page
365
End Page
372
DOI
10.1016/j.neuroimage.2010.06.067

Magnetic resonance microscopy-based analyses of the brains of normal and ethanol-exposed fetal mice.

BACKGROUND: The application of magnetic resonance microscopy (MRM) to the study of normal and abnormal prenatal mouse development has facilitated discovery of dysmorphology following prenatal ethanol insult. The current analyses extend this work, providing a regional brain volume-based description of normal brain growth and illustrating the consequences of gestational day (GD) 10 ethanol exposure in the fetal mouse. METHODS: To assess normal growth, control C57Bl/6J fetuses collected on GD 16, GD 16.5, and GD 17 were scanned using a 9.4-T magnet, resulting in 29-μm isotropic resolution images. For the ethanol teratogenicity studies, C57Bl/6J dams were administered intraperitoneal ethanol (2.9 g/kg) at 10 days, 0 hr, and 10 days, 4 hr, after fertilization, and fetuses were collected for analyses on GD 17. From individual MRM scans, linear measurements and regional brain volumes were determined and compared. RESULTS: In control fetuses, each of the assessed brain regions increased in volume, whereas ventricular volumes decreased between GD 16 and GD 17. Illustrating a global developmental delay, prenatal ethanol exposure resulted in reduced body volumes, crown-rump lengths, and a generalized decrease in regional brain volumes compared with GD 17 controls. However, compared with GD 16.5, morphologically matched controls, ethanol exposure resulted in volume increases in the lateral and third ventricles as well as a disproportionate reduction in cortical volume. CONCLUSIONS: The normative data collected in this study facilitate the distinction between GD 10 ethanol-induced developmental delay and frank dysmorphology. This work illustrates the utility of MRM-based analyses for developmental toxicology studies and extends our knowledge of the stage-dependency of ethanol teratogenesis.

Authors
O'Leary-Moore, SK; Parnell, SE; Godin, EA; Dehart, DB; Ament, JJ; Khan, AA; Johnson, GA; Styner, MA; Sulik, KK
MLA Citation
O'Leary-Moore, SK, Parnell, SE, Godin, EA, Dehart, DB, Ament, JJ, Khan, AA, Johnson, GA, Styner, MA, and Sulik, KK. "Magnetic resonance microscopy-based analyses of the brains of normal and ethanol-exposed fetal mice." Birth Defects Res A Clin Mol Teratol 88.11 (November 2010): 953-964.
PMID
20842647
Source
pubmed
Published In
Birth Defects Research Part A: Clinical and Molecular Teratology
Volume
88
Issue
11
Publish Date
2010
Start Page
953
End Page
964
DOI
10.1002/bdra.20719

Contrast-enhanced in vivo magnetic resonance microscopy of the mouse brain enabled by noninvasive opening of the blood-brain barrier with ultrasound.

The use of contrast agents for neuroimaging is limited by the blood-brain barrier (BBB), which restricts entry into the brain. To administer imaging agents to the brain of rats, intracarotid infusions of hypertonic mannitol have been used to open the BBB. However, this technically challenging approach is invasive, opens only a limited region of the BBB, and is difficult to extend to mice. In this work, the BBB was opened in mice, using unfocused ultrasound combined with an injection of microbubbles. This technique has several notable features: it (a) can be performed transcranially in mice; (b) takes only 3 min and uses only commercially available components; (c) opens the BBB throughout the brain; (d) causes no observed histologic damage or changes in behavior (with peak-negative acoustic pressures of 0.36 MPa); and (e) allows recovery of the BBB within 4 h. Using this technique, Gadopentetate Dimeglumine (Gd-DTPA) was administered to the mouse brain parenchyma, thereby shortening T(1) and enabling the acquisition of high-resolution (52 × 52 × 100 micrometers(3)) images in 51 min in vivo. By enabling the administration of both existing anatomic contrast agents and the newer molecular/sensing contrast agents, this technique may be useful for the study of mouse models of neurologic function and pathology with MRI.

Authors
Howles, GP; Bing, KF; Qi, Y; Rosenzweig, SJ; Nightingale, KR; Johnson, GA
MLA Citation
Howles, GP, Bing, KF, Qi, Y, Rosenzweig, SJ, Nightingale, KR, and Johnson, GA. "Contrast-enhanced in vivo magnetic resonance microscopy of the mouse brain enabled by noninvasive opening of the blood-brain barrier with ultrasound." Magn Reson Med 64.4 (October 2010): 995-1004.
PMID
20740666
Source
pubmed
Published In
Magnetic Resonance in Medicine
Volume
64
Issue
4
Publish Date
2010
Start Page
995
End Page
1004
DOI
10.1002/mrm.22411

Improving temporal resolution of pulmonary perfusion imaging in rats using the partially separable functions model.

Dynamic contrast-enhanced MRI (or DCE-MRI) is a useful tool for measuring blood flow and perfusion, and it has found use in the study of pulmonary perfusion in animal models. However, DCE-MRI experiments are difficult in small animals such as rats. A recently developed method known as Interleaved Radial Imaging and Sliding window-keyhole (IRIS) addresses this problem by using a data acquisition scheme that covers (k,t)-space with data acquired from multiple bolus injections of a contrast agent. However, the temporal resolution of IRIS is limited by the effects of temporal averaging inherent in the sliding window and keyhole operations. This article describes a new method to cover (k,t)-space based on the theory of partially separable functions (PSF). Specifically, a sparse sampling of (k,t)-space is performed to acquire two data sets, one with high-temporal resolution and the other with extended k-space coverage. The high-temporal resolution training data are used to determine the temporal basis functions of the PSF model, whereas the other data set is used to determine the spatial variations of the model. The proposed method was validated by simulations and demonstrated by an experimental study. In this particular study, the proposed method achieved a temporal resolution of 32 msec.

Authors
Brinegar, C; Schmitter, SS; Mistry, NN; Johnson, GA; Liang, Z-P
MLA Citation
Brinegar, C, Schmitter, SS, Mistry, NN, Johnson, GA, and Liang, Z-P. "Improving temporal resolution of pulmonary perfusion imaging in rats using the partially separable functions model." Magn Reson Med 64.4 (October 2010): 1162-1170.
PMID
20564601
Source
pubmed
Published In
Magnetic Resonance in Medicine
Volume
64
Issue
4
Publish Date
2010
Start Page
1162
End Page
1170
DOI
10.1002/mrm.22500

MAGNETIC RESONANCE IMAGING-BASED ANALYSES OF A FETAL ALCOHOL SPECTRUM DISORDERS MOUSE MODEL

Authors
Sulik, KK; O'Leary-Moore, SK; Parnell, SE; Godin, EA; Styner, MA; Lipinski, RJ; Johnson, GA
MLA Citation
Sulik, KK, O'Leary-Moore, SK, Parnell, SE, Godin, EA, Styner, MA, Lipinski, RJ, and Johnson, GA. "MAGNETIC RESONANCE IMAGING-BASED ANALYSES OF A FETAL ALCOHOL SPECTRUM DISORDERS MOUSE MODEL." August 10, 2010.
Source
wos-lite
Published In
Alcoholism: Clinical and Experimental Research
Volume
34
Issue
8
Publish Date
2010
Start Page
31A
End Page
31A

Static and dynamic cardiac modelling: Initial strides and results towards a quantitatively accurate mechanical heart model

Magnetic Resonance Imaging (MRI) has exhibited significant potential for quantifying cardiac function and dysfunction in the mouse. Recent advances in highresolution cardiac MR imaging techniques have contributed to the development of acquisition approaches that allow fast and accurate description of anatomic structures, and accurate surface and finite element (FE) mesh model constructions for study of global mechanical function in normal and transgenic mice. This study presents work in progress for construction of quantitatively accurate threedimensional (3D) and 4D dynamic surface and FE models of murine left ventricular (LV) muscle in C57BL/6J (n=10) mice. Constructed models are subsequently imported into commercial software packages for the solution of the constitutive equations that characterize mechanical function, including computation of the stress and strain fields. They are further used with solid-free form fabrication processes to construct model-based material renditions of the human and mouse hearts. ©2010 IEEE.

Authors
Constantinides, C; Aristokleous, N; Johnson, GA; Perperides, D
MLA Citation
Constantinides, C, Aristokleous, N, Johnson, GA, and Perperides, D. "Static and dynamic cardiac modelling: Initial strides and results towards a quantitatively accurate mechanical heart model." August 9, 2010.
Source
scopus
Published In
2010 7th IEEE International Symposium on Biomedical Imaging: From Nano to Macro, ISBI 2010 - Proceedings
Publish Date
2010
Start Page
496
End Page
499
DOI
10.1109/ISBI.2010.5490300

Multishot PROPELLER for high-field preclinical MRI.

With the development of numerous mouse models of cancer, there is a tremendous need for an appropriate imaging technique to study the disease evolution. High-field T(2)-weighted imaging using PROPELLER (Periodically Rotated Overlapping ParallEL Lines with Enhanced Reconstruction) MRI meets this need. The two-shot PROPELLER technique presented here provides (a) high spatial resolution, (b) high contrast resolution, and (c) rapid and noninvasive imaging, which enables high-throughput, longitudinal studies in free-breathing mice. Unique data collection and reconstruction makes this method robust against motion artifacts. The two-shot modification introduced here retains more high-frequency information and provides higher signal-to-noise ratio than conventional single-shot PROPELLER, making this sequence feasible at high fields, where signal loss is rapid. Results are shown in a liver metastases model to demonstrate the utility of this technique in one of the more challenging regions of the mouse, which is the abdomen.

Authors
Pandit, P; Qi, Y; Story, J; King, KF; Johnson, GA
MLA Citation
Pandit, P, Qi, Y, Story, J, King, KF, and Johnson, GA. "Multishot PROPELLER for high-field preclinical MRI." Magn Reson Med 64.1 (July 2010): 47-53.
PMID
20572138
Source
pubmed
Published In
Magnetic Resonance in Medicine
Volume
64
Issue
1
Publish Date
2010
Start Page
47
End Page
53
DOI
10.1002/mrm.22376

MAGNETIC RESONANCE MICROSCOPY AND DIFFUSION TENSOR IMAGING DEFINE STAGE-DEPENDENT CHANGES IN BRAIN MORPHOLOGY AFTER PRENATAL ETHANOL EXPOSURE IN MICE

Authors
O'Leary-Moore, SK; Parnell, SE; Godin, EA; Johnson, GA; Styner, M; Oguz, I; Budin, F; Jiang, Y; Dehart, DB; Sulik, KK
MLA Citation
O'Leary-Moore, SK, Parnell, SE, Godin, EA, Johnson, GA, Styner, M, Oguz, I, Budin, F, Jiang, Y, Dehart, DB, and Sulik, KK. "MAGNETIC RESONANCE MICROSCOPY AND DIFFUSION TENSOR IMAGING DEFINE STAGE-DEPENDENT CHANGES IN BRAIN MORPHOLOGY AFTER PRENATAL ETHANOL EXPOSURE IN MICE." June 2010.
Source
wos-lite
Published In
Alcoholism: Clinical and Experimental Research
Volume
34
Issue
6
Publish Date
2010
Start Page
298A
End Page
298A

Ultrasonic disruption of the blood-brain barrier enables in vivo functional mapping of the mouse barrel field cortex with manganese-enhanced MRI.

Though mice are the dominant model system for studying the genetic and molecular underpinnings of neuroscience, functional neuroimaging in mice remains technically challenging. One approach, Activation-Induced Manganese-enhanced MRI (AIM MRI), has been used successfully to map neuronal activity in rodents. In AIM MRI, manganese(2+) acts a calcium analog and accumulates in depolarized neurons. Because manganese(2+) shortens T1, regions of elevated neuronal activity enhance in MRI. However, because manganese does not cross the blood-brain barrier (BBB), the need to osmotically disrupt the BBB has limited the use of AIM MRI, particularly in mice. In this work, the BBB was opened in mice using unfocused, transcranial ultrasound in combination with gas-filled microbubbles. Using this noninvasive technique to open the BBB bilaterally, manganese could be quickly administered to the whole mouse brain. With this approach, AIM MRI was used to map the neuronal response to unilateral mechanical stimulation of the vibrissae in lightly sedated mice. The resultant 3D activation map agreed well with published representations of the vibrissae regions of the barrel field cortex. The anterior portions of the barrel field cortex corresponding to the more rostral vibrissae showed greater activation, consistent with previous literature. Because the ultrasonic opening of the BBB is simple, fast, and noninvasive, this approach is suitable for high-throughput and longitudinal studies in awake mice. This approach enables a new way to map neuronal activity in mice with manganese.

Authors
Howles, GP; Qi, Y; Johnson, GA
MLA Citation
Howles, GP, Qi, Y, and Johnson, GA. "Ultrasonic disruption of the blood-brain barrier enables in vivo functional mapping of the mouse barrel field cortex with manganese-enhanced MRI." Neuroimage 50.4 (May 1, 2010): 1464-1471.
PMID
20096789
Source
pubmed
Published In
NeuroImage
Volume
50
Issue
4
Publish Date
2010
Start Page
1464
End Page
1471
DOI
10.1016/j.neuroimage.2010.01.050

Microscopic diffusion tensor imaging of the mouse brain.

Diffusion tensor imaging (DTI) data at 43 mum isotropic resolution has been acquired on the intact adult mouse brain in 28-h scan time by using a streamlined protocol, including specimen fixation and staining, image acquisition, reconstruction, post-processing, and distribution. An intermediate registration of each component image is required to achieve the desired microscopic resolution. Multiple parameters have been derived, including fractional anisotropy, axial and radial diffusivity, and a color-coded orientation map of the primary eigenvector. Each DTI dataset was mapped to a common reference space to facilitate future standardized analysis. Fiber tracking has also been demonstrated, providing 3D connection information. This protocol to acquire high-resolution DTI data in a robust and repeatable fashion will serve as a foundation to quantitatively study mouse brain integrity and white matter architecture, at what we believe to be the highest spatial resolution yet attained.

Authors
Jiang, Y; Johnson, GA
MLA Citation
Jiang, Y, and Johnson, GA. "Microscopic diffusion tensor imaging of the mouse brain." Neuroimage 50.2 (April 1, 2010): 465-471.
PMID
20034583
Source
pubmed
Published In
NeuroImage
Volume
50
Issue
2
Publish Date
2010
Start Page
465
End Page
471
DOI
10.1016/j.neuroimage.2009.12.057

Remote sites of structural atrophy predict later amyloid formation in a mouse model of Alzheimer's disease.

Magnetic resonance (MR) imaging can provide a longitudinal view of neurological disease through repeated imaging of patients at successive stages of impairment. Until recently, the difficulty of manual delineation has limited volumetric analyses of MR data sets to a few select regions and a small number of subjects. Increased throughput offered by faster imaging methods, automated segmentation, and deformation-based morphometry have recently been applied to overcome this limitation with mouse models of neurological conditions. We use automated analyses to produce an unbiased view of volumetric changes in a transgenic mouse model for Alzheimer's disease (AD) at two points in the progression of disease: immediately before and shortly after the onset of amyloid formation. In addition to the cortex and hippocampus, where atrophy has been well documented in AD patients, we identify volumetric losses in the pons and substantia nigra where neurodegeneration has not been carefully examined. We find that deficits in cortical volume precede amyloid formation in this mouse model, similar to presymptomatic atrophy seen in patients with familial AD. Unexpectedly, volumetric losses identified by MR outside of the forebrain predict locations of future amyloid formation, such as the inferior colliculus and spinal nuclei, which develop pathology at very late stages of disease. Our work provides proof-of-principle that MR microscopy can expand our view of AD by offering a complete and unbiased examination of volumetric changes that guide us in revisiting the canonical neuropathology.

Authors
Badea, A; Johnson, GA; Jankowsky, JL
MLA Citation
Badea, A, Johnson, GA, and Jankowsky, JL. "Remote sites of structural atrophy predict later amyloid formation in a mouse model of Alzheimer's disease." Neuroimage 50.2 (April 1, 2010): 416-427.
PMID
20035883
Source
pubmed
Published In
NeuroImage
Volume
50
Issue
2
Publish Date
2010
Start Page
416
End Page
427
DOI
10.1016/j.neuroimage.2009.12.070

Cardiovascular phenotyping of the mouse heart using a 4D radial acquisition and liposomal Gd-DTPA-BMA.

MR microscopy has enormous potential for small-animal cardiac imaging because it is capable of producing volumetric images at multiple time points to accurately measure cardiac function. MR has not been used as frequently as ultrasound to measure cardiac function in the small animal because the MR methods required relatively long scan times, limiting throughput. Here, we demonstrate four-dimensional radial acquisition in conjunction with a liposomal blood pool agent to explore functional differences in three populations of mice: six C57BL/6J mice, six DBA/2J mice, and six DBA/2J CSQ+ mice, all with the same gestational age and approximately the same weight. Cardiovascular function was determined by measuring both left ventricular and right ventricular end diastolic volume, end systolic volume, stroke volume, and ejection fraction. Statistical significance was observed in end diastolic volume, end systolic volume, and ejection fraction for left ventricular measurements between all three populations of mice. No statistically significant difference was observed in stroke volume in either the left or right ventricle for any of the three populations of mice. This study shows that MRI is capable of efficient, high-throughput, four-dimensional cardiovascular phenotyping of the mouse.

Authors
Bucholz, E; Ghaghada, K; Qi, Y; Mukundan, S; Rockman, HA; Johnson, GA
MLA Citation
Bucholz, E, Ghaghada, K, Qi, Y, Mukundan, S, Rockman, HA, and Johnson, GA. "Cardiovascular phenotyping of the mouse heart using a 4D radial acquisition and liposomal Gd-DTPA-BMA." Magn Reson Med 63.4 (April 2010): 979-987.
PMID
20373399
Source
pubmed
Published In
Magnetic Resonance in Medicine
Volume
63
Issue
4
Publish Date
2010
Start Page
979
End Page
987
DOI
10.1002/mrm.22259

Quantitative analysis of hyperpolarized 3He ventilation changes in mice challenged with methacholine.

The capability to use high-resolution (3)He MRI to depict regional ventilation changes and airway narrowing in mice challenged with methacholine (MCh) offers the opportunity to gain new insights into the study of asthma. However, to fully exploit the value of this novel technique, it is important to move beyond visual inspection of the images toward automated and quantitative analysis. To address this gap, we describe a postprocessing approach to create ventilation difference maps to better visualize and quantify regional ventilation changes before and after MCh challenge. We show that difference maps reveal subtle changes in airway caliber, and highlight both focal and diffuse regional alterations in ventilation. Ventilation changes include both hypoventilation and compensatory areas of hyperventilation. The difference maps can be quantified by a histogram plot of the ventilation changes, in which the standard deviation increases with MCh dose (R(2) = 0.89). This method of analysis is shown to be more sensitive than simple threshold-based detection of gross ventilation defects.

Authors
Mistry, NN; Thomas, A; Kaushik, SS; Johnson, GA; Driehuys, B
MLA Citation
Mistry, NN, Thomas, A, Kaushik, SS, Johnson, GA, and Driehuys, B. "Quantitative analysis of hyperpolarized 3He ventilation changes in mice challenged with methacholine." Magn Reson Med 63.3 (March 2010): 658-666.
PMID
20187176
Source
pubmed
Published In
Magnetic Resonance in Medicine
Volume
63
Issue
3
Publish Date
2010
Start Page
658
End Page
666
DOI
10.1002/mrm.22311

Ventilation/perfusion imaging in a rat model of airway obstruction.

The global increase in asthma, chronic obstructive pulmonary disease, and other pulmonary diseases has stimulated interest in preclinical rat models of pulmonary disease. Imaging methods for study of these models is particularly appealing since the results can be readily translated to the clinical setting. Comprehensive understanding of lung function can be achieved by performing registered pulmonary ventilation and perfusion imaging studies in the same animal. While ventilation imaging has been addressed for small animals, quantitative pulmonary perfusion imaging has not been feasible until recently, with our proposed technique for quantitative perfusion imaging using multiple contrast-agent injections and a view-sharing radial imaging technique. Here, we combine the method with registered ventilation imaging using hyperpolarized (3)He in an airway obstruction rodent model. To our knowledge, this is the first comprehensive quantitative assessment of lung function in small animals at high spatial resolution. Standard deviation of the log (V/Q) is used as a quantitative biomarker to differentiate heterogeneity between the control and treatment group. The estimated value of the biomarker lies within the normal range of values reported in the literature. The biomarker that was extracted using the imaging technique described in this work showed statistically significant differences between the control rats and those with airway obstruction.

Authors
Mistry, NN; Qi, Y; Hedlund, LW; Johnson, GA
MLA Citation
Mistry, NN, Qi, Y, Hedlund, LW, and Johnson, GA. "Ventilation/perfusion imaging in a rat model of airway obstruction." Magn Reson Med 63.3 (March 2010): 728-735.
PMID
20146375
Source
pubmed
Published In
Magnetic Resonance in Medicine
Volume
63
Issue
3
Publish Date
2010
Start Page
728
End Page
735
DOI
10.1002/mrm.22221

Active staining of mouse embryos for magnetic resonance microscopy.

Magnetic resonance histology (MRH) has found considerable application in structural phenotyping in the mouse embryo. MRH employs the same fundamental principles as clinical MRI, albeit with spatial resolution up to six orders of magnitude higher than that in clinical studies. Critical to obtaining this enormous gain in resolution is the need to enhance the weak signal from these microscopic voxels. This has been accomplished through the use of active staining, a method to simultaneously fix the embryonic/fetal tissues, while reducing the spin lattice relaxation time (T1). We describe here the methods that allow one to balance the fixation, which reduces the nuclear magnetic resonance (NMR) signal, with the enhancement of signal derived from the reduction in T1. Methods are included to cover the ranges of embryonic specimens from E10.5 through E19.5.

Authors
Petiet, A; Johnson, GA
MLA Citation
Petiet, A, and Johnson, GA. "Active staining of mouse embryos for magnetic resonance microscopy." Methods in molecular biology (Clifton, N.J.) 611 (January 2010): 141-149.
PMID
19960328
Source
epmc
Published In
Methods in molecular biology (Clifton, N.J.)
Volume
611
Publish Date
2010
Start Page
141
End Page
149
DOI
10.1007/978-1-60327-345-9_11

Lung perfusion imaging in small animals using 4D micro-CT at heartbeat temporal resolution.

PURPOSE: Quantitative in vivo imaging of lung perfusion in rodents can provide critical information for preclinical studies. However, the combined challenges of high temporal and spatial resolution have made routine quantitative perfusion imaging difficult in small animals. The purpose of this work is to demonstrate 4D micro-CT for perfusion imaging in rodents at heartbeat temporal resolution and isotropic spatial resolution. METHODS: We have recently developed a dual tube/detector micro-CT scanner that is well suited to capture first pass kinetics of a bolus of contrast agent used to compute perfusion information. Our approach is based on the paradigm that similar time density curves can be reproduced in a number of consecutive, small volume injections of iodinated contrast agent at a series of different angles. This reproducibility is ensured by the high-level integration of the imaging components of our system with a microinjector, a mechanical ventilator, and monitoring applications. Sampling is controlled through a biological pulse sequence implemented in LABVIEW. Image reconstruction is based on a simultaneous algebraic reconstruction technique implemented on a graphic processor unit. The capabilities of 4D micro-CT imaging are demonstrated in studies on lung perfusion in rats. RESULTS: We report 4D micro-CT imaging in the rat lung with a heartbeat temporal resolution (approximately 150 ms) and isotropic 3D reconstruction with a voxel size of 88 microm based on sampling using 16 injections of 50 microL each. The total volume of contrast agent injected during the experiments (0.8 mL) was less than 10% of the total blood volume in a rat. This volume was not injected in a single bolus, but in multiple injections separated by at least 2 min interval to allow for clearance and adaptation. We assessed the reproducibility of the time density curves with multiple injections and found that these are very similar. The average time density curves for the first eight and last eight injections are slightly different, i.e., for the last eight injections, both the maximum of the average time density curves and its area under the curve are decreased by 3.8% and 7.2%, respectively, relative to the average time density curves based on the first eight injections. The radiation dose associated with our 4D micro-CT imaging is 0.16 Gy and is therefore in the range of a typical micro-CT dose. CONCLUSIONS: 4D micro-CT-based perfusion imaging demonstrated here has immediate application in a wide range of preclinical studies such as tumor perfusion, angiogenesis, and renal function. Although our imaging system is in many ways unique, we believe that our approach based on the multiple injection paradigm can be used with the newly developed flat-panel slip-ring-based micro-CT to increase their temporal resolution in dynamic perfusion studies.

Authors
Badea, CT; Johnston, SM; Subashi, E; Qi, Y; Hedlund, LW; Johnson, GA
MLA Citation
Badea, CT, Johnston, SM, Subashi, E, Qi, Y, Hedlund, LW, and Johnson, GA. "Lung perfusion imaging in small animals using 4D micro-CT at heartbeat temporal resolution." Med Phys 37.1 (January 2010): 54-62.
PMID
20175466
Source
pubmed
Published In
Medical physics
Volume
37
Issue
1
Publish Date
2010
Start Page
54
End Page
62
DOI
10.1118/1.3264619

Magnetic resonance microscopy defines ethanol-induced brain abnormalities in prenatal mice: effects of acute insult on gestational day 7.

This magnetic resonance microscopy (MRM)-based report is the second in a series designed to illustrate the spectrum of craniofacial and central nervous system (CNS) dysmorphia resulting from single- and multiple-day maternal ethanol treatment. The study described in this report examined the consequences of ethanol exposure on gestational day (GD) 7 in mice, a time in development when gastrulation and neural plate development begins; corresponding to the mid- to late third week postfertilization in humans. Acute GD 7 ethanol exposure in mice has previously been shown to result in CNS defects consistent with holoprosencephaly (HPE) and craniofacial anomalies typical of those in Fetal Alcohol Syndrome (FAS). MRM has facilitated further definition of the range of GD 7 ethanol-induced defects.C57Bl/6J female mice were intraperitoneally (i.p.) administered vehicle or 2 injections of 2.9 g/kg ethanol on day 7 of pregnancy. Stage-matched control and ethanol-exposed GD 17 fetuses selected for imaging were immersion fixed in a Bouins/Prohance solution. MRM was conducted at either 7.0 Tesla (T) or 9.4 T. Resulting 29 microm isotropic spatial resolution scans were segmented and reconstructed to provide 3D images. Linear and volumetric brain measures, as well as morphological features, were compared for control and ethanol-exposed fetuses. Following MRM, selected specimens were processed for routine histology and light microscopic examination.Gestational day 7 ethanol exposure resulted in a spectrum of median facial and forebrain deficiencies, as expected. This range of abnormalities falls within the HPE spectrum; a spectrum for which facial dysmorphology is consistent with and typically is predictive of that of the forebrain. In addition, other defects including median facial cleft, cleft palate, micrognathia, pituitary agenesis, and third ventricular dilatation were identified. MRM analyses also revealed cerebral cortical dysplasia/heterotopias resulting from this acute, early insult and facilitated a subsequent focused histological investigation of these defects.Individual MRM scans and 3D reconstructions of fetal mouse brains have facilitated demonstration of a broad range of GD 7 ethanol-induced morphological abnormality. These results, including the discovery of cerebral cortical heterotopias, elucidate the teratogenic potential of ethanol insult during the third week of human prenatal development.

Authors
Godin, EA; O'Leary-Moore, SK; Khan, AA; Parnell, SE; Ament, JJ; Dehart, DB; Johnson, BW; Allan Johnson, G; Styner, MA; Sulik, KK
MLA Citation
Godin, EA, O'Leary-Moore, SK, Khan, AA, Parnell, SE, Ament, JJ, Dehart, DB, Johnson, BW, Allan Johnson, G, Styner, MA, and Sulik, KK. "Magnetic resonance microscopy defines ethanol-induced brain abnormalities in prenatal mice: effects of acute insult on gestational day 7." Alcoholism, clinical and experimental research 34.1 (January 2010): 98-111.
PMID
19860813
Source
epmc
Published In
Alcoholism: Clinical and Experimental Research
Volume
34
Issue
1
Publish Date
2010
Start Page
98
End Page
111
DOI
10.1111/j.1530-0277.2009.01071.x

Free-space fluorescence tomography with adaptive sampling based on anatomical information from microCT.

Image reconstruction is one of the main challenges for fluorescence tomography. For in vivo experiments on small animals, in particular, the inhomogeneous optical properties and irregular surface of the animal make free-space image reconstruction challenging because of the difficulties in accurately modeling the forward problem and the finite dynamic range of the photodetector. These two factors are fundamentally limited by the currently available forward models and photonic technologies. Nonetheless, both limitations can be significantly eased using a signal processing approach. We have recently constructed a free-space panoramic fluorescence diffuse optical tomography system to take advantage of co-registered microCT data acquired from the same animal. In this article, we present a data processing strategy that adaptively selects the optical sampling points in the raw 2-D fluorescent CCD images. Specifically, the general sampling area and sampling density are initially specified to create a set of potential sampling points sufficient to cover the region of interest. Based on 3-D anatomical information from the microCT and the fluorescent CCD images, data points are excluded from the set when they are located in an area where either the forward model is known to be problematic (e.g., large wrinkles on the skin) or where the signal is unreliable (e.g., saturated or low signal-to-noise ratio). Parallel Monte Carlo software was implemented to compute the sensitivity function for image reconstruction. Animal experiments were conducted on a mouse cadaver with an artificial fluorescent inclusion. Compared to our previous results using a finite element method, the newly developed parallel Monte Carlo software and the adaptive sampling strategy produced favorable reconstruction results.

Authors
Zhang, X; Badea, CT; Hood, G; Wetzel, AW; Stiles, JR; Johnson, GA
MLA Citation
Zhang, X, Badea, CT, Hood, G, Wetzel, AW, Stiles, JR, and Johnson, GA. "Free-space fluorescence tomography with adaptive sampling based on anatomical information from microCT." United States. 2010.
PMID
21743784
Source
pubmed
Published In
Proceedings of SPIE - The International Society for Optical Engineering
Volume
7757
Issue
775706
Publish Date
2010
DOI
10.1117/12.841891

lGPU-based iterative reconstruction with total variation minimization for micro-CT

Authors
Johnston, SM; Johnson, GA; Badea, CT
MLA Citation
Johnston, SM, Johnson, GA, and Badea, CT. "lGPU-based iterative reconstruction with total variation minimization for micro-CT." 2010.
Source
wos-lite
Published In
Proceedings of SPIE - The International Society for Optical Engineering
Volume
7622
Publish Date
2010
DOI
10.1117/12.844368

GPU-based iterative reconstruction with total variation minimization for micro-CT

Dynamic imaging with micro-CT often produces poorly-distributed sets of projections, and reconstructions of this data with filtered backprojection algorithms (FBP) may be affected by artifacts. Iterative reconstruction algorithms and total variation (TV) denoising are promising alternatives to FBP, but may require running times that are frustratingly long. This obstacle can be overcome by implementing reconstruction algorithms on graphics processing units (GPU). This paper presents an implementation of a family of iterative reconstruction algorithms with TV denoising on a GPU, and a series of tests to optimize and compare the ability of different algorithms to reduce artifacts. The mathematical and computational details of the implementation are explored. The performance, measured by the accuracy of the reconstruction versus the running time, is assessed in simulations with a virtual phantom and in an in vivo scan of a mouse. We conclude that the simultaneous algebraic reconstruction technique with TV minimization (SART-TV) is a time-effective reconstruction algorithm for producing reconstructions with fewer artifacts than FBP. © 2010 SPIE.

Authors
Johnston, SM; Johnson, GA; Badea, CT
MLA Citation
Johnston, SM, Johnson, GA, and Badea, CT. "GPU-based iterative reconstruction with total variation minimization for micro-CT." 2010.
Source
scival
Published In
Proceedings of SPIE
Volume
7622
Issue
PART 2
Publish Date
2010
DOI
10.1117/12.844368

Purkinje cell loss in experimental autoimmune encephalomyelitis.

Gray matter atrophy observed by brain MRI is an important correlate to clinical disability and disease duration in multiple sclerosis. The objective of this study was to link brain atrophy visualized by neuroimaging to its underlying neuropathology using the MS model, experimental autoimmune encephalomyelitis (EAE). Volumetric changes in brains of EAE mice, as well as matched healthy normal controls, were quantified by collecting post-mortem high-resolution T2-weighted magnetic resonance microscopy and actively stained magnetic resonance histology images. Anatomical delineations demonstrated a significant decrease in the volume of the whole cerebellum, cerebellar cortex, and molecular layer of the cerebellar cortex in EAE as compared to normal controls. The pro-apoptotic marker caspase-3 was detected in Purkinje cells and a significant decrease in Purkinje cell number was found in EAE. Cross modality and temporal correlations revealed a significant association between Purkinje cell loss on neuropathology and atrophy of the molecular layer of the cerebellar cortex by neuroimaging. These results demonstrate the power of using combined population atlasing and neuropathology approaches to discern novel insights underlying gray matter atrophy in animal models of neurodegenerative disease.

Authors
MacKenzie-Graham, A; Tiwari-Woodruff, SK; Sharma, G; Aguilar, C; Vo, KT; Strickland, LV; Morales, L; Fubara, B; Martin, M; Jacobs, RE; Johnson, GA; Toga, AW; Voskuhl, RR
MLA Citation
MacKenzie-Graham, A, Tiwari-Woodruff, SK, Sharma, G, Aguilar, C, Vo, KT, Strickland, LV, Morales, L, Fubara, B, Martin, M, Jacobs, RE, Johnson, GA, Toga, AW, and Voskuhl, RR. "Purkinje cell loss in experimental autoimmune encephalomyelitis." NeuroImage 48.4 (December 2009): 637-651.
PMID
19589388
Source
epmc
Published In
NeuroImage
Volume
48
Issue
4
Publish Date
2009
Start Page
637
End Page
651
DOI
10.1016/j.neuroimage.2009.06.073

High-resolution magnetic resonance angiography in the mouse using a nanoparticle blood-pool contrast agent.

High-resolution magnetic resonance angiography is already a useful tool for studying mouse models of human disease. Magnetic resonance angiography in the mouse is typically performed using time-of-flight contrast. In this work, a new long-circulating blood-pool contrast agent-a liposomal nanoparticle with surface-conjugated gadolinium (SC-Gd liposomes)-was evaluated for use in mouse neurovascular magnetic resonance angiography. A total of 12 mice were imaged. Scan parameters were optimized for both time-of-flight and SC-Gd contrast. Compared to time-of-flight contrast, SC-Gd liposomes (0.08 mmol/kg) enabled improved small-vessel contrast-to-noise ratio, larger field of view, shorter scan time, and imaging of venous structures. For a limited field of view, time-of-flight and SC-Gd were not significantly different; however, SC-Gd provided better contrast-to-noise ratio when the field of view encompassed the whole brain (P < 0.001) or the whole neurovascular axis (P < 0.001). SC-Gd allowed acquisition of high-resolution magnetic resonance angiography (52 x 52 x 100 micrometer(3) or 0.27 nL), with 123% higher (P < 0.001) contrast-to-noise ratio in comparable scan time ( approximately 45 min). Alternatively, SC-Gd liposomes could be used to acquire high-resolution magnetic resonance angiography (0.27 nL) with 32% higher contrast-to-noise ratio (P < 0.001) in 75% shorter scan time (12 min).

Authors
Howles, GP; Ghaghada, KB; Qi, Y; Mukundan, S; Johnson, GA
MLA Citation
Howles, GP, Ghaghada, KB, Qi, Y, Mukundan, S, and Johnson, GA. "High-resolution magnetic resonance angiography in the mouse using a nanoparticle blood-pool contrast agent." Magnetic resonance in medicine 62.6 (December 2009): 1447-1456.
PMID
19902507
Source
epmc
Published In
Magnetic Resonance in Medicine
Volume
62
Issue
6
Publish Date
2009
Start Page
1447
End Page
1456
DOI
10.1002/mrm.22154

Quantitative blood flow measurements in the small animal cardiopulmonary system using digital subtraction angiography.

PURPOSE: The use of preclinical rodent models of disease continues to grow because these models help elucidate pathogenic mechanisms and provide robust test beds for drug development. Among the major anatomic and physiologic indicators of disease progression and genetic or drug modification of responses are measurements of blood vessel caliber and flow. Moreover, cardiopulmonary blood flow is a critical indicator of gas exchange. Current methods of measuring cardiopulmonary blood flow suffer from some or all of the following limitations--they produce relative values, are limited to global measurements, do not provide vasculature visualization, are not able to measure acute changes, are invasive, or require euthanasia. METHODS: In this study, high-spatial and high-temporal resolution x-ray digital subtraction angiography (DSA) was used to obtain vasculature visualization, quantitative blood flow in absolute metrics (ml/min instead of arbitrary units or velocity), and relative blood volume dynamics from discrete regions of interest on a pixel-by-pixel basis (100 x 100 microm2). RESULTS: A series of calibrations linked the DSA flow measurements to standard physiological measurement using thermodilution and Fick's method for cardiac output (CO), which in eight anesthetized Fischer-344 rats was found to be 37.0 +/- 5.1 ml/min. Phantom experiments were conducted to calibrate the radiographic density to vessel thickness, allowing a link of DSA cardiac output measurements to cardiopulmonary blood flow measurements in discrete regions of interest. The scaling factor linking relative DSA cardiac output measurements to the Fick's absolute measurements was found to be 18.90 x CODSA = COFick. CONCLUSIONS: This calibrated DSA approach allows repeated simultaneous visualization of vasculature and measurement of blood flow dynamics on a regional level in the living rat.

Authors
Lin, M; Marshall, CT; Qi, Y; Johnston, SM; Badea, CT; Piantadosi, CA; Johnson, GA
MLA Citation
Lin, M, Marshall, CT, Qi, Y, Johnston, SM, Badea, CT, Piantadosi, CA, and Johnson, GA. "Quantitative blood flow measurements in the small animal cardiopulmonary system using digital subtraction angiography." Med Phys 36.11 (November 2009): 5347-5358.
PMID
19994543
Source
pubmed
Published In
Medical physics
Volume
36
Issue
11
Publish Date
2009
Start Page
5347
End Page
5358
DOI
10.1118/1.3231823

Three-dimensional reconstruction in free-space whole-body fluorescence tomography of mice using optically reconstructed surface and atlas anatomy.

We present a 3-D image reconstruction method for free-space fluorescence tomography of mice using hybrid anatomical prior information. Specifically, we use an optically reconstructed surface of the experimental animal and a digital mouse atlas to approximate the anatomy of the animal as structural priors to assist image reconstruction. Experiments are carried out on a cadaver of a nude mouse with a fluorescent inclusion (2.4-mm-diam cylinder) implanted in the chest cavity. Tomographic fluorescence images are reconstructed using an iterative algorithm based on a finite element method. Coregistration of the fluorescence reconstruction and micro-CT (computed tomography) data acquired afterward show good localization accuracy (localization error 1.2+/-0.6 mm). Using the optically reconstructed surface, but without the atlas anatomy, image reconstruction fails to show the fluorescent inclusion correctly. The method demonstrates the utility of anatomical priors in support of free-space fluorescence tomography.

Authors
Zhang, X; Badea, CT; Johnson, GA
MLA Citation
Zhang, X, Badea, CT, and Johnson, GA. "Three-dimensional reconstruction in free-space whole-body fluorescence tomography of mice using optically reconstructed surface and atlas anatomy." J Biomed Opt 14.6 (November 2009): 064010-.
PMID
20059248
Source
pubmed
Published In
Journal of Biomedical Optics
Volume
14
Issue
6
Publish Date
2009
Start Page
064010
DOI
10.1117/1.3258836

Rapid production of specialized animal handling devices using computer-aided design and solid freeform fabrication.

To develop a process for rapidly and inexpensively producing customized animal handling devices for small animal imaging.To meet the specific needs of a particular imaging experiment, measurements are taken from imaging data and the animal handling devices are designed using 3D computer-aided design (CAD) software. Parts are produced in a few days using solid freeform fabrication (SFF, a.k.a. rapid prototyping).This process is illustrated with the production of an animal handling system for stereotaxically prescribed therapeutic ultrasound and MRI of the mouse brain. The device provides integrated head-fixation, anesthesia delivery, and physiological monitoring in a modular system. Design and production took approximately 1 week and the cost was a small fraction of a traditional machine shop.Commercial animal handling products typically have limited functionality and are not integrated with other laboratory infrastructure. However, using CAD and SFF, sophisticated animal handling devices can be produced to meet the specific experimental needs. This process is typically faster and less expensive than using a traditional machine shop, and the products are more robust than typical homemade devices. Using high-quality purpose-built devices permits experiments to be executed with greater consistency and higher throughput.

Authors
Howles, GP; Nouls, JC; Qi, Y; Johnson, GA
MLA Citation
Howles, GP, Nouls, JC, Qi, Y, and Johnson, GA. "Rapid production of specialized animal handling devices using computer-aided design and solid freeform fabrication." Journal of magnetic resonance imaging : JMRI 30.2 (August 2009): 466-471.
PMID
19629999
Source
epmc
Published In
Journal of Magnetic Resonance Imaging
Volume
30
Issue
2
Publish Date
2009
Start Page
466
End Page
471
DOI
10.1002/jmri.21821

Genetic dissection of the mouse CNS using magnetic resonance microscopy.

Advances in magnetic resonance microscopy (MRM) make it practical to map gene variants responsible for structural variation in brains of many species, including mice and humans. We review results of a systematic genetic analysis of MRM data using as a case study a family of well characterized lines of mice.MRM has matured to the point that we can generate high contrast, high-resolution images even for species as small as a mouse, with a brain merely 1/3000th the size of humans. We generated 21.5-micron data sets for a diverse panel of BXD mouse strains to gauge the extent of genetic variation, and as a prelude to comprehensive genetic and genomic analyses. Here we review MRM capabilities and image segmentation methods; heritability of brain variation; covariation of the sizes of brain regions; and correlations between MRM and classical histological data sets.The combination of high throughput MRM and genomics will improve our understanding of the genetic basis of structure-function correlations. Sophisticated mouse models will be critical in converting correlations into mechanisms and in determining genetic and epigenetic causes of differences in disease susceptibility.

Authors
Badea, A; Johnson, GA; Williams, RW
MLA Citation
Badea, A, Johnson, GA, and Williams, RW. "Genetic dissection of the mouse CNS using magnetic resonance microscopy." Current opinion in neurology 22.4 (August 2009): 379-386. (Review)
PMID
19542887
Source
epmc
Published In
Current Opinion in Neurology
Volume
22
Issue
4
Publish Date
2009
Start Page
379
End Page
386
DOI
10.1097/wco.0b013e32832d9b86

EFFECTS OF ACUTE GESTATIONAL DAY 10 ETHANOL EXPOSURE ON THE DEVELOPING MOUSE BRAIN: A HIGH-RESOLUTION MAGNETIC RESONANCE MICROSCOPY STUDY

Authors
O'Leary-Moore, SK; Godin, EA; Parnell, SE; Dehart, DB; Ament, JJ; Johnson, GA; Styner, M; Sulik, KK
MLA Citation
O'Leary-Moore, SK, Godin, EA, Parnell, SE, Dehart, DB, Ament, JJ, Johnson, GA, Styner, M, and Sulik, KK. "EFFECTS OF ACUTE GESTATIONAL DAY 10 ETHANOL EXPOSURE ON THE DEVELOPING MOUSE BRAIN: A HIGH-RESOLUTION MAGNETIC RESONANCE MICROSCOPY STUDY." June 2009.
Source
wos-lite
Published In
Alcoholism: Clinical and Experimental Research
Volume
33
Issue
6
Publish Date
2009
Start Page
132A
End Page
132A

Magnetic resonance microscopy defines ethanol-induced brain abnormalities in prenatal mice: effects of acute insult on gestational day 8.

Magnetic resonance microscopy (MRM), magnetic resonance imaging (MRI) at microscopic levels, provides unprecedented opportunities to aid in defining the full spectrum of ethanol's insult to the developing brain. This is the first in a series of reports that, collectively, will provide an MRM-based atlas of developmental stage-dependent structural brain abnormalities in a Fetal Alcohol Spectrum Disorders (FASD) mouse model. The ethanol exposure time and developmental stage examined for this report is gestational day (GD) 8 in mice, when the embryos are at early neurulation stages; stages present in humans early in the fourth week postfertilization.For this study, pregnant C57Bl/6J mice were administered an ethanol dosage of 2.8 g/kg intraperitoneally at 8 days, 0 hour and again at 8 days, 4 hours postfertilization. On GD 17, fetuses that were selected for MRM analyses were immersion fixed in a Bouin's/Prohance solution. Control fetuses from vehicle-treated dams were stage-matched to those that were ethanol-exposed. The fetal mice were scanned ex vivo at 7.0 T and 512 x 512 x 1024 image arrays were acquired using 3-D spin warp encoding. The resulting 29 microm (isotropic) resolution images were processed using ITK-SNAP, a 3-D segmentation/visualization tool. Linear and volume measurements were determined for selected brain, head, and body regions of each specimen. Comparisons were made between control and treated fetuses, with an emphasis on determining (dis)proportionate changes in specific brain regions.As compared with controls, the crown-rump lengths of stage-matched ethanol-exposed GD 17 fetuses were significantly reduced, as were brain and whole body volumes. Volume reductions were notable in every brain region examined, with the exception of the pituitary and septal region, and were accompanied by increased ventricular volumes. Disproportionate regional brain volume reductions were most marked on the right side and were significant for the olfactory bulb, hippocampus, and cerebellum; the latter being the most severely affected. Additionally, the septal region and the pituitary were disproportionately large. Linear measures were consistent with those of volume. Other dysmorphologic features noted in the MR scans were choanal stenosis and optic nerve coloboma.This study demonstrates that exposure to ethanol occurring in mice at stages corresponding to the human fourth week postfertilization results in structural brain abnormalities that are readily identifiable at fetal stages of development. In addition to illustrating the utility of MR microscopy for analysis of an FASD mouse model, this work provides new information that confirms and extends human clinical observations. It also provides a framework for comparison of structural brain abnormalities resulting from ethanol exposure at other developmental stages and dosages.

Authors
Parnell, SE; O'Leary-Moore, SK; Godin, EA; Dehart, DB; Johnson, BW; Allan Johnson, G; Styner, MA; Sulik, KK
MLA Citation
Parnell, SE, O'Leary-Moore, SK, Godin, EA, Dehart, DB, Johnson, BW, Allan Johnson, G, Styner, MA, and Sulik, KK. "Magnetic resonance microscopy defines ethanol-induced brain abnormalities in prenatal mice: effects of acute insult on gestational day 8." Alcoholism, clinical and experimental research 33.6 (June 2009): 1001-1011.
PMID
19302087
Source
epmc
Published In
Alcoholism: Clinical and Experimental Research
Volume
33
Issue
6
Publish Date
2009
Start Page
1001
End Page
1011
DOI
10.1111/j.1530-0277.2009.00921.x

Genetic dissection of the mouse brain using high-field magnetic resonance microscopy.

Magnetic resonance (MR) imaging has demonstrated that variation in brain structure is associated with differences in behavior and disease state. However, it has rarely been practical to prospectively test causal models that link anatomical and functional differences in humans. In the present study we have combined classical mouse genetics with high-field MR to systematically explore and test such structure-functional relations across multiple brain regions. We segmented 33 regions in two parental strains-C57BL/6J (B) and DBA/2J (D)-and in nine BXD recombinant inbred strains. All strains have been studied extensively for more than 20 years using a battery of genetic, functional, anatomical, and behavioral assays. We compared levels of variation within and between strains and sexes, by region, and by system. Average within-strain variation had a coefficient of variation (CV) of 1.6% for the whole brain; while the CV ranged from 2.3 to 3.6% for olfactory bulbs, cortex and cerebellum, and up to approximately 18% for septum and laterodorsal thalamic nucleus. Variation among strain averages ranged from 6.7% for cerebellum, 7.6% for whole brain, 9.0% for cortex, up to approximately 26% for the ventricles, laterodorsal thalamic nucleus, and the interpeduncular nucleus. Heritabilities averaged 0.60+/-0.18. Sex differences were not significant with the possible (and unexpected) exception of the pons ( approximately 20% larger in males). A correlation matrix of regional volumes revealed high correlations among functionally related parts of the CNS (e.g., components of the limbic system), and several high correlations between regions that are not anatomically connected, but that may nonetheless be functionally or genetically coupled.

Authors
Badea, A; Johnson, GA; Williams, RW
MLA Citation
Badea, A, Johnson, GA, and Williams, RW. "Genetic dissection of the mouse brain using high-field magnetic resonance microscopy." NeuroImage 45.4 (May 2009): 1067-1079.
PMID
19349225
Source
epmc
Published In
NeuroImage
Volume
45
Issue
4
Publish Date
2009
Start Page
1067
End Page
1079
DOI
10.1016/j.neuroimage.2009.01.021

Least-square NUFFT methods applied to 2-D and 3-D radially encoded MR image reconstruction.

Radially encoded MRI has gained increasing attention due to its motion insensitivity and reduced artifacts. However, because its samples are collected nonuniformly in the k-space, multidimensional (especially 3-D) radially sampled MRI image reconstruction is challenging. The objective of this paper is to develop a reconstruction technique in high dimensions with on-the-fly kernel calculation. It implements general multidimensional nonuniform fast Fourier transform (NUFFT) algorithms and incorporates them into a k-space image reconstruction framework. The method is then applied to reconstruct from the radially encoded k-space data, although the method is applicable to any non-Cartesian patterns. Performance comparisons are made against the conventional Kaiser-Bessel (KB) gridding method for 2-D and 3-D radially encoded computer-simulated phantoms and physically scanned phantoms. The results show that the NUFFT reconstruction method has better accuracy-efficiency tradeoff than the KB gridding method when the kernel weights are calculated on the fly. It is found that for a particular conventional kernel function, using its corresponding deapodization function as a scaling factor in the NUFFT framework has the potential to improve accuracy. In particular, when a cosine scaling factor is used, the NUFFT method is faster than KB gridding method since a closed-form solution is available and is less computationally expensive than the KB kernel (KB griding requires computation of Bessel functions). The NUFFT method has been successfully applied to 2-D and 3-D in vivo studies on small animals.

Authors
Song, J; Liu, Y; Gewalt, SL; Cofer, G; Johnson, GA; Liu, QH
MLA Citation
Song, J, Liu, Y, Gewalt, SL, Cofer, G, Johnson, GA, and Liu, QH. "Least-square NUFFT methods applied to 2-D and 3-D radially encoded MR image reconstruction." IEEE Trans Biomed Eng 56.4 (April 2009): 1134-1142.
PMID
19174334
Source
pubmed
Published In
IEEE Transactions on Biomedical Engineering
Volume
56
Issue
4
Publish Date
2009
Start Page
1134
End Page
1142
DOI
10.1109/TBME.2009.2012721

Development of a noncontact 3-D fluorescence tomography system for small animal in vivo imaging.

Fluorescence imaging is an important tool for tracking molecular-targeting probes in preclinical studies. It offers high sensitivity, but nonetheless low spatial resolution compared to other leading imaging methods such CT and MRI. We demonstrate our methodological development in small animal in vivo whole-body imaging using fluorescence tomography. We have implemented a noncontact fluid-free fluorescence diffuse optical tomography system that uses a raster-scanned continuous-wave diode laser as the light source and an intensified CCD camera as the photodetector. The specimen is positioned on a motorized rotation stage. Laser scanning, data acquisition, and stage rotation are controlled via LabVIEW applications. The forward problem in the heterogeneous medium is based on a normalized Born method, and the sensitivity function is determined using a Monte Carlo method. The inverse problem (image reconstruction) is performed using a regularized iterative algorithm, in which the cost function is defined as a weighted sum of the L-2 norms of the solution image, the residual error, and the image gradient. The relative weights are adjusted by two independent regularization parameters. Our initial tests of this imaging system were performed with an imaging phantom that consists of a translucent plastic cylinder filled with tissue-simulating liquid and two thin-wall glass tubes containing indocyanine green. The reconstruction is compared to the output of a finite element method-based software package NIRFAST and has produced promising results.

Authors
Zhang, X; Badea, C; Jacob, M; Johnson, GA
MLA Citation
Zhang, X, Badea, C, Jacob, M, and Johnson, GA. "Development of a noncontact 3-D fluorescence tomography system for small animal in vivo imaging." United States. February 16, 2009.
PMID
19587837
Source
pubmed
Published In
Proceedings of SPIE - The International Society for Optical Engineering
Volume
7191
Publish Date
2009
Start Page
nihpa106691
DOI
10.1117/12.808199

A material decomposition method for dual energy micro-CT

The attenuation of x-rays in matter is dependent on the energy of the x-rays and the atomic composition of the matter. Attenuation measurements at multiple x-ray energies can be used to improve the identification of materials. We present a method to estimate the fractional composition of three materials in an object from x-ray CT measurements at two different energies. The energies can be collected from measurements from a single source-detector system at two points in time, or from a dual source-detector system at one point in time. This method sets up a linear system of equations from the measurements and finds the solution through a geometric construction of the inverse matrix equation. This method enables the estimation of the blood fraction within a region of living tissue in which blood containing an iodinated contrast agent is mixed with two other materials. We verified this method using x-ray CT simulations implemented in MATLAB, investigated the parameters needed to optimize the estimation, and then applied the method to a mouse model of lung cancer. A direct application of this method is the estimation of blood fraction in lung tumors in preclinical studies. This work was performed at the Duke Center for In Vivo Microscopy, an NCRR/NCI National Resource (P41 RR005959/U24 CA092656), and also supported by NCI R21 CA124584. ©2009 SPIE.

Authors
Johnston, SM; Johnson, GA; Badea, CT
MLA Citation
Johnston, SM, Johnson, GA, and Badea, CT. "A material decomposition method for dual energy micro-CT." 2009.
Source
scival
Published In
Proceedings of SPIE
Volume
7258
Publish Date
2009
DOI
10.1117/12.811673

4D micro-CT-based perfusion imaging in small animals

Quantitative in-vivo imaging of lung perfusion in rodents can provide critical information for preclinical studies. However, the combined challenges of high temporal and spatial resolution have made routine quantitative perfusion imaging difficult in rodents. We have recently developed a dual tube/detector micro-CT scanner that is well suited to capture first-pass kinetics of a bolus of contrast agent used to compute perfusion information. Our approach is based on the paradigm that the same time density curves can be reproduced in a number of consecutive, small (i.e. 50μL ) injections of iodinated contrast agent at a series of different angles. This reproducibility is ensured by the high-level integration of the imaging components of our system, with a micro-injector, a mechanical ventilator, and monitoring applications. Sampling is controlled through a biological pulse sequence implemented in LabVIEW. Image reconstruction is based on a simultaneous algebraic reconstruction technique implemented on a GPU. The capabilities of 4D micro-CT imaging are demonstrated in studies on lung perfusion in rats. We report 4D micro-CT imaging in the rat lung with a heartbeat temporal resolution of 140 ms and reconstructed voxels of 88 μm. The approach can be readily extended to a wide range of important preclinical models, such as tumor perfusion and angiogenesis, and renal function. © 2009 SPIE.

Authors
Badea, CT; Johnston, SM; Lin, M; Hedlund, LW; Johnson, GA
MLA Citation
Badea, CT, Johnston, SM, Lin, M, Hedlund, LW, and Johnson, GA. "4D micro-CT-based perfusion imaging in small animals." 2009.
Source
scival
Published In
Proceedings of SPIE
Volume
7258
Publish Date
2009
DOI
10.1117/12.811213

Dissecting the Mechanism of Tumor Response to Radiation Therapy with Primary Lung Cancers in Mice

Authors
Perez, BA; Ghafoori, AP; Johnston, SM; Jeffords, LB; Kim, Y; Badea, CT; Johnson, GA; Kirsch, DG
MLA Citation
Perez, BA, Ghafoori, AP, Johnston, SM, Jeffords, LB, Kim, Y, Badea, CT, Johnson, GA, and Kirsch, DG. "Dissecting the Mechanism of Tumor Response to Radiation Therapy with Primary Lung Cancers in Mice." 2009.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
75
Issue
3
Publish Date
2009
Start Page
S537
End Page
S537

In vivo small-animal imaging using micro-CT and digital subtraction angiography.

Small-animal imaging has a critical role in phenotyping, drug discovery and in providing a basic understanding of mechanisms of disease. Translating imaging methods from humans to small animals is not an easy task. The purpose of this work is to review in vivo x-ray based small-animal imaging, with a focus on in vivo micro-computed tomography (micro-CT) and digital subtraction angiography (DSA). We present the principles, technologies, image quality parameters and types of applications. We show that both methods can be used not only to provide morphological, but also functional information, such as cardiac function estimation or perfusion. Compared to other modalities, x-ray based imaging is usually regarded as being able to provide higher throughput at lower cost and adequate resolution. The limitations are usually associated with the relatively poor contrast mechanisms and potential radiation damage due to ionizing radiation, although the use of contrast agents and careful design of studies can address these limitations. We hope that the information will effectively address how x-ray based imaging can be exploited for successful in vivo preclinical imaging.

Authors
Badea, CT; Drangova, M; Holdsworth, DW; Johnson, GA
MLA Citation
Badea, CT, Drangova, M, Holdsworth, DW, and Johnson, GA. "In vivo small-animal imaging using micro-CT and digital subtraction angiography." Physics in medicine and biology 53.19 (October 2008): R319-R350. (Review)
PMID
18758005
Source
epmc
Published In
Physics in Medicine and Biology
Volume
53
Issue
19
Publish Date
2008
Start Page
R319
End Page
R350
DOI
10.1088/0031-9155/53/19/r01

High-resolution magnetic resonance histology of the embryonic and neonatal mouse: a 4D atlas and morphologic database.

Engineered mice play an ever-increasing role in defining connections between genotype and phenotypic expression. The potential of magnetic resonance microscopy (MRM) for morphologic phenotyping in the mouse has previously been demonstrated; however, applications have been limited by long scan times, availability of the technology, and a foundation of normative data. This article describes an integrated environment for high-resolution study of normal, transgenic, and mutant mouse models at embryonic and neonatal stages. Three-dimensional images are shown at an isotropic resolution of 19.5 microm (voxel volumes of 8 pL), acquired in 3 h at embryonic days 10.5-19.5 (10 stages) and postnatal days 0-32 (6 stages). A web-accessible atlas encompassing this data was developed, and for critical stages of embryonic development (prenatal days 14.5-18.5), >200 anatomical structures have been identified and labeled. Also, matching optical histology and analysis tools are provided to compare multiple specimens at multiple developmental stages. The utility of the approach is demonstrated in characterizing cardiac septal defects in conditional mutant embryos lacking the Smoothened receptor gene. Finally, a collaborative paradigm is presented that allows sharing of data across the scientific community. This work makes magnetic resonance microscopy of the mouse embryo and neonate broadly available with carefully annotated normative data and an extensive environment for collaborations.

Authors
Petiet, AE; Kaufman, MH; Goddeeris, MM; Brandenburg, J; Elmore, SA; Johnson, GA
MLA Citation
Petiet, AE, Kaufman, MH, Goddeeris, MM, Brandenburg, J, Elmore, SA, and Johnson, GA. "High-resolution magnetic resonance histology of the embryonic and neonatal mouse: a 4D atlas and morphologic database." Proceedings of the National Academy of Sciences of the United States of America 105.34 (August 19, 2008): 12331-12336.
PMID
18713865
Source
epmc
Published In
Proceedings of the National Academy of Sciences of USA
Volume
105
Issue
34
Publish Date
2008
Start Page
12331
End Page
12336
DOI
10.1073/pnas.0805747105

Application of MOSFET detectors for dosimetry in small animal radiography using short exposure times.

Digital subtraction angiography (DSA) X-ray imaging for small animals can be used for functional phenotyping given its ability to capture rapid physiological changes at high spatial and temporal resolution. The higher temporal and spatial requirements for small-animal imaging drive the need for short, high-flux X-ray pulses. However, high doses of ionizing radiation can affect the physiology. The purpose of this study was to verify and apply metal oxide semiconductor field effect transistor (MOSFET) technology to dosimetry for small-animal diagnostic imaging. A tungsten anode X-ray source was used to expose a tissue-equivalent mouse phantom. Dose measurements were made on the phantom surface and interior. The MOSFETs were verified with thermoluminescence dosimeters (TLDs). Bland-Altman analysis showed that the MOSFET results agreed with the TLD results (bias, 0.0625). Using typical small animal DSA scan parameters, the dose ranged from 0.7 to 2.2 cGy. Application of the MOSFETs in the small animal environment provided two main benefits: (1) the availability of results in near real-time instead of the hours needed for TLD processes and (2) the ability to support multiple exposures with different X-ray techniques (various of kVp, mA and ms) using the same MOSFET. This MOSFET technology has proven to be a fast, reliable small animal dosimetry method for DSA imaging and is a good system for dose monitoring for serial and gene expression studies.

Authors
De Lin, M; Toncheva, G; Nguyen, G; Kim, S; Anderson-Evans, C; Johnson, GA; Yoshizumi, TT
MLA Citation
De Lin, M, Toncheva, G, Nguyen, G, Kim, S, Anderson-Evans, C, Johnson, GA, and Yoshizumi, TT. "Application of MOSFET detectors for dosimetry in small animal radiography using short exposure times." Radiat Res 170.2 (August 2008): 260-263.
PMID
18666818
Source
pubmed
Published In
Radiation Research
Volume
170
Issue
2
Publish Date
2008
Start Page
260
End Page
263
DOI
10.1667/RR1328.1

A micro-CT analysis of murine lung recruitment in bleomycin-induced lung injury.

The effects of lung injury on pulmonary recruitment are incompletely understood. X-ray computed tomography (CT) has been a valuable tool in assessing changes in recruitment during lung injury. With the development of preclinical CT scanners designed for thoracic imaging in rodents, it is possible to acquire high-resolution images during the evolution of a pulmonary injury in living mice. We quantitatively assessed changes in recruitment caused by intratracheal bleomycin at 1 and 3 wk after administration using micro-CT in 129S6/SvEvTac mice. Twenty female mice were administered 2.5 U of bleomycin or saline and imaged with micro-CT at end inspiration and end expiration. Mice were extubated and allowed to recover from anesthesia and then reevaluated in vivo for quasi-static compliance measurements, followed by harvesting of the lungs for collagen analysis and histology. CT images were converted to histograms and analyzed for mean lung attenuation (MLA). MLA was significantly greater for bleomycin-exposed mice at week 1 for both inspiration (P<0.0047) and exhalation (P<0.0377) but was not significantly different for week 3 bleomycin-exposed mice. However, week 3 bleomycin-exposed mice did display significant increases in MLA shift from expiration to inspiration compared with either group of control mice (P<0.005), suggesting increased lung recruitment at this time point. Week 1 bleomycin-exposed mice displayed normal shifts in MLA with inspiration, suggesting normal lung recruitment despite significant radiographic and histological changes. Lung alveolar recruitment is preserved in a mouse model of bleomycin-induced parenchymal injury despite significant changes in radiographic and physiological parameters.

Authors
Shofer, S; Badea, C; Qi, Y; Potts, E; Foster, WM; Johnson, GA
MLA Citation
Shofer, S, Badea, C, Qi, Y, Potts, E, Foster, WM, and Johnson, GA. "A micro-CT analysis of murine lung recruitment in bleomycin-induced lung injury." J Appl Physiol (1985) 105.2 (August 2008): 669-677.
PMID
18566189
Source
pubmed
Published In
Journal of applied physiology (Bethesda, Md. : 1985)
Volume
105
Issue
2
Publish Date
2008
Start Page
669
End Page
677
DOI
10.1152/japplphysiol.00980.2007

Four-dimensional MR microscopy of the mouse heart using radial acquisition and liposomal gadolinium contrast agent.

Magnetic resonance microscopy (MRM) has become an important tool for small animal cardiac imaging. In relation to competing technologies (microCT and ultrasound), MR is limited by spatial resolution, temporal resolution, and acquisition time. All three of these limitations have been addressed by developing a four-dimensional (4D) (3D plus time) radial acquisition (RA) sequence. The signal-to-noise ratio (SNR) has been optimized by minimizing the echo time (TE) (300 us). The temporal resolution and throughput have been improved by center-out trajectories resulting in repetition time (TR) <2.5 ms. The contrast has been enhanced through the use of a liposomal blood pool agent that reduces the T(1) of the blood to <400 ms. We have developed protocols for three specific applications: 1) high-throughput with spatial resolution of 87 x 87 x 352 um(3) (voxel volume = 2.7 nL) and acquisition time of 16 min; 2) high-temporal resolution with spatial resolution of 87 x 87 x 352 um(3) (voxel volume = 2.7 nL) and temporal resolution at 4.8 ms and acquisition time of 32 minutes; and 3) high-resolution isotropic imaging at 87 x 87 x 87 um(3) (voxel volume = 0.68 nL) and acquisition time of 31 min. The 4D image arrays allow direct measure of cardiac functional parameters dependent on chamber volumes, e.g., ejection fraction (EF), end diastolic volume (EDV), and end systolic volume (ESV).

Authors
Bucholz, E; Ghaghada, K; Qi, Y; Mukundan, S; Johnson, GA
MLA Citation
Bucholz, E, Ghaghada, K, Qi, Y, Mukundan, S, and Johnson, GA. "Four-dimensional MR microscopy of the mouse heart using radial acquisition and liposomal gadolinium contrast agent." Magnetic resonance in medicine 60.1 (July 2008): 111-118.
PMID
18581419
Source
epmc
Published In
Magnetic Resonance in Medicine
Volume
60
Issue
1
Publish Date
2008
Start Page
111
End Page
118
DOI
10.1002/mrm.21618

Intracardiac septation requires hedgehog-dependent cellular contributions from outside the heart.

Septation of the mammalian heart into four chambers requires the orchestration of multiple tissue progenitors. Abnormalities in this process can result in potentially fatal atrioventricular septation defects (AVSD). The contribution of extracardiac cells to atrial septation has recently been recognized. Here, we use a genetic marker and novel magnetic resonance microscopy techniques to demonstrate the origins of the dorsal mesenchymal protrusion in the dorsal mesocardium, and its substantial contribution to atrioventricular septation. We explore the functional significance of this tissue to atrioventricular septation through study of the previously uncharacterized AVSD phenotype of Shh(-/-) mutant mouse embryos. We demonstrate that Shh signaling is required within the dorsal mesocardium for its contribution to the atria. Failure of this addition results in severe AVSD. These studies demonstrate that AVSD can result from a primary defect in dorsal mesocardium, providing a new paradigm for the understanding of human AVSD.

Authors
Goddeeris, MM; Rho, S; Petiet, A; Davenport, CL; Johnson, GA; Meyers, EN; Klingensmith, J
MLA Citation
Goddeeris, MM, Rho, S, Petiet, A, Davenport, CL, Johnson, GA, Meyers, EN, and Klingensmith, J. "Intracardiac septation requires hedgehog-dependent cellular contributions from outside the heart." Development 135.10 (May 2008): 1887-1895.
PMID
18441277
Source
pubmed
Published In
Development (Cambridge)
Volume
135
Issue
10
Publish Date
2008
Start Page
1887
End Page
1895
DOI
10.1242/dev.016147

Geometric calibration for a dual tube/detector micro-CT system.

The authors describe a dual tube/detector micro-computed tomography (micro-CT) system that has the potential to improve temporal resolution and material contrast in small animal imaging studies. To realize this potential, it is necessary to precisely calibrate the geometry of a dual micro-CT system to allow the combination of projection data acquired with each individual tube/detector in a single reconstructed image. The authors present a geometric calibration technique that uses multiple projection images acquired with the two imaging chains while rotating a phantom containing a vertical array of regularly spaced metallic beads. The individual geometries of the imaging chains are estimated from the phantom projection images using analytical methods followed by a refinement procedure based on nonlinear optimization. The geometric parameters are used to create the cone beam projection matrices required by the reconstruction process for each imaging chain. Next, a transformation between the two projection matrices is found that allows the combination of projection data in a single reconstructed image. The authors describe this technique, test it with a series of computer simulations, and then apply it to data collected from their dual tube/detector micro-CT system. The results demonstrate that the proposed technique is accurate, robust, and produces images free of misalignment artifacts.

Authors
Johnston, SM; Johnson, GA; Badea, CT
MLA Citation
Johnston, SM, Johnson, GA, and Badea, CT. "Geometric calibration for a dual tube/detector micro-CT system." Med Phys 35.5 (May 2008): 1820-1829.
PMID
18561657
Source
pubmed
Published In
Medical physics
Volume
35
Issue
5
Publish Date
2008
Start Page
1820
End Page
1829
DOI
10.1118/1.2900000

A dual micro-CT system for small animal imaging.

Micro-CT is a non-invasive imaging modality usually used to assess morphology in small animals. In our previous work, we have demonstrated that functional micro-CT imaging is also possible. This paper describes a dual micro-CT system with two fixed x-ray/detectors developed to address such challenging tasks as cardiac or perfusion studies in small animals. A two-tube/detector system ensures simultaneous acquisition of two projections, thus reducing scanning time and the number of contrast injections in perfusion studies by a factor of two. The system is integrated with software developed in-house for cardio-respiratory monitoring and gating. The sampling geometry was optimized for 88 microns in such a way that the geometric blur of the focal spot matches the Nyquist sample at the detector. A geometric calibration procedure allows one to combine projection data from the two chains into a single reconstructed volume. Image quality was measured in terms of spatial resolution, uniformity, noise, and linearity. The modulation transfer function (MTF) at 10% is 3.4 lp/mm for single detector reconstructions and 2.3 lp/mm for dual tube/detector reconstructions. We attribute this loss in spatial resolution to the compounding of slight errors in the separate single chain calibrations. The dual micro-CT system is currently used in studies for morphological and functional imaging of both rats and mice.

Authors
Badea, CT; Johnston, S; Johnson, B; Lin, M; Hedlund, LW; Johnson, GA
MLA Citation
Badea, CT, Johnston, S, Johnson, B, Lin, M, Hedlund, LW, and Johnson, GA. "A dual micro-CT system for small animal imaging." United States. April 18, 2008.
PMID
22049304
Source
pubmed
Published In
Proceedings of SPIE - The International Society for Optical Engineering
Volume
6913
Publish Date
2008
Start Page
691342
DOI
10.1117/12.772303

Design of a superconducting volume coil for magnetic resonance microscopy of the mouse brain.

We present the design process of a superconducting volume coil for magnetic resonance microscopy of the mouse brain at 9.4T. The yttrium barium copper oxide coil has been designed through an iterative process of three-dimensional finite-element simulations and validation against room temperature copper coils. Compared to previous designs, the Helmholtz pair provides substantially higher B(1) homogeneity over an extended volume of interest sufficiently large to image biologically relevant specimens. A custom-built cryogenic cooling system maintains the superconducting probe at 60+/-0.1K. Specimen loading and probe retuning can be carried out interactively with the coil at operating temperature, enabling much higher through-put. The operation of the probe is a routine, consistent procedure. Signal-to-noise ratio in a mouse brain increased by a factor ranging from 1.1 to 2.9 as compared to a room-temperature solenoid coil optimized for mouse brain microscopy. We demonstrate images encoded at 10x10x20mum for an entire mouse brain specimen with signal-to-noise ratio of 18 and a total acquisition time of 16.5h, revealing neuroanatomy unseen at lower resolution. Phantom measurements show an effective spatial resolution better than 20mum.

Authors
Nouls, JC; Izenson, MG; Greeley, HP; Johnson, GA
MLA Citation
Nouls, JC, Izenson, MG, Greeley, HP, and Johnson, GA. "Design of a superconducting volume coil for magnetic resonance microscopy of the mouse brain." Journal of magnetic resonance (San Diego, Calif. : 1997) 191.2 (April 2008): 231-238.
PMID
18221901
Source
epmc
Published In
Journal of Magnetic Resonance
Volume
191
Issue
2
Publish Date
2008
Start Page
231
End Page
238
DOI
10.1016/j.jmr.2007.12.018

Left ventricle volume measurements in cardiac micro-CT: the impact of radiation dose and contrast agent.

Micro-CT-based cardiac function estimation in small animals requires measurement of left ventricle (LV) volume at multiple time points during the cardiac cycle. Measurement accuracy depends on the image resolution, its signal and noise properties, and the analysis procedure. This work compares the accuracy of the Otsu thresholding and a region sampled binary mixture approach, for live mouse LV volume measurement using 100 microm resolution datasets. We evaluate both analysis methods after varying the volume of injected contrast agent and the number of projections used for CT reconstruction with a goal of permitting reduced levels of both X-ray and contrast agent doses.

Authors
Badea, CT; Wetzel, AW; Mistry, N; Pomerantz, S; Nave, D; Johnson, GA
MLA Citation
Badea, CT, Wetzel, AW, Mistry, N, Pomerantz, S, Nave, D, and Johnson, GA. "Left ventricle volume measurements in cardiac micro-CT: the impact of radiation dose and contrast agent." Computerized medical imaging and graphics : the official journal of the Computerized Medical Imaging Society 32.3 (April 2008): 239-250.
PMID
18243656
Source
epmc
Published In
Computerized Medical Imaging and Graphics
Volume
32
Issue
3
Publish Date
2008
Start Page
239
End Page
250
DOI
10.1016/j.compmedimag.2007.12.004

Optical clearing of unsectioned specimens for three-dimensional imaging via optical transmission and emission tomography.

Optical computed tomography (optical-CT) and optical emission computed tomography (optical-ECT) are new techniques that enable unprecedented high-resolution 3-D multimodal imaging of tissue structure and function. Applications include imaging macroscopic gene expression and microvasculature structure in unsectioned biological specimens up to 8 cm(3). A key requisite for these imaging techniques is effective sample preparation including optical clearing, which enables light transport through the sample while preserving the signal (either light absorbing stain or fluorescent proteins) in representative form. We review recent developments in optical-CT and optical-ECT, and compatible "fluorescence-friendly" optical clearing protocols.

Authors
Oldham, M; Sakhalkar, H; Oliver, T; Allan Johnson, G; Dewhirst, M
MLA Citation
Oldham, M, Sakhalkar, H, Oliver, T, Allan Johnson, G, and Dewhirst, M. "Optical clearing of unsectioned specimens for three-dimensional imaging via optical transmission and emission tomography." J Biomed Opt 13.2 (March 2008): 021113-. (Review)
PMID
18465962
Source
pubmed
Published In
Journal of Biomedical Optics
Volume
13
Issue
2
Publish Date
2008
Start Page
021113
DOI
10.1117/1.2907968

Multispectral imaging with three-dimensional rosette trajectories.

Two-dimensional intersecting k-space trajectories have previously been demonstrated to allow fast multispectral imaging. Repeated sampling of k-space points leads to destructive interference of the signal coming from the off-resonance spectral peaks; on-resonance data reconstruction yields images of the on-resonance peak, with some of the off-resonance energy being spread as noise in the image. A shift of the k-space data by a given off-resonance frequency brings a second frequency of interest on resonance, allowing the reconstruction of a second spectral peak from the same k-space data. Given the higher signal-to-noise per unit time characteristic of a 3D acquisition, we extended the concept of intersecting trajectories to three dimensions. A 3D, rosette-like pulse sequence was designed and implemented on a clinical 1.5T scanner. An iterative density compensation function was developed to weight the 3D intersecting trajectories before Fourier transformation. Three volunteers were scanned using this sequence and separate fat and water images were reconstructed from the same imaging dataset.

Authors
Bucholz, EK; Song, J; Johnson, GA; Hancu, I
MLA Citation
Bucholz, EK, Song, J, Johnson, GA, and Hancu, I. "Multispectral imaging with three-dimensional rosette trajectories." Magnetic resonance in medicine 59.3 (March 2008): 581-589.
PMID
18306410
Source
epmc
Published In
Magnetic Resonance in Medicine
Volume
59
Issue
3
Publish Date
2008
Start Page
581
End Page
589
DOI
10.1002/mrm.21551

A high-precision contrast injector for small animal x-ray digital subtraction angiography.

The availability of genetically altered animal models of human disease for basic research has generated great interest in new imaging methodologies. Digital subtraction angiography (DSA) offers an appealing approach to functional imaging in small animals because of the high spatial and temporal resolution, and the ability to visualize and measure blood flow. The micro-injector described here meets crucial performance parameters to ensure optimal vessel enhancement without significantly increasing the total blood volume or producing overlap of enhanced structures. The micro-injector can inject small, reproducible volumes of contrast agent at high flow rates with computer-controlled timing synchronized to cardiopulmonary activity. Iterative bench-top and live animal experiments with both rat and mouse have been conducted to evaluate the performance of this computer-controlled micro-injector, a first demonstration of a new device designed explicitly for the unique requirements of DSA in small animals. Injection protocols were optimized and screened for potential physiological impact. For the optimized protocols, we found that changes in the time-density curves for representative regions of interest in the thorax were due primarily to physiological changes, independent of micro-injector parameters.

Authors
de Lin, M; Ning, L; Badea, CT; Mistry, NN; Qi, Y; Johnson, GA
MLA Citation
de Lin, M, Ning, L, Badea, CT, Mistry, NN, Qi, Y, and Johnson, GA. "A high-precision contrast injector for small animal x-ray digital subtraction angiography." IEEE transactions on bio-medical engineering 55.3 (March 2008): 1082-1091.
PMID
18334400
Source
epmc
Published In
IEEE Transactions on Biomedical Engineering
Volume
55
Issue
3
Publish Date
2008
Start Page
1082
End Page
1091
DOI
10.1109/tbme.2007.909541

Pulmonary perfusion imaging in the rodent lung using dynamic contrast-enhanced MRI.

With the development of various models of pulmonary disease, there is tremendous interest in quantitative regional assessment of pulmonary function. While ventilation imaging has been addressed to a certain extent, perfusion imaging for small animals has not kept pace. In humans and large animals perfusion can be assessed using dynamic contrast-enhanced (DCE) MRI with a single bolus injection of a gadolinium (Gd)-based contrast agent. But the method developed for the clinic cannot be translated directly to image the rodent due to the combined requirements of higher spatial and temporal resolution. This work describes a novel image acquisition technique staggered over multiple, repeatable bolus injections of contrast agent using an automated microinjector, synchronized with image acquisition to achieve dynamic first-pass contrast enhancement in the rat lung. This allows dynamic first-pass imaging that can be used to quantify pulmonary perfusion. Further improvements are made in the spatial and temporal resolution by combining the multiple injection acquisition method with Interleaved Radial Imaging and "Sliding window-keyhole" reconstruction (IRIS). The results demonstrate a simultaneous increase in spatial resolution (<200 mum) and temporal resolution (<200 ms) over previous methods, with a limited loss in signal-to-noise-ratio.

Authors
Mistry, NN; Pollaro, J; Song, J; De Lin, M; Johnson, GA
MLA Citation
Mistry, NN, Pollaro, J, Song, J, De Lin, M, and Johnson, GA. "Pulmonary perfusion imaging in the rodent lung using dynamic contrast-enhanced MRI." Magnetic resonance in medicine 59.2 (February 2008): 289-297.
PMID
18228577
Source
epmc
Published In
Magnetic Resonance in Medicine
Volume
59
Issue
2
Publish Date
2008
Start Page
289
End Page
297
DOI
10.1002/mrm.21353

Automated segmentation of the actively stained mouse brain using multi-spectral MR microscopy.

Magnetic resonance microscopy (MRM) has created new approaches for high-throughput morphological phenotyping of mouse models of diseases. Transgenic and knockout mice serve as a test bed for validating hypotheses that link genotype to the phenotype of diseases, as well as developing and tracking treatments. We describe here a Markov random fields based segmentation of the actively stained mouse brain, as a prerequisite for morphological phenotyping. Active staining achieves higher signal to noise ratio (SNR) thereby enabling higher resolution imaging per unit time than obtained in previous formalin-fixed mouse brain studies. The segmentation algorithm was trained on isotropic 43-mum T1- and T2-weighted MRM images. The mouse brain was segmented into 33 structures, including the hippocampus, amygdala, hypothalamus, thalamus, as well as fiber tracts and ventricles. Probabilistic information used in the segmentation consisted of (a) intensity distributions in the T1- and T2-weighted data, (b) location, and (c) contextual priors for incorporating spatial information. Validation using standard morphometric indices showed excellent consistency between automatically and manually segmented data. The algorithm has been tested on the widely used C57BL/6J strain, as well as on a selection of six recombinant inbred BXD strains, chosen especially for their largely variant hippocampus.

Authors
Sharief, AA; Badea, A; Dale, AM; Johnson, GA
MLA Citation
Sharief, AA, Badea, A, Dale, AM, and Johnson, GA. "Automated segmentation of the actively stained mouse brain using multi-spectral MR microscopy." NeuroImage 39.1 (January 2008): 136-145.
PMID
17933556
Source
epmc
Published In
NeuroImage
Volume
39
Issue
1
Publish Date
2008
Start Page
136
End Page
145
DOI
10.1016/j.neuroimage.2007.08.028

Imaging techniques for small animal imaging models of pulmonary disease: Micro-CT (Toxicologic Pathology (2007) 35, 5 (9-64))

Authors
Johnson, K; Badea, C; Hedlund, L; Johnson, GA
MLA Citation
Johnson, K, Badea, C, Hedlund, L, and Johnson, GA. "Imaging techniques for small animal imaging models of pulmonary disease: Micro-CT (Toxicologic Pathology (2007) 35, 5 (9-64))." Toxicologic Pathology 36.6 (2008): 895--.
Source
scival
Published In
Toxicologic Pathology (Sage)
Volume
36
Issue
6
Publish Date
2008
Start Page
895-
DOI
10.1177/0192623308323921

A dual micro-CT system for small animal imaging - art. no. 691342

Authors
Badea, CT; Johnston, S; Johnson, B; Lin, M; Hedlund, LW; Johnson, GA
MLA Citation
Badea, CT, Johnston, S, Johnson, B, Lin, M, Hedlund, LW, and Johnson, GA. "A dual micro-CT system for small animal imaging - art. no. 691342." 2008.
Source
wos-lite
Published In
Proceedings of SPIE - The International Society for Optical Engineering
Volume
6913
Publish Date
2008
Start Page
91342
End Page
91342
DOI
10.1117/12.772303

3He MRI in mouse models of asthma.

In the study of asthma, a vital role is played by mouse models, because knockout or transgenic methods can be used to alter disease pathways and identify therapeutic targets that affect lung function. Assessment of lung function in rodents by available methods is insensitive because these techniques lack regional specificity. A more sensitive method for evaluating lung function in human asthma patients uses hyperpolarized (HP) (3)He MRI before and after bronchoconstriction induced by methacholine (MCh). We now report the ability to perform such (3)He imaging of MCh response in mice, where voxels must be approximately 3000 times smaller than in humans and (3)He diffusion becomes an impediment to resolving the airways. We show three-dimensional (3D) images that reveal airway structure down to the fifth branching and visualize ventilation at a resolution of 125 x 125 x 1000 microm(3). Images of ovalbumin (OVA)-sensitized mice acquired after MCh show both airway closure and ventilation loss. To also observe the MCh response in naive mice, we developed a non-slice-selective 2D protocol with 187 x 187 microm(2) resolution that was fast enough to record the MCh response and recovery with 12-s temporal resolution. The extension of (3)He MRI to mouse models should make it a valuable translational tool in asthma research.

Authors
Driehuys, B; Walker, J; Pollaro, J; Cofer, GP; Mistry, N; Schwartz, D; Johnson, GA
MLA Citation
Driehuys, B, Walker, J, Pollaro, J, Cofer, GP, Mistry, N, Schwartz, D, and Johnson, GA. "3He MRI in mouse models of asthma." Magn Reson Med 58.5 (November 2007): 893-900.
PMID
17969115
Source
pubmed
Published In
Magnetic Resonance in Medicine
Volume
58
Issue
5
Publish Date
2007
Start Page
893
End Page
900
DOI
10.1002/mrm.21306

Sparseness prior based iterative image reconstruction for retrospectively gated cardiac micro-CT.

Recent advances in murine cardiac studies with three-dimensional (3D) cone beam micro-CT used a retrospective gating technique. However, this sampling technique results in a limited number of projections with an irregular angular distribution due to the temporal resolution requirements and radiation dose restrictions. Both angular irregularity and undersampling complicate the reconstruction process, since they cause significant streaking artifacts. This work provides an iterative reconstruction solution to address this particular challenge. A sparseness prior regularized weighted l2 norm optimization is proposed to mitigate streaking artifacts based on the fact that most medical images are compressible. Total variation is implemented in this work as the regularizer for its simplicity. Comparison studies are conducted on a 3D cardiac mouse phantom generated with experimental data. After optimization, the method is applied to in vivo cardiac micro-CT data.

Authors
Song, J; Liu, QH; Johnson, GA; Badea, CT
MLA Citation
Song, J, Liu, QH, Johnson, GA, and Badea, CT. "Sparseness prior based iterative image reconstruction for retrospectively gated cardiac micro-CT." Med Phys 34.11 (November 2007): 4476-4483.
PMID
18072512
Source
pubmed
Published In
Medical physics
Volume
34
Issue
11
Publish Date
2007
Start Page
4476
End Page
4483
DOI
10.1118/1.2795830

Morphometric analysis of the C57BL/6J mouse brain.

Magnetic resonance microscopy (MRM), when used in conjunction with active staining, can produce high-resolution, high-contrast images of the mouse brain. Using MRM, we imaged in situ the fixed, actively stained brains of C57BL/6J mice in order to characterize the neuroanatomical phenotype and produce a digital atlas. The brains were scanned within the cranium vault to preserve the brain morphology, avoid distortions, and to allow an unbiased shape analysis. The high-resolution imaging used a T1-weighted scan at 21.5 microm isotropic resolution, and an eight-echo multi-echo scan, post-processed to obtain an enhanced T2 image at 43 microm resolution. The two image sets were used to segment the brain into 33 anatomical structures. Volume, area, and shape characteristics were extracted for all segmented brain structures. We also analyzed the variability of volumes, areas, and shape characteristics. The coefficient of variation of volume had an average value of 7.0%. Average anatomical images of the brain for both the T1-weighted and T2 images were generated, together with an average shape atlas, and a probabilistic atlas for 33 major structures. These atlases, with their associated meta-data, will serve as baseline for identifying neuroanatomical phenotypes of additional strains, and mouse models now under study. Our efforts were directed toward creating a baseline for comparison with other mouse strains and models of neurodegenerative diseases.

Authors
Badea, A; Ali-Sharief, AA; Johnson, GA
MLA Citation
Badea, A, Ali-Sharief, AA, and Johnson, GA. "Morphometric analysis of the C57BL/6J mouse brain." NeuroImage 37.3 (September 2007): 683-693.
PMID
17627846
Source
epmc
Published In
NeuroImage
Volume
37
Issue
3
Publish Date
2007
Start Page
683
End Page
693
DOI
10.1016/j.neuroimage.2007.05.046

High-throughput morphologic phenotyping of the mouse brain with magnetic resonance histology.

The Mouse Biomedical Informatics Research Network (MBIRN) has been established to integrate imaging studies of the mouse brain ranging from three-dimensional (3D) studies of the whole brain to focused regions at a sub-cellular scale. Magnetic resonance (MR) histology provides the entry point for many morphologic comparisons of the whole brain. We describe a standardized protocol that allows acquisition of 3D MR histology (43-microm resolution) images of the fixed, stained mouse brain with acquisition times <30 min. A higher resolution protocol with isotropic spatial resolution of 21.5 microm can be executed in 2 h. A third acquisition protocol provides an alternative image contrast (at 43-microm isotropic resolution), which is exploited in a statistically driven algorithm that segments 33 of the most critical structures in the brain. The entire process, from specimen perfusion, fixation and staining, image acquisition and reconstruction, post-processing, segmentation, archiving, and analysis, is integrated through a structured workflow. This yields a searchable database for archive and query of the very large (1.2 GB) images acquired with this standardized protocol. These methods have been applied to a collection of both male and female adult murine brains ranging over 4 strains and 6 neurologic knockout models. These collection and acquisition methods are now available to the neuroscience community as a standard web-deliverable service.

Authors
Johnson, GA; Ali-Sharief, A; Badea, A; Brandenburg, J; Cofer, G; Fubara, B; Gewalt, S; Hedlund, LW; Upchurch, L
MLA Citation
Johnson, GA, Ali-Sharief, A, Badea, A, Brandenburg, J, Cofer, G, Fubara, B, Gewalt, S, Hedlund, LW, and Upchurch, L. "High-throughput morphologic phenotyping of the mouse brain with magnetic resonance histology." NeuroImage 37.1 (August 2007): 82-89.
PMID
17574443
Source
epmc
Published In
NeuroImage
Volume
37
Issue
1
Publish Date
2007
Start Page
82
End Page
89
DOI
10.1016/j.neuroimage.2007.05.013

Cardiac micro-computed tomography for morphological and functional phenotyping of muscle LIM protein null mice.

The purpose of this study was to investigate the use of micro-computed tomography (micro-CT) for morphological and functional phenotyping of muscle LIM protein (MLP) null mice and to compare micro-CT with M-mode echocardiography. MLP null mice and controls were imaged using both micro-CT and M-mode echocardiography. For micro-CT, we used a custom-built scanner. Following a single intravenous injection of a blood pool contrast agent (Fenestra VC, ART Advanced Research Technologies, Saint-Laurent, QC) and using a cardiorespiratory gating, we acquired eight phases of the cardiac cycle (every 15 ms) and reconstructed three-dimensional data sets with 94-micron isotropic resolution. Wall thickness and volumetric measurements of the left ventricle were performed, and cardiac function was estimated. Micro-CT and M-mode echocardiography showed both morphological and functional aspects that separate MLP null mice from controls. End-diastolic and -systolic volumes were increased significantly three- and fivefold, respectively, in the MLP null mice versus controls. Ejection fraction was reduced by an average of 32% in MLP null mice. The data analysis shows that two imaging modalities provided different results partly owing to the difference in anesthesia regimens. Other sources of errors for micro-CT are also analyzed. Micro-CT can provide the four-dimensional data (three-dimensional isotropic volumes over time) required for morphological and functional phenotyping in mice.

Authors
Badea, CT; Hedlund, LW; Mackel, JFB; Mao, L; Rockman, HA; Johnson, GA
MLA Citation
Badea, CT, Hedlund, LW, Mackel, JFB, Mao, L, Rockman, HA, and Johnson, GA. "Cardiac micro-computed tomography for morphological and functional phenotyping of muscle LIM protein null mice." Mol Imaging 6.4 (July 2007): 261-268.
PMID
17711781
Source
pubmed
Published In
Molecular imaging : official journal of the Society for Molecular Imaging
Volume
6
Issue
4
Publish Date
2007
Start Page
261
End Page
268

Staining methods for magnetic resonance microscopy of the rat fetus.

To develop a magnetic resonance histology (MRH) staining and fixation method by immersion to enhance the signal-to-noise ratio (SNR) with a paramagnetic contrast agent permitting microscopic acquisition within a 3-hour scan time.Methods were optimized for embryonic day 18.5 (E18.5) rat fetuses and imaging at 9.4T with an RF refocused spin-echo pulse sequence (TR/TE = 75 msec/5.2 msec). Fixation/staining was performed by immersion in Bouin's fixative containing varied concentrations of ProHance (from 10:1 to 500:1 Bouin's:ProHance) and for varied immersion durations (up to 24 hours).The results showed a significant change in T1 and T2 relaxation times as a function of concentration of contrast agent and immersion duration. As the contrast agent penetrated the tissues, T1 was reduced as desired (typically by 10x), but at the same time T2 was profoundly reduced (typically by 3x) due to both protein cross-linking from the fixative and the high concentration of contrast agent. A systematic assessment of this staining protocol showed an increased SNR (by 5x) over that in unstained specimens.This staining protocol reduced scan time for very-high-resolution images (19.5 microm) to only 3 hours, making MRH a routine tool for evaluating fetal development.

Authors
Petiet, A; Hedlund, L; Johnson, GA
MLA Citation
Petiet, A, Hedlund, L, and Johnson, GA. "Staining methods for magnetic resonance microscopy of the rat fetus." Journal of magnetic resonance imaging : JMRI 25.6 (June 2007): 1192-1198.
PMID
17520739
Source
epmc
Published In
Journal of Magnetic Resonance Imaging
Volume
25
Issue
6
Publish Date
2007
Start Page
1192
End Page
1198
DOI
10.1002/jmri.20932

High-resolution imaging of murine myocardial infarction with delayed-enhancement cine micro-CT.

The objective of this study was to determine the feasibility of delayed-enhancement micro-computed tomography (microCT) imaging to quantify myocardial infarct size in experimental mouse models. A total of 20 mice were imaged 5 or 35 days after surgical ligation of the left coronary artery or sham surgery (n=6 or 7 per group). We utilized a prototype microCT that covers a three-dimensional (3D) volume with an isotropic spatial resolution of 100 microm. A series of image acquisitions were started after a 200 microl bolus of a high-molecular-weight blood pool CT agent to outline the ventricles. CT imaging was continuously performed over 60 min, while an intravenous constant infusion with iopamidol 370 was started at a dosage of 1 ml/h. Thirty minutes after the initiation of this infusion, signal intensity in Hounsfield units was significantly higher in the infarct than in the remote, uninjured myocardium. Cardiac morphology and motion were visualized with excellent contrast and in fine detail. In vivo CT determination of infarct size at the midventricular level was in good agreement with ex vivo staining with triphenyltetrazolium chloride [5 days post-myocardial infarction (MI): r(2)=0.86, P<0.01; 35 days post-MI: r(2)=0.92, P<0.01]. In addition, we detected significant left ventricular remodeling consisting of left ventricular dilation and decreased ejection fraction. 3D cine microCT reliably and rapidly quantifies infarct size and assesses murine anatomy and physiology after coronary ligation, despite the small size and fast movement of the mouse heart. This efficient imaging tool is a valuable addition to the current phenotyping armamentarium and will allow rapid testing of novel drugs and cell-based interventions in murine models.

Authors
Nahrendorf, M; Badea, C; Hedlund, LW; Figueiredo, J-L; Sosnovik, DE; Johnson, GA; Weissleder, R
MLA Citation
Nahrendorf, M, Badea, C, Hedlund, LW, Figueiredo, J-L, Sosnovik, DE, Johnson, GA, and Weissleder, R. "High-resolution imaging of murine myocardial infarction with delayed-enhancement cine micro-CT." Am J Physiol Heart Circ Physiol 292.6 (June 2007): H3172-H3178.
PMID
17322414
Source
pubmed
Published In
American journal of physiology. Heart and circulatory physiology
Volume
292
Issue
6
Publish Date
2007
Start Page
H3172
End Page
H3178
DOI
10.1152/ajpheart.01307.2006

Tomographic digital subtraction angiography for lung perfusion estimation in rodents.

In vivo measurements of perfusion present a challenge to existing small animal imaging techniques such as magnetic resonance microscopy, micro computed tomography, micro positron emission tomography, and microSPECT, due to combined requirements for high spatial and temporal resolution. We demonstrate the use of tomographic digital subtraction angiography (TDSA) for estimation of perfusion in small animals. TDSA augments conventional digital subtraction angiography (DSA) by providing three-dimensional spatial information using tomosynthesis algorithms. TDSA is based on the novel paradigm that the same time density curves can be reproduced in a number of consecutive injections of microL volumes of contrast at a series of different angles of rotation. The capabilities of TDSA are established in studies on lung perfusion in rats. Using an imaging system developed in-house, we acquired data for four-dimensional (4D) imaging with temporal resolution of 140 ms, in-plane spatial resolution of 100 microm, and slice thickness on the order of millimeters. Based on a structured experimental approach, we optimized TDSA imaging providing a good trade-off between slice thickness, the number of injections, contrast to noise, and immunity to artifacts. Both DSA and TDSA images were used to create parametric maps of perfusion. TDSA imaging has potential application in a number of areas where functional perfusion measurements in 4D can provide valuable insight into animal models of disease and response to therapeutics.

Authors
Badea, CT; Hedlund, LW; De Lin, M; Mackel, JSB; Samei, E; Johnson, GA
MLA Citation
Badea, CT, Hedlund, LW, De Lin, M, Mackel, JSB, Samei, E, and Johnson, GA. "Tomographic digital subtraction angiography for lung perfusion estimation in rodents." Med Phys 34.5 (May 2007): 1546-1555.
PMID
17555236
Source
pubmed
Published In
Medical physics
Volume
34
Issue
5
Publish Date
2007
Start Page
1546
End Page
1555
DOI
10.1118/1.2717384

Superparamagnetic iron oxide labeling and transplantation of adipose-derived stem cells in middle cerebral artery occlusion-injured mice.

OBJECTIVE: Adipose-derived stem cells are an alternative stem cell source for CNS therapies. The goals of the current study were to label adipose-derived stem cells with superparamagnetic iron oxide (SPIO) particles, to use MRI to guide the transplantation of adipose-derived stem cells in middle cerebral artery occlusion (MCAO)-injured mice, and to localize donor adipose-derived stem cells in the injured brain using MRI. We hypothesized that we would successfully label adipose-derived stem cells and image them with MRI. MATERIALS AND METHODS: Adipose-derived stem cells harvested from mice inbred for green fluorescent protein were labeled with SPIO ferumoxide particles through the use of poly-L-lysine. Adipose-derived stem cell viability, iron staining, and proliferation were measured after SPIO labeling, and the sensitivity of MRI in the detection of SPIO-labeled adipose-derived stem cells was assessed ex vivo. Adult mice (n = 12) were subjected to unilateral MCAO. Two weeks later, in vivo 7-T MRI was performed to guide stereotactic transplantation of SPIO-labeled adipose-derived stem cells into brain tissue adjacent to the infarct. After 24 hours, the mice were sacrificed for high-resolution ex vivo 7-T or 9.4-T MRI and histologic study. RESULTS: Adipose-derived stem cells were efficiently labeled with SPIO particles without loss of cell viability or proliferation. Using MRI, we guided precise transplantation of adipose-derived stem cells. MR images of mice given injections of SPIO-labeled adipose-derived stem cells had hypointense regions that correlated with the histologic findings in donor cells. CONCLUSION: MRI proved useful in transplantation of adipose-derived stem cells in vivo. This imaging technique may be useful for studies of CNS stem cell therapies.

Authors
Rice, HE; Hsu, EW; Sheng, H; Evenson, DA; Freemerman, AJ; Safford, KM; Provenzale, JM; Warner, DS; Johnson, GA
MLA Citation
Rice, HE, Hsu, EW, Sheng, H, Evenson, DA, Freemerman, AJ, Safford, KM, Provenzale, JM, Warner, DS, and Johnson, GA. "Superparamagnetic iron oxide labeling and transplantation of adipose-derived stem cells in middle cerebral artery occlusion-injured mice." AJR Am J Roentgenol 188.4 (April 2007): 1101-1108.
PMID
17377054
Source
pubmed
Published In
AJR. American journal of roentgenology
Volume
188
Issue
4
Publish Date
2007
Start Page
1101
End Page
1108
DOI
10.2214/AJR.06.0663

A micro-computed tomography-based method for the measurement of pulmonary compliance in healthy and bleomycin-exposed mice.

Micro-computed tomography (microCT) is being increasingly used to examine small animal models of pulmonary injury. The authors have developed a microCT technique suitable for the determination of pulmonary compliance in injured mice. Lung volumes in normal mice were radiographically determined at end-inspiration and end-expiration and pulmonary compliance was calculated at 2 time points 2 weeks apart, whereas a second group of mice were given bleomycin and imaged 3 weeks following drug administration. Compliance measurements were validated using a commercially available ventilator system. MicroCT pulmonary compliance measurements are suitable for longitudinal measurements, and correlate with physiologic measurements of pulmonary compliance.

Authors
Shofer, S; Badea, C; Auerbach, S; Schwartz, DA; Johnson, GA
MLA Citation
Shofer, S, Badea, C, Auerbach, S, Schwartz, DA, and Johnson, GA. "A micro-computed tomography-based method for the measurement of pulmonary compliance in healthy and bleomycin-exposed mice." Exp Lung Res 33.3-4 (April 2007): 169-183.
PMID
17558678
Source
pubmed
Published In
Experimental Lung Research (Informa)
Volume
33
Issue
3-4
Publish Date
2007
Start Page
169
End Page
183
DOI
10.1080/01902140701364458

Neuroanatomical phenotypes in the reeler mouse.

The reeler mouse (Reln) has been proposed as a neurodevelopmental model for certain neurological and psychiatric conditions and has been studied by qualitative histochemistry and electron microscopy. Using magnetic resonance microscopy (MRM), we have quantitated for the first time the neuromorphology of Reln mice at a resolution of 21.5 microm. The neuroanatomical phenotypes of heterozygous and homozygous mutant Reln mice were compared to those of wild type (WT) littermates using morphometry and texture analysis. The cortical, hippocampal, and cerebellar phenotypes of the heterozygous and homozygous mutant Reln mice were confirmed, and new features were revealed. The Reln(rl/rl) mice possessed a smaller brain, and both Reln(rl/+) and Reln(rl/rl) mice had increased ventricles compared to WT controls. Shape differences were found between WT and Reln(rl/rl) brains, specifically in cerebellum, olfactory bulbs, dorsomedial frontal and parietal cortex, certain regions of temporal and occipital lobes, as well as in the lateral ventricles and ventral hippocampus. These findings suggest that certain brain regions may be more severely impacted by the Reln mutation than others. Gadolinium-based active staining demonstrated that layers of the hippocampus were disorganized in Reln(rl/rl) mice and differences in thickness of these layers were identified between WT and Reln(rl/rl) mice. The intensity distributions characteristic to the dorsal, middle, and ventral hippocampus were altered in the Reln(rl/rl), especially in the ventral hippocampus. These differences were quantified using skewness and modeling the intensity distributions with a Gaussian mixture. Our results suggest that structural features of Reln(rl/rl) brain most closely phenocopy those of patients with Norman-Roberts lissencephaly.

Authors
Badea, A; Nicholls, PJ; Johnson, GA; Wetsel, WC
MLA Citation
Badea, A, Nicholls, PJ, Johnson, GA, and Wetsel, WC. "Neuroanatomical phenotypes in the reeler mouse." Neuroimage 34.4 (February 15, 2007): 1363-1374.
PMID
17185001
Source
pubmed
Published In
NeuroImage
Volume
34
Issue
4
Publish Date
2007
Start Page
1363
End Page
1374
DOI
10.1016/j.neuroimage.2006.09.053

Measurement and modeling of 4D live mouse heart volumes from CT time series

In vivo quantitative studies of cardiac function in mouse models provide information about cardiac pathophysiology in more detail than can be obtained in humans. Quantitative measurements of left ventricular (LV) volume at multiple contractile phases are particularly important. However, the mouse heart's small size and rapid motion present challenges for precise measurement in live animals. Researchers at Duke University's Center for In Vivo Microscopy (CIVM) have developed noninvasive time-gated microcomputed tomography (micro-CT) techniques providing the temporal and spatial resolutions required for in vivo characterization of cardiac structure and function. This paper describes analysis of the resulting reconstructions to produce volume measurements and corresponding models of heart motion. We believe these are the most precise noninvasive estimates of in vivo LV volume currently available. Our technique uses binary mixture models to directly recover volume estimates from reconstructed datasets. Unlike methods using segmentation followed by voxel counting, this approach provides statistical error estimates and maintains good precision at high noise levels. This is essential for long term multiple session experiments that must simultaneously minimize contrast agent and x-ray doses. The analysis tools are built into the Pittsburgh Supercomputing Center's Volume Browser (PSC-VB) that provides networked multi-site data sharing and collaboration including analysis and visualization functions. © 2007 SPIE-IS&T.

Authors
Wetzel, AW; Badea, CT; Pomerantz, SM; Mistry, N; Nave, D; Johnson, GA
MLA Citation
Wetzel, AW, Badea, CT, Pomerantz, SM, Mistry, N, Nave, D, and Johnson, GA. "Measurement and modeling of 4D live mouse heart volumes from CT time series." 2007.
Source
scival
Published In
Proceedings of SPIE - The International Society for Optical Engineering
Volume
6491
Publish Date
2007

Brain atlasing tool interoperation: NeuroTerrain-Smart Atlas synergistic visualization and analysis environment

Many research efforts using anatomical image analysis have as their goal to identify biologically relevant objects present within the image data, to provide a means to quantitatively analyze these objects, to compare the distribution of those objects to other features, and finally to properly annotate the objects so as to be able share this analysis in an integrated informatics framework. The neuroinformatics tools designed to achieve these ends have been developed in a fragmented manner with each resource developing access to unique data sets and analytical capabilities, Their integration would enrich the neuroinformatic network enabling queries and analysis across a number of resources. A central objective of the Biomedical Informatics Research Network (BIRN) is to achieve this integration and we present here a demonstration of how two such tools - the NeuroTerrain Atlas/NetOStat client and the SMART Atlas - can expose their functionality via a re-usable interface, so as to promote interoperation of tools and data. © 2007 IEEE.

Authors
Bug, W; Wong, WW; Gustafson, C; Johnson, GA; Martone, ME; Price, DL; Rosen, GD; Williams, RW; Zaslavsky, I; Nissanov, J
MLA Citation
Bug, W, Wong, WW, Gustafson, C, Johnson, GA, Martone, ME, Price, DL, Rosen, GD, Williams, RW, Zaslavsky, I, and Nissanov, J. "Brain atlasing tool interoperation: NeuroTerrain-Smart Atlas synergistic visualization and analysis environment." 2007.
Source
scival
Published In
Proceedings of the 3rd International IEEE EMBS Conference on Neural Engineering
Publish Date
2007
Start Page
280
End Page
283
DOI
10.1109/CNE.2007.369665

Imaging alveolar-capillary gas transfer using hyperpolarized 129Xe MRI.

Effective pulmonary gas exchange relies on the free diffusion of gases across the thin tissue barrier separating airspace from the capillary red blood cells (RBCs). Pulmonary pathologies, such as inflammation, fibrosis, and edema, which cause an increased blood-gas barrier thickness, impair the efficiency of this exchange. However, definitive assessment of such gas-exchange abnormalities is challenging, because no methods currently exist to directly image the gas transfer process. Here we exploit the solubility and chemical shift of (129)Xe, the magnetic resonance signal of which has been enhanced by 10(5) with hyperpolarization, to differentially image its transfer from the airspaces into the tissue barrier spaces and RBCs in the gas exchange regions of the lung. Based on a simple diffusion model, we estimate that this MR imaging method for measuring (129)Xe alveolar-capillary transfer is sensitive to changes in blood-gas barrier thickness of approximately 5 microm. We validate the successful separation of tissue barrier and RBC images and show the utility of this method in a rat model of pulmonary fibrosis where (129)Xe replenishment of the RBCs is severely impaired in regions of lung injury.

Authors
Driehuys, B; Cofer, GP; Pollaro, J; Mackel, JB; Hedlund, LW; Johnson, GA
MLA Citation
Driehuys, B, Cofer, GP, Pollaro, J, Mackel, JB, Hedlund, LW, and Johnson, GA. "Imaging alveolar-capillary gas transfer using hyperpolarized 129Xe MRI." Proc Natl Acad Sci U S A 103.48 (November 28, 2006): 18278-18283.
PMID
17101964
Source
pubmed
Published In
Proceedings of the National Academy of Sciences of USA
Volume
103
Issue
48
Publish Date
2006
Start Page
18278
End Page
18283
DOI
10.1073/pnas.0608458103

Micro radiography imaging of the rodent with phenylephrine induced vascular hypertension

Vascular tonicity plays a major role in regulating the blood pressure and the perfusion of organs, and hypertension is a major cause of morbidity and mortality in humans. We use phenylephrine, a vasoconstrictor, to create a model of hypertension in the rat. This work demonstrates the use of a micro-X-ray digital subtraction angiography (DSA) system to image pharmacologically mediated changes in the vascular system of the rat. Imaging physiological function in the rodent calls for high spatial and temporal resolutions and the use of a reproducible image acquisition chain. Dynamic vascular images and quantitative perfusion metrics were acquired before and after a vasoconstrictor, phenylephrine drug injection. Dramatic effects of the vasoconstrictor on vascular dynamics are seen in the prolonged blood flow mean transit time, amount of ventricular filling, the size increase of the pulmonary arteries and aorta, and a substantial increase in mean arterial pressure. © 2006 IEEE.

Authors
De Lin, M; Hedlund, L; Johnson, GA
MLA Citation
De Lin, M, Hedlund, L, and Johnson, GA. "Micro radiography imaging of the rodent with phenylephrine induced vascular hypertension." November 17, 2006.
Source
scopus
Published In
2006 3rd IEEE International Symposium on Biomedical Imaging: From Nano to Macro - Proceedings
Volume
2006
Publish Date
2006
Start Page
610
End Page
613

Multimodality imaging of pulmonary function in the rodent

The high spatial and temporal resolution demands for imaging physiological function in the rodent call for the use of novel ways to combine information from different imaging modalities. This work describes ventilation imaging using hyperpolarized (HP) 3He magnetic resonance imaging (MRI) and perfusion imaging using X-ray digital subtraction angiography (DSA). We illustrate the key steps needed to combine the complementary data from the two modalities to provide qualitative and quantitative information on gas exchange in the lungs. The results indicate that multimodality imaging of pulmonary function in small animals can provide functional information at higher spatial and temporal resolution compared to many traditional imaging techniques. © 2006 IEEE.

Authors
Mistry, N; De Lin, M; Hedlund, L; Johnson, GA
MLA Citation
Mistry, N, De Lin, M, Hedlund, L, and Johnson, GA. "Multimodality imaging of pulmonary function in the rodent." November 17, 2006.
Source
scopus
Published In
2006 3rd IEEE International Symposium on Biomedical Imaging: From Nano to Macro - Proceedings
Volume
2006
Publish Date
2006
Start Page
920
End Page
923

Functional imaging in small animals using tomographic digital subtraction angiography

We propose the use of Tomographic Digital Subtraction Angiography (TDSA) for functional imaging in small animals. TDSA combines the advantages of high temporal resolution of digital subtraction angiography (DSA) and high spatial resolution of micro-computed tomography (CT). TDSA augments projection imaging methods such as DSA by providing three-dimensional information using tomosynthesis or CT reconstruction algorithms. Thus, four-dimensional (4D) datasets with a temporal resolution on the order of 100 ms and spatial resolution ranging from 100 microns to 1 mm, depending on the scanning angle, can be obtained. The approach is based on the novel paradigm that the same time density curves can be reproduced in a number of consecutive injections of microL volumes of contrast at a series of different angles of rotation. © 2006 IEEE.

Authors
Badea, CT; Hedlund, LW; Lin, MD; Boslego, JF; Johnson, GA
MLA Citation
Badea, CT, Hedlund, LW, Lin, MD, Boslego, JF, and Johnson, GA. "Functional imaging in small animals using tomographic digital subtraction angiography." November 17, 2006.
Source
scopus
Published In
2006 3rd IEEE International Symposium on Biomedical Imaging: From Nano to Macro - Proceedings
Volume
2006
Publish Date
2006
Start Page
1208
End Page
1211

Optimized radiographic spectra for small animal digital subtraction angiography.

The increasing use of small animals in basic research has spurred interest in new imaging methodologies. Digital subtraction angiography (DSA) offers a particularly appealing approach to functional imaging in the small animal. This study examines the optimal x-ray, molybdenum (Mo) or tungsten (W) target sources, and technique to produce the highest quality small animal functional subtraction angiograms in terms of contrast and signal-difference-to-noise ratio squared (SdNR2). Two limiting conditions were considered-normalization with respect to dose and normalization against tube loading. Image contrast and SdNR2 were simulated using an established x-ray model. DSA images of live rats were taken at two representative tube potentials for the W and Mo sources. Results show that for small animal DSA, the Mo source provides better contrast. However, with digital detectors, SdNR2 is the more relevant figure of merit. The W source operated at kVps >60 achieved a higher SdNR2. The highest SdNR2 was obtained at voltages above 90 kVp. However, operation at the higher potential results in significantly greater dose and tube load and reduced contrast quantization. A reasonable tradeoff can be achieved at tube potentials at the beginning of the performance plateau, around 70 kVp, where the relative gain in SdNR2 is the greatest.

Authors
Lin, MD; Samei, E; Badea, CT; Yoshizumi, TT; Johnson, GA
MLA Citation
Lin, MD, Samei, E, Badea, CT, Yoshizumi, TT, and Johnson, GA. "Optimized radiographic spectra for small animal digital subtraction angiography." Med Phys 33.11 (November 2006): 4249-4257.
PMID
17153403
Source
pubmed
Published In
Medical physics
Volume
33
Issue
11
Publish Date
2006
Start Page
4249
End Page
4257
DOI
10.1118/1.2356646

Enhanced T2 contrast for MR histology of the mouse brain.

A 3D Carr-Purcell-Meiboom-Gill (CPMG) sequence was implemented to obtain enhanced T(2) contrast in actively stained (perfusion with fixative and contrast agent) mouse brains at 9.4 T. Short interecho spacing was used to minimize diffusion and susceptibility losses. The sequence produced 16 3D volumes with an interecho spacing of 7 ms for isotropic 43-mu-resolution images of the mouse brains in a scan time of 4 hr. To enhance the signal-to-noise ratio (SNR) and contrast, the multiecho frequency domain image contrast (MEFIC) method was applied, resulting in a composite image with T(2)-weighted contrast. The high SNR and contrast thus achieved revealed aspects of mouse brain morphology, such as multiple cortical layers, groups of thalamic nuclei, layers of the inferior and superior colliculus, and molecular and granular layers of the cerebellum, with a high degree of definition and contrast that was not previously achieved in T(2)-weighted acquisitions at high fields.

Authors
Sharief, AA; Johnson, GA
MLA Citation
Sharief, AA, and Johnson, GA. "Enhanced T2 contrast for MR histology of the mouse brain." Magnetic resonance in medicine 56.4 (October 2006): 717-725.
PMID
16964618
Source
epmc
Published In
Magnetic Resonance in Medicine
Volume
56
Issue
4
Publish Date
2006
Start Page
717
End Page
725
DOI
10.1002/mrm.21026

Three-dimensional imaging of xenograft tumors using optical computed and emission tomography.

The physical basis and preliminary applications of optical computed tomography (optical-CT) and optical emission computed tomography (optical-ECT) are introduced, as new techniques with potential to provide unique 3D information on a variety of aspects of tumor structure and function. A particular focus here is imaging tumor micro-vasculature, and the spatial distribution of viable tumor cells, although the techniques have the potential for much wider application. The principle attractiveness of optical-CT and optical-ECT are that high resolution (<20 microm) and high contrast co-registered 3D images of structure and function can be acquired for relatively large intact samples. The unique combination of high contrast and resolution offers advantages over micro-CT and micro-MRI, and the lack of requirement for sectioning offers advantages over confocal microscopy, conventional microscopy, and histological sectioning techniques. Optical-CT/ECT are implemented using in-house custom apparatus and a commercial dissecting microscope capable of both transmission and fluorescence imaging. Basic studies to characterize imaging performance are presented. Negligible geometrical distortion and accurate reconstruction of relative attenuation coefficients was observed. Optical-CT and optical-ECT are investigated here by application to high resolution imaging of HCT116 xenograft tumors, about 1 cc in dimension, which were transfected with constitutive red fluorescent protein (RFP). Tumor microvasculature was stained in vivo by tail vein injection of either passive absorbing dyes or active fluorescent markers (FITC conjugated lectin). Prior to imaging, the tumors were removed (ex vivo) and optically cleared in a key process to make the samples amenable to light transmission. The cleared tumors were imaged in three modes (i) optical-CT to image the 3D distribution of microvasculature as indicated by absorbing dye, (ii) optical-ECT using the FITC excitation and emission filter set, to determine microvasculature as indicated by lectin-endothelial binding, and (iii) optical-ECT using the DSRed2 filter set to determine the 3D distribution of viable tumor as indicated by RFP emission. A clear correlation was observed between the independent vasculature imaging modes (i) and (ii) and postimaging histological sections, providing substantial validation of the optical-CT and optical-ECT techniques. Strong correlation was also observed between the RFP imaging of mode iii, and modes i and ii, supporting the intuitive conclusion that well-perfused regions contain significant viable tumor. In summary, optical-CT and optical-ECT, when combined with new optical clearing techniques, represent powerful new imaging modalities with potential for providing unique information on the structure and function of tumors.

Authors
Oldham, M; Sakhalkar, H; Oliver, T; Wang, YM; Kirpatrick, J; Cao, Y; Badea, C; Johnson, GA; Dewhirst, M
MLA Citation
Oldham, M, Sakhalkar, H, Oliver, T, Wang, YM, Kirpatrick, J, Cao, Y, Badea, C, Johnson, GA, and Dewhirst, M. "Three-dimensional imaging of xenograft tumors using optical computed and emission tomography." Med Phys 33.9 (September 2006): 3193-3202.
PMID
17022212
Source
pubmed
Published In
Medical physics
Volume
33
Issue
9
Publish Date
2006
Start Page
3193
End Page
3202
DOI
10.1118/1.2217109

Tumor imaging in small animals with a combined micro-CT/micro-DSA system using iodinated conventional and blood pool contrast agents.

X-ray based micro-computed tomography (CT) and micro-digital subtraction angiography (DSA) are important non-invasive imaging modalities for following tumorogenesis in small animals. To exploit these imaging capabilities further, the two modalities were combined into a single system to provide both morphological and functional data from the same tumor in a single imaging session. The system is described and examples are given of imaging implanted fibrosarcoma tumors in rats using two types of contrast media: (a) a new generation of blood pool contrast agent containing iodine with a concentration of 130 mg/mL (Fenestratrade mark VC, Alerion Biomedical, San Diego, CA, USA) for micro-CT and (b) a conventional iodinated contrast agent (Isovue(R)-370 mg/mL iodine, trademark of Bracco Diagnostics, Princeton, NJ, USA) for micro-DSA. With the blood pool contrast agent, the 3D vascular architecture is revealed in exquisite detail at 100 microm resolution. Micro-DSA images, in perfect registration with the 3D micro-CT datasets, provide complementary functional information such as mean transit times and relative blood flow through the tumor. This imaging approach could be used to understand tumor angiogenesis better and be the basis for evaluating anti-angiogenic therapies.

Authors
Badea, CT; Hedlund, LW; De Lin, M; Boslego Mackel, JF; Johnson, GA
MLA Citation
Badea, CT, Hedlund, LW, De Lin, M, Boslego Mackel, JF, and Johnson, GA. "Tumor imaging in small animals with a combined micro-CT/micro-DSA system using iodinated conventional and blood pool contrast agents." Contrast Media Mol Imaging 1.4 (July 2006): 153-164.
PMID
17193692
Source
pubmed
Published In
Contrast Media & Molecular Imaging
Volume
1
Issue
4
Publish Date
2006
Start Page
153
End Page
164
DOI
10.1002/cmmi.103

A liposomal nanoscale contrast agent for preclinical CT in mice.

The goal of this study was to determine if an iodinated, liposomal contrast agent could be used for high-resolution, micro-CT of low-contrast, small-size vessels in a murine model.A second-generation, liposomal blood pool contrast agent encapsulating a high concentration of iodine (83-105 mg I/mL) was evaluated. A total of five mice weighing between 20 and 28 g were infused with equivalent volume doses (500 microL of contrast agent/25 g of mouse weight) and imaged with our micro-CT system for intervals of up to 240 min postinfusion. The animals were anesthetized, mechanically ventilated, and vital signs monitored allowing for simultaneous cardiac and respiratory gating of image acquisition.Initial enhancement of about 900 H in the aorta was obtained, which decreased to a plateau level of approximately 800 H after 2 hr. Excellent contrast discrimination was shown between the myocardium and cardiac blood pool (650-700 H). No significant nephrogram was identified, indicating the absence of renal clearance of the agent.The liposomal-based iodinated contrast agent shows long residence time in the blood pool, very high attenuation within submillimeter vessels, and no significant renal clearance rendering it an effective contrast agent for murine vascular imaging using a micro-CT scanner.

Authors
Mukundan, S; Ghaghada, KB; Badea, CT; Kao, C-Y; Hedlund, LW; Provenzale, JM; Johnson, GA; Chen, E; Bellamkonda, RV; Annapragada, A
MLA Citation
Mukundan, S, Ghaghada, KB, Badea, CT, Kao, C-Y, Hedlund, LW, Provenzale, JM, Johnson, GA, Chen, E, Bellamkonda, RV, and Annapragada, A. "A liposomal nanoscale contrast agent for preclinical CT in mice." AJR. American journal of roentgenology 186.2 (February 2006): 300-307.
PMID
16423931
Source
epmc
Published In
AJR. American journal of roentgenology
Volume
186
Issue
2
Publish Date
2006
Start Page
300
End Page
307
DOI
10.2214/ajr.05.0523

Optimization of multiplanar reformations from isotropic data sets acquired with 16-detector row helical CT scanner.

Institutional review board approval and waiver of consent were obtained for the patient component of this retrospective HIPAA-compliant study. By using an anthropomorphic phantom and metal oxide semiconductor field effect transistor detectors, radiation dose was determined for one eight-detector row and two 16-detector row computed tomographic (CT) protocols. A custom phantom was scanned by using the three protocols to identify isotropy. Contrast-to-noise ratios (CNRs) were determined for the same protocols by using a third phantom. Seven patients had undergone isotropic 16-detector row CT of the abdomen and pelvis. Anonymized coronal reformations at various thicknesses were ranked qualitatively by three radiologists. Effective dose equivalents were similar for the eight- and 16-detector row protocols. When transverse and coronal reformations of data acquired in the custom phantom were compared, coronal reformations obtained with the 16-detector row and 0.625-mm section thickness protocol were found to be nearly identical to the transverse image for all sets of line pairs. CNRs were consistently highest on 5-mm-thick coronal reformations (CNR range, 1.2-3.3). For qualitative assessment, 2- and 3-mm-thick coronal reformations were consistently preferred.

Authors
Jaffe, TA; Nelson, RC; Johnson, GA; Lee, ER; Yoshizumi, TT; Lowry, CR; Bullard, AB; DeLong, DM; Paulson, EK
MLA Citation
Jaffe, TA, Nelson, RC, Johnson, GA, Lee, ER, Yoshizumi, TT, Lowry, CR, Bullard, AB, DeLong, DM, and Paulson, EK. "Optimization of multiplanar reformations from isotropic data sets acquired with 16-detector row helical CT scanner." Radiology 238.1 (January 2006): 292-299.
PMID
16373774
Source
pubmed
Published In
Radiology
Volume
238
Issue
1
Publish Date
2006
Start Page
292
End Page
299
DOI
10.1148/radiol.2381050404

Imaging methods for morphological and functional phenotyping of the rodent heart.

Small animal imaging has a critical role in phenotyping, drug discovery, and in providing a basic understanding of mechanisms of disease. Translating imaging methods from humans to small animals is not an easy task. The purpose of this work is to compare two cardiac imaging modalities, i.e., magnetic resonance microscopy (MRM) and microcomputed tomography (CT) for preclinical studies on rodents. We present the two technologies, the parameters that they can measure, the types of alterations that they can detect, and show how these imaging methods compare to techniques available in clinical medicine. While this paper does not refer per se to the cardiac risk assessment for drug or chemical development, we hope that the information will effectively address how MRM and micro-CT might be exploited to measure biomarkers critical for safety assessment.

Authors
Badea, CT; Bucholz, E; Hedlund, LW; Rockman, HA; Johnson, GA
MLA Citation
Badea, CT, Bucholz, E, Hedlund, LW, Rockman, HA, and Johnson, GA. "Imaging methods for morphological and functional phenotyping of the rodent heart." Toxicologic pathology 34.1 (January 2006): 111-117.
PMID
16507552
Source
epmc
Published In
Toxicologic Pathology (Sage)
Volume
34
Issue
1
Publish Date
2006
Start Page
111
End Page
117
DOI
10.1080/01926230500404126

Automated segmentation of neuroanatomical structures in multispectral MR microscopy of the mouse brain.

We present the automated segmentation of magnetic resonance microscopy (MRM) images of the C57BL/6J mouse brain into 21 neuroanatomical structures, including the ventricular system, corpus callosum, hippocampus, caudate putamen, inferior colliculus, internal capsule, globus pallidus, and substantia nigra. The segmentation algorithm operates on multispectral, three-dimensional (3D) MR data acquired at 90-microm isotropic resolution. Probabilistic information used in the segmentation is extracted from training datasets of T2-weighted, proton density-weighted, and diffusion-weighted acquisitions. Spatial information is employed in the form of prior probabilities of occurrence of a structure at a location (location priors) and the pairwise probabilities between structures (contextual priors). Validation using standard morphometry indices shows good consistency between automatically segmented and manually traced data. Results achieved in the mouse brain are comparable with those achieved in human brain studies using similar techniques. The segmentation algorithm shows excellent potential for routine morphological phenotyping of mouse models.

Authors
Ali, AA; Dale, AM; Badea, A; Johnson, GA
MLA Citation
Ali, AA, Dale, AM, Badea, A, and Johnson, GA. "Automated segmentation of neuroanatomical structures in multispectral MR microscopy of the mouse brain." NeuroImage 27.2 (August 2005): 425-435.
PMID
15908233
Source
epmc
Published In
NeuroImage
Volume
27
Issue
2
Publish Date
2005
Start Page
425
End Page
435
DOI
10.1016/j.neuroimage.2005.04.017

Reproductive cytotoxicity is predicted by magnetic resonance microscopy and confirmed by ubiquitin-proteasome immunohistochemistry in a theophylline-induced model of rat testicular and epididymal toxicity.

This study investigated the testicular changes in the rat induced by the nonspecific phosphodiesterase inhibitor, theophylline using magnetic resonance microscopy (MRM) and ubiquitin immunostaining techniques. In vivo T1- and T2-weighted images were acquired at 2 T under anesthesia. Increased signal observed in the theophylline-treated rats suggests that leakage of MRM contrast was occurring. In vivo MRM results indicate that day 16 testis displayed an increased T1-weighted water signal in the area of the seminiferous tubule that decreased by day 32. These findings were validated by histopathology, suggesting that in vivo MRM has the sensitivity to predict changes in testis and epididymal tissues. The participation of the ubiquitin system was investigated, using probes for various markers of the ubiquitin-proteasome pathway. MRM can be used to detect subtle changes in the vascular perfusion of organ systems, and the up-regulation/mobilization of ubiquitin-proteasome pathway may be one of the mechanisms used in theophylline-treated epididymis to remove damaged cells before storage in the cauda epididymis. The combined use of in vivo MRM and subsequent tissue or seminal analysis for the presence of ubiquitin in longitudinal studies may become an important biomarker for assessing testis toxicities drug studies.

Authors
Tengowski, MW; Sutovsky, P; Hedlund, LW; Guyot, DJ; Burkhardt, JE; Thompson, WE; Sutovsky, M; Johnson, GA
MLA Citation
Tengowski, MW, Sutovsky, P, Hedlund, LW, Guyot, DJ, Burkhardt, JE, Thompson, WE, Sutovsky, M, and Johnson, GA. "Reproductive cytotoxicity is predicted by magnetic resonance microscopy and confirmed by ubiquitin-proteasome immunohistochemistry in a theophylline-induced model of rat testicular and epididymal toxicity." Microscopy and microanalysis : the official journal of Microscopy Society of America, Microbeam Analysis Society, Microscopical Society of Canada 11.4 (August 2005): 300-312.
PMID
16079014
Source
epmc
Published In
Microscopy and microanalysis : the official journal of Microscopy Society of America, Microbeam Analysis Society, Microscopical Society of Canada
Volume
11
Issue
4
Publish Date
2005
Start Page
300
End Page
312

Magnetic resonance imaging at microscopic resolution reveals subtle morphological changes in a mouse model of dopaminergic hyperfunction.

Structural abnormalities of the basal ganglia have been documented in several neuropsychiatric conditions associated with dysregulation of the dopamine system. However, the histological nature underlying these changes is largely unknown. Using magnetic resonance imaging at microscopic resolution (MRI, 9.4 T with 43 microm isotropic spatial resolution) and stereological techniques, we have investigated the effect of increased dopamine neurotransmission on brain morphology in mice with elevated extracellular dopamine, the dopamine transporter knockout (DAT-KO) mice. We first demonstrate the usefulness of MRI at microscopic resolution for the accurate identification and measurement of volumes of specific subregions, accounting for less than 0.03% (0.16 mm(3)) of the volume of a mouse brain. Furthermore, the MRI analysis reveals a significantly lower volume (-9%) of the anterior striatum of DAT-KO mice, while the volume of other dopamine-related structures such as the posterior striatum and the substantia nigra pars reticulata is unchanged in comparison to wild type littermates. Stereological analysis performed in the same brains reveals that one important structural factor accounting for this selective change in volume is a reduction of 18% in the absolute number of neuronal cell bodies. The feasibility of assessing accurately small morphological alterations in mouse models, where the molecular and histological pathologies can be easily compared in a controlled manner, provides a paradigm to examine the relevance of selective brain volumetric changes associated with a number of neuropathological conditions.

Authors
Cyr, M; Caron, MG; Johnson, GA; Laakso, A
MLA Citation
Cyr, M, Caron, MG, Johnson, GA, and Laakso, A. "Magnetic resonance imaging at microscopic resolution reveals subtle morphological changes in a mouse model of dopaminergic hyperfunction." NeuroImage 26.1 (May 2005): 83-90.
PMID
15862208
Source
epmc
Published In
NeuroImage
Volume
26
Issue
1
Publish Date
2005
Start Page
83
End Page
90
DOI
10.1016/j.neuroimage.2005.01.039

4-D micro-CT of the mouse heart.

PURPOSE: Demonstrate noninvasive imaging methods for in vivo characterization of cardiac structure and function in mice using a micro-CT system that provides high photon fluence rate and integrated motion control. MATERIALS AND METHODS: Simultaneous cardiac- and respiratory-gated micro-CT was performed in C57BL/6 mice during constant intravenous infusion of a conventional iodinated contrast agent (Isovue-370), and after a single intravenous injection of a blood pool contrast agent (Fenestra VC). Multiple phases of the cardiac cycle were reconstructed with contrast to noise and spatial resolution sufficient for quantitative assessment of cardiac function. RESULTS: Contrast enhancement with Isovue-370 increased over time with a maximum of approximately 500 HU (aorta) and 900 HU (kidney cortex). Fenestra VC provided more constant enhancement over 3 hr, with maximum enhancement of approximately 620 HU (aorta) and approximately 90 HU (kidney cortex). The maximum enhancement difference between blood and myocardium in the heart was approximately 250 HU for Isovue-370 and approximately 500 HU for Fenestra VC. In mice with Fenestra VC, volumetric measurements of the left ventricle were performed and cardiac function was estimated by ejection fraction, stroke volume, and cardiac output. CONCLUSION: Image quality with Fenestra VC was sufficient for morphological and functional studies required for a standardized method of cardiac phenotyping of the mouse.

Authors
Badea, CT; Fubara, B; Hedlund, LW; Johnson, GA
MLA Citation
Badea, CT, Fubara, B, Hedlund, LW, and Johnson, GA. "4-D micro-CT of the mouse heart." Mol Imaging 4.2 (April 2005): 110-116.
PMID
16105509
Source
pubmed
Published In
Molecular imaging : official journal of the Society for Molecular Imaging
Volume
4
Issue
2
Publish Date
2005
Start Page
110
End Page
116

Effects of breathing and cardiac motion on spatial resolution in the microscopic imaging of rodents.

One can acquire high-resolution pulmonary and cardiac images in live rodents with MR microscopy by synchronizing the image acquisition to the breathing cycle across multiple breaths, and gating to the cardiac cycle. The precision with which one can synchronize image acquisition to the motion defines the ultimate resolution limit that can be attained in such studies. The present work was performed to evaluate how reliably the pulmonary and cardiac structures return to the same position from breath to breath and beat to beat across the prolonged period required for MR microscopy. Radiopaque beads were surgically glued to the abdominal surface of the diaphragm and on the cardiac ventricles of anesthetized, mechanically ventilated rats. We evaluated the range of motion for the beads (relative to a reference vertebral bead) using digital microradiography with two specific biological gating methods: 1) ventilation synchronous acquisition, and 2) both ventilation synchronous and cardiac-gated acquisitions. The standard deviation (SD) of the displacement was < or =100 microm, which is comparable to the resolution limit for in vivo MRI imposed by signal-to-noise ratio (SNR) constraints. With careful control of motion, its impact on resolution can be limited. This work provides the first quantitative measure of the motion-imposed resolution limits for in vivo imaging.

Authors
Maï, W; Badea, CT; Wheeler, CT; Hedlund, LW; Johnson, GA
MLA Citation
Maï, W, Badea, CT, Wheeler, CT, Hedlund, LW, and Johnson, GA. "Effects of breathing and cardiac motion on spatial resolution in the microscopic imaging of rodents." Magnetic resonance in medicine 53.4 (April 2005): 858-865.
PMID
15799053
Source
epmc
Published In
Magnetic Resonance in Medicine
Volume
53
Issue
4
Publish Date
2005
Start Page
858
End Page
865
DOI
10.1002/mrm.20400

Ventilation-synchronous magnetic resonance microscopy of pulmonary structure and ventilation in mice.

Increasing use of transgenic animal models for pulmonary disease has raised the need for methods to assess pulmonary structure and function in a physiologically stable mouse. We report here an integrated protocol using magnetic resonance microscopy with gadolinium (Gd)-labeled starburst dendrimer (G6-1B4M-Gd, MW = 192 +/- 1 kDa, R(h) = 5.50 +/- 0.04 nm) and hyperpolarized (3)helium ((3)He) gas to acquire images that demonstrate pulmonary vasculature and ventilated airways in live mice (n = 9). Registered three-dimensional images of (1)H and (3)He were acquired during breath-hold at 2.0 T using radial acquisition (total acquisition time of 38 and 25 min, respectively). The macromolecular Gd-labeled dendrimer (a half-life of approximately 80 min) increased the signal-to-noise by 81 +/- 30% in the left ventricle, 43 +/- 22% in the lung periphery, and -4 +/- 5% in the chest wall, thus increasing the contrast of these structures relative to the less vascular surrounding tissues. A constant-flow ventilator was developed for the mouse to deliver varied gas mixtures of O(2) and N(2) (or (3)He) during imaging. To avoid hypoxemia, instrumental dead space was minimized and corrections were made to tidal volume lost due to gas compression. The stability of the physiologic support was assessed by the lack of spontaneous breathing and maintenance of a constant heart rate. We were able to stabilize the mouse for >8 hr using ventilation of 105 breath/min and approximately 0.2 mL/breath. The feasibility of acquiring both pulmonary vasculature and ventilated airways was demonstrated in the mouse lung with in-plane spatial resolution of 70 x 70 microm(2) and slice thickness of 800 microm.

Authors
Chen, BT; Yordanov, AT; Johnson, GA
MLA Citation
Chen, BT, Yordanov, AT, and Johnson, GA. "Ventilation-synchronous magnetic resonance microscopy of pulmonary structure and ventilation in mice." Magnetic resonance in medicine 53.1 (January 2005): 69-75.
PMID
15690504
Source
epmc
Published In
Magnetic Resonance in Medicine
Volume
53
Issue
1
Publish Date
2005
Start Page
69
End Page
75
DOI
10.1002/mrm.20307

Morphology of the small-animal lung using magnetic resonance microscopy.

Small-animal imaging with magnetic resonance microscopy (MRM) has become an important tool in biomedical research. When MRM is used to image perfusion-fixed and "stained" whole mouse specimens, cardiopulmonary morphology can be visualized, nondestructively, in exquisite detail in all three dimensions. This capability can be a valuable tool for morphologic phenotyping of different mouse strains commonly used in genomics research. When these imaging techniques are combined with specialized methods for biological motion control and animal support, the lungs of the live, small animal can be imaged. Although in vivo imaging may not achieve the high resolution possible with a fixed specimen, dynamic functional studies and survival studies that follow the progression of pulmonary change related to disease or environmental exposure are possible. By combining conventional proton imaging with gas imaging, using hyperpolarized 3He, it is possible to image the tissue and gas compartments of the lung. This capability is illustrated in studies on an emphysema model in rats and on radiation damage of the lung. With further improvements in imaging and animal handling technology, we will be able to image faster and at higher resolutions, making MRM an even more valuable research tool.

Authors
Hedlund, LW; Johnson, GA
MLA Citation
Hedlund, LW, and Johnson, GA. "Morphology of the small-animal lung using magnetic resonance microscopy." January 2005.
PMID
16352752
Source
epmc
Published In
Proceedings of the American Thoracic Society
Volume
2
Issue
6
Publish Date
2005
Start Page
481
End Page
502
DOI
10.1513/pats.200507-074ds

Volumetric micro-CT system for in vivo microscopy

Two of the major barriers to improved image quality in micro-CT are the reduced signal to noise imposed by the smaller voxels and the effects of physiologic motion. The most direct approach to increase the signal to noise ratio (SNR) is to increase the flux. This is not possible in most of laboratory and commercial micro-CT systems that are currently in use. We adopted a design that allows the use of high instantaneous X-ray flux combined with synchronization to physiologic motion. High quality imaging of moving organs such as the heart or the lungs is directly dependent on appropriate gating techniques. For this purpose, we acquired X-ray projections using a flexible controller to enable sophisticated biological pulse sequences to minimize the effects of motion. This paper reports on the development of a volumetric micro-CT scanner dedicated to structural and functional phenotyping of the live mouse. © 2004 IEEE.

Authors
Badea, CT; Hedlund, LW; Wheeler, CT; Mai, W; Johnson, GA
MLA Citation
Badea, CT, Hedlund, LW, Wheeler, CT, Mai, W, and Johnson, GA. "Volumetric micro-CT system for in vivo microscopy." December 1, 2004.
Source
scopus
Published In
2004 2nd IEEE International Symposium on Biomedical Imaging: Macro to Nano
Volume
2
Publish Date
2004
Start Page
1377
End Page
1380

Effects of breathing motion on the spatial resolution in microscopic imaging techniques of rodents

Magnetic resonance microscopy is capable of producing high-resolution pulmonary images in live rodents by synchronizing the image acquisition across multiple breaths. The precision with which one can control motion will probably define the resolution limit that can be attained in such studies. This work was performed to evaluate how reliably the respiratory structures return to the same position from breath to breath each time data are acquired. Radio-opaque beads were surgically glued on the diaphragm of anesthetized, mechanically ventilated rats. Their range of motion (relative to a reference vertebral bead) was evaluated using digital micro-radiography with two specific biological pulse sequences: (1) ventilation synchronous acquisition, and (2) both ventilation synchronous and cardiac gated acquisition. The standard deviation of the displacement was on the order of, or less than 100 microns, which is comparable to the resolution limit for in vivo magnetic resonance imaging imposed by signal to noise constraints. With careful control of motion, its impact on resolution can be limited. This work provides the first quantitative measure of the motion imposed resolution limits for in vivo imaging. ©2004 IEEE.

Authors
Mai, W; Badea, CT; Wheeler, CT; Hedlund, LW; Johnson, GA
MLA Citation
Mai, W, Badea, CT, Wheeler, CT, Hedlund, LW, and Johnson, GA. "Effects of breathing motion on the spatial resolution in microscopic imaging techniques of rodents." December 1, 2004.
Source
scopus
Published In
2004 2nd IEEE International Symposium on Biomedical Imaging: Macro to Nano
Volume
1
Publish Date
2004
Start Page
472
End Page
475

Micro-CT with respiratory and cardiac gating.

Cardiopulmonary imaging in rodents using micro-computed tomography (CT) is a challenging task due to both cardiac and pulmonary motion and the limited fluence rate available from micro-focus x-ray tubes of most commercial systems. Successful imaging in the mouse requires recognition of both the spatial and temporal scales and their impact on the required fluence rate. Smaller voxels require an increase in the total number of photons (integrated fluence) used in the reconstructed image for constant signal-to-noise ratio. The faster heart rates require shorter exposures to minimize cardiac motion blur imposing even higher demands on the fluence rate. We describe a system with fixed tube/detector and with a rotating specimen. A large focal spot x-ray tube capable of producing high fluence rates with short exposure times was used. The geometry is optimized to match focal spot blur with detector pitch and the resolution limits imposed by the reproducibility of gating. Thus, it is possible to achieve isotropic spatial resolution of 100 microm with a fluence rate at the detector 250 times that of a conventional cone beam micro-CT system with rotating detector and microfocal x-ray tube. Motion is minimized for any single projection with 10 ms exposures that are synchronized to both cardiac and breathing motion. System performance was validated in vivo by studies of the cardiopulmonary structures in C57BL/6 mice, demonstrating the value of motion integration with a bright x-ray source.

Authors
Badea, C; Hedlund, LW; Johnson, GA
MLA Citation
Badea, C, Hedlund, LW, and Johnson, GA. "Micro-CT with respiratory and cardiac gating." Med Phys 31.12 (December 2004): 3324-3329.
PMID
15651615
Source
pubmed
Published In
Medical physics
Volume
31
Issue
12
Publish Date
2004
Start Page
3324
End Page
3329
DOI
10.1118/1.1812604

Dynamic lung morphology of methacholine-induced heterogeneous bronchoconstriction.

Hyperpolarized (HP) 3helium (3He) dynamic MRI was used to investigate airway response in rats following intravenous (i.v.) bolus administration of a contractile agent, methacholine (MCh). The method provides direct visualization of the ventilated regions within the lung. Heterogeneous bronchoconstriction following the i.v. MCh injection was evident using this technique. These 3He dynamic lung images revealed that the inspired fresh air was shunted to the less-constricted regions after the MCh challenge in a similar manner as described by Laplace's relationship for the stability between adjacent alveoli. The airways in the more-constricted regions became nearly closed, resulting in air trapping, while the airways in the less-constricted regions remained effectively open, leading to overinflation. These data suggest a lung model of airway constriction partitioned into ventilated and nonventilated regions. These nonventilated regions are heterogeneously distributed in the lung and this distribution cannot be deduced from spirometric measurement of the whole lung. We demonstrate that a combination of functional 3He images and anatomical 1H images provide an effective method to diagnose regional lung abnormalities in rats.

Authors
Chen, BT; Johnson, GA
MLA Citation
Chen, BT, and Johnson, GA. "Dynamic lung morphology of methacholine-induced heterogeneous bronchoconstriction." Magnetic resonance in medicine 52.5 (November 2004): 1080-1086.
PMID
15508158
Source
epmc
Published In
Magnetic Resonance in Medicine
Volume
52
Issue
5
Publish Date
2004
Start Page
1080
End Page
1086
DOI
10.1002/mrm.20251

Neurotoxicity of carbonyl sulfide in F344 rats following inhalation exposure for up to 12 weeks.

Carbonyl sulfide (COS), a high-priority Clean Air Act chemical, was evaluated for neurotoxicity in short-term studies. F344 rats were exposed to 75-600 ppm COS 6 h per day, 5 days per week for up to 12 weeks. In rats exposed to 500 or 600 ppm for up to 4 days, malacia and microgliosis were detected in numerous neuroanatomical regions of the brain by conventional optical microscopy and magnetic resonance microscopy (MRM). After a 2-week exposure to 400 ppm, rats were evaluated using a functional observational battery. Slight gait abnormality was detected in 50% of the rats and hypotonia was present in all rats exposed to COS. Decreases in motor activity, and forelimb and hindlimb grip strength were also detected. In rats exposed to 400 ppm for 12 weeks, predominant lesions were in the parietal cortex area 1 (necrosis) and posterior colliculus (neuronal loss, microgliosis, hemorrhage), and occasional necrosis was present in the putamen, thalamus, and anterior olivary nucleus. Carbonyl sulfide specifically targeted the auditory system including the olivary nucleus, nucleus of the lateral lemniscus, and posterior colliculus. Consistent with these findings were alterations in the amplitude of the brainstem auditory evoked responses (BAER) for peaks N3, P4, N4, and N5 that represented changes in auditory transmission between the anterior olivary nucleus to the medial geniculate nucleus in animals after exposure for 2 weeks to 400 ppm COS. A concentration-related decrease in cytochrome oxidase activity was detected in the posterior colliculus and parietal cortex of exposed rats as early as 3 weeks. Cytochrome oxidase activity was significantly decreased at COS concentrations that did not cause detectable lesions, suggesting that disruption of the mitochondrial respiratory chain may precede these brain lesions. Our studies demonstrate that this environmental air contaminant has the potential to cause a wide spectrum of brain lesions that are dependent on the degree and duration of exposure.

Authors
Morgan, DL; Little, PB; Herr, DW; Moser, VC; Collins, B; Herbert, R; Johnson, GA; Maronpot, RR; Harry, GJ; Sills, RC
MLA Citation
Morgan, DL, Little, PB, Herr, DW, Moser, VC, Collins, B, Herbert, R, Johnson, GA, Maronpot, RR, Harry, GJ, and Sills, RC. "Neurotoxicity of carbonyl sulfide in F344 rats following inhalation exposure for up to 12 weeks." Toxicology and applied pharmacology 200.2 (October 2004): 131-145.
PMID
15476866
Source
epmc
Published In
Toxicology and Applied Pharmacology
Volume
200
Issue
2
Publish Date
2004
Start Page
131
End Page
145
DOI
10.1016/j.taap.2004.04.013

Contribution of magnetic resonance microscopy in the 12-week neurotoxicity evaluation of carbonyl sulfide in Fischer 344 rats.

In this carbonyl sulfide (COS) study, magnetic resonance microscopy (MRM) and detailed light microscopic evaluation effectively functioned in parallel to assure that the distribution and degree of pathology in the brain was accurately represented. MRM is a powerful imaging modality that allows for excellent identification of neuroanatomical structures coupled with the ability to acquire 200 or more cross-sectional images of the brain, and the ability to display them in multiple planes. F344 rats were exposed to 200-600 ppm COS for up to 12 weeks. Prior to MRM, rats were anesthetized and cardiac perfused with McDowell Trump's fixative containing a gadolinium MR contrast medium. Fixed specimens were scanned at the Duke Center for In Vivo Microscopy on a 9.4 Tesla magnetic resonance system adapted explicitly for microscopic imaging. An advantage of MRM in this study was the ability to identify lesions in rats that appeared clinically normal prior to sacrifice and the opportunity to identify lesions in areas of the brain which would not be included in conventional studies. Other advantages include the ability to examine the brain in multiple planes (transverse, dorsal, sagittal) and obtain and save the MRM images in a digital format that allows for postexperimental data processing and manipulation. MRM images were correlated with neuroanatomical and neuropathological findings. All suspected MRM images were compared to corresponding H&E slides. An important aspect of this study was that MRM was critical in defining our strategy for sectioning the brain, and for designing mechanistic studies (cytochrome oxidase evaluations) and functional assessments (electrophysiology studies) on specifically targeted anatomical sites following COS exposure.

Authors
Sills, RC; Morgan, DL; Herr, DW; Little, PB; George, NM; Ton, TV; Love, NE; Maronpot, RR; Johnson, GA
MLA Citation
Sills, RC, Morgan, DL, Herr, DW, Little, PB, George, NM, Ton, TV, Love, NE, Maronpot, RR, and Johnson, GA. "Contribution of magnetic resonance microscopy in the 12-week neurotoxicity evaluation of carbonyl sulfide in Fischer 344 rats." Toxicologic pathology 32.5 (September 2004): 501-510.
PMID
15603534
Source
epmc
Published In
Toxicologic Pathology (Sage)
Volume
32
Issue
5
Publish Date
2004
Start Page
501
End Page
510
DOI
10.1080/01926230490493918

Applications of magnetic resonance microscopy.

Magnetic resonance imaging (MRI) has enjoyed enormous clinical success since the first demonstration of the method more than 30 years ago. An increasing number of pharmaceutical manufacturers seeking new biomarkers for assessing drug efficacy and toxicity are turning to MRI. A specific application of MRI promises to revolutionize pathology for the basic scientist in the same way MRI has forever altered the standard of care in the clinical domain. More specifically, this application is the use of magnetic resonance microscopy (MRM) in conjunction with new staining methodologies that now make MRM routinely available to the widest range of investigators.

Authors
Maronpot, RR; Sills, RC; Johnson, GA
MLA Citation
Maronpot, RR, Sills, RC, and Johnson, GA. "Applications of magnetic resonance microscopy." Toxicologic pathology 32 Suppl 2 (July 2004): 42-48.
PMID
15503663
Source
epmc
Published In
Toxicologic Pathology (Sage)
Volume
32 Suppl 2
Publish Date
2004
Start Page
42
End Page
48
DOI
10.1080/01926230490451707

Cine magnetic resonance microscopy of the rat heart using cardiorespiratory-synchronous projection reconstruction.

PURPOSE: To tailor a cardiac magnetic resonance (MR) microscopy technique for the rat that combines improvements in pulse sequence design and physiologic control to acquire high-resolution images of cardiac structure and function. MATERIALS AND METHODS: Projection reconstruction (PR) was compared to conventional Cartesian techniques in point-spread function simulations and experimental studies to evaluate its artifact sensitivity. Female Sprague-Dawley rats were imaged at 2.0 T using PR with direct encoding of the free induction decay. Specialized physiologic support and monitoring equipment ensured consistency of biological motion and permitted synchronization of imaging with the cardiac and respiratory cycles. RESULTS: The reduced artifact sensitivity of PR offered improved delineation of cardiac and pulmonary structures. Ventilatory synchronization further increased the signal-to-noise ratio by reducing inter-view variability. High-quality short-axis and long-axis cine images of the rat heart were acquired with 10-msec temporal resolution and microscopic spatial resolution down to 175 microm x 175 microm x 1 mm. CONCLUSION: Integrating careful biological control with an optimized pulse sequence significantly limits both the source and impact of image artifacts. This work represents a novel integration of techniques designed to support measurement of cardiac morphology and function in rodent models of cardiovascular disease.

Authors
Brau, ACS; Hedlund, LW; Johnson, GA
MLA Citation
Brau, ACS, Hedlund, LW, and Johnson, GA. "Cine magnetic resonance microscopy of the rat heart using cardiorespiratory-synchronous projection reconstruction." Journal of magnetic resonance imaging : JMRI 20.1 (July 2004): 31-38.
PMID
15221806
Source
epmc
Published In
Journal of Magnetic Resonance Imaging
Volume
20
Issue
1
Publish Date
2004
Start Page
31
End Page
38
DOI
10.1002/jmri.20089

Contribution of magnetic resonance microscopy in the biologic and mechanistic assessment of carbonyl sulfide neurotoxicity in F344 rats

Authors
Sills, RC; Morgan, DL; Maronpot, RR; Johnson, GA
MLA Citation
Sills, RC, Morgan, DL, Maronpot, RR, and Johnson, GA. "Contribution of magnetic resonance microscopy in the biologic and mechanistic assessment of carbonyl sulfide neurotoxicity in F344 rats." TOXICOLOGY AND APPLIED PHARMACOLOGY 197.3 (June 15, 2004): 151-152.
Source
wos-lite
Published In
Toxicology and Applied Pharmacology
Volume
197
Issue
3
Publish Date
2004
Start Page
151
End Page
152

Development of a 4-D digital mouse phantom for molecular imaging research.

PURPOSE: We develop a realistic and flexible 4-D digital mouse phantom and investigate its usefulness in molecular imaging research. METHODS: Organ shapes were modeled with non-uniform rational B-spline (NURBS) surfaces based on high-resolution 3-D magnetic resonance microscopy (MRM) data. Cardiac and respiratory motions were modeled based on gated magnetic resonance imaging (MRI) data obtained from normal mice. Pilot simulation studies in single-photon emission computed tomography (SPECT) and X-ray computed tomography (CT) were performed to demonstrate the utility of the phantom. RESULTS: NURBS are an efficient and flexible way to accurately model the anatomy and cardiac and respiratory motions for a realistic 4-D digital mouse phantom. The phantom is capable of producing realistic molecular imaging data from which imaging devices and techniques can be evaluated. CONCLUSION: The phantom provides a unique and useful tool in molecular imaging research. It can be used in the development of new imaging instrumentation, image acquisition strategies, and image processing and reconstruction methods.

Authors
Segars, WP; Tsui, BMW; Frey, EC; Johnson, GA; Berr, SS
MLA Citation
Segars, WP, Tsui, BMW, Frey, EC, Johnson, GA, and Berr, SS. "Development of a 4-D digital mouse phantom for molecular imaging research." Molecular imaging and biology : MIB : the official publication of the Academy of Molecular Imaging 6.3 (May 2004): 149-159.
PMID
15193249
Source
epmc
Published In
Molecular Imaging and Biology
Volume
6
Issue
3
Publish Date
2004
Start Page
149
End Page
159
DOI
10.1016/j.mibio.2004.03.002

Measurement of fat/water ratios in rat liver using 3D three-point dixon MRI.

Hepatic steatosis, or fatty liver, is commonly observed during the animal phase of drug safety studies. A noninvasive three-dimensional (3D) three-point Dixon method was used to quantitatively evaluate the fatty livers of rats induced by an experimental microsomal transfer protein (MTP) inhibitor, in an effort to develop a safety biomarker that could be translated to human studies. The method was implemented at 2.0 T for in vivo studies, and at 7.1 T for higher-resolution magnetic resonance (MR) histologic studies. In three separate protocols to study dose response and longitudinal evolution, intrahepatic fatty accumulation was detected by this method and confirmed by chemical and histologic assessments. Consistent with the pathologic changes, the fat/water ratios estimated by the MR technique increased significantly at doses of 1 mg/kg and 100 mg/kg of MTP inhibitor after 14 days of continuous administration. Among the more important findings were: 1). with the 3D three-point Dixon method, in vivo longitudinal studies of liver fat distribution can be conducted at significantly higher resolution than has previously been reported; 2). MR histology allows delineation of distribution at the microscopic scale of 0.0024 mm(3) resolution; and 3). the 3D three-point Dixon technique provides relative estimates of liver fat content and distribution at a high confidence level. This technique will be applicable in future studies in which fatty liver is a potential safety issue.

Authors
Zhang, X; Tengowski, M; Fasulo, L; Botts, S; Suddarth, SA; Johnson, GA
MLA Citation
Zhang, X, Tengowski, M, Fasulo, L, Botts, S, Suddarth, SA, and Johnson, GA. "Measurement of fat/water ratios in rat liver using 3D three-point dixon MRI." Magn Reson Med 51.4 (April 2004): 697-702.
PMID
15065241
Source
pubmed
Published In
Magnetic Resonance in Medicine
Volume
51
Issue
4
Publish Date
2004
Start Page
697
End Page
702
DOI
10.1002/mrm.20005

Functional pulmonary MR microscopy in mice

Authors
Chen, BT; Yordanov, AT; Johnson, GA
MLA Citation
Chen, BT, Yordanov, AT, and Johnson, GA. "Functional pulmonary MR microscopy in mice." FASEB JOURNAL 18.5 (March 24, 2004): A785-A785.
Source
wos-lite
Published In
The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume
18
Issue
5
Publish Date
2004
Start Page
A785
End Page
A785

Utilizing MRI information to estimate F18-FDG distributions in rat flank tumors

This paper investigates the potential of magnetic resonance imaging (MRI) to improve the estimation of within-tumor variations in F18-FDG concentration. An image model is described for incorporating MRI images into positron emission tomography (PET) and single photon emission computed tomog-raphy (SPECT) radiotracer image reconstruction. The model promotes greater smoothing, of estimated radiotracer concentration, among nearby voxels that have more nearly similar MRI signals. R3230 mammary adenocarcinomas are grown on rat flanks. Autoradiography, histology, and T2-weighted MRI are used to demonstrate that the above image model accurately reflects true F18-FDG distributions in R3230 tumors. In vivo F18-FDG distributions are then reconstructed from PET projection data, with and without incorporating MRI. The F18-FDG images reconstructed with MRI show greater detail, and this additional detail is consistent with the results of the autoradiography and histology studies. © 2004 IEEE.

Authors
Bowsher, JE; Yuan, H; Hedlund, LW; Turkington, TG; Akabani, G; Badea, A; Kurylo, WC; Wheeler, CT; Cofer, GP; Dewhirst, MW; Johnson, GA
MLA Citation
Bowsher, JE, Yuan, H, Hedlund, LW, Turkington, TG, Akabani, G, Badea, A, Kurylo, WC, Wheeler, CT, Cofer, GP, Dewhirst, MW, and Johnson, GA. "Utilizing MRI information to estimate F18-FDG distributions in rat flank tumors." 2004.
Source
scival
Published In
IEEE Nuclear Science Symposium Conference Record
Volume
4
Publish Date
2004
Start Page
2488
End Page
2492

Optimized radiographic spectra for digital subtraction angiography in the mouse

The availability of genetically altered mouse models of human disease and the increasing use of small animals in basic research have spurred extraordinary interest in new imaging methodologies - particularly magnetic resonance microscopy, microCT, and microPET. To date, very little attention has been given to planar radiographic imaging. Yet there exists enormous potential for this modality given the ease of use and its potential speed. Functional imaging in mouse models can be addressed particularly well through the use of digital subtraction angiography. We describe here a system designed explicitly for digital subtraction angiography in the mouse and the optimization of acquisition parameters required to perform the highest quality functional subtraction angiograms. We focus on optimization of contrast using selective K-edge filters and the optimization of contrast agent though a carefully controlled biological pulse sequence. © 2004 IEEE.

Authors
Lin, MD; Badea, CT; Johnson, GA
MLA Citation
Lin, MD, Badea, CT, and Johnson, GA. "Optimized radiographic spectra for digital subtraction angiography in the mouse." 2004.
Source
scival
Published In
2004 2nd IEEE International Symposium on Biomedical Imaging: Macro to Nano
Volume
2
Publish Date
2004
Start Page
1412
End Page
1415

Approaching cardiac development in three dimensions by magnetic resonance microscopy

Authors
Yelbuz, TM; Zhang, XW; Choma, MA; Stadt, HA; Zdanowicz, M; Johnson, GA; Kirby, ML
MLA Citation
Yelbuz, TM, Zhang, XW, Choma, MA, Stadt, HA, Zdanowicz, M, Johnson, GA, and Kirby, ML. "Approaching cardiac development in three dimensions by magnetic resonance microscopy." CIRCULATION 108.22 (December 2, 2003): E154-E155.
Source
wos-lite
Published In
Circulation
Volume
108
Issue
22
Publish Date
2003
Start Page
E154
End Page
E155
DOI
10.1161/01.CIR.0000102940.17908.CA

Images in cardiovascular medicine. Approaching cardiac development in three dimensions by magnetic resonance microscopy.

Authors
Yelbuz, TM; Zhang, X; Choma, MA; Stadt, HA; Zdanowicz, M; Johnson, GA; Kirby, ML
MLA Citation
Yelbuz, TM, Zhang, X, Choma, MA, Stadt, HA, Zdanowicz, M, Johnson, GA, and Kirby, ML. "Images in cardiovascular medicine. Approaching cardiac development in three dimensions by magnetic resonance microscopy." Circulation 108.22 (December 2, 2003): e154-e155.
PMID
14656909
Source
pubmed
Published In
Circulation
Volume
108
Issue
22
Publish Date
2003
Start Page
e154
End Page
e155
DOI
10.1161/01.CIR.0000102940.17908.CA

Myocardial volume and organization are changed by failure of addition of secondary heart field myocardium to the cardiac outflow tract.

Cardiac neural crest ablation results in primary myocardial dysfunction and failure of the secondary heart field to add the definitive myocardium to the cardiac outflow tract. The current study was undertaken to understand the changes in myocardial characteristics in the heart tube, including volume, proliferation, and cell size when the myocardium from the secondary heart field fails to be added to the primary heart tube. We used magnetic resonance and confocal microscopy to determine that the volume of myocardium in the looped heart was dramatically reduced and the compact layer of myocardium was thinner after neural crest ablation, especially in the outflow tract and ventricular regions. Proliferation measured by 5-bromo-2'-deoxyuridine incorporation was elevated at only one stage during looping, cell death was normal and myocardial cell size was increased. Taken together, these results indicate that there are fewer myocytes in the heart. By incubation day 8 when the heart would have normally completed septation, the anterior (ventral) wall of the right ventricle and right ventricular outflow tract was significantly thinner in the neural crest-ablated embryos than normal, but the thickness of the compact myocardium was normal in all other regions of the heart. The decreased volume and number of myocardial cells in the heart tube after neural crest ablation most likely reflects the amount of myocardium added by the secondary heart field.

Authors
Yelbuz, TM; Waldo, KL; Zhang, X; Zdanowicz, M; Parker, J; Creazzo, TL; Johnson, GA; Kirby, ML
MLA Citation
Yelbuz, TM, Waldo, KL, Zhang, X, Zdanowicz, M, Parker, J, Creazzo, TL, Johnson, GA, and Kirby, ML. "Myocardial volume and organization are changed by failure of addition of secondary heart field myocardium to the cardiac outflow tract." Developmental dynamics : an official publication of the American Association of Anatomists 228.2 (October 2003): 152-160.
PMID
14517987
Source
epmc
Published In
Developmental Dynamics
Volume
228
Issue
2
Publish Date
2003
Start Page
152
End Page
160
DOI
10.1002/dvdy.10364

Improved preparation of chick embryonic samples for magnetic resonance microscopy.

Previous work demonstrated the power of three-dimensional (3D) magnetic resonance microscopy (MRM) to follow complicated morphologic development in the embryonic cardiovascular system. In this study we describe a new dual-contrast method for specimen preparation that combines perfusion fixation and immersion in fixative with macro- and small molecular gadolinium agents to provide enhanced definition of both the heart wall and chamber. MRM was performed at 9.4 T with image resolutions of 25, 31, and 50 microm isotropic voxels for three stages of chick embryos (day 4, day 5.5, and day 9), and compared to histological sections of the same embryos. The results show considerable improvement of image quality over previous efforts, with better signal-to-noise ratio (SNR) and contrast between the cardiac chamber and myocardial wall. Excellent correlation was shown between the MRM images and histological sections. Thus, 3D high-resolution MRM in combination with the dual-contrast technique is useful for acquiring quantitative 3D morphologic data regarding heart development.

Authors
Zhang, X; Yelbuz, TM; Cofer, GP; Choma, MA; Kirby, ML; Johnson, GA
MLA Citation
Zhang, X, Yelbuz, TM, Cofer, GP, Choma, MA, Kirby, ML, and Johnson, GA. "Improved preparation of chick embryonic samples for magnetic resonance microscopy." Magnetic resonance in medicine 49.6 (June 2003): 1192-1195.
PMID
12768599
Source
epmc
Published In
Magnetic Resonance in Medicine
Volume
49
Issue
6
Publish Date
2003
Start Page
1192
End Page
1195
DOI
10.1002/mrm.10460

Optimization of eight-element multi-detector row helical CT technology for evaluation of the abdomen.

PURPOSE: To evaluate protocols for abdominal imaging with an eight-element multi-detector row computed tomographic (CT) scanner. MATERIALS AND METHODS: An eight-element helical CT scanner was used to acquire data in two phantoms with four-element (pitch, 0.75 and 1.5; section thickness, 1.25, 2.5, and 5.0 mm) and eight-element (pitch, 0.625, 0.875, 1.35 and 1.675; section thickness, 1.25 and 2.5 mm) protocols. One phantom was used for low-contrast detectability and streak artifact; the other, for high-contrast performance. Protocols included near constant radiation dose (140 kV and varied tube current, confirmed by using the above protocols to scan a dedicated radiation dose phantom). Data were analyzed by three blinded readers for streak artifacts, contrast-to-noise ratio, and z-axis resolution (contrast-transfer function). Statistical analysis included studentized range tests. RESULTS: Contrast-to-noise ratios for four and eight elements were not consistently different. Qualitative evaluation for streak artifacts revealed fewer artifacts for all eight-element 1.25-mm-thick section protocols, as compared with eight-element 2.5-mm protocols. All eight-element 2.5-mm protocols except that with 27.0 mm per rotation had fewer streak artifacts than did four-element protocols (P =.02-.04). Contrast-transfer functions along the z axis for eight-element protocols were better than those for four-element protocols, demonstrating improved z-axis resolution (P <.05). CONCLUSION: Images acquired at eight sections per rotation demonstrated no sacrifice of contrast-to-noise ratio, improved z-axis resolution, and fewer streak artifacts, even when radiation dose was similar to that for four-element CT.

Authors
Gupta, AK; Nelson, RC; Johnson, GA; Paulson, EK; Delong, DM; Yoshizumi, TT
MLA Citation
Gupta, AK, Nelson, RC, Johnson, GA, Paulson, EK, Delong, DM, and Yoshizumi, TT. "Optimization of eight-element multi-detector row helical CT technology for evaluation of the abdomen." Radiology 227.3 (June 2003): 739-745.
PMID
12702826
Source
pubmed
Published In
Radiology
Volume
227
Issue
3
Publish Date
2003
Start Page
739
End Page
745
DOI
10.1148/radiol.2273020591

Measurement of regional lung function in rats using hyperpolarized 3helium dynamic MRI.

Dynamic regional lung function was investigated in rats using a radial acquisition cine (RA-CINE) pulse sequence together with hyperpolarized (HP) (3)He gas delivered by a constant flow ventilator. Based on regional differences in the behavior of inspired air, the lung was conceptually divided into two regions (the major airways and the peripheral airspace) for purposes of functional analysis. To measure regional function in the major airways, a large RF flip angle (24 degrees) was applied to reduce (3)He magnetization in the peripheral airspace, and signal intensity (SI) was normalized with the projected airway diameter to estimate local airflow. Higher normalized signal intensity was observed in the left branch airway as compared to the right branch airway. To determine regional function in the peripheral airspace, a small RF flip angle (6 degrees) was used. Incremental increases of peripheral SI in successive lung images were consistent with the increase in lung volume. A new "skipping" scanning strategy using dummy frames allows a trade-off between the number of frames acquired for dynamic information, the RF flip angle, and the penetration depth of (3)He magnetization into the lung. This work provides a novel approach to simultaneously assess dynamic regional function and morphology.

Authors
Chen, BT; Brau, ACS; Johnson, GA
MLA Citation
Chen, BT, Brau, ACS, and Johnson, GA. "Measurement of regional lung function in rats using hyperpolarized 3helium dynamic MRI." Magnetic resonance in medicine 49.1 (January 2003): 78-88.
PMID
12509822
Source
epmc
Published In
Magnetic Resonance in Medicine
Volume
49
Issue
1
Publish Date
2003
Start Page
78
End Page
88
DOI
10.1002/mrm.10336

Magnetic resonance histology for morphologic phenotyping.

Magnetic resonance histology (MRH) images of the whole mouse have been acquired at 100-micron isotropic resolution at 2.0 T with image arrays of 256 x 256 x 1024. Higher resolution (50 x 50 x 50 microns) of limited volumes has been acquired at 7.1T with image arrays of 512 x 512 x 512. Even higher resolution images (20 x 20 x 20 microns) of isolated organs have been acquired at 9.4 T. The volume resolution represents an increase of 625000 x over conventional clinical MRI. The technological basis is summarized that will allow basic scientists to begin using MRH as a routine method for morphologcic phenotyping of the mouse. MRH promises four unique attributes over conventional histology: 1). MRH is non-destructive; 2). MRH exploits the unique contrast mechanisms that have made MRI so successful clinically; 3). MRH is 3-dimensional; and 4). the data are inherently digital. We demonstrate the utility in morphologic phenotyping a whole C57BL/6J mouse.

Authors
Johnson, GA; Cofer, GP; Fubara, B; Gewalt, SL; Hedlund, LW; Maronpot, RR
MLA Citation
Johnson, GA, Cofer, GP, Fubara, B, Gewalt, SL, Hedlund, LW, and Maronpot, RR. "Magnetic resonance histology for morphologic phenotyping." Journal of magnetic resonance imaging : JMRI 16.4 (October 2002): 423-429.
PMID
12353257
Source
epmc
Published In
Journal of Magnetic Resonance Imaging
Volume
16
Issue
4
Publish Date
2002
Start Page
423
End Page
429
DOI
10.1002/jmri.10175

Application of magnetic resonance microscopy to tissue engineering: a polylactide model.

Absorbable polymers are unique materials that find application as temporary scaffolds in tissue engineering. They are often extremely sensitive to histological processing and, for this reason, studying fragile, tissue-engineered constructs before implantation can be quite difficult. This research investigates the use of noninvasive imaging using magnetic resonance microscopy (MRM) as a tool to enhance the assessment of these cellular constructs. A series of cellular, polylactide constructs was developed and analyzed using a battery of tests, including MRM. Distribution of rat aortic smooth muscle cells within the scaffolds was compared as one example of a tissue engineering MRM application. Cells were loaded in varying amounts using static and dynamic methods. It was found that the cellular component was readily identified and the polymer microstructure readily assessed. Specifically, the MRM results showed a heterogeneous distribution of cells due to static loading and a homogenous distribution associated with dynamic loading, results that were not visible through biochemical tests, scanning electron microscopy, or histological evaluation independently. MRM also allowed differentiation between different levels of cellular loading. The current state of MRM is such that it is extremely useful in the refinement of polymer processing and cell seeding methods. This method has the potential, with technological advances, to be of future use in the characterization of cell-polymer interactions.

Authors
Burg, KJL; Delnomdedieu, M; Beiler, RJ; Culberson, CR; Greene, KG; Halberstadt, CR; Holder, WD; Loebsack, AB; Roland, WD; Johnson, GA
MLA Citation
Burg, KJL, Delnomdedieu, M, Beiler, RJ, Culberson, CR, Greene, KG, Halberstadt, CR, Holder, WD, Loebsack, AB, Roland, WD, and Johnson, GA. "Application of magnetic resonance microscopy to tissue engineering: a polylactide model." Journal of biomedical materials research 61.3 (September 2002): 380-390.
PMID
12115463
Source
epmc
Published In
Journal of Biomedical Materials Research
Volume
61
Issue
3
Publish Date
2002
Start Page
380
End Page
390
DOI
10.1002/jbm.10146

Imaging inflammation: direct visualization of perivascular cuffing in EAE by magnetic resonance microscopy.

PURPOSE: To determine if the architectural features revealed by magnetic resonance microscopy (MRM) allow one to detect microscopic abnormalities associated with neuroinflammation in fixed brain sections from animals with experimental allergic encephalomyelitis (EAE), an animal model for multiple sclerosis (MS). MATERIALS AND METHODS: Imaging was performed at the Center for In Vivo Microscopy (CIVM) using a 9.4-Tesla, 89-mm bore, superconducting magnet with actively shielded gradients capable of 850 mT/m. A number of MR contrasts and spatial resolutions were explored. RESULTS: The assessment of EAE brain showed that it is possible to visualize perivascular cuffing in vitro by MRM on three-dimensional T1 proton stains. CONCLUSION: Inflammatory cell infiltration is a prerequisite for the development of lesions in EAE and MS. Thus, the ability to directly detect individual perivascular cuffs of inflammation may provide a useful means of monitoring the time course of inflammatory events, as conventional histopathological scoring of perivascular cuffs is utilized, but in the absence of sectioning and staining.

Authors
Gareau, PJ; Wymore, AC; Cofer, GP; Johnson, GA
MLA Citation
Gareau, PJ, Wymore, AC, Cofer, GP, and Johnson, GA. "Imaging inflammation: direct visualization of perivascular cuffing in EAE by magnetic resonance microscopy." Journal of magnetic resonance imaging : JMRI 16.1 (July 2002): 28-36.
PMID
12112500
Source
epmc
Published In
Journal of Magnetic Resonance Imaging
Volume
16
Issue
1
Publish Date
2002
Start Page
28
End Page
36
DOI
10.1002/jmri.10136

MRI of the lungs using hyperpolarized noble gases.

The nuclear spin polarization of the noble gas isotopes (3)He and (129)Xe can be increased using optical pumping methods by four to five orders of magnitude. This extraordinary gain in polarization translates directly into a gain in signal strength for MRI. The new technology of hyperpolarized (HP) gas MRI holds enormous potential for enhancing sensitivity and contrast in pulmonary imaging. This review outlines the physics underlying the optical pumping process, imaging strategies coping with the nonequilibrium polarization, and effects of the alveolar microstructure on relaxation and diffusion of the noble gases. It presents recent progress in HP gas MRI and applications ranging from MR microscopy of airspaces to imaging pulmonary function in patients and suggests potential directions for future developments.

Authors
Möller, HE; Chen, XJ; Saam, B; Hagspiel, KD; Johnson, GA; Altes, TA; de Lange, EE; Kauczor, H-U
MLA Citation
Möller, HE, Chen, XJ, Saam, B, Hagspiel, KD, Johnson, GA, Altes, TA, de Lange, EE, and Kauczor, H-U. "MRI of the lungs using hyperpolarized noble gases." Magnetic resonance in medicine 47.6 (June 2002): 1029-1051.
PMID
12111949
Source
epmc
Published In
Magnetic Resonance in Medicine
Volume
47
Issue
6
Publish Date
2002
Start Page
1029
End Page
1051
DOI
10.1002/mrm.10173

Image based phenotyping: The visible mouse

Authors
Johnson, GA; Hedlund, LW
MLA Citation
Johnson, GA, and Hedlund, LW. "Image based phenotyping: The visible mouse." FASEB JOURNAL 16.5 (March 22, 2002): A1091-A1091.
Source
wos-lite
Published In
The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume
16
Issue
5
Publish Date
2002
Start Page
A1091
End Page
A1091

Morphologic phenotyping with MR microscopy: the visible mouse.

A method for rapid morphologic phenotyping is demonstrated by using magnetic resonance microscopy. Whole fixed C57BL/6J mice were imaged at 110-microm isotropic resolution; limited volumes of the intact specimen, at 50-microm isotropic resolution; and isolated organs, at 25-microm isotropic resolution. The three-dimensional imaging technique was applied to uricase knockout mice to demonstrate the method for the evaluation of morphologic phenotype.

Authors
Johnson, GA; Cofer, GP; Gewalt, SL; Hedlund, LW
MLA Citation
Johnson, GA, Cofer, GP, Gewalt, SL, and Hedlund, LW. "Morphologic phenotyping with MR microscopy: the visible mouse." Radiology 222.3 (March 2002): 789-793.
PMID
11867802
Source
pubmed
Published In
Radiology
Volume
222
Issue
3
Publish Date
2002
Start Page
789
End Page
793
DOI
10.1148/radiol.2223010531

Optimization of eight-element multi-detector helical CT for imaging the abdomen

Authors
Gupta, AK; Johnson, GA; Nelson, RC
MLA Citation
Gupta, AK, Johnson, GA, and Nelson, RC. "Optimization of eight-element multi-detector helical CT for imaging the abdomen." Radiology 222.2 (February 2002): 589-589. (Academic Article)
Source
manual
Published In
Radiology
Volume
222
Issue
2
Publish Date
2002
Start Page
589
End Page
589

Fiber-optic stethoscope: a cardiac monitoring and gating system for magnetic resonance microscopy.

A fundamental problem associated with using the conventional electrocardiograph (ECG) to monitor a subject's cardiac activity during magnetic resonance imaging (MRI) is the distortion of the ECG due to electromagnetic interference. This problem is particularly pronounced in MR microscopy (MRI of small animals at microscopic resolutions (< 0.03 mm(3))) because the strong, rapidly-switching magnetic field gradients induce artifacts in the animal's ECG that often mimic electrophysiologic activity, impairing the use of the ECG for cardiac monitoring and gating purposes. The fiber-optic stethoscope system offers a novel approach to measuring cardiac activity that, unlike the ECG, is immune to electromagnetic effects. The fiber-optic stethoscope is perorally inserted into the esophagus of small animals to optically detect pulsatile compression of the esophageal wall. The optical system is shown to provide a robust cardiac monitoring and gating signal in rats and mice during routine cardiac MR microscopy.

Authors
Brau, ACS; Wheeler, CT; Hedlund, LW; Johnson, GA
MLA Citation
Brau, ACS, Wheeler, CT, Hedlund, LW, and Johnson, GA. "Fiber-optic stethoscope: a cardiac monitoring and gating system for magnetic resonance microscopy." Magn Reson Med 47.2 (February 2002): 314-321.
PMID
11810675
Source
pubmed
Published In
Magnetic Resonance in Medicine
Volume
47
Issue
2
Publish Date
2002
Start Page
314
End Page
321

Liver: single breath-hold dynamic subtraction CT with multi-detector row helical technology feasibility study.

Fifty-two patients with known or suspected hypervascular malignancy were examined to determine the technical feasibility of performing single-breath-hold dynamic subtraction computed tomography (CT) of the liver with multi-detector row helical CT. The precontrast and hepatic arterial CT scans, which were acquired during the same breath hold, were subtracted. The mean liver-to-muscle contrast ratio on the precontrast, hepatic arterial, and subtracted images was 1.3, 1.4, and 2.3, respectively. In 13 patients with lesions, the subtracted images showed a 2.5-fold increase in mean lesion contrast compared with the hepatic arterial CT scans.

Authors
Spielmann, AL; Nelson, RC; Lowry, CR; Johnson, GA; Sundaramoothy, G; Sheafor, DH; Paulson, EK
MLA Citation
Spielmann, AL, Nelson, RC, Lowry, CR, Johnson, GA, Sundaramoothy, G, Sheafor, DH, and Paulson, EK. "Liver: single breath-hold dynamic subtraction CT with multi-detector row helical technology feasibility study." Radiology 222.1 (January 2002): 278-283. (Academic Article)
PMID
11756737
Source
manual
Published In
Radiology
Volume
222
Issue
1
Publish Date
2002
Start Page
278
End Page
283

Mechanical ventilation for imaging the small animal lung.

This review emphasizes some of the challenges and benefits of in vivo imaging of the small animal lung. Because mechanical ventilation plays a key role in high-quality, high-resolution imaging of the small animal lung, the article focuses particularly on the problems of ventilation support, control of breathing motion and lung volume, and imaging during different phases of the breathing cycle. Solutions for these problems are discussed primarily in relation to magnetic resonance imaging, both conventional proton imaging and the newer, hyperpolarized helium imaging of pulmonary airways. Examples of applications of these imaging solutions to normal and diseased lung are illustrated in the rat and guinea pig. Although difficult to perform, pulmonary imaging in the small animal can be a valuable source of information not only for the normal lung, but also for the lung challenged by disease.

Authors
Hedlund, LW; Johnson, GA
MLA Citation
Hedlund, LW, and Johnson, GA. "Mechanical ventilation for imaging the small animal lung." ILAR J 43.3 (2002): 159-174. (Review)
PMID
12105383
Source
pubmed
Published In
ILAR Journal
Volume
43
Issue
3
Publish Date
2002
Start Page
159
End Page
174

An engineering approach to image-based phenotyping

Authors
Johnson, GA; Cofer, GP; Gewalt, SL; Hedlund, LW; IEEE, ; IEEE,
MLA Citation
Johnson, GA, Cofer, GP, Gewalt, SL, Hedlund, LW, IEEE, , and IEEE, . "An engineering approach to image-based phenotyping." 2002.
Source
wos-lite
Published In
2002 IEEE INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING, PROCEEDINGS
Publish Date
2002
Start Page
381
End Page
383

Multi-detector vs single-detector CT: The organ doses are higher than you think

Authors
Paulson, EK; Yoshizumi, TT; Frush, DP; Johnson, GA
MLA Citation
Paulson, EK, Yoshizumi, TT, Frush, DP, and Johnson, GA. "Multi-detector vs single-detector CT: The organ doses are higher than you think." RADIOLOGY 221 (November 2001): 403-403.
Source
wos-lite
Published In
Radiology
Volume
221
Publish Date
2001
Start Page
403
End Page
403

Radiation dose from helical CT in children: Comparison of multi-slice and single-slice protocols

Authors
Frush, DP; Yoshizumi, TT; Paulson, EK; Johnson, GA
MLA Citation
Frush, DP, Yoshizumi, TT, Paulson, EK, and Johnson, GA. "Radiation dose from helical CT in children: Comparison of multi-slice and single-slice protocols." RADIOLOGY 221 (November 2001): 246-246.
Source
wos-lite
Published In
Radiology
Volume
221
Publish Date
2001
Start Page
246
End Page
246

Using technology to develop a hepatic lipidosis blomarker in the rat

Authors
Tengowski, MW; Suddarth, SA; Cofer, GP; Wheeler, CT; Botts, S; Fasulo, LM; Jeffries-Griffor, JL; Amacher, DE; Lawton, MP; Hedlund, LW; Zhang, XW; Burkhardt, JE; Johnson, GA
MLA Citation
Tengowski, MW, Suddarth, SA, Cofer, GP, Wheeler, CT, Botts, S, Fasulo, LM, Jeffries-Griffor, JL, Amacher, DE, Lawton, MP, Hedlund, LW, Zhang, XW, Burkhardt, JE, and Johnson, GA. "Using technology to develop a hepatic lipidosis blomarker in the rat." MOLECULAR BIOLOGY OF THE CELL 12 (November 2001): 261A-261A.
Source
wos-lite
Published In
Molecular Biology of the Cell
Volume
12
Publish Date
2001
Start Page
261A
End Page
261A

Diabetes insipidus in uricase-deficient mice: a model for evaluating therapy with poly(ethylene glycol)-modified uricase.

Uricase-deficient mice develop uric acid nephropathy, with high mortality rates before weaning. Urate excretion was quantitated and renal function was better defined in this study, to facilitate the use of these mice as a model for evaluating poly(ethylene glycol)-modified recombinant mammalian uricases (PEG-uricase) as a potential therapy for gout and uric acid nephropathy. The uric acid/creatinine ratio in the urine of uricase-deficient mice ranges from 10 to >30; on a weight basis, these mice excrete 20- to 40-fold more urate than do human subjects. These mice consistently develop a severe defect in renal concentrating ability, resulting in an approximately sixfold greater urine volume and a fivefold greater fluid requirement, compared with normal mice. This nephrogenic diabetes insipidus leads to dehydration and death of nursing mice but, with adequate water replacement, high urine flow protects adults from progressive renal damage. Treatment of uricase-deficient mice with PEG-uricase markedly reduced urate levels and, when initiated before weaning, preserved the renal architecture (as evaluated by magnetic resonance micros-copy) and prevented the loss of renal concentrating function. PEG-uricase was far more effective and less immunogenic than unmodified uricase. Retention of uricase in most mammals and its loss in humans and some other primates may reflect the evolution of renal function under different environmental conditions. PEG-uricase could provide an effective therapy for uric acid nephropathy and refractory gout in human patients.

Authors
Kelly, SJ; Delnomdedieu, M; Oliverio, MI; Williams, LD; Saifer, MG; Sherman, MR; Coffman, TM; Johnson, GA; Hershfield, MS
MLA Citation
Kelly, SJ, Delnomdedieu, M, Oliverio, MI, Williams, LD, Saifer, MG, Sherman, MR, Coffman, TM, Johnson, GA, and Hershfield, MS. "Diabetes insipidus in uricase-deficient mice: a model for evaluating therapy with poly(ethylene glycol)-modified uricase." J Am Soc Nephrol 12.5 (May 2001): 1001-1009.
PMID
11316859
Source
pubmed
Published In
Journal of the American Society of Nephrology : JASN
Volume
12
Issue
5
Publish Date
2001
Start Page
1001
End Page
1009

Registered (1)H and (3)He magnetic resonance microscopy of the lung.

Using in vivo magnetic resonance microscopy, registered (1)H and hyperpolarized (3)He images of the rat lung were obtained with a resolution of 0.098 x 0.098 x 0.469 mm (4.5 x 10(-3) mm(3)). The requisite stability and SNR was achieved through an integration of scan-synchronous ventilation, dual-frequency RF coils, anisotropic projection encoding, and variable RF excitation. The total acquisition time was 21 min for the (3)He images and 64 min for the (1)H image. Airways down to the 6th and 7th orders are clearly visible. Magn Reson Med 45:365-370, 2001.

Authors
Johnson, GA; Cofer, GP; Hedlund, LW; Maronpot, RR; Suddarth, SA
MLA Citation
Johnson, GA, Cofer, GP, Hedlund, LW, Maronpot, RR, and Suddarth, SA. "Registered (1)H and (3)He magnetic resonance microscopy of the lung." Magn Reson Med 45.3 (March 2001): 365-370.
PMID
11241691
Source
pubmed
Published In
Magnetic Resonance in Medicine
Volume
45
Issue
3
Publish Date
2001
Start Page
365
End Page
370

Measurements of hyperpolarized gas properties in the lung. Part III: (3)He T(1).

Hyperpolarized (3)He spin-lattice relaxation was investigated in the guinea pig lung using spectroscopy and imaging techniques with a repetitive RF pulse series. T(1) was dominated by interactions with oxygen and was used to measure the alveolar O(2) partial pressure. In animals ventilated with a mixture of 79% (3)He and 21% O(2), T(1) dropped from 19.6 sec in vivo to 14.6 sec after cardiac arrest, reflecting the termination of the intrapulmonary gas exchange. The initial difference in oxygen concentration between inspired and alveolar air, and the temporal decay during apnea were related to functional parameters. Estimates of oxygen uptake were 29 +/- 11 mL min(-1) kg(-1) under normoxic conditions, and 9.0 +/- 2.0 mL min(-1) kg(-1) under hypoxic conditions. Cardiac output was estimated to be 400 +/- 160 mL min(-1) kg(-1). The functional residual capacity derived from spirometric magnetic resonance experiments varied with body mass between 5.4 +/- 0.3 mL and 10.7 +/- 1.1 mL. Magn Reson Med 45:421-430, 2001.

Authors
Möller, HE; Hedlund, LW; Chen, XJ; Carey, MR; Chawla, MS; Wheeler, CT; Johnson, GA
MLA Citation
Möller, HE, Hedlund, LW, Chen, XJ, Carey, MR, Chawla, MS, Wheeler, CT, and Johnson, GA. "Measurements of hyperpolarized gas properties in the lung. Part III: (3)He T(1)." Magn Reson Med 45.3 (March 2001): 421-430.
PMID
11241699
Source
pubmed
Published In
Magnetic Resonance in Medicine
Volume
45
Issue
3
Publish Date
2001
Start Page
421
End Page
430

Distributed multiuser visualization of time varying anatomical data

© 2001 IEEE.We describe a networked environment for navigating and visualizing 3-dimensional anatomical data with extensions for time varying volumes. The Duke Center for In Vivo Microscopy (CIVM) has been capturing volumetric data of mice using magnetic resonance microscopy. Current data sets are 51Z3 with 16 bit precision per voxel at an isotropic resolution of 50 microns. A new instrument will provide larger 512 ∗ 512 ∗ 2048 volumes. Because magnetic resonance imaging is nondestructive, both rapid time series and longer interval developmental series can be taken from living specimens. Our work builds on techniques put in place at the Pittsburgh Supercomputing Center and the University of Michigan for navigating Visible Human data using a client-server implementation, but applied to CIVM mouse data. Extension of the system to 4-dimensional data sets involves changes to compressed data representations and client viewing mechanisms. An essential aspect of the mouse studies is to facilitate comparison between different specimens, or even the same specimen over time, for studies of morphologic phenotype expression in gene knockouts.

Authors
Wetzel, AW; Pomerantz, S; Nave, D; Meixner, W; Johnson, GA
MLA Citation
Wetzel, AW, Pomerantz, S, Nave, D, Meixner, W, and Johnson, GA. "Distributed multiuser visualization of time varying anatomical data." January 1, 2001.
Source
scopus
Volume
2001-January
Publish Date
2001
Start Page
109
End Page
114
DOI
10.1109/AIPR.2001.991211

Registered 1H and 3He magnetic resonance microscopy of the lung

Using in vivo magnetic resonance microscopy, registered 1H and hyperpolarized 3He images of the rat lung were obtained with a resolution of 0.098 × 0.098 × 0.469 mm (4.5 × 10-3 mm3). The requisite stability and SNR was achieved through an integration of scan-synchronous ventilation, dual-frequency RF coils, anisotropic projection encoding, and variable RF excitation. The total acquisition time was 21 min for the 3He images and 64 min for the 1H image. Airways down to the 6th and 7th orders are clearly visible. © 2001 Wiley-Liss, Inc.

Authors
Johnson, GA; Cofer, GP; Hedlund, LW; Maronpot, RR; Suddarth, SA
MLA Citation
Johnson, GA, Cofer, GP, Hedlund, LW, Maronpot, RR, and Suddarth, SA. "Registered 1H and 3He magnetic resonance microscopy of the lung." Magnetic Resonance in Medicine 45.3 (2001): 365-370.
Source
scival
Published In
Magnetic Resonance in Medicine
Volume
45
Issue
3
Publish Date
2001
Start Page
365
End Page
370
DOI
10.1002/1522-2594(200103)45:3<365::AID-MRM1047>3.0.CO;2-0

Magnetic resonance microscopy predicts findings in a theophylline-induced rat model of reproductive toxicity

Authors
Tengowski, MW; Hedlund, LW; Guyot, DJ; Burkhardt, JE; Johnson, GA
MLA Citation
Tengowski, MW, Hedlund, LW, Guyot, DJ, Burkhardt, JE, and Johnson, GA. "Magnetic resonance microscopy predicts findings in a theophylline-induced rat model of reproductive toxicity." MOLECULAR BIOLOGY OF THE CELL 11 (December 2000): 125A-125A.
Source
wos-lite
Published In
Molecular Biology of the Cell
Volume
11
Publish Date
2000
Start Page
125A
End Page
125A

Detection of emphysema in rat lungs by using magnetic resonance measurements of 3He diffusion.

Emphysema is a pulmonary disease characterized by alveolar wall destruction, resulting in enlargement of gas exchange spaces without fibrosis. This condition is a part of chronic obstructive pulmonary disease (COPD), which causes 3.5% of deaths worldwide [Anonymous (1990) World Health Stat. Q. Special, 1-51] and contributes greatly to the global burden of disease [Murray, C. J. & Lopez, A. D. (1996) Science 274, 740-743]. Alveolar regeneration has been shown in animal models and could have potential for clinical treatment of early-stage emphysema. However, current techniques for detection of emphysema are not sensitive at the initial stages. Early-stage human panacinar emphysema is modeled in elastase-treated animals. Here, we provide an in vivo imaging method for differentiating normal and emphysematous rat lungs by measuring the apparent diffusion coefficient (ADC) of hyperpolarized (3)He by using magnetic resonance imaging. These data show that the ADC is significantly larger in elastase-treated rats, indicating alveolar expansion. Whereas these rats were clinically asymptomatic, conventional histology confirmed presence of injury. Our results indicate that measurement of the hyperpolarized (3)He ADC can be a valuable research tool and has potential application in the clinical setting.

Authors
Chen, XJ; Hedlund, LW; Möller, HE; Chawla, MS; Maronpot, RR; Johnson, GA
MLA Citation
Chen, XJ, Hedlund, LW, Möller, HE, Chawla, MS, Maronpot, RR, and Johnson, GA. "Detection of emphysema in rat lungs by using magnetic resonance measurements of 3He diffusion." Proc Natl Acad Sci U S A 97.21 (October 10, 2000): 11478-11481.
PMID
11027348
Source
pubmed
Published In
Proceedings of the National Academy of Sciences of USA
Volume
97
Issue
21
Publish Date
2000
Start Page
11478
End Page
11481
DOI
10.1073/pnas.97.21.11478

MR-compatible ventilator for small animals: computer-controlled ventilation for proton and noble gas imaging.

We describe an MR-compatible ventilator that is computer controlled to generate a variety of breathing patterns, to minimize image degrading effects of breathing motion, and to support delivery of gas anesthesia and experimental inhalational gases. A key feature of this ventilator is the breathing valve that attaches directly to the endotracheal tube to reduce dead volume and allows independent control of inspiratory and expiratory phases of ventilation. This ventilator has been used in a wide variety of MR and x-ray microscopy studies of small animals, especially for MR imaging the lungs with hyperpolarized gases ((3)He & (129)Xe).

Authors
Hedlund, LW; Cofer, GP; Owen, SJ; Allan Johnson, G
MLA Citation
Hedlund, LW, Cofer, GP, Owen, SJ, and Allan Johnson, G. "MR-compatible ventilator for small animals: computer-controlled ventilation for proton and noble gas imaging." Magn Reson Imaging 18.6 (July 2000): 753-759.
PMID
10930785
Source
pubmed
Published In
Magnetic Resonance Imaging
Volume
18
Issue
6
Publish Date
2000
Start Page
753
End Page
759

Magnetic resonance microscopy of the C57BL mouse brain

Authors
Benveniste, H; Kim, K; Zhang, L; Johnson, GA
MLA Citation
Benveniste, H, Kim, K, Zhang, L, and Johnson, GA. "Magnetic resonance microscopy of the C57BL mouse brain." NEUROIMAGE 11.6 (June 2000): 601-611.
Source
wos-lite
Published In
NeuroImage
Volume
11
Issue
6
Publish Date
2000
Start Page
601
End Page
611
DOI
10.1006/nimg.2000.0567

Magnetic resonance microscopy of the C57BL mouse brain.

With the rapid progression in gene technologies, transgenic, targeted, and chemically induced mutations in mice are continually created. The major goal of these studies is to understand and characterize the effects of genotype on anatomy, physiology, and behavior and ultimately the role of genotype in development of disease. The demand for imaging techniques with high spatial resolution potential is rising because such imaging tools would expedite anatomical phenotyping in the genetically altered mice. Magnetic resonance microscopy (MRM) is a noninvasive, inherently three-dimensional (3D) imaging technique capable of visualizing several anatomical structures in the small mouse. The 3D nature of MRM also allows for interpretation of complex spatial relationships between substructures, which is important when phenotyping anatomically. The goal of this paper is to systematically describe three major brain regions in the C57BL/6J mouse at microanatomical spatial resolution ranges using in vitro MRM. We explore different MR contrast parameters, voxel sizes, and signal-to-noise ratios to best characterize C57BL/6J mouse brain microstructure by MRM. Further, we compare all MRM images with Nissl-stained brain sections. Major findings were as follows: T2* MR images visualized several gross anatomical regions in the mouse brain but not, for example, subregions within the hippocampus. Diffusion proton stains on the other hand were superior to T2* MR images and delineated many subregions within the hippocampus proper. Finally, contrast enhancement facilitated visualization of hippocampal anatomy on the T2* MR images. The results of this study are part of an ongoing initiative at our Center focused on creating a complete C57BL/6J mouse anatomical 3D image database by MRM.

Authors
Benveniste, H; Kim, K; Zhang, L; Johnson, GA
MLA Citation
Benveniste, H, Kim, K, Zhang, L, and Johnson, GA. "Magnetic resonance microscopy of the C57BL mouse brain." Neuroimage 11.6 Pt 1 (June 2000): 601-611.
PMID
10860789
Source
pubmed
Published In
NeuroImage
Volume
11
Issue
6 Pt 1
Publish Date
2000
Start Page
601
End Page
611
DOI
10.1006/nimg.2000.0567

Mixing oxygen with hyperpolarized (3)He for small-animal lung studies.

Hyperpolarized helium (HP (3)He) is useful for direct MR imaging of the gas spaces of small animal lungs. Previously, breaths of 100% HP (3)He were alternated with breaths of air to maximize helium signal in the lungs and to minimize the depolarizing effects of O(2). However, for high-resolution imaging requiring many HP (3)He breaths (hundreds) and for pulmonary disease studies, a method was needed to simultaneously deliver O(2) and HP (3)He with each breath without significant loss of polarization. We modified our existing computer-controlled ventilator by adding a plastic valve, additional relays and a controller. O(2) and HP (3)He are mixed at the beginning of each breath within the body of a breathing valve, which is attached directly to the endotracheal tube. With this mixing method, we found that T(1) relaxation of HP (3)He in the guinea pig lung was about 20 s compared to 30 s with alternate air/HP (3)He breathing. Because imaging times during each breath are short (about 500 ms), the HP (3)He signal loss from O(2) contact is calculated to be less than 5%. We concluded that the advantages of mixing HP (3)He with O(2), such as shorter imaging times (reduced T(1) losses in reservoir) and improved physiologic stability, outweigh the small signal loss from the depolarizing effects of oxygen on HP (3)He.

Authors
Hedlund, LW; Möller, HE; Chen, XJ; Chawla, MS; Cofer, GP; Johnson, GA
MLA Citation
Hedlund, LW, Möller, HE, Chen, XJ, Chawla, MS, Cofer, GP, and Johnson, GA. "Mixing oxygen with hyperpolarized (3)He for small-animal lung studies." NMR Biomed 13.4 (June 2000): 202-206.
PMID
10867697
Source
pubmed
Published In
Nmr in Biomedicine
Volume
13
Issue
4
Publish Date
2000
Start Page
202
End Page
206

T1rho imaging using magnetization-prepared projection encoding (MaPPE).

T1rho contrast weighting using a magnetization-prepared projection encoding (MaPPE) pulse sequence was investigated. Fast radial imaging was implemented by applying magnetization preparation pulses, each followed by multiple RF alpha pulses encoding radial trajectories of k-space. Acquiring multiple views per preparatory pulse imposes view-to-view variation; the resultant distortion of the point-spread function is examined. The issue of maximizing signal while preserving the intended contrast weighting is addressed. Under modification of repetition time and flip angle (alpha), three distinct behavior regimes of the sequence are identified. The utility of the pulse sequence as a quantitative relaxation measurement tool is also examined by comparing imaging and spectroscopy experiments. A mouse was imaged in vitro to demonstrate the viability of application to MR histology. These images exhibit the utility of spinlocking and projection encoding as an aftemative contrast source to both T2-weighted MaPPE images and conventional T2-weighted spin-echo images.

Authors
Nugent, AC; Johnson, GA
MLA Citation
Nugent, AC, and Johnson, GA. "T1rho imaging using magnetization-prepared projection encoding (MaPPE)." Magn Reson Med 43.3 (March 2000): 421-428.
PMID
10725885
Source
pubmed
Published In
Magnetic Resonance in Medicine
Volume
43
Issue
3
Publish Date
2000
Start Page
421
End Page
428

Hyperpolarized 3He microspheres as a novel vascular signal source for MRI.

Hyperpolarized (HP) 3He can be encapsulated within biologically compatible microspheres while retaining sufficient polarization to be used as a signal source for MRI. Two microsphere sizes were used, with mean diameters of 5.3 +/- 1.3 microm and 10.9 +/- 3.0 microm. These suspensions ranged in concentration from 0.9-7.0% gas by volume. Spectroscopic measurements in phantoms at 2 T yielded 3He relaxation times that varied with gas concentration. At the highest 3He concentration, the spinlattice relaxation time, T1, was 63.8 +/- 9.4 sec, while the transverse magnetization decayed with a time constant of T2* = 11.0 +/- 0.4 msec. In vivo MR images of the pelvic veins in a rat were acquired during intravenous injection of 3He microspheres (SNR approximately equal 15). Advantages such as intravascular confinement, lack of background signal, and limited recirculation indicate quantitative perfusion measurements may be improved using this novel signal source.

Authors
Chawla, MS; Chen, XJ; Cofer, GP; Hedlund, LW; Kerby, MB; Ottoboni, TB; Johnson, GA
MLA Citation
Chawla, MS, Chen, XJ, Cofer, GP, Hedlund, LW, Kerby, MB, Ottoboni, TB, and Johnson, GA. "Hyperpolarized 3He microspheres as a novel vascular signal source for MRI." Magn Reson Med 43.3 (March 2000): 440-445.
PMID
10725887
Source
pubmed
Published In
Magnetic Resonance in Medicine
Volume
43
Issue
3
Publish Date
2000
Start Page
440
End Page
445

Abnormal water metabolism in mice lacking the type 1A receptor for ANG II.

Mice lacking AT(1A) receptors for ANG II have a defect in urinary concentration manifested by an inability to increase urinary osmolality to levels seen in controls after thirsting. This defect results in extreme serum hypertonicity during water deprivation. In the basal state, plasma vasopressin levels are similar in wild-type controls and Agtr1a -/- mice. Plasma vasopressin levels increase normally in the AT(1A) receptor-deficient mice after 24 h of water deprivation, suggesting that the defect in urine concentration is intrinsic to the kidney. Using magnetic resonance microscopy, we find that the absence of AT(1A) receptors is associated with a modest reduction in the distance from the kidney surface to the tip of the papilla. However, this structural abnormality seems to play little role in the urinary concentrating defect in Agtr1a -/- mice since the impairment is largely reproduced in wild-type mice by treatment with an AT(1)-receptor antagonist. These studies demonstrate a critical role for the AT(1A) receptor in maintaining inner medullary structures in the kidney and in regulating renal water excretion.

Authors
Oliverio, MI; Delnomdedieu, M; Best, CF; Li, P; Morris, M; Callahan, MF; Johnson, GA; Smithies, O; Coffman, TM
MLA Citation
Oliverio, MI, Delnomdedieu, M, Best, CF, Li, P, Morris, M, Callahan, MF, Johnson, GA, Smithies, O, and Coffman, TM. "Abnormal water metabolism in mice lacking the type 1A receptor for ANG II." Am J Physiol Renal Physiol 278.1 (January 2000): F75-F82.
PMID
10644657
Source
pubmed
Published In
American Journal of Physiology: Renal Physiology
Volume
278
Issue
1
Publish Date
2000
Start Page
F75
End Page
F82

Virtual neuropathology: Three-dimensional visualization of lesions due to toxic insult

A first-pass approach incorporating high-field magnetic resonance imaging (MRI) was used for rapid detection of neuropathologic lesions in fixed rat brains. This inherently 3-dimensional and nondestructive technique provides high-resolution, high-contrast images of fixed neuronal tissue in the absence of sectioning or staining. This technique, magnetic resonance microscopy (MRM), was used to identify diverse lesions in 2 well-established rat neurotoxicity models. The intrinsic contrast in the images delineated lesions that were identified using a battery of histologic stains, some of which would not be used in routine screening. Furthermore, the MRM images provided the locations of lesions, which were verified upon subsequent sectioning and staining of the same samples. The inherent contrast generated by water properties is exploited in MRM by choosing suitable pulse sequences, or proton stains. This approach provides the potential for a comprehensive initial MRM screen for neurotoxicity in preclinical models with the capability for extrapolation to clinical analyses using classical MRI.

Authors
Lester, DS; Pine, PS; Delnomdedieu, M; Johannessen, JN; Johnson, GA
MLA Citation
Lester, DS, Pine, PS, Delnomdedieu, M, Johannessen, JN, and Johnson, GA. "Virtual neuropathology: Three-dimensional visualization of lesions due to toxic insult." Toxicologic Pathology 28.1 (2000): 100-104.
PMID
10668995
Source
scival
Published In
Toxicologic Pathology (Sage)
Volume
28
Issue
1
Publish Date
2000
Start Page
100
End Page
104

Imaging using magnetization-prepared projection encoding (MaPPE)

T(1p), contrast weighting using a magnetization-prepared projection encoding (MaPPE) pulse sequence was investigated. Fast radial imaging was implemented by applying magnetization preparation pulses, each followed by multiple RF α pulses encoding radial trajectories of k-space. Acquiring multiple views per preparatory pulse imposes view-to-view variation; the resultant distortion of the point-spread function is examined. The issue of maximizing signal while preserving the intended contrast weighting is addressed. Under modification of repetition time and flip angle (α), three distinct behavior regimes of the sequence are identified. The utility of the pulse sequence as a quantitative relaxation measurement tool is also examined by comparing imaging and spectroscopy experiments. A mouse was imaged in vitro to demonstrate the viability of application to MR histology. These images exhibit the utility of spinlocking and projection encoding as an alternative contrast source to both T2-weighted MaPPE images and conventional T2-weighted spin-echo images. (C) 2000 Wiley-Liss, Inc.

Authors
Nugent, AC; Johnson, GA
MLA Citation
Nugent, AC, and Johnson, GA. "Imaging using magnetization-prepared projection encoding (MaPPE)." Magnetic Resonance in Medicine 43.3 (2000): 421-428.
Source
scival
Published In
Magnetic Resonance in Medicine
Volume
43
Issue
3
Publish Date
2000
Start Page
421
End Page
428
DOI
10.1002/(SICI)1522-2594(200003)43:3<421::AID-MRM14>3.0.CO;2-X

Abnormal water metabolism in mice lacking the type 1A receptor for ANG II

Mice lacking AT1(A) receptors for ANG II have a defect in urinary concentration manifested by an inability to increase urinary osmolality to levels seen in controls after thirsting. This defect results in extreme serum hypertonicity during water deprivation. In the basal state, plasma vasopressin levels are similar in wild-type controls and Agtr 1a -/- mice. Plasma vasopressin levels increase normally in the AT(1A) receptor-deficient mice after 24 h of water deprivation, suggesting that the defect in urine concentration is intrinsic to the kidney. Using magnetic resonance microscopy, we find that the absence of AT(1A) receptors is associated with a modest reduction in the distance from the kidney surface to the tip of the papilla. However, this structural abnormality seems to play little role in the urinary concentrating defect in Agtr 1a -/- mice since the impairment is largely reproduced in wild-type mice by treatment with an AT1-receptor antagonist. These studies demonstrate a critical role for the AT(1A) receptor in maintaining inner medullary structures in the kidney and in regulating renal water excretion.

Authors
Oliverio, MI; Delnomdedieu, M; Best, CF; Li, P; Morris, M; Callahan, MF; Johnson, GA; Smithies, O; Coffman, TM
MLA Citation
Oliverio, MI, Delnomdedieu, M, Best, CF, Li, P, Morris, M, Callahan, MF, Johnson, GA, Smithies, O, and Coffman, TM. "Abnormal water metabolism in mice lacking the type 1A receptor for ANG II." American Journal of Physiology - Renal Physiology 278.1 47-1 (2000): F75-F82.
Source
scival
Published In
American journal of physiology. Renal physiology
Volume
278
Issue
1 47-1
Publish Date
2000
Start Page
F75
End Page
F82

Detection of neuritic plaques in Alzheimer's disease by magnetic resonance microscopy.

Magnetic resonance microscopy (MRM) theoretically provides the spatial resolution and signal-to-noise ratio needed to resolve neuritic plaques, the neuropathological hallmark of Alzheimer's disease (AD). Two previously unexplored MR contrast parameters, T2* and diffusion, are tested for plaque-specific contrast to noise. Autopsy specimens from nondemented controls (n = 3) and patients with AD (n = 5) were used. Three-dimensional T2* and diffusion MR images with voxel sizes ranging from 3 x 10(-3) mm(3) to 5.9 x 10(-5) mm(3) were acquired. After imaging, specimens were cut and stained with a microwave king silver stain to demonstrate neuritic plaques. From controls, the alveus, fimbria, pyramidal cell layer, hippocampal sulcus, and granule cell layer were detected by either T2* or diffusion contrast. These structures were used as landmarks when correlating MRMs with histological sections. At a voxel resolution of 5.9 x 10(-5) mm(3), neuritic plaques could be detected by T2*. The neuritic plaques emerged as black, spherical elements on T2* MRMs and could be distinguished from vessels only in cross-section when presented in three dimension. Here we provide MR images of neuritic plaques in vitro. The MRM results reported provide a new direction for applying this technology in vivo. Clearly, the ability to detect and follow the early progression of amyloid-positive brain lesions will greatly aid and simplify the many possibilities to intervene pharmacologically in AD.

Authors
Benveniste, H; Einstein, G; Kim, KR; Hulette, C; Johnson, GA
MLA Citation
Benveniste, H, Einstein, G, Kim, KR, Hulette, C, and Johnson, GA. "Detection of neuritic plaques in Alzheimer's disease by magnetic resonance microscopy." Proc Natl Acad Sci U S A 96.24 (November 23, 1999): 14079-14084.
PMID
10570201
Source
pubmed
Published In
Proceedings of the National Academy of Sciences of USA
Volume
96
Issue
24
Publish Date
1999
Start Page
14079
End Page
14084

Single breath-hold dynamic subtraction CT of the liver using-multidetector helical technology

Authors
Nelson, RC; Johnson, GA; Spielman, AL; Lowry, CR; Sundaramoorthy, G; Sheafor, DH
MLA Citation
Nelson, RC, Johnson, GA, Spielman, AL, Lowry, CR, Sundaramoorthy, G, and Sheafor, DH. "Single breath-hold dynamic subtraction CT of the liver using-multidetector helical technology." Radiology 213P (November 1999): 125-125. (Academic Article)
Source
manual
Published In
Radiology
Volume
213P
Publish Date
1999
Start Page
125
End Page
125

Spatially resolved measurements of hyperpolarized gas properties in the lung in vivo. Part II: T *(2).

The transverse relaxation time, T *(2), of hyperpolarized (HP) gas in the lung in vivo is an important parameter for pulse sequence optimization and image contrast. We obtained T *(2) maps of HP (3)He and (129)Xe in guinea pig lungs (n = 17) and in human lungs. Eight different sets of (3)He guinea pig studies were acquired, with variation of slice selection, tidal volume, and oxygen level. For example, for a (3)He tidal volume of 3 cm(3) and no slice selection, the average T *(2) in the trachea was 14.7 ms and 8.0 ms in the intrapulmonary airspaces. The equivalent (129)Xe experiment yielded an average T *(2) of 40.8 ms in the trachea and 18.5 ms in the intrapulmonary airspaces. The average (3)He T *(2) in the human intrapulmonary airspaces was 9.4 ms. The relaxation behavior was predicted by treating the lung as a porous medium, resulting in good agreement between estimated and measured T *(2) values in the intrapulmonary airspaces. Magn Reson Med 42:729-737, 1999.

Authors
Chen, XJ; Möller, HE; Chawla, MS; Cofer, GP; Driehuys, B; Hedlund, LW; MacFall, JR; Johnson, GA
MLA Citation
Chen, XJ, Möller, HE, Chawla, MS, Cofer, GP, Driehuys, B, Hedlund, LW, MacFall, JR, and Johnson, GA. "Spatially resolved measurements of hyperpolarized gas properties in the lung in vivo. Part II: T *(2)." Magn Reson Med 42.4 (October 1999): 729-737.
PMID
10502762
Source
pubmed
Published In
Magnetic Resonance in Medicine
Volume
42
Issue
4
Publish Date
1999
Start Page
729
End Page
737

Spatially resolved measurements of hyperpolarized gas properties in the lung in vivo. Part I: diffusion coefficient.

In imaging of hyperpolarized noble gases, a knowledge of the diffusion coefficient (D) is important both as a contrast mechanism and in the design of pulse sequences. We have made diffusion coefficient maps of both hyperpolarized (3)He and (129)Xe in guinea pig lungs. Along the length of the trachea, (3)He D values were on average 2.4 cm(2)/sec, closely reproducing calculated values for free gas (2.05 cm(2)/sec). The (3)He D values measured perpendicular to the length of the trachea were approximately a factor of two less, indicating restriction to diffusion. Further evidence of restricted diffusion was seen in the distal pulmonary airspaces as the average (3)He D was 0.16 cm(2)/sec. An additional cause for the smaller (3)He D in the lung was due to the presence of air, which is composed of heavier and larger gases. The (129)Xe results show similar trends, with the trachea D averaging 0.068 cm(2)/sec and the lung D averaging 0.021 cm(2)/sec. Magn Reson Med 42:721-728, 1999.

Authors
Chen, XJ; Möller, HE; Chawla, MS; Cofer, GP; Driehuys, B; Hedlund, LW; Johnson, GA
MLA Citation
Chen, XJ, Möller, HE, Chawla, MS, Cofer, GP, Driehuys, B, Hedlund, LW, and Johnson, GA. "Spatially resolved measurements of hyperpolarized gas properties in the lung in vivo. Part I: diffusion coefficient." Magn Reson Med 42.4 (October 1999): 721-728.
PMID
10502761
Source
pubmed
Published In
Magnetic Resonance in Medicine
Volume
42
Issue
4
Publish Date
1999
Start Page
721
End Page
728

Cerebral hemorrhage and edema following brain biopsy in rats: Significance of mean arterial blood pressure

Authors
Benveniste, HD; Kim, KR; Hedlund, LW; Johnson, GA; Friedman, AH
MLA Citation
Benveniste, HD, Kim, KR, Hedlund, LW, Johnson, GA, and Friedman, AH. "Cerebral hemorrhage and edema following brain biopsy in rats: Significance of mean arterial blood pressure." ANESTHESIOLOGY 91.3A (September 1999): U371-U371.
Source
wos-lite
Published In
Anesthesiology
Volume
91
Issue
3A
Publish Date
1999
Start Page
U371
End Page
U371

In vivo diffusion-weighted magnetic resonance microscopy of rat spinal cord: effect of ischemia and intrathecal hyperbaric 5% lidocaine.

BACKGROUND AND OBJECTIVES: Pathophysiologic mechanisms underlying persistent neurologic deficits after continuous spinal anesthesia using hyperbaric 5% lidocaine are still not well understood. It has been suggested that high-dose intrathecal lidocaine induces irreversible conduction block and even ischemia in white matter tracts by breakdown of the blood-nerve barrier. In this study, we use diffusion-weighted magnetic resonance microscopy to characterize the effect of intrathecal hyperbaric 5% lidocaine in rat spinal cord. The parameter measured with DWM, is an "apparent diffusion coefficient," (ADC), which can be used to exclude the presence of ischemia. METHODS: Female Fischer CDF rats were used. Group 1 (n = 5) was exposed to ischemia, group 2 (n = 7) was exposed to intrathecal 5% hyperbaric lidocaine, and group 3 (n = 5) was exposed to intrathecal 7.5% glucose. Diffusion-weighted MR images in group 1 were acquired before and after ischemia induced by cardiac arrest and in groups 2 and 3 rats prior to and during perfusion of the spinal catheter with either 5% hyperbaric lidocaine or 7.5% glucose. RESULTS: Ischemia decreased the ADC by 40% in gray matter and by 30% in white matter of spinal cord. Continuous intrathecal anesthesia with hyperbaric 5% lidocaine did not affect the spinal cord ADC. Further, 7.5% intrathecal glucose had no effect on ADCs in gray or white matter of spinal cord. CONCLUSIONS: Ischemia reduced the ADC in both spinal cord white and gray matter. Hyperbaric 5% lidocaine did not affect the spinal cord ADC during the first 1.5 hours. We suggest that 5% hyperbaric lidocaine does not induce irreversible neurologic deficits by causing spinal cord ischemia.

Authors
Benveniste, H; Qui, H; Hedlund, LW; Hüttemeier, PC; Steele, SM; Johnson, GA
MLA Citation
Benveniste, H, Qui, H, Hedlund, LW, Hüttemeier, PC, Steele, SM, and Johnson, GA. "In vivo diffusion-weighted magnetic resonance microscopy of rat spinal cord: effect of ischemia and intrathecal hyperbaric 5% lidocaine." Reg Anesth Pain Med 24.4 (July 1999): 311-318.
PMID
10445769
Source
pubmed
Published In
Regional Anesthesia and Pain Medicine
Volume
24
Issue
4
Publish Date
1999
Start Page
311
End Page
318

A high-temperature superconducting Helmholtz probe for microscopy at 9.4 T.

The design and operation of a high-temperature superconducting (HTS) probe for magnetic resonance microscopy (MRM) at 400 MHz are presented. The design of the probe includes a Helmholtz coil configuration and a stable open-cycle cooling mechanism. Characterization of coil operating parameters is presented to demonstrate the suitability of cryo-cooled coils for MRM. Specifically, the performance of the probe is evaluated by comparison of signal-to-noise (SNR) performance with that of a copper Helmholtz pair, analysis of B1 field homogeneity, and quantification of thermal stability. Images are presented to demonstrate the SNR advantage of the probe for typical MRM applications.

Authors
Hurlston, SE; Brey, WW; Suddarth, SA; Johnson, GA
MLA Citation
Hurlston, SE, Brey, WW, Suddarth, SA, and Johnson, GA. "A high-temperature superconducting Helmholtz probe for microscopy at 9.4 T." Magn Reson Med 41.5 (May 1999): 1032-1038.
PMID
10332887
Source
pubmed
Published In
Magnetic Resonance in Medicine
Volume
41
Issue
5
Publish Date
1999
Start Page
1032
End Page
1038

Magnetic resonance angiography with hyperpolarized 129Xe dissolved in a lipid emulsion.

Hyperpolarized (HP) 129Xe can be dissolved in biologically compatible lipid emulsions while maintaining sufficient polarization for in vivo vascular imaging. For xenon in Intralipid 30%, in vitro spectroscopy at 2 T yielded a chemical shift of 197 +/- 1 ppm with reference to xenon gas, a spin-lattice relaxation time T1 = 25.3 +/- 2.1 sec, and a T2* time constant of 37 +/- 5 msec. Angiograms of the abdominal and pelvic veins in the rat obtained with 129Xe MRI after intravenous injection of HP 129Xe/Intralipid 30% into the tail demonstrated signal-to-noise ratios between 8 and 29. An analysis of the inflow effect on time-of-flight images of two segments of the inferior vena cava yielded additional information. The mean blood flow velocity was 34.7 +/- 1.0 mm/sec between the junction of the caudal veins and the kidneys and 13.3 +/- 0.8 mm/sec at the position of the diaphragm. The mean volume flow rates in these segments were 7.2 +/- 3.4 ml/min and 11.0 +/- 2.8 ml/min, respectively. Intravenous delivery of HP 129Xe dissolved in a carrier may lead to novel biomedical applications of laser-polarized gases.

Authors
Möller, HE; Chawla, MS; Chen, XJ; Driehuys, B; Hedlund, LW; Wheeler, CT; Johnson, GA
MLA Citation
Möller, HE, Chawla, MS, Chen, XJ, Driehuys, B, Hedlund, LW, Wheeler, CT, and Johnson, GA. "Magnetic resonance angiography with hyperpolarized 129Xe dissolved in a lipid emulsion." Magn Reson Med 41.5 (May 1999): 1058-1064.
PMID
10332890
Source
pubmed
Published In
Magnetic Resonance in Medicine
Volume
41
Issue
5
Publish Date
1999
Start Page
1058
End Page
1064

Functional MR microscopy of the lung using hyperpolarized 3He.

A new strategy designed to provide functional magnetic resonance images of the lung in small animals at microscopic resolution using hyperpolarized 3He is described. The pulse sequence is based on a combination of radial acquisition (RA) and CINE techniques, referred to as RA-CINE, and is designed for use with hyperpolarized 3He to explore lung ventilation with high temporal and spatial resolution in small animal models. Ventilation of the live guinea pig is demonstrated with effective temporal resolution of 50 msec and in-plane spatial resolution of <100 microm using hyperpolarized 3He. The RA-CINE sequence allows one to follow gas inflow and outflow in the airways as well as in the distal part of the lungs. Regional analysis of signal intensity variations can be performed and can help assess functional lung parameters such as residual gas volume and lung compliance to gas inflow.

Authors
Viallon, M; Cofer, GP; Suddarth, SA; Möller, HE; Chen, XJ; Chawla, MS; Hedlund, LW; Crémillieux, Y; Johnson, GA
MLA Citation
Viallon, M, Cofer, GP, Suddarth, SA, Möller, HE, Chen, XJ, Chawla, MS, Hedlund, LW, Crémillieux, Y, and Johnson, GA. "Functional MR microscopy of the lung using hyperpolarized 3He." Magn Reson Med 41.4 (April 1999): 787-792.
PMID
10332855
Source
pubmed
Published In
Magnetic Resonance in Medicine
Volume
41
Issue
4
Publish Date
1999
Start Page
787
End Page
792

Sensitivity and resolution in 3D NMR microscopy of the lung with hyperpolarized noble gases.

Three-dimensional magnetic resonance images of the guinea pig lung were acquired in vivo using hyperpolarized (HP) noble gases and radial projection encoding (PE). Results obtained with 3He (voxel size 17 microl) demonstrated high image quality showing airway structure down to the 5th or 6th generations. Signal-to-noise ratios (SNRs) of 129Xe images (voxel size 40 microl) were lower by about 1 order of magnitude as a consequence of the smaller gyromagnetic ratio, a more rapid relaxation in the gas reservoir, and lower polarization and isotope abundance. Comparison between experimentally obtained SNRs and results from calculations based on a model that accounts for the three-dimensional PE acquisition scheme and the non-equilibrium situation in HP gas imaging yielded excellent agreement for small flip angles. A theoretical examination of the potential resolution in HP gas MR microscopy of the lungs suggests that in vivo visualization of alveolar clusters distal to respiratory bronchioles may be possible.

Authors
Möller, HE; Chen, XJ; Chawla, MS; Cofer, GP; Driehuys, B; Hedlund, LW; Suddarth, SA; Johnson, GA
MLA Citation
Möller, HE, Chen, XJ, Chawla, MS, Cofer, GP, Driehuys, B, Hedlund, LW, Suddarth, SA, and Johnson, GA. "Sensitivity and resolution in 3D NMR microscopy of the lung with hyperpolarized noble gases." Magn Reson Med 41.4 (April 1999): 800-808.
PMID
10332857
Source
pubmed
Published In
Magnetic Resonance in Medicine
Volume
41
Issue
4
Publish Date
1999
Start Page
800
End Page
808

3-Dimensional visualization of lesions in rat brain using magnetic resonance imaging microscopy.

High-resolution (< 50 microm) magnetic resonance imaging microscopy (MRM) has been used to identify brain regions and localization of excitotoxin-induced lesions in fixed rat brains, subsequently confirmed using standard histology. The anatomical extent of lesions identified by MRM was identical to that seen in histological sections and various histopathological changes could be visualized. In contrast to the time involved in preparing and examining histological sections, lesions in intact brains could be rapidly identified and visualized in three dimensions by examining digitally generated sections in any plane. This study shows that MRM has tremendous potential as a prescreening tool for neurotoxicity and neuropathology. These observations suggest that MRM has the potential to affect pathology much as conventional MRI has influenced clinical imaging.

Authors
Lester, DS; Lyon, RC; McGregor, GN; Engelhardt, RT; Schmued, LC; Johnson, GA; Johannessen, JN
MLA Citation
Lester, DS, Lyon, RC, McGregor, GN, Engelhardt, RT, Schmued, LC, Johnson, GA, and Johannessen, JN. "3-Dimensional visualization of lesions in rat brain using magnetic resonance imaging microscopy." Neuroreport 10.4 (March 17, 1999): 737-741.
PMID
10208540
Source
pubmed
Published In
NeuroReport
Volume
10
Issue
4
Publish Date
1999
Start Page
737
End Page
741

Magnetic resonance imaging of embryos: an Internet resource for the study of embryonic development.

The recent amassing of gene expression data to study development in mammals has led to an increased demand for access to human embryological data. The difficulty of obtaining well-preserved human embryos presents an important challenge to studying human development. The Multidimensional Human Embryo project is generating an image data set based on magnetic resonance microscopy of specimens from the highly respected Carnegie Collection of Human Embryos. The data are available from a web site to facilitate the work of clinicians, investigators, and students of human development. A consequence of the project will be to preserve a highly respected, yet impermanent, collection of human embryos and minimize the need for collecting new specimens.

Authors
Smith, BR; Huff, DS; Johnson, GA
MLA Citation
Smith, BR, Huff, DS, and Johnson, GA. "Magnetic resonance imaging of embryos: an Internet resource for the study of embryonic development." Comput Med Imaging Graph 23.1 (January 1999): 33-40.
PMID
10091866
Source
pubmed
Published In
Computerized Medical Imaging and Graphics
Volume
23
Issue
1
Publish Date
1999
Start Page
33
End Page
40

Performance of a high-temperature superconducting probe for in vivo microscopy at 2.0 T.

The use of a high-temperature superconducting probe for in vivo magnetic resonance microscopy at 2 T is described. To evaluate the performance of the probe, a series of SNR comparisons are carried out. The SNR increased by a factor of 3.7 compared with an equivalent copper coil. Quantitative measures of the SNR gain are in good agreement with theoretical predictions. A number of issues that are unique to the application of HTS coils are examined, including the difficulty in obtaining homogenous excitation without degrading the SNR of the probe. The use of the HTS probe in transmit-receive mode is simple to implement but results in nonuniform excitation. The effect of using the probe in this mode of operation on the T1 and T2 contrast is investigated. Methods for improving homogeneity are explored, such as employing a transmit volume coil. It is found that the cost of using an external transmit coil is an increased probe noise temperature and a reduced SNR by approximately 30%. Other important aspects of the probe are considered, including the effect of temperature on probe stability. Three-dimensional in vivo imaging sets are acquired to assess the stability of the probe for long scans. High-resolution images of the rat brain demonstrate the utility of the probe for microscopy applications.

Authors
Miller, JR; Hurlston, SE; Ma, QY; Face, DW; Kountz, DJ; MacFall, JR; Hedlund, LW; Johnson, GA
MLA Citation
Miller, JR, Hurlston, SE, Ma, QY, Face, DW, Kountz, DJ, MacFall, JR, Hedlund, LW, and Johnson, GA. "Performance of a high-temperature superconducting probe for in vivo microscopy at 2.0 T." Magn Reson Med 41.1 (January 1999): 72-79.
PMID
10025613
Source
pubmed
Published In
Magnetic Resonance in Medicine
Volume
41
Issue
1
Publish Date
1999
Start Page
72
End Page
79

Virtual neuropathology: A new approach to preclinical pathology using magnetic resonance imaging microscopy

Authors
Lester, DS; Johannessen, JN; Pine, PS; McGregor, GN; Johnson, GA
MLA Citation
Lester, DS, Johannessen, JN, Pine, PS, McGregor, GN, and Johnson, GA. "Virtual neuropathology: A new approach to preclinical pathology using magnetic resonance imaging microscopy." Spectroscopy (Santa Monica) 14.7 (1999): 17-22.
Source
scival
Published In
Spectroscopy
Volume
14
Issue
7
Publish Date
1999
Start Page
17
End Page
22

Spinal cord neural anatomy in rats examined by in vivo magnetic resonance microscopy.

BACKGROUND AND OBJECTIVES: Magnetic resonance microscopy (MRM) is a technique that is worthwhile for anesthesiologists because it allows spinal cord and plexus anatomy to be visualized three dimensionally and followed over time in the same animal. For example, the long-term effect of indwelling intrathecal or plexus catheters can be studied in situ, and convective and diffusive forces within intrathecal, epidural, or nerve sheath spaces can be investigated. Further, diffusion-weighted MRM, which measures an "apparent diffusion coefficient" (ADC), can be used to track the presence of ischemia, hypoperfusion, or cytotoxic edema. This study investigates problems associated with the use of in vivo MRM for spinal cord and peripheral nerve studies in the rat. METHODS: Twenty-one anesthetized female Fisher CDF rats were used. Group 1 (n=7) was used for anatomic three-dimensional studies. Groups 2 (n=4), 3 (n=4), and 4 (n=6) were used for measurements of the ADC. Group 2 served as controls, group 3 received lumbar intrathecal catheters, and group 4 received cervical intrathecal catheters. RESULTS: Cervical spine, lumbar spine, and spinal nerves and ganglia were accurately visualized with MRM. As a rule, spinal cord gray and white matter were better demonstrated using diffusion-weighted proton stains. By contrast, T2-weighted proton staining superiorly demonstrated structures surrounding the spinal cord. In groups 3 and 4, indwelling intrathecal catheters did not affect the spinal cord ADC, indicating normal blood flow and no cytotoxic edema. Contrast studies revealed nonhomogeneous distribution of contrast predominately in the lateral and ventral intrathecal space. CONCLUSION: Three-dimensional diffusion-weighted MRM displays cervical and lumbar spine anatomy accurately in vivo. Apparent diffusion coefficients measurements are feasible in rat cervical spinal cord with intrathecal catheters. Spinal cord ADCs are unaffected by intrathecal catheters, indicating normal spinal cord perfusion.

Authors
Benveniste, H; Qui, H; Hedlund, LW; D'Ercole, F; Johnson, GA
MLA Citation
Benveniste, H, Qui, H, Hedlund, LW, D'Ercole, F, and Johnson, GA. "Spinal cord neural anatomy in rats examined by in vivo magnetic resonance microscopy." Reg Anesth Pain Med 23.6 (November 1998): 589-599.
PMID
9840856
Source
pubmed
Published In
Regional Anesthesia and Pain Medicine
Volume
23
Issue
6
Publish Date
1998
Start Page
589
End Page
599

Signal dynamics in magnetic resonance imaging of the lung with hyperpolarized noble gases.

The nonequilibrium bulk magnetic moment of hyperpolarized (HP) noble gases generated by optical pumping has unique characteristics. Based on the Bloch equations, a model was developed describing the signal dynamics of HP gases used in magnetic resonance imaging (MRI) of the lung with special consideration to the breathing cycle. Experimental verification included extensive investigations with HP 3He and 129Xe during both inspiration and held breath in live guinea pigs. Radial acquisition was used to investigate the view variations with a temporal resolution of 5 ms. Agreement between theoretical predictions and in vivo results was excellent. Additionally, information about effects from noble gas diffusion and spin-lattice relaxation was obtained. In vivo results for T1 were 28.8 +/- 1.8 s for 3He and 31.3 +/- 1.8 s for 129Xe. Comparison with in vitro data indicated that relaxation in the pulmonary gas space is dominated by dipolar coupling with molecular oxygen. The results provide a quantitative basis for optimizing pulse sequence design in HP gas MRI of the lung.

Authors
Möller, HE; Chen, XJ; Chawla, MS; Driehuys, B; Hedlund, LW; Johnson, GA
MLA Citation
Möller, HE, Chen, XJ, Chawla, MS, Driehuys, B, Hedlund, LW, and Johnson, GA. "Signal dynamics in magnetic resonance imaging of the lung with hyperpolarized noble gases." J Magn Reson 135.1 (November 1998): 133-143.
PMID
9799687
Source
pubmed
Published In
Journal of Magnetic Resonance
Volume
135
Issue
1
Publish Date
1998
Start Page
133
End Page
143
DOI
10.1006/jmre.1998.1563

In vivo magnetic resonance vascular imaging using laser-polarized 3He microbubbles.

Laser-polarized gases (3He and 129Xe) are currently being used in magnetic resonance imaging as strong signal sources that can be safely introduced into the lung. Recently, researchers have been investigating other tissues using 129Xe. These studies use xenon dissolved in a carrier such as lipid vesicles or blood. Since helium is much less soluble than xenon in these materials, 3He has been used exclusively for imaging air spaces. However, considering that the signal of 3He is more than 10 times greater than that of 129Xe for presently attainable polarization levels, this work has focused on generating a method to introduce 3He into the vascular system. We addressed the low solubility issue by producing suspensions of 3He microbubbles. Here, we provide the first vascular images obtained with laser-polarized 3He. The potential increase in signal and absence of background should allow this technique to produce high-resolution angiographic images. In addition, quantitative measurements of blood flow velocity and tissue perfusion will be feasible.

Authors
Chawla, MS; Chen, XJ; Möller, HE; Cofer, GP; Wheeler, CT; Hedlund, LW; Johnson, GA
MLA Citation
Chawla, MS, Chen, XJ, Möller, HE, Cofer, GP, Wheeler, CT, Hedlund, LW, and Johnson, GA. "In vivo magnetic resonance vascular imaging using laser-polarized 3He microbubbles." Proc Natl Acad Sci U S A 95.18 (September 1, 1998): 10832-10835.
PMID
9724790
Source
pubmed
Published In
Proceedings of the National Academy of Sciences of USA
Volume
95
Issue
18
Publish Date
1998
Start Page
10832
End Page
10835

Measuring the progression of foreign-body reaction to silicone implants using in vivo MR microscopy.

We used in vivo magnetic resonance (MR) microscopy to follow the growth of fibrous capsule as a foreign body reaction to silicone implants in rats. Anesthetized rats were imaged 1, 7, 14, and 28 days after silicone-coated MR imaging coils were sutured to their neck muscles. On the twenty-eighth day, rats were sacrificed and coils and adjacent tissues were removed en bloc and fixed in formalin, reimaged with MR, and sectioned for conventional histology. Three-dimensional (3-D) spin-echo [3DFT] acquisition gave in-plane resolution of 32 x 32 microns in vivo and 16 x 16 microns ex vivo. All MR images showed a diffuse band of elevated signal intensity between the silicone of the coil and adjacent tissue. The border of the hyperintense band was thin and not well defined at seven days post-implantation. From 7-28 days, the band showed relatively homogeneous signal intensity and its thickness increased 44% on the rectus muscle side and 78% on the subcutaneous side. The capsule thickness determined either by MR in vivo and ex vivo microscopy or conventional histology was not significantly different, and there was a significant correlation between thickness measurements among those methods. MR in vivo microscopy provides sufficient resolution and spatial information to serially evaluate the growth of the foreign body fibrous capsule over time, thus achieving greater accuracy and consistency in measurements.

Authors
Qiu, HH; Hedlund, LW; Neuman, MR; Edwards, CR; Black, RD; Cofer, GP; Johnson, GA
MLA Citation
Qiu, HH, Hedlund, LW, Neuman, MR, Edwards, CR, Black, RD, Cofer, GP, and Johnson, GA. "Measuring the progression of foreign-body reaction to silicone implants using in vivo MR microscopy." IEEE Trans Biomed Eng 45.7 (July 1998): 921-927.
PMID
9644901
Source
pubmed
Published In
IEEE Transactions on Biomedical Engineering
Volume
45
Issue
7
Publish Date
1998
Start Page
921
End Page
927
DOI
10.1109/10.686800

Hyperpolarized 3He NMR lineshape measurements in the live guinea pig lung.

Spatially localized lineshapes of hyperpolarized (HP) 3He in guinea pig lungs have been measured in vivo. Three different axial slice locations, each containing different compositions of airway sizes and orientations, were studied. Gas peaks from major bronchi (2 ppm) and alveoli (-2 ppm) were distinguished. The gas phase spectra show structural features that are a result of frequency shifts caused by bulk magnetic susceptibility. For a given slice, the spectral lineshapes reflect the airway composition within the slice location, according to theory. The peak assignments given here also agree with previous studies done by Wagshul et al. with HP 129Xe. At each of the slice locations, data were acquired during two phases of the breathing cycle, resulting in a relative frequency shift of approximately 0.3 ppm in the superior slices. Spectra obtained over a number of breaths show the dynamics of the gas buildup in the lung and provide further evidence supporting the peak assignments.

Authors
Chen, XJ; Chawla, MS; Cofer, GP; Hedlund, LW; Möller, HE; Johnson, GA
MLA Citation
Chen, XJ, Chawla, MS, Cofer, GP, Hedlund, LW, Möller, HE, and Johnson, GA. "Hyperpolarized 3He NMR lineshape measurements in the live guinea pig lung." Magn Reson Med 40.1 (July 1998): 61-65.
PMID
9660554
Source
pubmed
Published In
Magnetic Resonance in Medicine
Volume
40
Issue
1
Publish Date
1998
Start Page
61
End Page
65

Time-course imaging of rat embryos in utero with magnetic resonance microscopy (vol 39, pg 673, 1998)

Authors
Smith, BR; Sattuck, MD; Hedlund, LW; Johnson, GA
MLA Citation
Smith, BR, Sattuck, MD, Hedlund, LW, and Johnson, GA. "Time-course imaging of rat embryos in utero with magnetic resonance microscopy (vol 39, pg 673, 1998)." Magnetic Resonance In Medicine 39.6 (June 1998): CP2-CP2. (Academic Article)
Source
manual
Published In
Magnetic Resonance In Medicine
Volume
39
Issue
6
Publish Date
1998
Start Page
CP2
End Page
CP2

Time-course imaging of rat embryos in utero with magnetic resonance microscopy.

Magnetic resonance (MR) microscopy was used to noninvasively investigate the development of live rat embryos in utero. The difficulty in making sequential observations of a developing mammalian embryo has frustrated developmental biologists for many years. Most current technologies analyze normal and abnormal development by observing end point phenotypes (in fixed specimens) rather than investigating the live embryo. MR microscopy was adapted to allow rat litters to be scanned three times each (at 1- to 3-day intervals) and has produced images of live developing embryos. It was demonstrated that repeated anesthesia and imaging protocols produced no gross malformations in the rat pups that were subsequently delivered and observed. Three-dimensional projection encoding with phase rewinders produced isotropic [256(3)] image data sets in about 30 minutes with excellent tissue contrast arising from steady-state effects in the amniotic fluid.

Authors
Smith, BR; Shattuck, MD; Hedlund, LW; Johnson, GA
MLA Citation
Smith, BR, Shattuck, MD, Hedlund, LW, and Johnson, GA. "Time-course imaging of rat embryos in utero with magnetic resonance microscopy." Magn Reson Med 39.4 (April 1998): 673-677.
PMID
9543433
Source
pubmed
Published In
Magnetic Resonance in Medicine
Volume
39
Issue
4
Publish Date
1998
Start Page
673
End Page
677

Magnetic resonance microscopy and histopathology: comparative approach of bromobenzene-induced hepatotoxicity in the rat.

The development of magnetic resonance (MR) microscopy has provided new approaches to histology and histopathology. Recent work has shown the promise of increased sensitivity in animal models of chemically induced hepatotoxicity. However, the field is so new that there is little experience to relate changes seen in MR micrographs to the more traditional optical images stained with hematoxylin and eosin. This work compares the sensitivity and reproducibility of MR microscopy with conventional histopathology in detecting bromobenzene-induced hepatotoxicity in the rat. A time-course study was undertaken to provide a range of histopathologies. Specimens were studied at 24, 48, 72, and 96 hours after exposure to 10% of the median lethal dose of bromobenzene. Using 4 animals per group (a total of 32 rats) added statistical significance to the study and defined a range of interanimal variability over 96 hours. This work shows that MR microscopy, besides being nondestructive and three-dimensional, is at least as sensitive as conventional hematoxylin-eosin staining in detecting bromobenzene-induced centrilobular lesions and recovery of the hepatocellular architecture in the rat. This study further suggests that, as we begin to understand the underlying mechanisms of contrast in MR histology, MR may, in fact, supply even higher specificity than more traditional studies: variations were observed in MR images of treated livers at a given time point that could be not be differentiated based on the grading of necrosis and inflammation on hematoxylin-eosin-stained sections.

Authors
Delnomdedieu, M; Hedlund, LW; Maronpot, RR; Johnson, GA
MLA Citation
Delnomdedieu, M, Hedlund, LW, Maronpot, RR, and Johnson, GA. "Magnetic resonance microscopy and histopathology: comparative approach of bromobenzene-induced hepatotoxicity in the rat." Hepatology 27.2 (February 1998): 526-532.
PMID
9462653
Source
pubmed
Published In
Hepatology
Volume
27
Issue
2
Publish Date
1998
Start Page
526
End Page
532
DOI
10.1002/hep.510270229

A fast spin echo technique with circular sampling.

This paper presents a fast spin echo (FSE) imaging method that employs circular sampling of k-space. The technique has been implemented on a 2 Tesla imaging system and validated on both phantoms and living animals. Experimental studies have shown that circular sampling can produce artifact-free FSE images without the need of phase correction. Although not fully explored, preliminary results also show that circular sampling may have advantages over the conventional rectilinear FSE in signal-to-noise ratio and imaging efficiency. A major disadvantage is the increased sensitivity to off-resonance effects. The authors expect that the FSE technique with circular sampling will find its applications in magnetic resonance microscopy, neuro-functional imaging, and real-time dynamic studies.

Authors
Zhou, X; Liang, ZP; Gewalt, SL; Cofer, GP; Lauterbur, PC; Johnson, GA
MLA Citation
Zhou, X, Liang, ZP, Gewalt, SL, Cofer, GP, Lauterbur, PC, and Johnson, GA. "A fast spin echo technique with circular sampling." Magn Reson Med 39.1 (January 1998): 23-27.
PMID
9438433
Source
pubmed
Published In
Magnetic Resonance in Medicine
Volume
39
Issue
1
Publish Date
1998
Start Page
23
End Page
27

MR microscopy of lung airways with hyperpolarized 3He.

A technique using hyperpolarized (HP) 3He to image the small airways of the lung by using moderate flip angles and a short scanning period during early inspiration is demonstrated. Flip angles (alpha) ranging from 10-90 degrees were used in guinea pig experiments with scanning during the entire inspiration period. A second series acquired data throughout a short window of the ventilatory cycle with alpha = 45 degrees. The success of the animal studies has motivated implementation of similar imaging techniques in the clinical arena. Human studies involved imaging over the total inspiration period with alpha approximately 10 degrees. The first series of guinea pig experiments demonstrated that larger flip angles (50-90 degrees) destroy the magnetization before it reaches the smaller airways. At moderate flip angles (20-40 degrees), airway branching down to the fourth generation was apparent. Fifth-order branchings were seen in the images of the second series. The trachea down to fourth generation pulmonary airway branching, along with some distal air spaces, was seen in the human lung images.

Authors
Chen, XJ; Chawla, MS; Hedlund, LW; Möller, HE; MacFall, JR; Johnson, GA
MLA Citation
Chen, XJ, Chawla, MS, Hedlund, LW, Möller, HE, MacFall, JR, and Johnson, GA. "MR microscopy of lung airways with hyperpolarized 3He." Magn Reson Med 39.1 (January 1998): 79-84.
PMID
9438440
Source
pubmed
Published In
Magnetic Resonance in Medicine
Volume
39
Issue
1
Publish Date
1998
Start Page
79
End Page
84

A new window into the lung

Authors
Johnson, GA; Hedlund, L; MacFall, J
MLA Citation
Johnson, GA, Hedlund, L, and MacFall, J. "A new window into the lung." Physics World 11.11 (1998): 35-38.
Source
scival
Published In
Physics World
Volume
11
Issue
11
Publish Date
1998
Start Page
35
End Page
38

Magnetic resonance imaging of hyperpolarized 129Xe produced by spin exchange with diode-laser pumped Cs

We report the results of experiments leading to the production of an image of a polarized 129Xe sample prepared by spin exchange with Cs, optically pumped with a spectrally narrowed 894.3 nm diode laser. Representative images of the average electron spin polarization are shown. Appreciable cesium electron polarization values were achieved, and a nuclear polarization of about 2.5% was measured for 129Xe. The absolute nuclear polarization was measured by water-calibrated free induction decay of the nuclear magnetic resonance signal, and the polarized xenon imaged using a 2 T magnetic resonance imaging system. © 1998 American Institute of Physics.

Authors
Levron, D; Walter, DK; Appelt, S; Fitzgerald, RJ; Kahn, D; Korbly, SE; Sauer, KL; Happer, W; Earles, TL; Mawst, LJ; al, E
MLA Citation
Levron, D, Walter, DK, Appelt, S, Fitzgerald, RJ, Kahn, D, Korbly, SE, Sauer, KL, Happer, W, Earles, TL, Mawst, LJ, and al, E. "Magnetic resonance imaging of hyperpolarized 129Xe produced by spin exchange with diode-laser pumped Cs." Applied Physics Letters 73.18 (1998): 2666-2668. (Academic Article)
Source
manual
Published In
Applied Physics Letters
Volume
73
Issue
18
Publish Date
1998
Start Page
2666
End Page
2668
DOI
10.1063/1.122547

Magnetic resonance microscopy of Alzheimer's disease: Senile plaques - A whiter shade of pale?

Authors
Benveniste, H; Einstein, G; Kim, KR; Johnson, GA
MLA Citation
Benveniste, H, Einstein, G, Kim, KR, and Johnson, GA. "Magnetic resonance microscopy of Alzheimer's disease: Senile plaques - A whiter shade of pale?." NeuroImage 7.4 PART II (1998): S519-.
Source
scival
Published In
NeuroImage
Volume
7
Issue
4 PART II
Publish Date
1998
Start Page
S519

Erratum: Time-course imaging of rat embryos in utero with magnetic resonance microscopy (Magnetic Resonance in Medicine (1998) 39 (673-677))

Authors
Smith, BR; Sattuck, MD; Hedlund, LW; Johnson, GA
MLA Citation
Smith, BR, Sattuck, MD, Hedlund, LW, and Johnson, GA. "Erratum: Time-course imaging of rat embryos in utero with magnetic resonance microscopy (Magnetic Resonance in Medicine (1998) 39 (673-677))." Magnetic Resonance in Medicine 39.6 (1998): x-.
Source
scival
Published In
Magnetic Resonance in Medicine
Volume
39
Issue
6
Publish Date
1998
Start Page
x

MR microimaging of the lung using volume projection encoding.

Radial acquisition (RA) techniques have been extended to produce isotropic, three-dimensional images of lung in live laboratory animals at spatial resolution down to 0.013 mm3 with a signal-to-noise ratio of 30:1. The pulse sequence and reconstruction algorithm have been adapted to allow acquisition of image matrices of up to 256(3) in less than 15 min. Scan-synchronous ventilation has been incorporated to limit breathing motion artifacts. The imaging sequence permits randomizing and/or discarding selected views to minimize the consequences of breathing motion. The signal in lung parenchyma was measured as a function of flip angle (alpha) for different repetition times and found to follow the predictions for which there is an optimum excitation (Ernst) angle. A single T1 relaxation value of 780 +/- 54 ms fits all data from six guinea pigs at 2.0 T. This T1 value parameterizes the signal and allows for a priori optimization, such as calculation of the Ernst angle appropriate for lung imaging.

Authors
Shattuck, MD; Gewalt, SL; Glover, GH; Hedlund, LW; Johnson, GA
MLA Citation
Shattuck, MD, Gewalt, SL, Glover, GH, Hedlund, LW, and Johnson, GA. "MR microimaging of the lung using volume projection encoding." Magn Reson Med 38.6 (December 1997): 938-942.
PMID
9402195
Source
pubmed
Published In
Magnetic Resonance in Medicine
Volume
38
Issue
6
Publish Date
1997
Start Page
938
End Page
942

Automated feedback control of body temperature for small animal studies with MR microscopy.

A temperature control system consisting of a thermistor, signal processor, and computer algorithm was developed for magnetic resonance (MR) microscopy of small live animals. With control of body temperature within +/- 0.2 degree C of the set point, heart rate is stabilized and, in turn, repetition time (TR) during cardiac-gated studies is less variable. Thus, image quality and resolution are improved.

Authors
Qiu, HH; Cofer, GP; Hedlund, LW; Johnson, GA
MLA Citation
Qiu, HH, Cofer, GP, Hedlund, LW, and Johnson, GA. "Automated feedback control of body temperature for small animal studies with MR microscopy." IEEE Trans Biomed Eng 44.11 (November 1997): 1107-1113.
PMID
9353990
Source
pubmed
Published In
IEEE Transactions on Biomedical Engineering
Volume
44
Issue
11
Publish Date
1997
Start Page
1107
End Page
1113
DOI
10.1109/10.641338

Root form and function meshed by MRI.

Authors
McFall, JS; Johnson, GA
MLA Citation
McFall, JS, and Johnson, GA. "Root form and function meshed by MRI." PLANT PHYSIOLOGY 114.3 (July 1997): 20002-20002.
Source
wos-lite
Published In
Plant physiology
Volume
114
Issue
3
Publish Date
1997
Start Page
20002
End Page
20002

Dynamics of magnetization in hyperpolarized gas MRI of the lung.

The magnetization in hyperpolarized gas (HP) MRI is generated by laser polarization that is independent of the magnet and imaging process. As a consequence, there is no equilibrium magnetization during the image acquisition. The competing processes of gas inflow and depolarization of the spins lead to large changes in signal as one samples k-space. A model is developed of dynamic changes in polarization of hyperpolarized 3He during infusion and in vivo imaging of the lung and verified experimentally in a live guinea pig. Projection encoding is used to measure the view-to-view variation with temporal resolution < 4 ms. Large excitation angles effectively sample the magnetization in the early stages of inflow, highlighting larger airways, while smaller excitation angles produce images of the more distal spaces. The work provides a basis for pulse sequences designed to effectively exploit HP MRI in the lung.

Authors
Johnson, GA; Cates, G; Chen, XJ; Cofer, GP; Driehuys, B; Happer, W; Hedlund, LW; Saam, B; Shattuck, MD; Swartz, J
MLA Citation
Johnson, GA, Cates, G, Chen, XJ, Cofer, GP, Driehuys, B, Happer, W, Hedlund, LW, Saam, B, Shattuck, MD, and Swartz, J. "Dynamics of magnetization in hyperpolarized gas MRI of the lung." Magn Reson Med 38.1 (July 1997): 66-71.
PMID
9211381
Source
pubmed
Published In
Magnetic Resonance in Medicine
Volume
38
Issue
1
Publish Date
1997
Start Page
66
End Page
71

Magnetic resonance microscopy in basic studies of brain structure and function.

Authors
Johnson, GA; Benveniste, H; Engelhardt, RT; Qiu, H; Hedlund, LW
MLA Citation
Johnson, GA, Benveniste, H, Engelhardt, RT, Qiu, H, and Hedlund, LW. "Magnetic resonance microscopy in basic studies of brain structure and function." Ann N Y Acad Sci 820 (May 30, 1997): 139-147. (Review)
PMID
9237453
Source
pubmed
Published In
Annals of the New York Academy of Sciences
Volume
820
Publish Date
1997
Start Page
139
End Page
147

Digital image-intensifier radiography at a level I trauma center.

Authors
Vandemark, RM; Fay, ME; Porter, FR; Johnson, GA
MLA Citation
Vandemark, RM, Fay, ME, Porter, FR, and Johnson, GA. "Digital image-intensifier radiography at a level I trauma center." AJR Am J Roentgenol 168.4 (April 1997): 944-946.
PMID
9124145
Source
pubmed
Published In
AJR. American journal of roentgenology
Volume
168
Issue
4
Publish Date
1997
Start Page
944
End Page
946
DOI
10.2214/ajr.168.4.9124145

Quality control phantom for digital chest radiography.

PURPOSE: To develop and test a chest phantom for routine quality control testing of digital radiography systems. MATERIALS AND METHODS: The phantom was constructed from sheets of copper, aluminum, and acrylic, which were cut and arranged to yield a radiographic projection resembling that of a human thorax. Regional test objects allowed quantitative assessment of optical density, contrast detail, and spatial resolution. Validation tests were performed to assess image stability in a stable imaging environment and sensitivity to changes in image quality when they occur. RESULTS: The phantom yielded consistent pseudoclinical images when used in a routine quality control program and facilitated detection of simulated problems that were induced in imaging system performance. CONCLUSION: The chest phantom enables quantitative, full-system testing of digital radiography system as they are used clinically for chest radiography.

Authors
Chotas, HG; Floyd, CE; Johnson, GA; Ravin, CE
MLA Citation
Chotas, HG, Floyd, CE, Johnson, GA, and Ravin, CE. "Quality control phantom for digital chest radiography." Radiology 202.1 (January 1997): 111-116.
PMID
8988199
Source
pubmed
Published In
Radiology
Volume
202
Issue
1
Publish Date
1997
Start Page
111
End Page
116
DOI
10.1148/radiology.202.1.8988199

Optimized radiofrequency coils for increased signal-to-noise ratio in magnetic resonance microscopy

The signal-to-noise ratio (SNR) is a major obstacle to achieving increased resolution in magnetic resonance microscopy (MRM). The SNR considerations for MRM are presented, with particular attention to the role of judicious receiver coil design in maximizing sensitivity and limiting noise contributions both from the sample and the coil. We present a number of different coil configurations that have been optimized for particular applications of MRM in the biological sciences. An overview of the literature regarding derivations of the SNR for birdcage-configuration volume coils, inductively coupled surface coils, and surgically implanted coils is presented in a unified fashion. Microscopy coils designed to reduce the total volume of excitation, thus coupling more closely to a given region of interest, are discussed. The volume coil is presented in terms of its application to lung imaging in small animals at 2 T and imaging of stroke at 7 T. The performance of traditional surface coils is demonstrated by application to spinal cord imaging in the rat. Finally, implanted coils are examined, as used in studies of the carotid arteries. © 1997 John Wiley & Sons, Inc.

Authors
Hurlston, SE; Cofer, GP; Johnson, GA
MLA Citation
Hurlston, SE, Cofer, GP, and Johnson, GA. "Optimized radiofrequency coils for increased signal-to-noise ratio in magnetic resonance microscopy." International Journal of Imaging Systems and Technology 8.3 (1997): 277-284.
Source
scival
Published In
International Journal of Imaging Systems and Technology
Volume
8
Issue
3
Publish Date
1997
Start Page
277
End Page
284

Convection and flow in porous media. Part 1. Visualization by magnetic resonance imaging

We describe an experimental study of porous media convection (PMC) from onset to 8Rac. The goal of this work is to provide non-invasive imaging and high-precision heat transport measurements to test theories of convection in PMC. We obtain velocity information and visualize the convection patterns using magnetic resonance imaging (MRI). We study both ordered and disordered packings of mono-disperse spheres of diameter d = 3.204 ± 0.029 mm, in circular, rectangular, and hexagonal planforms. In general, the structure of the medium plays a role which is not predicted by theories which assume a homogeneous system. Disordered media are prepared by pouring mono-disperse spheres into the container. Large ordered regions of close packing for the spheres, with grain boundaries and isolated defects, characterize these media. The defects and grain boundaries play an important role in pattern formation in disordered media. Any deviation from close packing produces a region of larger porosity, hence locally larger permeability. The result is spatial variations in the Rayleigh number, Ra. We define the critical Ra, Rac, as the Rayleigh number at the onset of convection in the ordered regions. We find that stable localized convective regions exist around grain boundaries and defects at Ra < Rac. These remain as pinning sites for the convection patterns in the ordered regions as Ra increases above Rac up to 5Rac, the highest Ra studied in the disordered media. In ordered media, spheres are packed such that the only deviations from close packing occur within a thin (<d) region near the vertical walls. Stable localized convection begins at 0.5Rac in the wall regions but appears to play only a weak role in the pattern formation of the interior regions (bulk), since different stable patterns are observed in the bulk at the same Ra after each cycling of Ra below Rac, even for similar patterns of small rolls in the wall regions. The experiments provide a test of the following predictions for PMC: (i) that straight parallel rolls should be linearly stable for Rac < Ra < 5Rac; (ii) that at onset, the rolls should have a dimensionless wavevector qc = π; (iii) that at the upper end of this range rolls should lose stability to cross-rolls; (iv) that the initial slope of the Nusselt curve should be 2; (v) that there should be a rapid decay of vertical vorticity - hence no complex flows, such as those which occur for Rayleigh-Bénard convection (RBC) within the nominal regime of stable parallel rolls. These predictions are in partial agreement with our findings for the bulk convection in the ordered media. We observe roll-like structures which relax rapidly to stable patterns between Rac and 5Rac. However we find a wavenumber which is 0.7π compared to π derived from linear stability theory. We find an asymmetry between the size of the upflowing regions and downflowing regions as Ra grows above Rac. The ratio of the volume of the upflowing to the volume of the downflowing regions decreases as Ra increases and leads to a novel time-dependent state, which does not consist of cross-rolls. This time-dependent state begins at 6Rac and is observed up to 8Rac, the largest Ra which we studied. It seems likely that the occurrence of this state is linked to departures from the Boussinesq approximation at higher Ra. We also find that the slope of the Nusselt curve is 0.7, which does not agree with the predicted value of 2.

Authors
Shattuck, MD; Behringer, RP; Johnson, GA; Georgiadis, JG
MLA Citation
Shattuck, MD, Behringer, RP, Johnson, GA, and Georgiadis, JG. "Convection and flow in porous media. Part 1. Visualization by magnetic resonance imaging." Journal of Fluid Mechanics 332 (1997): 215-245.
Source
scival
Published In
Journal of Fluid Mechanics
Volume
332
Publish Date
1997
Start Page
215
End Page
245

Tumor cell endocytosis imaging facilitates delineation of the glioma-brain interface

We describe a method for measuring tumor cell endocytosis in vivo and provide the anatomic correlate of this tumor cell function using a superparamagnetic and histologically detectable marker for cell uptake (MION). Rats (n = 22) were intrahemispherically implanted with a thymidine kinase (TK)-positive 9L gliosarcoma cell line, where TK served as the tumor marker. Twenty-four hours after intravenous injection of 10 mg Fe/kg of MION, rat brains were removed and underwent MR imaging ex vivo at near-microscopic resolution (isotropic voxel size of 86 μm, 9.4 T) prior to histologic processing. The imaging probe accumulated within tumor cells adjacent to the hyperpermeable tumor-brain interface including microscopic deposits and along finger-like invasions of the tumor into brain, facilitating the demarcation of the true histologic tumor border in three dimensions by MR microscopy. The method has potential research and clinical implications for delineating the tumor-brain interface prior to therapy and/or for providing a rational basis for imaging nanocolloid drug delivery to solid tumors.

Authors
Zimmer, C; Jr, SCW; Engelhardt, RT; Johnson, GA; Kramm, C; Breakefield, XO; Weissleder, R
MLA Citation
Zimmer, C, Jr, SCW, Engelhardt, RT, Johnson, GA, Kramm, C, Breakefield, XO, and Weissleder, R. "Tumor cell endocytosis imaging facilitates delineation of the glioma-brain interface." Experimental Neurology 143.1 (1997): 61-69.
PMID
9000446
Source
scival
Published In
Experimental Neurology
Volume
143
Issue
1
Publish Date
1997
Start Page
61
End Page
69
DOI
10.1006/exnr.1996.6350

Magnetic resonance imaging of continuous spinal anesthesia with hyperbaric lidocaine: Root or white matter lesion?

Introduction: Persistent neurologic deficits in patients after continuous spinal anesthesia with hyperbaric lidocaine may have been erroneously characterized as a cauda equina syndrome (1,2). First, clinical reports of symptoms rarely include pain (typical for cauda equina lesions) but most often consist of saddle anesthesia, paraplegia and sphincter dysfunction (typical for conus medullaris lesions). Secondly, spinal cord damage in dogs after intrathecal procaine (3) or lidocaine (4) is confined only to the myelin sheath beneath the pia mater and not nerve roots. In this study we use diffusion-weighted magnetic resonance imaging (DWI) to further characterize hyperbaric lidocaine-induced spinal cord damage. DWI measures diffusion of free protons and is a very sensitive detector of white or gray matter injury (5). Normal spinal cord gray and white matter as well as nerve roots are clearly visualized by DWI because the proton diffusion coefficient (DC) - the critical parameter measured with DWI - within these tissues differs. The effect of hyperbaric 5% lidocaine on the spinal cord diffusion coefficient will be compared with those found in ischémie conditions. Methods: The study was approved by the Duke University Animal Care Institutional Committee. Nine female adult Fisher rats (weighing 150-190g) were anesthetized with isoflurane, intubated and mechanically ventilated. Catheters were inserted into the right external jugular vein and carotid artery. Heart rate, arterial blood pressure and body temperature was monitored continuously. Diffusion-weighted MR images (DWI) were acquired at the level of C6 in five rats before and after ischemia induced by cardiac arrest. In another four rats catheters were first placed intrathecally via the atlanto-occipital membrane. Subsequently, DWI's were acquired at the level of C6 before and during 3 hr continuous intrathecal perfusion with 5% hyperbaric lidocaine. Hemodynamic stability during lidocaine administration was maintained with i.v. hydration, atropine and ephedrine as needed. All imaging was done on a 7 T magnet using a standard spin echo diffusion pulse sequence (5). Results: Ischemia reduced the diffusion coefficient (DC) of white matter by 25%, gray matter by 45% and nerve roots/dorsal root ganglia by 35%. Figure 1 shows that one hour of continuous intrathecal administration of 5% hyperbaric lidocaine reduces the DC of white matter by 15% and that the changes are not as profound as those found during ischemia (results are presented as mean ± SD). Figure 2 shows that in contrast to white matter, DCs of adjacent nerve roots are unaffected by 5 % hyperbaric lidocaine. Discussion: The present study has led to the following conclusion: (1) diffusion-weighted imaging of spinal cord in rats with indwelling intrathecal catheters is possible in vivo, (2) the diffusion coefficient of white matter is reduced by 15% after 1 hr of 5% hyperbaric lidocaine indicating onset of cytotoxic edema, (3) the lidocaine-induced changes in the white matter DC do not reach ischémie levels, (4) adjacent gray matter as well as nerve roots are unaffected. Ongoing work will provide information as to the exact pathophysiological sequence of events which lead to irreversible spinal cord damage during continuous spinal anesthesia with high dose hyperbaric 5% lidocaine. It is our goal that this research will be applicable to local anesthesia toxicity studies and useful as a future neurotoxicity screening tool for new intralhecal drugs designed for both anesthesia and analgesia.

Authors
Bcnveniste, H; Hüttemeier, PC; Qiu, H; Steele, S; Hedlund, LW; Johnson, GA
MLA Citation
Bcnveniste, H, Hüttemeier, PC, Qiu, H, Steele, S, Hedlund, LW, and Johnson, GA. "Magnetic resonance imaging of continuous spinal anesthesia with hyperbaric lidocaine: Root or white matter lesion?." Regional Anesthesia 22.2 SUPPL. (1997): 15--.
Source
scival
Published In
Regional anesthesia
Volume
22
Issue
2 SUPPL.
Publish Date
1997
Start Page
15-

Quality control phantom for digital chest radiography

Authors
Chotas, HG; Floyd, CE; Johnson, GA; Ravin, CE
MLA Citation
Chotas, HG, Floyd, CE, Johnson, GA, and Ravin, CE. "Quality control phantom for digital chest radiography." RADIOLOGY 201 (November 1996): 685-685.
Source
wos-lite
Published In
Radiology
Volume
201
Publish Date
1996
Start Page
685
End Page
685

Functional imaging of the lung.

Authors
Johnson, GA; Hedlund, LW
MLA Citation
Johnson, GA, and Hedlund, LW. "Functional imaging of the lung." Nat Med 2.11 (November 1996): 1192-.
PMID
8898741
Source
pubmed
Published In
Nature Medicine
Volume
2
Issue
11
Publish Date
1996
Start Page
1192

Magnetic resonance microscopy of embryos.

We demonstrate that magnetic resonance (MR) microscopy provides a mechanism to investigate normal and abnormal developmental anatomy in a non-destructive and distortion-free manner. Techniques for the fixation, embedding, perfusion and image acquisition of embryos between 3 and 30 mm crown rump length are described. We describe the perfusion of a contrast agent to enhance images of the developing embryonic vasculature. Data are acquired as three-dimensional isotropic arrays which permit images to be reformatted retrospectively in any plane. The data are available for archiving, distributing and for post-acquisition manipulations. MR microscopy is a fast technique for producing three-dimensional reconstructions and is free from registration and sectioning artifacts.

Authors
Smith, BR; Linney, E; Huff, DS; Johnson, GA
MLA Citation
Smith, BR, Linney, E, Huff, DS, and Johnson, GA. "Magnetic resonance microscopy of embryos." Comput Med Imaging Graph 20.6 (November 1996): 483-490.
PMID
9007215
Source
pubmed
Published In
Computerized Medical Imaging and Graphics
Volume
20
Issue
6
Publish Date
1996
Start Page
483
End Page
490

Human lung air spaces: potential for MR imaging with hyperpolarized He-3.

Two healthy volunteers who had inhaled approximately 0.75 L of laser-polarized helium-3 gas underwent magnetic resonance imaging at 1.5 T with fast gradient-echo pulse sequences and small flip angles ( < 10 degrees). Thick-section (20 mm) coronal images, time-course data (30 images collected every 1.8 seconds), and thin-section (6 mm) images were acquired. Subjects were able to breathe the gas (12% polarization) without difficulty. Thick-section images were of good quality and had a signal-to-noise ratio (S/N) of 32:1 near the surface coil and 16:1 farther away. The time images showed regional differences, which indicated potential value for quantitation. High-resolution images showed greater detail and a S/N of approximately 6:1.

Authors
MacFall, JR; Charles, HC; Black, RD; Middleton, H; Swartz, JC; Saam, B; Driehuys, B; Erickson, C; Happer, W; Cates, GD; Johnson, GA; Ravin, CE
MLA Citation
MacFall, JR, Charles, HC, Black, RD, Middleton, H, Swartz, JC, Saam, B, Driehuys, B, Erickson, C, Happer, W, Cates, GD, Johnson, GA, and Ravin, CE. "Human lung air spaces: potential for MR imaging with hyperpolarized He-3." Radiology 200.2 (August 1996): 553-558.
PMID
8685356
Source
pubmed
Published In
Radiology
Volume
200
Issue
2
Publish Date
1996
Start Page
553
End Page
558
DOI
10.1148/radiology.200.2.8685356

A new in vivo method for quantitative analysis of stroke lesions using diffusion-weighted magnetic resonance microscopy

Authors
Hall, WL; Benveniste, H; Hedlund, LW; Johnson, GA
MLA Citation
Hall, WL, Benveniste, H, Hedlund, LW, and Johnson, GA. "A new in vivo method for quantitative analysis of stroke lesions using diffusion-weighted magnetic resonance microscopy." NEUROIMAGE 3.3 (June 1996): 158-166.
Source
wos-lite
Published In
NeuroImage
Volume
3
Issue
3
Publish Date
1996
Start Page
158
End Page
166
DOI
10.1006/nimg.1996.0017

In vivo He-3 MR images of guinea pig lungs.

The authors imaged the lungs of live guinea pigs with hyperpolarized (HP) helium-3 as a magnetic resonance (MR) signal source. HP He-3 gas produced through spin exchange with rubidium metal vapor was delivered through an MR-compatible, small-animal ventilator. Two- and three-dimensional lung images acquired with ventilation-gated, radial k-space sampling showed complete ventilation of both lungs. All images were of high quality, demonstrating that HP He-3 allows high-signal-intensity MR imaging in living systems.

Authors
Black, RD; Middleton, HL; Cates, GD; Cofer, GP; Driehuys, B; Happer, W; Hedlund, LW; Johnson, GA; Shattuck, MD; Swartz, JC
MLA Citation
Black, RD, Middleton, HL, Cates, GD, Cofer, GP, Driehuys, B, Happer, W, Hedlund, LW, Johnson, GA, Shattuck, MD, and Swartz, JC. "In vivo He-3 MR images of guinea pig lungs." Radiology 199.3 (June 1996): 867-870.
PMID
8638019
Source
pubmed
Published In
Radiology
Volume
199
Issue
3
Publish Date
1996
Start Page
867
End Page
870
DOI
10.1148/radiology.199.3.8638019

T1 rho relaxation and its application to MR histology.

The application of T1 rho an an alternative contrast parameter in high-field magnetic resonance histology (MRH) has been investigated. Spectroscopic measurements of T1 rho were performed on 5.75% agar and 1.0 mM MnCI2 phantoms at 9.4 T to validate the accuracy of the imaging measurements. Image studies were performed at 2.0 and 9.4 T on perfusion-fixed 17.5-day-old mouse embryos. T1, T2, and T1 rho relaxation times were calculated for the phantoms and muscle, diencephalon, and liver tissues. The 5.75% agar phantom and all tissues showed T1 rho dispersion with B1L, whereas the 1.0 mM MnCI2 phantom showed no significant B1L dependence. T1 rho dispersion with B(O) was observed arising from the effects of diffusion through susceptibility-induced gradients. T1 rho shows promise as a contrast parameter in high-field MRH because it is capable of producing T2-like contrast without the susceptibility artifacts associated with T2-weighted images.

Authors
Engelhardt, RT; Johnson, GA
MLA Citation
Engelhardt, RT, and Johnson, GA. "T1 rho relaxation and its application to MR histology." Magn Reson Med 35.5 (May 1996): 781-786.
PMID
8722830
Source
pubmed
Published In
Magnetic Resonance in Medicine
Volume
35
Issue
5
Publish Date
1996
Start Page
781
End Page
786

Magnetic resonance microscopy--a new tool for the toxicologic pathologist.

Parallel to its many applications in medical imaging, magnetic resonance (MR) microscopy is a potentially powerful tool in toxicologic pathology. Because of the intrinsic qualities of MR microscopy (noninvasiveness, 3-dimensionality, and slicing in any chosen plane), the scientist has a new means by which to investigate different types of lesions based on differential contrast. By choosing appropriate proton stains to probe the state of the water in tissues, organ structure and vasculature can be seen and progressive lesion development can be followed in a given animal. This paper discusses toxicologic pathology applications for MR microscopy and compares MR microscopy with conventional histopathology using a time-course study of bromobenzene-induced hepatotoxicity in rats. Hematoxylin and eosin (H&E)-stained histological sections are compared with MR microscopy images from fixed tissue blocks to demonstrate one of the applications of MR microscopy to toxicologic pathology. The results indicate that MR microscopy is as sensitive as conventional H&E staining in detecting bromobenzene-induced hepatic lesions.

Authors
Delnomdedieu, M; Hedlund, LW; Johnson, GA; Maronpot, RR
MLA Citation
Delnomdedieu, M, Hedlund, LW, Johnson, GA, and Maronpot, RR. "Magnetic resonance microscopy--a new tool for the toxicologic pathologist." Toxicol Pathol 24.1 (January 1996): 36-44. (Review)
PMID
8839279
Source
pubmed
Published In
Toxicologic Pathology (Sage)
Volume
24
Issue
1
Publish Date
1996
Start Page
36
End Page
44
DOI
10.1177/019262339602400106

T1p relaxation and its application to MR histology

The application of T1p as an alternative contrast parameter in high-field magnetic resonance histology (MRH) has been investigated. Spectroscopic measurements of T1p were performed on 5.75% agar and 1.0 mM MnCl2 phantoms at 9.4 T to validate the accuracy of the imaging measurements. Image studies were performed at 2.0 and 9.4 T on perfusion-fixed 17.5-day-old mouse embryos. T1, T2, and T1p relaxation times were calculated for the phantoms and muscle, diencephalon, and liver tissues. The 5.75% agar phantom and all tissues showed T1p dispersion with B1L, whereas the 1.0 mM MnCl2 phantom showed no significant B1L dependence. T1p dispersion with B0 was observed arising from the effects of diffusion through susceptibility-induced gradients. T1p shows promise as a contrast parameter in high-field MRH because it is capable of producing T2-like contrast without the susceptibility artifacts associated with T2-weighted images.

Authors
Engelhardt, RT; Johnson, GA
MLA Citation
Engelhardt, RT, and Johnson, GA. "T1p relaxation and its application to MR histology." Magnetic Resonance in Medicine 35.5 (1996): 781-786. (Academic Article)
Source
manual
Published In
Magnetic Resonance in Medicine
Volume
35
Issue
5
Publish Date
1996
Start Page
781
End Page
786

Multiple-window spectrum estimation applied to in vivo NMR spectroscopy

Multiple-window spectrum estimation (MWSE) is a method of deriving frequency spectra from time series. A set of apodizing windows is applied to the time data and each windowed data set is Fourier transformed. The windows are prolate spheroidal sequences. These form the orthonormal set of functions that is maximally concentrated in both time and frequency domains. An iterative algorithm is then applied to the data set to find a leastsquares estimate of the power spectrum. In addition, statistical tests may be applied to determine the existence of periodic components at particular frequencies, their amplitudes, phases, and positions. The method is quantitative and makes no lineshape assumptions. Computer simulations were used to compare MWSE performance with that of conventional Fourier-transform processing with quantification by curve fitting. Signal-to-noise ratio, spectral resolution, linearity, and susceptibility to artifacts were compared. MWSE gives similar signal-to-noise ratio and spectral resolution to Fourier-transform data and is linear over three orders of magnitude but is much more robust with respect to artifacts. In particular, data truncation introduces no baseline distortion, broad baseline humps are removed automatically, and large solvent peaks may be easily removed without affecting adjacent lines. No separate phase correction is required. MWSE gives more accurate quantitative spectra, particularly when the time data are imperfect. The method is, therefore, particularly appropriate for processing in vivo data. The utility of the MWSE method is demonstrated on in vivo 'H, 31P, and 13C NMR spectroscopy data. e 1996 Academic Press, Inc.

Authors
Johnson, G; Thomson, DJ; Wu, EX; Williams, SCR
MLA Citation
Johnson, G, Thomson, DJ, Wu, EX, and Williams, SCR. "Multiple-window spectrum estimation applied to in vivo NMR spectroscopy." Journal of Magnetic Resonance - Series B 110.2 (1996): 138-149.
Source
scival
Published In
Journal of Magnetic Resonance, Series B
Volume
110
Issue
2
Publish Date
1996
Start Page
138
End Page
149

Detection of bromobenzene-induced hepatocellular necrosis using magnetic resonance microscopy.

The authors used magnetic resonance (MR) microscopy to assess hepatic tissue damage induced by bromobenzene both in living rats and in fixed rat liver tissues. Experiments were conducted at 7 Tesla on three groups of Fisher rats treated with bromobenzene at a single dose of 68, 135, and 269 mg/kg, respectively. Optical microscopy of hematoxylin and eosin stained sections showed liver damage only at the highest dose, whereas with MR microscopy, tissue alterations were detected at all three doses both in vivo and ex vivo. The contrast mechanism of the superior sensitivity of MR microscopy is believed to be related to the changes in local diffusion coefficients that accompany cellular degeneration and death, although other contrast mechanisms may also be involved. The superior sensitivity of MR microscopy, as demonstrated in this study, has many implications for potential use of MR techniques to perform in vivo histology.

Authors
Zhou, X; Maronpot, RR; Hedlund, LW; Cofer, GP; Johnson, GA
MLA Citation
Zhou, X, Maronpot, RR, Hedlund, LW, Cofer, GP, and Johnson, GA. "Detection of bromobenzene-induced hepatocellular necrosis using magnetic resonance microscopy." Magn Reson Med 34.6 (December 1995): 853-857.
PMID
8598812
Source
pubmed
Published In
Magnetic Resonance in Medicine
Volume
34
Issue
6
Publish Date
1995
Start Page
853
End Page
857

3-DIMENSIONAL ROOT-GROWTH, TURNOVER AND TRANSPORT AS SEEN WITH MAGNETIC-RESONANCE MICROSCOPY

Authors
MACFALL, IS; JOHNSON, GA
MLA Citation
MACFALL, IS, and JOHNSON, GA. "3-DIMENSIONAL ROOT-GROWTH, TURNOVER AND TRANSPORT AS SEEN WITH MAGNETIC-RESONANCE MICROSCOPY." PLANT PHYSIOLOGY 108.2 (June 1995): 31-31.
Source
wos-lite
Published In
Plant physiology
Volume
108
Issue
2
Publish Date
1995
Start Page
31
End Page
31

MR microscopy of the rat carotid artery after balloon injury by using an implanted imaging coil.

Neointimal hyperplasia after angioplasty was followed in vivo in rats by using MR microscopy and surgically implanted RF imaging coils. By using an inductively coupled pick-up coil, the arteries were imaged 4 days before and 3, 7, and 14 days after angioplasty with a 3DFT spin echo sequence. Eight of 10 angioplastied rats showed moderate to severe stensois based MR measures of lumen diameter reduction from baseline images. There was a good correlation between total wall thickness between MR and hematoxylin and eosin (H&E)-stained sections obtained on the last day. Arteries in the intact and sham groups remained unchanged from baseline measurements. Because this imaging technique examines the artery under in vivo conditions of arterial pressure and flow, it promises to be a useful tool for evaluating pharmacological and mechanical methods of reducing the incidence of vascular stenosis.

Authors
Summers, RM; Hedlund, LW; Cofer, GP; Gottsman, MB; Manibo, JF; Johnson, GA
MLA Citation
Summers, RM, Hedlund, LW, Cofer, GP, Gottsman, MB, Manibo, JF, and Johnson, GA. "MR microscopy of the rat carotid artery after balloon injury by using an implanted imaging coil." Magn Reson Med 33.6 (June 1995): 785-789.
PMID
7651114
Source
pubmed
Published In
Magnetic Resonance in Medicine
Volume
33
Issue
6
Publish Date
1995
Start Page
785
End Page
789

MR imaging with hyperpolarized 3He gas.

Magnetic resonance images of the lungs of a guinea pig have been produced using hyperpolarized helium as the source of the MR signal. The resulting images are not yet sufficiently optimized to reveal fine structural detail within the lung, but the spectacular signal from this normally signal-deficient organ system offers great promise for eventual in vivo imaging experiments. Fast 2D and 3D GRASS sequences with very small flip angles were employed to conserve the norenewable longitudinal magnetization. We discuss various unique features associated with performing MRI with hyperpolarized gases, such as the selection of the noble gas species, polarization technique, and constraints on the MR pulse sequence.

Authors
Middleton, H; Black, RD; Saam, B; Cates, GD; Cofer, GP; Guenther, R; Happer, W; Hedlund, LW; Johnson, GA; Juvan, K
MLA Citation
Middleton, H, Black, RD, Saam, B, Cates, GD, Cofer, GP, Guenther, R, Happer, W, Hedlund, LW, Johnson, GA, and Juvan, K. "MR imaging with hyperpolarized 3He gas." Magn Reson Med 33.2 (February 1995): 271-275.
PMID
7707920
Source
pubmed
Published In
Magnetic Resonance in Medicine
Volume
33
Issue
2
Publish Date
1995
Start Page
271
End Page
275

Performance of a High-Temperature Superconducting Resonator for High-Field Imaging

The practicalities involved with the use of a superconducting microimaging probe are outlined so that the power and problems associated with this technology can be assessed. The nonlinearity of the transmission characteristics of this class of probe, the intrinsic limits on bandwidth, the long ring-down times, the potential for spin damping, and the difficulties of suppressing Johnson noise are all discussed. Recent refinements that have delivered a factor of 30 gain in SNR (signal-to-noise ratio) relative to copper coils at room temperature are presented. Further reductions in noise sources should yield a gain of a factor of 60 in SNR. © 1995 Academic Press. All rights reserved.

Authors
Black, RD; Early, TA; Johnson, GA
MLA Citation
Black, RD, Early, TA, and Johnson, GA. "Performance of a High-Temperature Superconducting Resonator for High-Field Imaging." Journal of Magnetic Resonance, Series A 113.1 (1995): 74-80.
Source
scival
Published In
Journal of Magnetic Resonance - Series A
Volume
113
Issue
1
Publish Date
1995
Start Page
74
End Page
80
DOI
10.1006/jmra.1995.1058

Magnetic resonance microscopy of the rat carotid artery at 300 megahertz.

RATIONALE AND OBJECTIVES: Magnetic resonance microscopy (MRM) has evolved from a technical curiosity to a tool with which researchers can study important disease models. But MRM is not simply an extension of clinical magnetic resonance imaging. In this article, the unique adaptations of MRM required in the study of carotid artery disease are outlined. The techniques of MRM are integrated into a specific model of carotid artery disease in the rat to allow in vivo studies of vascular wall thickening after removal of the vascular endothelium. METHODS: Imaging was performed at 300 MHz in 250-gm Sprague-Dawley rats using surgically implanted radiofrequency coils to localize the region of interest and to provide an increase in the signal-to-noise ratio over that of volume or surface coils. A three-dimensional Fourier encoding sequence was modified with flow-dephasing gradients to minimize signal and artifacts from moving blood. RESULTS: In vivo images were acquired with spatial resolution of 25 x 25 x 400 microns and signal-to-noise ratio more than sufficient to define the morphology of the vascular wall. Significant changes in the intensity and distribution of signal were visible in the area surrounding the vessel after angioplasty. CONCLUSIONS: Signal-to-noise improvements from surgically implanted coils coupled to a three-dimensional radiofrequency-refocused sequence with flow-dephasing gradients were sufficient to define the wall of the carotid artery. The diffusion-weighted pulse sequence detects signal changes in the area surrounding the vessel after angioplasty. The MRM techniques described and the contrast observed allow us, for the first time to follow in vivo the early stage of developing atherosclerosis in the vessel wall and closely surrounding tissue.

Authors
Arnder, L; Zhou, X; Cofer, GP; Hedlund, LW; Johnson, GA
MLA Citation
Arnder, L, Zhou, X, Cofer, GP, Hedlund, LW, and Johnson, GA. "Magnetic resonance microscopy of the rat carotid artery at 300 megahertz." Invest Radiol 29.9 (September 1994): 822-826.
PMID
7995700
Source
pubmed
Published In
Investigative Radiology
Volume
29
Issue
9
Publish Date
1994
Start Page
822
End Page
826

3-DIMENSIONAL MAGNETIC-RESONANCE MICROANGIOGRAPHY OF RAT NEUROVASCULATURE

Authors
MELLIN, AF; COFER, GP; SMITH, BR; SUDDARTH, SA; HEDLUND, LW; JOHNSON, GA
MLA Citation
MELLIN, AF, COFER, GP, SMITH, BR, SUDDARTH, SA, HEDLUND, LW, and JOHNSON, GA. "3-DIMENSIONAL MAGNETIC-RESONANCE MICROANGIOGRAPHY OF RAT NEUROVASCULATURE." MAGNETIC RESONANCE IN MEDICINE 32.2 (August 1994): 199-205.
Source
wos-lite
Published In
Magnetic Resonance in Medicine
Volume
32
Issue
2
Publish Date
1994
Start Page
199
End Page
205
DOI
10.1002/mrm.1910320208

Three dimensional magnetic resonance microangiography of rat neurovasculature.

Techniques are described to perform three dimensional (3D) MR microangiography. We have combined the use of a blood pool agent (Gd-DTPA-complexed with bovine serum albumin), three dimensional Fourier encoding, careful animal stabilization, and volume rendering to permit imaging with voxels of 60 x 60 x 60 microns. 3DFT encoding has been performed at 7.1 T with very large arrays (256 x 512 x 512). Interactive volume rendering allows a number of unique display opportunities that effectively exploit these isotropic 3D arrays.

Authors
Mellin, AF; Cofer, GP; Smith, BR; Suddarth, SA; Hedlund, LW; Johnson, GA
MLA Citation
Mellin, AF, Cofer, GP, Smith, BR, Suddarth, SA, Hedlund, LW, and Johnson, GA. "Three dimensional magnetic resonance microangiography of rat neurovasculature." Magn Reson Med 32.2 (August 1994): 199-205.
PMID
7968442
Source
pubmed
Published In
Magnetic Resonance in Medicine
Volume
32
Issue
2
Publish Date
1994
Start Page
199
End Page
205

Studies on bromobenzene-induced hepatotoxicity using in vivo MR microscopy with surgically implanted RF coils.

Using surgically implanted RF coils at 300 MHz, three-dimensional microscopic MR images of rat liver were obtained in vivo to follow the development of pathology induced by bromobenzene exposure. Formalin fixed specimens of liver from these animals were also imaged using in vitro MR microscopy, followed by conventional optical microscopy. All MR images were acquired using a spin-warp pulse sequence with TR = 950 ms and TE = 23 ms. The in vivo images were reconstructed as 256(2) x 32 arrays with a voxel size of (50 microns)2 x 219 microns, while the in vitro images were reconstructed as 256(2) x 128 arrays, giving an isotropic resolution at (39 microns)3. Based on results from six animals, we have found in all animals exposed to bromobenzene, image intensity decreased in specific hepatic tissue regions. These regions were well correlated to low signal intensity areas observed in in vitro MR images at higher resolution. Conventional optical microscopy indicated that the low signal intensity regions corresponded to areas of necrosis. The decrease in signal intensity is consistent with increased local diffusion coefficients as a result of necrosis. This study demonstrates that MR microscopy with implanted RF coils can be successfully used to follow tissue pathological changes in living tissues.

Authors
Zhou, X; Maronpot, RR; Cofer, GP; Hedlund, LW; Johnson, GA
MLA Citation
Zhou, X, Maronpot, RR, Cofer, GP, Hedlund, LW, and Johnson, GA. "Studies on bromobenzene-induced hepatotoxicity using in vivo MR microscopy with surgically implanted RF coils." Magn Reson Med 31.6 (June 1994): 619-627.
PMID
8057814
Source
pubmed
Published In
Magnetic Resonance in Medicine
Volume
31
Issue
6
Publish Date
1994
Start Page
619
End Page
627

Imaging the cochlea by magnetic resonance microscopy.

The isolated, fixed cochlea of the mustached bat was studied with three dimensional magnetic resonance (MR) microscopy. The cochlea of this animal is about 4 mm in diameter and its entire volume was imaged. With the field of view and matrix size used, the volume elements (voxels) making up the volume data set were isotropic 25 x 25 x 25 micron cubes. Three dimensional (3D) MR microscopy based on isotropic voxels has many advantages over commonly used light microscopy: 1) it is non destructive; 2) it is much less time consuming; 3) no dehydration is required and shrinkage is minimized; 4) the data set can be used to create sections in any desired plane; 5) the proper alignment of sections is inherent in the 3D acquisition so that no reference points are required; 6) the entire data set can be viewed from any point of view in a volume rendered image; 7) the data is digital and features can be enhanced by computer image processing; and 8) the isotropic dimensions of the voxels make the data well-suited for structural reconstructions and measurements. Good images of the osseous spiral lamina, spiral ligament, scala tympani, scala vestibuli, and nerve bundles were obtained. The vestibular (Reissner's) membrane was easily identified in the mustached bat and it appears to bulge into the scala vestibuli. The visibility of this structure suggests that MR microscopy would be well-suited for studies of endolymphatic hydrops.

Authors
Henson, MM; Henson, OW; Gewalt, SL; Wilson, JL; Johnson, GA
MLA Citation
Henson, MM, Henson, OW, Gewalt, SL, Wilson, JL, and Johnson, GA. "Imaging the cochlea by magnetic resonance microscopy." Hear Res 75.1-2 (May 1994): 75-80.
PMID
8071156
Source
pubmed
Published In
Hearing Research
Volume
75
Issue
1-2
Publish Date
1994
Start Page
75
End Page
80

Magnetic resonance imaging of chronic myocardial infarcts in formalin-fixed human autopsy hearts.

BACKGROUND: In post-myocardial infarction patients, three-dimensional structure of the infarct as well as infarct size are likely to be important factors affecting mortality, cardiac function, and arrhythmias. Current morphological methods for determining three-dimensional infarct structure in autopsied hearts are inexact and time consuming. The cardiac magnetic resonance imaging techniques used in living patients have shown potential in determining infarct size and structure but have limited resolution for morphometric postmortem studies. The recent development of magnetic resonance microscopy raises the possibility that three-dimensional infarct structure can be quantified at microscopic levels in autopsied hearts. The purpose of this study was to determine the ability of magnetic resonance imaging at different spatial resolutions to differentiate infarcted from noninfarcted myocardium. METHODS AND RESULTS: Magnetic resonance imaging was performed at 2.0 T on cross sections taken from 10 autopsied hearts containing old myocardial infarcts. T1 was derived from six images with repetition times (TRs) for each image ranging from 100 to 3200 milliseconds. T2 was derived from multi-echo images with echo times (TEs) ranging from 10 to 60 milliseconds. Resolution was approximately 400 x 400 microns in 2-mm-thick slices. Sites of infarcted and noninfarcted tissue were identified from histological sections taken from each slice, and the T1 and T2 values of these sites were obtained. Microscopic images were acquired with voxels of 100 x 100 x 625 microns, representing tissue volumes more than 1000-fold smaller than conventional clinical images. In all cases, T1 of infarcted tissue (459 +/- 266 milliseconds, mean +/- SD) was greater than that of noninfarcted tissue (272 +/- 163 milliseconds). Also, in all cases, T2 of infarcted tissue (49 +/- 14 milliseconds) was greater than that of noninfarcted tissue (35 +/- 8 milliseconds). CONCLUSIONS: T1 and T2 values for infarcted tissue are significantly different from those of noninfarcted tissue (P < .001). Based on these findings, it should be possible to develop techniques to perform three-dimensional imaging and quantitation of infarcts with a resolution of 400 microns or less. When volumetric three-dimensional imaging was performed using a T1-weighted sequence, the resulting 256(3) arrays supported isotropic resolution at 400 microns (voxel volume, 0.064 mm3). Subsequent volume rendering using a compositing algorithm clearly shows the infarcted areas in three dimensions. The techniques demonstrate the potential for quantitative three-dimensional cardiac morphometry using magnetic resonance imaging.

Authors
Hsu, JC; Johnson, GA; Smith, WM; Reimer, KA; Ideker, RE
MLA Citation
Hsu, JC, Johnson, GA, Smith, WM, Reimer, KA, and Ideker, RE. "Magnetic resonance imaging of chronic myocardial infarcts in formalin-fixed human autopsy hearts." Circulation 89.5 (May 1994): 2133-2140.
PMID
8181138
Source
pubmed
Published In
Circulation
Volume
89
Issue
5
Publish Date
1994
Start Page
2133
End Page
2140

Magnetic resonance microscopy of mouse embryos.

The increased use of the mouse as a model for various aspects of mammalian biology has caused a renewed interest in developing strategies for examining and comparing normal and abnormal mouse embryonic development and anatomy. In this study, we have explored the use of magnetic resonance microscopy as a tool for these purposes. Techniques for the fixation, embedding, perfusion, and image acquisition of mouse embryos are described. The perfusion of bovine serum albumin-diethylenetriamine pentaacetic anhydride-gadolinium as a contrast agent enhances images of the developing embryonic vasculature during critical stages of organogenesis and allows for comparisons when embryos have been treated with teratogens such as retinoic acid. The acquired three-dimensional data sets are available for archiving, distributing, and postacquisition manipulations such as computer segmentation of anatomical structures.

Authors
Smith, BR; Johnson, GA; Groman, EV; Linney, E
MLA Citation
Smith, BR, Johnson, GA, Groman, EV, and Linney, E. "Magnetic resonance microscopy of mouse embryos." Proc Natl Acad Sci U S A 91.9 (April 26, 1994): 3530-3533.
PMID
8170941
Source
pubmed
Published In
Proceedings of the National Academy of Sciences of USA
Volume
91
Issue
9
Publish Date
1994
Start Page
3530
End Page
3533

Utility of postmortem magnetic resonance imaging in clinical neuropathology.

Over 200 brains were examined by postmortem magnetic resonance imaging to determine the utility of this imaging procedure as an adjunct to the standard postmortem examination of the brain and spinal cord. One unembalmed cadaver was also studied using a conventional 1.5-tesla (T) field-strength unit, and three formalin-fixed sections of the hippocampus were imaged using a high field-strength (7.0-T) prototype imaging system. The postmortem magnetic resonance images proved to be an invaluable aid that complemented the standard pathologic examination of the brain and spinal cord. The compelling advantages of this postmortem radiographic procedure included the three-dimensional aspects of the images; the ability to detect mineral (ie, iron) deposits; small focal lesions such as hemorrhages or infarcts; and the ability to evaluate the extent of cerebral edema. For the same reasons, as well as its archival potential for documenting the topographic distribution of pathologic processes, this technique has great promise for forensic cases. High field-strength (7.0-T) imaging brought the resolution of magnetic resonance to the microscopic level and reaffirmed the potential value of magnetic resonance imaging for diagnostic and investigative studies in which both the histologic and fine radiologic features of lesions are of interest.

Authors
Boyko, OB; Alston, SR; Fuller, GN; Hulette, CM; Johnson, GA; Burger, PC
MLA Citation
Boyko, OB, Alston, SR, Fuller, GN, Hulette, CM, Johnson, GA, and Burger, PC. "Utility of postmortem magnetic resonance imaging in clinical neuropathology." Arch Pathol Lab Med 118.3 (March 1994): 219-225.
PMID
8135623
Source
pubmed
Published In
Archives of Pathology and Laboratory Medicine
Volume
118
Issue
3
Publish Date
1994
Start Page
219
End Page
225

MAGNETIC-RESONANCE MICROSCOPY OF WATER-MOVEMENT THROUGH FUSIFORM RUST GALLS OF PINE

Authors
SPAINE, P; MACFALL, JS; JOHNSON, GA
MLA Citation
SPAINE, P, MACFALL, JS, and JOHNSON, GA. "MAGNETIC-RESONANCE MICROSCOPY OF WATER-MOVEMENT THROUGH FUSIFORM RUST GALLS OF PINE." 1994.
Source
wos-lite
Published In
RESEARCH AND APPLICATIONS OF CHEMICAL SCIENCES IN FORESTRY
Volume
104
Publish Date
1994
Start Page
11
End Page
16

The architecture of plant vasculature and transport as seen with magnetic resonance microscopy

Authors
MacFall, JS; Johnson, GA
MLA Citation
MacFall, JS, and Johnson, GA. "The architecture of plant vasculature and transport as seen with magnetic resonance microscopy." Canadian Journal of Botany 72.11 (1994): 1561-1573.
Source
scival
Published In
Canadian Journal of Botany
Volume
72
Issue
11
Publish Date
1994
Start Page
1561
End Page
1573

USE OF MAGNETIC-RESONANCE-IMAGING IN THE STUDY OF PLANTS AND SOILS

Authors
MACFALL, JS; JOHNSON, GA
MLA Citation
MACFALL, JS, and JOHNSON, GA. "USE OF MAGNETIC-RESONANCE-IMAGING IN THE STUDY OF PLANTS AND SOILS." 1994.
Source
wos-lite
Published In
SSSA special publication series
Issue
36
Publish Date
1994
Start Page
99
End Page
113

MAGNETIC-RESONANCE MICROSCOPY (MRM) OF WATER TRANSPORT AND BINDING IN FUSIFORM RUST GALLS

Authors
MACFALL, JS; SPAINE, PC; DOUDRICK, RE; JOHNSON, GA
MLA Citation
MACFALL, JS, SPAINE, PC, DOUDRICK, RE, and JOHNSON, GA. "MAGNETIC-RESONANCE MICROSCOPY (MRM) OF WATER TRANSPORT AND BINDING IN FUSIFORM RUST GALLS." 1994.
Source
wos-lite
Published In
RESEARCH AND APPLICATIONS OF CHEMICAL SCIENCES IN FORESTRY
Volume
104
Publish Date
1994
Start Page
17
End Page
17

NONDESTRUCTIVE, 3-DIMENSIONAL STUDY OF ROOT-GROWTH WITH MAGNETIC-RESONANCE MICROSCOPY (MRM)

Authors
MACFALL, JS; JOHNSON, GA
MLA Citation
MACFALL, JS, and JOHNSON, GA. "NONDESTRUCTIVE, 3-DIMENSIONAL STUDY OF ROOT-GROWTH WITH MAGNETIC-RESONANCE MICROSCOPY (MRM)." 1994.
Source
wos-lite
Published In
RESEARCH AND APPLICATIONS OF CHEMICAL SCIENCES IN FORESTRY
Volume
104
Publish Date
1994
Start Page
18
End Page
18

Reduction of ringing and blurring artifacts in fast spin-echo imaging.

A simple method was devised to reduce ringing and blurring artifacts caused by discontinuous T2 weighting of k-space data in fast spin-echo magnetic resonance (MR) imaging. The method demodulates the weighting function along the phase-encoding direction by using multiple T2 values derived from a set of non-phase-encoded echoes obtained from an extra excitation. The performance of this method was evaluated by computer simulations and experiments, which confirmed its capability of effectively reducing or, in some cases, even completely removing the ringing and blurring artifacts. The results also show that the proposed method produces better results than other artifact reduction methods. The method is particularly useful at high magnetic field strengths (7.1-9.4 T) and with strong gradients (> 20 G/cm) used in MR microscopy, in which the apparent T2 values are short for most tissues. The authors expect that the proposed method will find useful applications in various fast spin-echo pulse sequences.

Authors
Zhou, X; Liang, ZP; Cofer, GP; Beaulieu, CF; Suddarth, SA; Johnson, GA
MLA Citation
Zhou, X, Liang, ZP, Cofer, GP, Beaulieu, CF, Suddarth, SA, and Johnson, GA. "Reduction of ringing and blurring artifacts in fast spin-echo imaging." J Magn Reson Imaging 3.5 (September 1993): 803-807.
PMID
8400569
Source
pubmed
Published In
Journal of Magnetic Resonance Imaging
Volume
3
Issue
5
Publish Date
1993
Start Page
803
End Page
807

Diffusion-weighted MR microscopy with fast spin-echo.

A diffusion-weighted fast spin-echo (FSE) imaging sequence for high-field MR microscopy was developed and experimentally validated in a phantom and in a live rat. Pulsed diffusion gradients were executed before and after the initial 180 degrees pulse in the FSE pulse train. This produced diffusion-related reductions in image signal intensity corresponding to gradient ("b") factors between 1.80 and 1352 s/mm2. The degree of diffusion weighting was demonstrated to be independent of echo train length for experiments using trains up to 16 echoes long. Quantitative measurements on a phantom and on a live rat produced diffusion coefficients consistent with literature values. Importantly, the eight- to 16-fold increase in imaging efficiency with FSE was not accompanied by a significant loss of spatial resolution or contrast. This permits acquisition of in vivo three-dimensional data in time periods that are appropriate for evolving biological processes. The combination of accurate diffusion weighting and high spatial resolution provided by FSE makes the technique particularly useful for MR microscopy.

Authors
Beaulieu, CF; Zhou, X; Cofer, GP; Johnson, GA
MLA Citation
Beaulieu, CF, Zhou, X, Cofer, GP, and Johnson, GA. "Diffusion-weighted MR microscopy with fast spin-echo." Magn Reson Med 30.2 (August 1993): 201-206.
PMID
8366801
Source
pubmed
Published In
Magnetic Resonance in Medicine
Volume
30
Issue
2
Publish Date
1993
Start Page
201
End Page
206

High-field MR microscopy using fast spin-echoes.

Fast spin-echo imaging has been investigated with attention to the requirements and opportunities for high-field MR microscopy. Two- and three-dimensional versions were implemented at 2.0 T, 7.1 T, and 9.4 T. At these fields, at least eight echoes were collectable with a 10 ms TE from fixed tissue specimens and living animals, giving an eightfold improvement in imaging efficiency. To reduce the phase-encoding gradient amplitude and its duty cycle, a modified pulse sequence with phase accumulation was developed. Images obtained using this pulse sequence exhibited comparable signal-to-noise (SNR) to those obtained from the conventional fast spin-echo pulse sequences. Signal losses due to imperfections in RF pulses and lack of phase rewinders were offset in this sequence by reduced diffusion losses incurred with the gradients required for MR microscopy. Image SNR, contrast, edge effects and spatial resolution for three k-space sampling schemes were studied experimentally and theoretically. One method of sampling k-space, 4-GROUP FSE, was found particularly useful in producing varied T2 contrast at high field. Two-dimensional images of tissue specimens were obtained in a total acquisition time of 1 to 2 min with in-plane resolution between 30 to 70 microns, and 3D images with 256(3) arrays were acquired from fixed rat brain tissue (isotropic voxel = 70 microns) and a living rat (isotropic voxel = 117 microns) in approximately 4.5 h.

Authors
Zhou, X; Cofer, GP; Suddarth, SA; Johnson, GA
MLA Citation
Zhou, X, Cofer, GP, Suddarth, SA, and Johnson, GA. "High-field MR microscopy using fast spin-echoes." Magn Reson Med 30.1 (July 1993): 60-67.
PMID
8371676
Source
pubmed
Published In
Magnetic Resonance in Medicine
Volume
30
Issue
1
Publish Date
1993
Start Page
60
End Page
67

MAGNETIC-RESONANCE-IMAGING OF LEAVES

Authors
VERES, JS; COFER, GP; JOHNSON, GA
MLA Citation
VERES, JS, COFER, GP, and JOHNSON, GA. "MAGNETIC-RESONANCE-IMAGING OF LEAVES." NEW PHYTOLOGIST 123.4 (April 1993): 769-774.
Source
wos-lite
Published In
New Phytologist
Volume
123
Issue
4
Publish Date
1993
Start Page
769
End Page
774
DOI
10.1111/j.1469-8137.1993.tb03788.x

Histology by magnetic resonance microscopy.

Magnetic resonance microscopy (MRM) has advanced from a technical challenge to a practical tool in a wide range of basic sciences. This article focuses on the use of MRM as a tool for histological studies. The technical challenges of limited signal to noise have been overcome by improved radio-frequency (rf) coil design and 3DFT encoding with large arrays. Resolution limits imposed by motion in in vivo studies have been overcome by improved physiologic monitoring and control and projection encoding. Integration of technologies now permits routine studies in vivo down to 50 microns. MRM has also been applied to in vitro studies of fixed tissues where absence of motion allows studies down to 10 microns. The nondestructive nature of the technique allows repeated studies of the same sample, retrospective studies through any arbitrary plane, registered studies using different contrast mechanisms, and examination of valuable specimens. The many and unique proton contrasts provided by MRM, i.e., T1, T2, and diffusion weighting, permit direct examination of the state of water in tissues, something not possible with other microscopic techniques. Finally, the inherent three-dimensional nature of MRM allows acquisition of perfectly registered isotropic 3D arrays that, when displayed with appropriate visualization tools, provide new perspectives to histologic examination. The technology of MRM continues to develop rapidly. New pulse sequences are reducing acquisition times. New computer architectures allow larger arrays. A new class of superconducting rf probe has increased the signal to noise ratio by 10 times. These developments promise routine use of MRM in histology studies with resolution to 1 micron in the near future.

Authors
Johnson, GA; Benveniste, H; Black, RD; Hedlund, LW; Maronpot, RR; Smith, BR
MLA Citation
Johnson, GA, Benveniste, H, Black, RD, Hedlund, LW, Maronpot, RR, and Smith, BR. "Histology by magnetic resonance microscopy." Magn Reson Q 9.1 (March 1993): 1-30. (Review)
PMID
8512830
Source
pubmed
Published In
Magnetic resonance quarterly
Volume
9
Issue
1
Publish Date
1993
Start Page
1
End Page
30

A high-temperature superconducting receiver for nuclear magnetic resonance microscopy.

A high-temperature superconducting-receiver system for use in nuclear magnetic resonance (NMR) microscopy is described. The scaling behavior of sources of sample and receiver-coil noise is analyzed, and it is demonstrated that Johnson, or thermal, noise in the receiver coil is the factor that limits resolution. The behavior of superconductors in the environment of an NMR experiment is examined, and a prototypical system for imaging biological specimens is discussed. Preliminary spin-echo images are shown, and the ultimate limits of the signal-to-noise ratio of the probe are investigated.

Authors
Black, RD; Early, TA; Roemer, PB; Mueller, OM; Mogro-Campero, A; Turner, LG; Johnson, GA
MLA Citation
Black, RD, Early, TA, Roemer, PB, Mueller, OM, Mogro-Campero, A, Turner, LG, and Johnson, GA. "A high-temperature superconducting receiver for nuclear magnetic resonance microscopy." Science 259.5096 (February 5, 1993): 793-795.
PMID
8430331
Source
pubmed
Published In
Science
Volume
259
Issue
5096
Publish Date
1993
Start Page
793
End Page
795

In vitro MR microscopy of the hippocampus in Alzheimer's disease.

We used MR microscopy at 7 tesla to identify the anatomy of the degenerating hippocampus in Alzheimer's disease (AD), which we then correlated with the histopathologic findings in the same specimens. The specimens studied were resected postmortem from 13 patients with confirmed AD and from nine age-matched controls. We imaged the specimens in the coronal plane using either three-dimensional Fourier encoding or single-slice Carr, Purcell, Meiboom, Gill (CPMG) spin echo sequences. On all specimens imaged with the CPMG pulse sequence, we calculated the T2 relaxation times for subfields within the hippocampus. Histologic sections were taken from each specimen and compared with the corresponding MR image. Using histologic boundaries, we quantified the number of neuritic plaques and neurofibrillary tangles in each hippocampal subfield. We measured the area, morphometric characteristics, and width of identifiable signal variant regions on each image and compared these measurements with the histopathologic findings. The mean cross-sectional area of the hippocampus in AD was decreased by 31% compared with the control group. This atrophy was highly correlated with tangle counts within the hippocampus, but not with plaque counts. The width of the gray matter in hippocampal area CA1, as identified by MR, correlated with the total area of the hippocampus. An age-related decrease in the size of a low-signal region that corresponds histologically to input projections comprising part of the perforant pathway was identified. Measurements of the T2 relaxation times of hippocampal subfields showed little regional variability and were not accurate indicators of disease presence or severity (p > 0.05).

Authors
Huesgen, CT; Burger, PC; Crain, BJ; Johnson, GA
MLA Citation
Huesgen, CT, Burger, PC, Crain, BJ, and Johnson, GA. "In vitro MR microscopy of the hippocampus in Alzheimer's disease." Neurology 43.1 (January 1993): 145-152.
PMID
8423879
Source
pubmed
Published In
Neurology
Volume
43
Issue
1
Publish Date
1993
Start Page
145
End Page
152

MR microscopy of the rat lung using projection reconstruction.

Projection reconstruction has been implemented with self-refocused selection pulses on a small bore, 2.0 T MR microscope, to allow imaging of lung parenchyma. Scan synchronous ventilation and cardiac gating have been integrated with the sequence to minimize motion artifacts. A systematic survey of the pulse sequence parameters has been undertaken in conjunction with the biological gating parameters to optimize resolution and signal-to-noise (SNR). The resulting projection images with effective echo time of < 300 microseconds allow definition of lung parenchyma with an SNR improvement of approximately 15 x over a more conventional 2DFT short echo gradient sequence.

Authors
Gewalt, SL; Glover, GH; Hedlund, LW; Cofer, GP; MacFall, JR; Johnson, GA
MLA Citation
Gewalt, SL, Glover, GH, Hedlund, LW, Cofer, GP, MacFall, JR, and Johnson, GA. "MR microscopy of the rat lung using projection reconstruction." Magn Reson Med 29.1 (January 1993): 99-106.
PMID
8419748
Source
pubmed
Published In
Magnetic Resonance in Medicine
Volume
29
Issue
1
Publish Date
1993
Start Page
99
End Page
106

Detection of infarcted tissue the heart by magnetic resonance imaging

Morphological analysis of myocardial infarct structure has demonstrated that there is probably an anatomical basis for the induction and maintenance of ventricular tachycardia. The further study of this phenomenon requires an efficient, accurate method for quantitative analysis of pathological anatomy. We have evaluated the ability of magnetic resonance imaging to distinguish between normal and infarcted tissue in formalin-fixed human hearts with distant myocardial infarctions.

Authors
Smith, WM; Hsu, JCM; Johnson, GA; Reimer, KA; Ideker, RE
MLA Citation
Smith, WM, Hsu, JCM, Johnson, GA, Reimer, KA, and Ideker, RE. "Detection of infarcted tissue the heart by magnetic resonance imaging." Proceedings of the Annual Conference on Engineering in Medicine and Biology 15.pt 1 (1993): 485-486.
Source
scival
Published In
Proceedings of the Annual Conference on Engineering in Medicine and Biology
Volume
15
Issue
pt 1
Publish Date
1993
Start Page
485
End Page
486

EXCITOTOXICITY AND ISCHEMIA IN THE RAT-BRAIN STUDIED IN-VIVO WITH HIGH-RESOLUTION MAGNETIC-RESONANCE-IMAGING

Authors
BENVENISTE, H; JOHNSON, GA; KOZNIEWSKA, E; MAIESE, K; NARITOMI, H; POVLISHOCK, JT; HOSSMANN, KA
MLA Citation
BENVENISTE, H, JOHNSON, GA, KOZNIEWSKA, E, MAIESE, K, NARITOMI, H, POVLISHOCK, JT, and HOSSMANN, KA. "EXCITOTOXICITY AND ISCHEMIA IN THE RAT-BRAIN STUDIED IN-VIVO WITH HIGH-RESOLUTION MAGNETIC-RESONANCE-IMAGING." 1993.
Source
wos-lite
Published In
International Congress Series
Volume
1031
Publish Date
1993
Start Page
369
End Page
376

Observation of the Oxygen Diffusion Barrier in Soybean (Glycine max) Nodules with Magnetic Resonance Microscopy.

The effects of selected gas perfusion treatments on the spinlattice relaxation times (T(1)) of the soybean (Glycine max) nodule cortex and inner nodule tissue were studied with (1)H high resolution magnetic resonance microscopy. Three gas treatments were used: (a) perfusion with O(2) followed by N(2); (b) O(2) followed by O(2); and (c) air followed by N(2). Soybean plants with intact attached nodules were placed into the bore of a superconducting magnet and a selected root with nodules was perfused with the gas of interest. Magnetic resonance images were acquired with repetition times from 50 to 3200 ms. The method of partial saturation was used to calculate T(1) times on selected regions of the image. Calculated images based on T(1) showed longer T(1) values in the cortex than in the inner nodule during all of the gas perfusions. When nodules were perfused with O(2)-O(2), there was no significant change in the T(1) of the nodule between the two gas treatments. When the nodule was perfused with O(2)-N(2) or air-N(2), however, the T(1) of both the cortex and inner nodule increased. In these experiments, the increase in T(1) of the cortex was 2- to 3-fold greater than the increase observed in the inner nodule. A similar change in T(1) was found in detached live nodules, but there was no change in T(1) with selective gas perfusion of detached dead nodules. These observations suggest that cortical cells respond differently to selected gas perfusion than the inner nodule, with the boundary of T(1) change sharply delineated at the interface of the inner nodule and the inner cortex.

Authors
Macfall, JS; Pfeffer, PE; Rolin, DB; Macfall, JR; Johnson, GA
MLA Citation
Macfall, JS, Pfeffer, PE, Rolin, DB, Macfall, JR, and Johnson, GA. "Observation of the Oxygen Diffusion Barrier in Soybean (Glycine max) Nodules with Magnetic Resonance Microscopy." Plant Physiol 100.4 (December 1992): 1691-1697.
PMID
16653185
Source
pubmed
Published In
Plant physiology
Volume
100
Issue
4
Publish Date
1992
Start Page
1691
End Page
1697

In vivo magnetic resonance imaging of the blue crab, Callinectes sapidus: effect of cadmium accumulation in tissues on proton relaxation properties.

Nuclear magnetic resonance imaging (MRI) has been used to visualize the internal anatomy of a living blue crab. The resolution obtained in these studies was sufficient to distinguish individual organs by the differences in their proton densities and proton relaxation properties. T1 (spin-lattice relaxation time)-weighted imaging revealed the lipid-rich nature of the hepatopancreas and gonadal tissue. To evaluate the effect of metal-induced stress on the different organs, crabs were exposed to elevated levels of cadmium in their diet, which resulted in increased concentrations of both cadmium and copper in the hepatopancreas. The spin-spin relaxation time, T2, of mobile protons in the metal-exposed tissue was significantly greater than T2 in the control tissues. These measurements suggest that the excess copper in the exposed tissues was diamagnetic [Cu(I)], since the presence of paramagnetic copper [Cu(II)] would result in a decrease of observed T2 values. We hypothesize that the increased T2 value is a reflection of increased free water in the hepatopancreas. These studies show that magnetic resonance imaging is an important nondestructive tool for the study of morphological and physiological changes that occur in marine invertebrates in response to anthropogenic and natural stresses.

Authors
Brouwer, M; Engel, DW; Bonaventura, J; Johnson, GA
MLA Citation
Brouwer, M, Engel, DW, Bonaventura, J, and Johnson, GA. "In vivo magnetic resonance imaging of the blue crab, Callinectes sapidus: effect of cadmium accumulation in tissues on proton relaxation properties." The Journal of experimental zoology 263.1 (August 1992): 32-40.
PMID
1645119
Source
epmc
Published In
Journal of Experimental Zoology
Volume
263
Issue
1
Publish Date
1992
Start Page
32
End Page
40
DOI
10.1002/jez.1402630105

Mechanism of detection of acute cerebral ischemia in rats by diffusion-weighted magnetic resonance microscopy.

BACKGROUND AND PURPOSE: The aim of this study was to measure apparent diffusion coefficients in rat brain tissue exposed to ouabain, glutamate, and N-methyl-D-aspartate and to compare them with apparent diffusion coefficients found in acute cerebral ischemia. METHODS: The apparent diffusion coefficient was measured using magnetic resonance microscopy in four groups of Sprague-Dawley rats after occlusion of the right middle cerebral artery and ipsilateral common carotid artery (n = 7), after ouabain exposure (n = 6), during glutamate exposure (n = 7), or during N-methyl-D-aspartate exposure (n = 3). Ouabain, glutamate, and N-methyl-D-aspartate were applied via an intracerebrally implanted microdialysis membrane. RESULTS: Three hours after the induction of focal cerebral ischemia, a 33% reduction in the apparent diffusion coefficient was observed in the right dorsolateral corpus striatum and olfactory cortex. After ouabain exposure, reductions in the apparent diffusion coefficient were observed within a 1,500-microns radius of the microdialysis membrane. Quantitative analysis revealed that apparent diffusion coefficient values in ischemic and ouabain-exposed tissue fell within the same range. Glutamate and N-methyl-D-aspartate reduced the brain tissue apparent diffusion coefficient by 35% and 40%, respectively. CONCLUSIONS: On the basis of these findings, we conclude that ischemia-induced apparent diffusion coefficient reductions are likely caused by a shift of extracellular to intracellular water.

Authors
Benveniste, H; Hedlund, LW; Johnson, GA
MLA Citation
Benveniste, H, Hedlund, LW, and Johnson, GA. "Mechanism of detection of acute cerebral ischemia in rats by diffusion-weighted magnetic resonance microscopy." Stroke 23.5 (May 1992): 746-754.
PMID
1374575
Source
pubmed
Published In
Stroke
Volume
23
Issue
5
Publish Date
1992
Start Page
746
End Page
754

MR microscopy of chick embryo vasculature.

Six-day-old chick embryos were examined with magnetic resonance microscopy after vascular perfusion fixation and perfusion with gadolinium-doped gelatin to high-light the developing vascular anatomy. Gadolinium gelatin, with its short T1, provided a source of signal contrast within the vessels. The entire embryo was embedded in gelatin to minimize susceptibility artifacts that are prevalent at the high field strength (7.0 T) used. A series of single-section spin-echo images were acquired with various TRs to determine the optimal imaging sequence for a three-dimensional (3D) acquisition. The combination of gadolinium gelatin in the vascular spaces, gelatin embedding of the specimen, and optimal acquisition parameters yielded a 3D stack of high-resolution images that was readily reconstructed and rendered to effectively demonstrate the developing thoracic vessels in the embryo.

Authors
Smith, BR; Effmann, EL; Johnson, GA
MLA Citation
Smith, BR, Effmann, EL, and Johnson, GA. "MR microscopy of chick embryo vasculature." J Magn Reson Imaging 2.2 (March 1992): 237-240.
PMID
1562778
Source
pubmed
Published In
Journal of Magnetic Resonance Imaging
Volume
2
Issue
2
Publish Date
1992
Start Page
237
End Page
240

A probe for specimen magnetic resonance microscopy.

One of the primary limits to spatial resolution in magnetic resonance (MR) microscopy is the limited signal. The purpose of this study is to build a radiofrequency (rf) probe for MR microscopy of fixed specimens at 300 MHz. The design criteria for the probe were (1) high sensitivity; (2) good rf homogeneity; (3) minimization of BO variations. All probes were Helmholtz pairs operating at 300 MHz. Coils were constructed from copper/Teflon/copper microwave substrate which eliminated susceptibility problems from solder and discrete capacitors. Signal-to-noise ratio (SNR) was compared with a conventional solenoid. Phantoms of agar gels and saline-filled tubes were used to characterize the SNR and homogeneity. SNR measurements of the coil pairs showed a marked improvement (up to 60%) over that of the reference solenoid. The region of homogeneity was defined as a 10% variation in signal intensity. This correlated with the coil's inner diameter. Graphs of SNR versus diameter, separation, and copper foil width allowed for optimization of the structure. Using this coil, MR microscopy is now possible on small, fixed specimens with pixels as small as 20 x 20 x 30 microns. Work is currently under way exploiting the SNR and homogeneity provided by this probe to determine the degree to which MR microscopy might add to the pathologists' diagnostic tools.

Authors
Banson, ML; Cofer, GP; Black, R; Johnson, GA
MLA Citation
Banson, ML, Cofer, GP, Black, R, and Johnson, GA. "A probe for specimen magnetic resonance microscopy." Invest Radiol 27.2 (February 1992): 157-164.
PMID
1601608
Source
pubmed
Published In
Investigative Radiology
Volume
27
Issue
2
Publish Date
1992
Start Page
157
End Page
164

Surface coil imaging of rat spine at 7.0 T.

An inductively coupled surface coil for imaging the rat spine at 7 T is described. This planar circular probe was made from microwave substrate to limit the size of the coil and to minimize the magnetic susceptibility. The surface coil was used as a single transmit/receive coil and as a receive-only coil with a birdcage body coil for excitation. The signal-to-noise ratio (SNR) of the probe was compared to a 5-cm birdcage coil and exceeded the birdcage coil's SNR by three to six times at superficial structures. The main advantages of the probe are an improved SNR for superficial structures and a simple design and use. Images with 50 x 50 x 500 micron voxels were obtained of the rat spine with excellent anatomical detail.

Authors
Banson, ML; Cofer, GP; Hedlund, LW; Johnson, GA
MLA Citation
Banson, ML, Cofer, GP, Hedlund, LW, and Johnson, GA. "Surface coil imaging of rat spine at 7.0 T." Magn Reson Imaging 10.6 (1992): 929-934.
PMID
1461090
Source
pubmed
Published In
Magnetic Resonance Imaging
Volume
10
Issue
6
Publish Date
1992
Start Page
929
End Page
934

COMPARATIVE WATER-UPTAKE BY ROOTS OF DIFFERENT AGES IN SEEDLINGS OF LOBLOLLY-PINE (PINUS-TAEDA L)

Authors
MACFALL, JS; JOHNSON, GA; KRAMER, PJ
MLA Citation
MACFALL, JS, JOHNSON, GA, and KRAMER, PJ. "COMPARATIVE WATER-UPTAKE BY ROOTS OF DIFFERENT AGES IN SEEDLINGS OF LOBLOLLY-PINE (PINUS-TAEDA L)." NEW PHYTOLOGIST 119.4 (December 1991): 551-560.
Source
wos-lite
Published In
New Phytologist
Volume
119
Issue
4
Publish Date
1991
Start Page
551
End Page
560
DOI
10.1111/j.1469-8137.1991.tb01047.x

DISTINGUISHING PLANT-TISSUES WITH MAGNETIC-RESONANCE MICROSCOPY

Authors
VERES, JS; COFER, GP; JOHNSON, GA
MLA Citation
VERES, JS, COFER, GP, and JOHNSON, GA. "DISTINGUISHING PLANT-TISSUES WITH MAGNETIC-RESONANCE MICROSCOPY." AMERICAN JOURNAL OF BOTANY 78.12 (December 1991): 1704-1711.
Source
wos-lite
Published In
American journal of botany
Volume
78
Issue
12
Publish Date
1991
Start Page
1704
End Page
1711
DOI
10.2307/2444849

MR imaging of microcirculation in rat brain: correlation with carbon dioxide-induced changes in blood flow.

Considerable interest has been shown in developing a magnetic resonance (MR) imaging technique with quantitative capability in the evaluation of tissue microcirculation ("perfusion"). In the present study, the flow-dephased/flow-compensated (FD/FC) technique is evaluated for measuring rat cerebral blood flow (CBF) under nearly optimal laboratory conditions. Imaging was performed on a 2.0-T system equipped with shielded gradient coils. Rat CBF was varied by manipulating arterial carbon dioxide pressure (PaCO2). In parallel experiments, optimized MR imaging studies (seven rats) were compared with laser Doppler flowmetry (LDF) studies (nine rats). LDF values showed a high degree of correlation between CBF and PaCO2, agreeing with results in the literature. MR imaging values, while correlating with PaCO2, showed considerable scatter. The most likely explanation is unavoidable rat motion during the requisite long imaging times. Because of this motion sensitivity, the FD/FC technique cannot provide a quantitative measure of CBF. It can, however, provide a qualitative picture.

Authors
Maki, JH; Benveniste, H; MacFall, JR; Piantadosi, CA; Johnson, GA
MLA Citation
Maki, JH, Benveniste, H, MacFall, JR, Piantadosi, CA, and Johnson, GA. "MR imaging of microcirculation in rat brain: correlation with carbon dioxide-induced changes in blood flow." J Magn Reson Imaging 1.6 (November 1991): 673-681.
PMID
1823172
Source
pubmed
Published In
Journal of Magnetic Resonance Imaging
Volume
1
Issue
6
Publish Date
1991
Start Page
673
End Page
681

Small object contrast in AMBER and conventional chest radiography.

The ability of a commercially available scanning equalization system for chest radiography to render small object contrast in the lung-, mediastinum-, and subdiaphragm-equivalent regions of an acrylic chest phantom was quantitatively evaluated. Images from nine chest phantoms that represented a wide range of patient sizes and dynamic ranges of x-ray transmittance were analyzed. Subject contrast was measured with a photostimulable phosphor detector, and images were acquired in both equalized and nonequalized (conventional) imaging modes. Available subject contrast in the lung-equivalent region was 8%-15% lower in the equalized images compared with the nonequalized images in all phantoms (patient types); contrast in the mediastinum-, retro-cardiac-, and subdiaphragm-equivalent regions was 11%-63% higher in the equalized images, with the degree of improvement increasing as patient size and dynamic range increased. Images of each phantom were also acquired with the screen-film systems currently in use at the authors' institution, permitting an assessment of the relative performance (in terms of radiographic contrast) of these imagers with and without use of equalization.

Authors
Chotas, HG; Van Metter, RL; Johnson, GA; Ravin, CE
MLA Citation
Chotas, HG, Van Metter, RL, Johnson, GA, and Ravin, CE. "Small object contrast in AMBER and conventional chest radiography." Radiology 180.3 (September 1991): 853-859.
PMID
1871306
Source
pubmed
Published In
Radiology
Volume
180
Issue
3
Publish Date
1991
Start Page
853
End Page
859
DOI
10.1148/radiology.180.3.1871306

PREMORTEM AND POSTMORTEM DIFFUSION-COEFFICIENTS IN RAT NEURAL AND MUSCLE TISSUES

Authors
MACFALL, JR; MAKI, JH; JOHNSON, GA; HEDLUND, LW; COFER, GP
MLA Citation
MACFALL, JR, MAKI, JH, JOHNSON, GA, HEDLUND, LW, and COFER, GP. "PREMORTEM AND POSTMORTEM DIFFUSION-COEFFICIENTS IN RAT NEURAL AND MUSCLE TISSUES." MAGNETIC RESONANCE IN MEDICINE 20.1 (July 1991): 89-99.
Source
wos-lite
Published In
Magnetic Resonance in Medicine
Volume
20
Issue
1
Publish Date
1991
Start Page
89
End Page
99
DOI
10.1002/mrm.1910200110

Pre- and postmortem diffusion coefficients in rat neural and muscle tissues.

Pulsed gradient diffusion-weighted spin-echo images (7 to 11 gradient strengths) were obtained in a coronal slice through the midbrain for five normal adult white rats before and after sacrifice in a 2-T CSI system with air temperature control. The pulse sequence was cardiac gated and respiratory synchronized in order to minimize motion artifacts (Tr greater than 2 s. Te = 30 ms). Diffusion coefficients reflecting several tissue compartments (D*) in brain and muscle were calculated and referenced to simultaneously imaged tubes of water. In the living animals, brain cortical matter had a value of D* = (0.82 +/- 0.02) x 10(-3) mm2/s. deeper brain regions had a value of D* = (0.73 +/- 0.02) x 10(-3) mm2/s, and the muscle had a value of D* = (1.4 +/- 0.1) x 10(-3) mm2/s. Postmortem the values in brain dropped by approximately 30%, while remaining constant in muscle. Signal intensity in the spin-echo images for muscle tissue rose by 50% over a 1- to 2-h interval after sacrifice while that of brain tissue remained relatively stable.

Authors
MacFall, JR; Maki, JH; Johnson, GA; Hedlund, LW; Cofer, GP
MLA Citation
MacFall, JR, Maki, JH, Johnson, GA, Hedlund, LW, and Cofer, GP. "Pre- and postmortem diffusion coefficients in rat neural and muscle tissues." Magn Reson Med 20.1 (July 1991): 89-99.
PMID
1943665
Source
pubmed
Published In
Magnetic Resonance in Medicine
Volume
20
Issue
1
Publish Date
1991
Start Page
89
End Page
99

Diffusion/microcirculation MRI in the rat brain.

The CO2 fraction of an anesthetized rat's breathing mixture was changed (from 0 to 10%) to attempt to change the brain microcirculation and observe these changes in diffusion measurements of the neural tissue. Brain apparent diffusion coefficients were measured to be (0.71 +/- 0.01) X 10(-3) mm2/s before sacrifice and (0.39 +/- 0.01) X 10(-3) mm2/s after sacrifice. Multiple diffusion components were observed, consistent with flowing material, but the extra components did not increase with increased CO2. It is proposed that the additional components may be due to extracellular, extravascular water such as CSF.

Authors
MacFall, JR; Maki, JH; Johnson, GA; Hedlund, L; Benveniste, H; Copher, G
MLA Citation
MacFall, JR, Maki, JH, Johnson, GA, Hedlund, L, Benveniste, H, and Copher, G. "Diffusion/microcirculation MRI in the rat brain." Magn Reson Med 19.2 (June 1991): 305-310.
PMID
1908936
Source
pubmed
Published In
Magnetic Resonance in Medicine
Volume
19
Issue
2
Publish Date
1991
Start Page
305
End Page
310

In vivo measurement of proton diffusion in the presence of coherent motion.

Measurement of the self-diffusion coefficient D of water in tissue has been performed traditionally using the technique proposed by Stejskal and Tanner. A variant of that technique is shown here, employing flow-compensated gradients that significantly reduce the sensitivity to small coherent motions that are common in body imaging. An interleaved sequence with four values of diffusion-sensitizing gradient (b) minimizes registration errors. Eddy currents and other systematic errors are reduced, permitting the measurement of standards in an imaging context within 5% of nonimaging values in the literature. The flow-compensated sequence permits the measure of D for tissues in the abdominal cavity of the rat. We present in vivo measurements of D for the following rat tissues; liver, kidney (cortex), kidney (medulla) muscle, brain, fat.

Authors
Johnson, GA; Maki, JH
MLA Citation
Johnson, GA, and Maki, JH. "In vivo measurement of proton diffusion in the presence of coherent motion." Invest Radiol 26.6 (June 1991): 540-545.
PMID
1650333
Source
pubmed
Published In
Investigative Radiology
Volume
26
Issue
6
Publish Date
1991
Start Page
540
End Page
545

Magnetic resonance microscopy of toxic renal injury induced by bromoethylamine in rats.

The alkylhalide 2-bromoethylamine hydrobromide (BEA) produces renal injury in rats that mimics analgesic-related renal injury in humans. Our purpose was to examine this injury, in vivo in rats, with magnetic resonance (MR) microscopy and correlate MR findings with findings from light microscopy of hematoxylin-eosin-stained sections. Rats (n = 48) were injected intravenously with BEA (150 mg/kg) or saline and imaged with MR 6, 48, and 336 hr later. The spin-spin relaxation time, T2, was measured from the cortex to the papilla. In other rats, we measured regional water content of the kidney. Renal injury was present 48 and 336 hr after BEA dosing based on increased renal organ weights, decreased urine specific gravity, and significant renal lesions (H & E). T2 was elevated in the inner stripe of the outer medulla in injured kidneys at 48 hr. The differences in T2 between cortex and outer medulla were also elevated 48 hr after BEA. In the inner medulla, there were no changes in T2 after BEA treatment. However, in all groups there were significant regional differences in T2. The value of T2 increased from outer to inner medulla and this gradient was directly correlated with water content. Thus, MR microscopy detected damage in the outer medulla after BEA injury but not the damage in the inner medulla. T2 appeared to reflect the water content in the different regions of the medulla. The noninvasive in vivo capability of MR microscopy, with its high sensitivity to tissue water, allows the toxicologist to monitor the progression and regression of toxic insult in the same animal. At present the technology is complicated. The precise and accurate measure of MR-sensitive parameters in live animals at microscopic resolution is difficult. However, as the technology matures, there will be significant improvements providing the toxicologist a unique in vivo tool.

Authors
Hedlund, LW; Maronpot, RR; Johnson, GA; Cofer, GP; Mills, GI; Wheeler, CT
MLA Citation
Hedlund, LW, Maronpot, RR, Johnson, GA, Cofer, GP, Mills, GI, and Wheeler, CT. "Magnetic resonance microscopy of toxic renal injury induced by bromoethylamine in rats." Fundam Appl Toxicol 16.4 (May 1991): 787-797.
PMID
1884916
Source
pubmed
Published In
Fundamental and Applied Toxicology
Volume
16
Issue
4
Publish Date
1991
Start Page
787
End Page
797

MR microscopy at 7.0 T: effects of brain iron.

The T2 of brain tissue is known to be field dependent, decreasing as B0 increases. Previous studies have attributed reduced T2 in the structures of the extrapyramidal motor system (EPMS) to high iron concentrations. The present study was designed to manipulate physiologic iron concentrations and study the effects on T2 and on the field dependence of T2 at 7.0 T in whole formalin-fixed brains. A rat model was devised in which iron concentrations in the structures of interest were altered by diet manipulation. Cerebral structures with different iron content were imaged and T2 measured with MR microscopy at both 2.0 and 7.0 T. T2 of all tissues was shorter by 40%-60% at 7.0 T. Although some dependence of T2 on iron concentration was evident, it was less than expected. The strongest correlation was in the substantia nigra. The highest-resolution studies, at 30 x 30 x 50 microns, show the myelin bundles in many of the EPMS structures but not in the substantia nigra. From these data, it appears that T2 at greater field strengths depends more on susceptibility-induced spin dephasing imposed by diffusion through the tissue microstructure than on the presence of iron.

Authors
Malisch, TW; Hedlund, LW; Suddarth, SA; Johnson, GA
MLA Citation
Malisch, TW, Hedlund, LW, Suddarth, SA, and Johnson, GA. "MR microscopy at 7.0 T: effects of brain iron." J Magn Reson Imaging 1.3 (May 1991): 301-305.
PMID
1802143
Source
pubmed
Published In
Journal of Magnetic Resonance Imaging
Volume
1
Issue
3
Publish Date
1991
Start Page
301
End Page
305

3-DIMENSIONAL MR MICROSCOPY WITH LARGE ARRAYS

Authors
SUDDARTH, SA; JOHNSON, GA
MLA Citation
SUDDARTH, SA, and JOHNSON, GA. "3-DIMENSIONAL MR MICROSCOPY WITH LARGE ARRAYS." MAGNETIC RESONANCE IN MEDICINE 18.1 (March 1991): 132-141.
Source
wos-lite
Published In
Magnetic Resonance in Medicine
Volume
18
Issue
1
Publish Date
1991
Start Page
132
End Page
141
DOI
10.1002/mrm.1910180114

Three-dimensional MR microscopy with large arrays.

MR microscopy of fixed specimens is described using large (256(3] arrays. Images are acquired at 7.0 T with voxels as small as 70 x 70 x 70 microns (3.4 x 10(-4) mm3), more than 25,000 times smaller than routine clinical body imaging. Separation of the acquisition, reconstruction, archival, and analysis onto networked workstations provides flexibility and efficiency in handling the large data sets. The isotropic data can be interactively displayed through any plane without loss of in-plane resolution. The potential for applications of MR microscopy in clinical pathology is addressed.

Authors
Suddarth, SA; Johnson, GA
MLA Citation
Suddarth, SA, and Johnson, GA. "Three-dimensional MR microscopy with large arrays." Magn Reson Med 18.1 (March 1991): 132-141.
PMID
2062225
Source
pubmed
Published In
Magnetic Resonance in Medicine
Volume
18
Issue
1
Publish Date
1991
Start Page
132
End Page
141

Quantitative proton magnetic resonance imaging in focal cerebral ischemia in rat brain.

Proton magnetic resonance (MR) imaging has been recommended as a diagnostic tool for the detection of focal cerebral ischemia. We compared microscopic MR images of rat brains after focal cerebral ischemia with evidence of histological damage found on corresponding silver-impregnated or cresyl violet-stained brain sections. Ten male Wistar rats were subjected to permanent unilateral occlusions of the right middle cerebral and common carotid arteries under halothane anesthesia. Twenty-four hours later the area of injury on MR images amounted to 26% of the total slice area, whereas only 9% of the total slice area was necrotic on histological sections from the same animals. The infarcted areas on tissue sections were surrounded by regions of selective neuronal injury in the cerebral cortex and occasionally in the hippocampus. The area of injury on MR images was larger than the combined areas of infarction and selective neuronal injury on histological sections. Areas of increased T2 values on MR images extended medially into noninfarcted striatum and laterally and dorsally into noninfarcted cortex. The lateral and dorsal areas on MR images frequently coincided with cortical areas in which considerable selective neuronal injury was present in the upper cortical layers. We hypothesize that the abnormal areas on MR images above histologically normal brain tissue represent the ischemic penumbra. If true, this is the first demonstration of the ischemic penumbra by MR imaging and may reflect our use of Wistar rats, a new image analysis technique, and ultra-high resolution MR imaging.

Authors
Benveniste, H; Cofer, GP; Piantadosi, CA; Davis, JN; Johnson, GA
MLA Citation
Benveniste, H, Cofer, GP, Piantadosi, CA, Davis, JN, and Johnson, GA. "Quantitative proton magnetic resonance imaging in focal cerebral ischemia in rat brain." Stroke 22.2 (February 1991): 259-268.
PMID
2003291
Source
pubmed
Published In
Stroke
Volume
22
Issue
2
Publish Date
1991
Start Page
259
End Page
268

INVIVO MAGNETIC-RESONANCE-IMAGING OF BLECHNUM FERNS - CHANGES IN T1 AND N(H) DURING DEHYDRATION AND REHYDRATION

Authors
VERES, JS; JOHNSON, GA; KRAMER, PJ
MLA Citation
VERES, JS, JOHNSON, GA, and KRAMER, PJ. "INVIVO MAGNETIC-RESONANCE-IMAGING OF BLECHNUM FERNS - CHANGES IN T1 AND N(H) DURING DEHYDRATION AND REHYDRATION." AMERICAN JOURNAL OF BOTANY 78.1 (January 1991): 80-88.
Source
wos-lite
Published In
American journal of botany
Volume
78
Issue
1
Publish Date
1991
Start Page
80
End Page
88
DOI
10.2307/2445231

Maximization of contrast-to-noise ratio to distinguish diffusion and microcirculatory flow.

Optimization of the contrast-to-noise ratio (CNR) is described for microcirculation magnetic resonance (MR) imaging techniques based on flow-compensated/flow-dephased sequences, both with and without even-echo rephasing. The authors present the most advantageous manner of applying flow-dephased gradients, such that dephasing is maximal while diffusion losses are minimal. The theoretical considerations include phase, diffusion, echo time, and bandwidth in the determination of the optimal parameters for microcirculation imaging. Studies in phantoms consisting of stationary and flowing copper sulfate in Sephadex columns demonstrate the validity of the calculations. Optimized in vivo images of a rat stroke model demonstrate the potential of the flow-compensated/flow-dephased technique and the importance of optimizing CNR.

Authors
Maki, JH; Benveniste, H; MacFall, JR; Johnson, GA
MLA Citation
Maki, JH, Benveniste, H, MacFall, JR, and Johnson, GA. "Maximization of contrast-to-noise ratio to distinguish diffusion and microcirculatory flow." J Magn Reson Imaging 1.1 (January 1991): 39-46.
PMID
1802129
Source
pubmed
Published In
Journal of Magnetic Resonance Imaging
Volume
1
Issue
1
Publish Date
1991
Start Page
39
End Page
46

The use of gradient flow compensation to separate diffusion and microcirculatory flow in MRI.

This paper describes a new MR imaging technique termed Modified Stejskal Tanner versus Flow Compensation (MST/FC) for the separation of diffusion and microcirculatory flow. The theory behind the sequence is explained, along with a five-component model of microcirculation applicable to any "perfusion" imaging technique. Phantom data is presented showing that (1) diffusion effects can be matched between MST and FC (suggesting the possibility of flow-compensated diffusion imaging), and (2) the technique is a quantitative method of separating diffusion and slow (less than 0.25 mm/s) tortuous flow through a Sephadex column. Furthermore, animal images show the technique to be feasible and quantitative in measuring rat brain microcirculation under normal, vasodilated (hypercarbia), and no-flow (post mortem) conditions.

Authors
Maki, JH; MacFall, JR; Johnson, GA
MLA Citation
Maki, JH, MacFall, JR, and Johnson, GA. "The use of gradient flow compensation to separate diffusion and microcirculatory flow in MRI." Magn Reson Med 17.1 (January 1991): 95-107.
PMID
1712421
Source
pubmed
Published In
Magnetic Resonance in Medicine
Volume
17
Issue
1
Publish Date
1991
Start Page
95
End Page
107

TIME-DEPENDENCE, SCALING AND PATTERN-FORMATION FOR FLOWING SAND

Authors
BAXTER, GW; LEONE, R; JOHNSON, GA; BEHRINGER, RP
MLA Citation
BAXTER, GW, LEONE, R, JOHNSON, GA, and BEHRINGER, RP. "TIME-DEPENDENCE, SCALING AND PATTERN-FORMATION FOR FLOWING SAND." EUROPEAN JOURNAL OF MECHANICS B-FLUIDS 10.2 (1991): 181-186.
Source
wos-lite
Published In
European Journal of Mechanics - B/Fluids
Volume
10
Issue
2
Publish Date
1991
Start Page
181
End Page
186

Magnetic resonance imaging of interstitial velocity distributions in porous media

In this article we report on a promising application of Magnetic Resonance Imaging (MRI), which can measure local interstitial velocity distributions inside fully-saturated porous media. We have extended the standard three-dimensional MRI sequence to include local velocity information. During flow, the moving spins of the fluid (in this case water) accumulate phase in the presence of magnetic field gradients. This phase is proportional to the local velocity. By repeating the measurement under the influence of different magnetic gradient strengths, we can reconstruct the velocity distribution in each volume element (voxel). Using this technique to study pressure-driven flow through a fully-saturated, cylindrical packed bed, we have observed flow channeling near the walls and an exponential distribution of velocities. (A)

Authors
Shattuck, M; Behringer, R; Geordiadis, J; Johnson, GA
MLA Citation
Shattuck, M, Behringer, R, Geordiadis, J, and Johnson, GA. "Magnetic resonance imaging of interstitial velocity distributions in porous media." (1991).
Source
scival
Publish Date
1991

Magnetic resonance imaging of interstitial velocity distributions in porous media

In this article we report on a promising application of Magnetic Resonance Imaging (MRI), which can measure local interstitial velocity distributions inside fully-saturated porous media. We have extended the standard three-dimensional MRI sequence to include local velocity information. During flow, the moving spins of the fluid (in this case water) accumulate phase in the presence of magnetic field gradients. This phase is proportional to the local velocity. By repeating the measurement under the influence of different magnetic gradient strengths, we can reconstruct the velocity distribution in each volume element (voxel). Using this technique to study pressure-driven flow through a fully-saturated, cylindrical packed bed, we have observed flow channeling near the walls and an exponential distribution of velocities.

Authors
Shattuck, M; Behringer, R; Geordiadis, J; Johnson, GA
MLA Citation
Shattuck, M, Behringer, R, Geordiadis, J, and Johnson, GA. "Magnetic resonance imaging of interstitial velocity distributions in porous media." American Society of Mechanical Engineers, Fluids Engineering Division (Publication) FED 125 (1991): 39-45.
Source
scival
Published In
American Society of Mechanical Engineers, Fluids Engineering Division (Publication) FED
Volume
125
Publish Date
1991
Start Page
39
End Page
45

Magnetic resonance microscopy of toxic renal injury induced by bromoethylamine in rats

The alkylhalide 2-bromoethylamine hydrobromide (BEA) produces renal injury in rats that mimics analgesic-related renal injury in humans. Our purpose was to examine this injury, in vivo in rats, with magnetic resonance (MR) microscopy and correlate MR findings with findings from light microscopy of hematoxylin-eosin-stained sections. Rats (n = 48) were injected intravenously with BEA (150 mg/kg) or saline and imaged with MR 6, 48, and 336 hr later. The spin-spin relaxation time, T2, was measured from the cortex to the papilla. In other rats, we measured regional water content of the kidney. Renal injury was present 48 and 336 hr after BEA dosing based on increased renal organ weights, decreased urine specific gravity, and significant renal lesions (H & E). T2 was elevated in the inner stripe of the outer medulla in injured kidneys at 48 hr. The differences in T2 between cortex and outer medulla were also elevated 48 hr after BEA. In the inner medulla, there were no changes in T2 after BEA treatment. However, in all groups there were significant regional differences in T2. The value of T2 increased from outer to inner medulla and this gradient was directly correlated with water content. Thus, MR microscopy detected damage in the outer medulla after BEA injury but not the damage in the inner medulla. T2 appeared to reflect the water content in the different regions of the medulla. The noninvasive in vivo capability of MR microscopy, with its high sensitivity to tissue water, allows the toxicologist to monitor the progression and regression of toxic insult in the same animal. At present the technology is complicated. The precise and accurate measure of MR-sensitive parameters in live animals at microscopic resolution is difficult. However, as the technology matures, there will be significant improvements providing the toxicologist a unique in vivo tool. © 1991.

Authors
Hedlund, LW; Maronpot, RR; Johnson, GA; Cofer, GP; Mills, GI; Wheeler, CT
MLA Citation
Hedlund, LW, Maronpot, RR, Johnson, GA, Cofer, GP, Mills, GI, and Wheeler, CT. "Magnetic resonance microscopy of toxic renal injury induced by bromoethylamine in rats." Fundamental and Applied Toxicology 16.4 (1991): 787-797.
Source
scival
Published In
Fundamental and Applied Toxicology
Volume
16
Issue
4
Publish Date
1991
Start Page
787
End Page
797

Maximizing contrast to noise with inductively coupled implanted coils.

Magnetic resonance (MR) microscopy with inductively coupled implanted coils has been used previously to follow loss and return of intra-medullary contrast as a result of nephrotoxic acute tubular necrosis with 117 microns resolution over a 2000 microns thick slice. The purpose of the current study was to further investigate the capabilities of in vivo MR microscopy by combining the implanted coil imaging technique with spin echo pulse sequence optimization done through signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) modeling. These models included consideration of the effects of T2* and sampling time on signal-to-noise and contrast-to-noise ratios. They were initially tested with GdCl3 and agar gel phantoms constructed to the relaxation time and spin density specifications of the intra-medullary junction which bridges the outer and inner stripe of the outer medulla. In vivo microscopy was performed using single turn radiofrequency (RF) coils that were surgically implanted around the left kidney of two rats and inductively coupled to an external "birdcage" body coil. The models revealed maximum CNR per unit imaging time at a TR of 800 msec. A TE of 16 msec proved to be the best compromise between loss of transverse magnetization and decreased bandwidth. These CNR predictions were supported by the gel phantom and in vivo data. Maximizing the CNR in the current study enabled us to improve the resolution of in vivo MR microscopy to 78 microns over a 1000 microns slice with an SNR of 40 and a CNR of eight in a total imaging time of 54 minutes.

Authors
Farmer, TH; Cofer, GP; Johnson, GA
MLA Citation
Farmer, TH, Cofer, GP, and Johnson, GA. "Maximizing contrast to noise with inductively coupled implanted coils." Invest Radiol 25.5 (May 1990): 552-558.
PMID
2345087
Source
pubmed
Published In
Investigative Radiology
Volume
25
Issue
5
Publish Date
1990
Start Page
552
End Page
558

Observation of a water-depletion region surrounding loblolly pine roots by magnetic resonance imaging.

Magnetic resonance imaging was used to study sand containing various amounts of water and roots of loblolly pine planted into similar sand. Spin-lattice (T1) relaxation times of sand with water contents ranging from 0 to 25% (wt/wt) ranged from 472 to 1265 ms and increased with water content. Spin-spin (T2) relaxation times ranged from 54 to 76 ms and did not change in a discernible pattern with water content. Based on water content and measured T1 and T2 values, the signal intensity of sand/water images was predicted to increase with water content in a linear fashion, with the slope of the lines increasing with the time of acquisition repetition (TR). Measured signal intensity from images of sand with various water contents was found to follow a similar pattern. This allows interpretation of dark images of sand/water to be regions of low water content, and bright images to have comparatively greater water content. Images of loblolly pine seedling roots planted in identical sand showed the formation of a distinct water-depletion region first around the woody taproot and later showed the region extended and expanded around the lateral roots and clusters of mycorrhizal short roots. This observation strongly suggests that water uptake is occurring through the suberized region of the woody taproot.

Authors
MacFall, JS; Johnson, GA; Kramer, PJ
MLA Citation
MacFall, JS, Johnson, GA, and Kramer, PJ. "Observation of a water-depletion region surrounding loblolly pine roots by magnetic resonance imaging." Proc Natl Acad Sci U S A 87.3 (February 1, 1990): 1203-1207.
PMID
11607063
Source
pubmed
Published In
Proceedings of the National Academy of Sciences of USA
Volume
87
Issue
3
Publish Date
1990
Start Page
1203
End Page
1207

Computer tomographic analysis of water distribution and flow in porous media

Computer tomography (CT) is the reconstruction by computer of a tomographic plane (slice) of an object. The tomograph is developed from multiple X-ray absorption measurements (scans) made around the periphery of the object. Recent research in soil science indicates that CT, which has been used in the medical field for 17 years, may find applications in assessing the degree of uniformity, or lack thereof, of soils and other porous media, in determining the flow paths of water and solutes through soils and porous materials, and in determing the flow paths of water and solutes to roots of plants. This paper discusses the general concept of CT, some of the capabilities associated with software used to format the CT readings into the desired images, and presents some CT scan data for several draining porous media. © 1990 Springer-Verlag.

Authors
Cassel, DK; Brown, JM; Johnson, GA
MLA Citation
Cassel, DK, Brown, JM, and Johnson, GA. "Computer tomographic analysis of water distribution and flow in porous media." Theoretical and Applied Climatology 42.4 (1990): 223-228.
Source
scival
Published In
Theoretical and Applied Climatology
Volume
42
Issue
4
Publish Date
1990
Start Page
223
End Page
228
DOI
10.1007/BF00865982

Use of nuclear magnetic resonance microscopy for noninvasive observations of root-soil water relations

As part of our strategy to study root-soil water relationships, it was necessary to develop a nondestructive technique to detect small changes in water distribution in and near the root. Nuclear magnetic resonance imaging (MRI), clinically used to nondestructively and noninvasively acquire anatomical information, can also be used to observe water distribution in roots, soils and other plant tissues. In MRI, a sample is placed in a strong magnetic field and a sequence of radio frequency (rf) pulses and magnetic field gradients is used to measure the concentration and relaxation properties of protons, chiefly those associated with water. This information is then reconstructed into a digital image representing the spatial distribution of water in plant tissues and soil. Today, intact roots less than 1 mm in diameter growing in soil or synthetic media can be clearly imaged in less than 4 minutes at resolutions typically less than 30μm. This permits rapid production of images that simultaneously distinguish temporal changes in water distribution in root tissue, the rhizosphere and the adjacent soil at microscopic levels. Applications of this technique for investigating plant-soil water relationships will be discussed. © 1990 Springer-Verlag.

Authors
Brown, JM; Kramer, PJ; Cofer, GP; Johnson, GA
MLA Citation
Brown, JM, Kramer, PJ, Cofer, GP, and Johnson, GA. "Use of nuclear magnetic resonance microscopy for noninvasive observations of root-soil water relations." Theoretical and Applied Climatology 42.4 (1990): 229-236.
Source
scival
Published In
Theoretical and Applied Climatology
Volume
42
Issue
4
Publish Date
1990
Start Page
229
End Page
236
DOI
10.1007/BF00865983

Magnetic resonance imaging of the thoracic cavity using a paused 3DFT acquisition technique.

A new pulse sequence designed for magnetic resonance imaging of the entire thoracic cavity is described. This sequence, called 3DPAUSE, is a rapid three-dimensional Fourier transform (3DFT) sequences with periodic pauses for breathing and additional rf pulses after each pause to restore the magnetization to steady-state before data acquisition resumes. Cardiac motion artifacts are effectively removed by signal averaging. Respiratory motion artifacts are removed by breath hold. Image artifacts caused by an inadequate number of pauses or by inappropriate placement of the pauses within a scan are shown, and ways to avoid these artifacts are discussed. 3DPAUSE provides the ability to acquire three-dimensional arrays in the thoracic cavity with minimal artifacts from respiratory and cardiac motions in a clinically reasonable time.

Authors
Stern, RL; Johnson, GA; Ravin, CE
MLA Citation
Stern, RL, Johnson, GA, and Ravin, CE. "Magnetic resonance imaging of the thoracic cavity using a paused 3DFT acquisition technique." Magn Reson Imaging 8.6 (1990): 747-753.
PMID
2266801
Source
pubmed
Published In
Magnetic Resonance Imaging
Volume
8
Issue
6
Publish Date
1990
Start Page
747
End Page
753

Integrated network for medical imaging research

There are a number of generic problems that researchers in medical imaging have in common. For example, researchers in MR, CT, PET, SPECT, DSA, and digital radiography all need to display and window digital images. We describe here an integrated with tools applicable to all of the current areas of medical imaging that enable researchers at Duke to share resources and solve software and hardware problems in a unified effort. We will show examples where efforts in a specific area of imaging research can be readily applied in new ways to different imaging modalities through the facilities provided in this integrated approach. We will point out some of the problems and opportunities in the research environment that are different from those encountered in clinical PACS system.

Authors
Johnson, GA; Chotas, HG; Suddarth, SA; Ziv, SB; Todd, BE
MLA Citation
Johnson, GA, Chotas, HG, Suddarth, SA, Ziv, SB, and Todd, BE. "Integrated network for medical imaging research." Proceedings of SPIE - The International Society for Optical Engineering 1234 pt 1 (1990): 159-166.
Source
scival
Published In
Proceedings of SPIE - The International Society for Optical Engineering
Volume
1234 pt 1
Publish Date
1990
Start Page
159
End Page
166

MR diffusion measurements in stroke models in rat brains

It is shown that tissue self-diffusion coefficients can be calculated from a series of diffusion-weighted MR (magnetic resonance) images. By variation of the time between diffusion sensitizing gradient pulses, the motions of tissue water may be characterized on varying length scales from 10 μm to 100 μm. Typically, the diffusion coefficient decreases as this diffusion time increases. Such characterization of tissue water properties may be of use in the study of the course of pathology in disease models.

Authors
MacFall, JR; Benveniste, H; Maki, J; Johnson, GA; Hedlund, L; Copher, G
MLA Citation
MacFall, JR, Benveniste, H, Maki, J, Johnson, GA, Hedlund, L, and Copher, G. "MR diffusion measurements in stroke models in rat brains." Proceedings of the Annual Conference on Engineering in Medicine and Biology pt 1 (1990): 67-68.
Source
scival
Published In
Proceedings of the Annual Conference on Engineering in Medicine and Biology
Issue
pt 1
Publish Date
1990
Start Page
67
End Page
68

Image optimization in a computed-radiography/photostimulable-phosphor system.

Photostimulable phosphor imaging is an exciting new technology that has several advantages over film/screen radiography, the most important of which is the linearity of the photostimulable phosphor system over a wide exposure latitude. The photostimulable phosphor image is digital, and as such, provides options of how the image is viewed by radiologists. This report discusses the various image-processing parameters available for a photostimulable phosphor system and describes a rational approach for selecting these parameters in portable chest radiography. As photostimulable phosphor imaging becomes more widely implemented, an understanding of the processing parameters will facilitate the production of images that take full advantage of the benefits of these systems.

Authors
Sherrier, RH; Chotas, HG; Johnson, GA; Chiles, C; Ravin, CE
MLA Citation
Sherrier, RH, Chotas, HG, Johnson, GA, Chiles, C, and Ravin, CE. "Image optimization in a computed-radiography/photostimulable-phosphor system." J Digit Imaging 2.4 (November 1989): 212-219.
PMID
2488166
Source
pubmed
Published In
Journal of Digital Imaging
Volume
2
Issue
4
Publish Date
1989
Start Page
212
End Page
219

Relaxation measurements at 300 MHz using MR microscopy.

Previous data on changes in tissue T1 with field have suggested the convergence of tissue T1 values toward a common value at high (greater than 4.0 T) fields. Measures of T2 dependence have suggested reduction of T2 with field. The purpose of this study was to observe the T1 and T2 at 85.5 and 300 MHz of microstructures in excised rat kidneys by employing MR microscopy. This study represents the first attempt of MR microscopy at 7.0 T with regard to the subject of magnetic field dependence of T1 and T2. As expected, T1 did increase with increasing field strength but not as dramatically as might be expected. Subtle differences in the microstructures of the kidney and the binding of water in those structures were discernible on the basis of T1 differences at 300 MHz. T2 values decreased, raising speculation concerning the mechanism for this dependence. The improved SNR permits smaller samples to be examined at much higher resolutions (greater than 30 X 30 X 200 microns), further extending the potentials for MR microscopy.

Authors
Dockery, SE; Suddarth, SA; Johnson, GA
MLA Citation
Dockery, SE, Suddarth, SA, and Johnson, GA. "Relaxation measurements at 300 MHz using MR microscopy." Magn Reson Med 11.2 (August 1989): 182-192.
PMID
2779411
Source
pubmed
Published In
Magnetic Resonance in Medicine
Volume
11
Issue
2
Publish Date
1989
Start Page
182
End Page
192

Magnetic resonance imaging of hepatic neoplasms in the rat.

Magnetic resonance imaging (MRI) at microscopic resolution was done on a live rat that had chemically induced hepatic neoplasms. Beginning at the anterior aspect of the liver, 16 contiguous transaxial slices (each 1.25 mm thick) were produced using three-dimensional Fourier transform sequences. The rat had been treated with diethylnitrosamine (200 mg/kg) at 70 days of age, and, subsequently, received periodic implants of 17a-ethynylestradiol for 60 weeks. Carr-Purcell-Meiboom-Gill (CPMG) sequences (repetition time = 2,000 and echo time = 20, 40, 60, 80 ms) were done to give quantitative measures of spin-spin relaxation times (T2). Pixel-by-pixel curve fitting from these multiple images yielded calculated T2 images. Histologic evaluation of three abnormal areas in the liver revealed solid and cystic hepatocellular adenomas. Although lesions were evident in early-echo images of the CPMG sequence, they were more apparent in the late-echo images. This was consistent with longer T2 relaxation times for the lesions. The voxels of dimensions (230 x 230 x 1,250 microns) permitted resolution of volume elements less than 0.07 mm3. This in turn permitted clear delineation of focal lesions less than 3 mm in diameter. The potential for MRI at microscopic resolution in toxicologic research is clearly demonstrated.

Authors
Johnson, GA; Thompson, MB; Cofer, GP; Campen, D; Maronpot, RR
MLA Citation
Johnson, GA, Thompson, MB, Cofer, GP, Campen, D, and Maronpot, RR. "Magnetic resonance imaging of hepatic neoplasms in the rat." Vet Pathol 26.4 (July 1989): 303-308.
PMID
2763419
Source
pubmed
Published In
Veterinary pathology
Volume
26
Issue
4
Publish Date
1989
Start Page
303
End Page
308
DOI
10.1177/030098588902600403

Pattern formation in flowing sand.

Authors
Baxter, GW; Behringer, RP; Fagert, T; Johnson, GA
MLA Citation
Baxter, GW, Behringer, RP, Fagert, T, and Johnson, GA. "Pattern formation in flowing sand." Phys Rev Lett 62.24 (June 12, 1989): 2825-2828.
PMID
10040101
Source
pubmed
Published In
Physical Review Letters
Volume
62
Issue
24
Publish Date
1989
Start Page
2825
End Page
2828
DOI
10.1103/PhysRevLett.62.2825

Implanted coil MR microscopy of renal pathology.

Inductively coupled implanted coils have been shown to provide up to a 10-fold increase in signal-to-noise ratio when compared to whole-body imaging of small animals. The current study was designed to extend the implanted coil imaging technique to a rodent model of renal pathology. Resonant radiofrequency (RF) coils were implanted around the left kidney of four rats and inductively coupled from within a birdcage body coil. All images were acquired at 2 T using a T1-weighted spin-echo sequence with TR = 500 ms and TE = 20 ms. In vivo MR microscopy with voxels of 117 x 117 x 2000 microns demonstrated cortex, inner and outer medulla, and major vascular structures on baseline images. Mercuric chloride-induced nephrotoxic acute tubular necrosis (ATN) diminished cortico-medullary contrast at 24 h after dosing with pathologic evaluation demonstrating nephrotoxic changes in the inner cortex. The kidney regained a baseline MR appearance 360 h after dosing and resolution of the damage was confirmed with histology. T1 data were gathered on excised kidneys as an adjunct to the images to help correlate the loss and return of cortico-medullary contrast with the pathology and pathophysiology of nephrotoxic ATN. With implanted RF coils we were able to demonstrate renal pathology and follow its subsequent resolution. Specifically, loss and return of cortico-medullary contrast as a result of nephrotoxic ATN were serially documented in four rats. Such serial in vivo studies performed on single animals should further the use of MR microscopy by minimizing the number of animals required for adequate biostatistics.

Authors
Farmer, TH; Johnson, GA; Cofer, GP; Maronpot, RR; Dixon, D; Hedlund, LW
MLA Citation
Farmer, TH, Johnson, GA, Cofer, GP, Maronpot, RR, Dixon, D, and Hedlund, LW. "Implanted coil MR microscopy of renal pathology." Magn Reson Med 10.3 (June 1989): 310-323.
PMID
2733588
Source
pubmed
Published In
Magnetic Resonance in Medicine
Volume
10
Issue
3
Publish Date
1989
Start Page
310
End Page
323

3-DIMENSIONAL IMAGING OF THE THORACIC CAVITY

Authors
STERN, RL; CLINE, HE; JOHNSON, GA; RAVIN, CE
MLA Citation
STERN, RL, CLINE, HE, JOHNSON, GA, and RAVIN, CE. "3-DIMENSIONAL IMAGING OF THE THORACIC CAVITY." INVESTIGATIVE RADIOLOGY 24.4 (April 1989): 282-288.
Source
wos-lite
Published In
Investigative Radiology
Volume
24
Issue
4
Publish Date
1989
Start Page
282
End Page
288
DOI
10.1097/00004424-198904000-00005

Three-dimensional imaging of the thoracic cavity.

Three-dimensional (3D) surface reconstruction techniques were applied to sets of computed tomographic (CT) images of the thoracic cavity. Emphasis was placed on extracting lung images. High quality, detailed 3D images of the lung surface and internal bronchial and vascular structures were produced.

Authors
Stern, RL; Cline, HE; Johnson, GA; Ravin, CE
MLA Citation
Stern, RL, Cline, HE, Johnson, GA, and Ravin, CE. "Three-dimensional imaging of the thoracic cavity." Invest Radiol 24.4 (April 1989): 282-288.
PMID
2745007
Source
pubmed
Published In
Investigative Radiology
Volume
24
Issue
4
Publish Date
1989
Start Page
282
End Page
288

Vascular morphology by three-dimensional magnetic resonance imaging.

A three-dimensional examination of blood vessels is provided using MR data from seven cases. The vascular surfaces are constructed with an algorithm that automatically follows the selected artery or vein and generates a projected three-dimensional gradient shaded image. Fast 3DFT pulse sequences were optimized to enhance the time-of-flight contrast of the intravascular region. By increasing the surface threshold value in a three-dimensional head study, the flesh of a patient's face was peeled away to demonstrate the superfacial temporal artery. Gated cardiac images show the great vessels and cardiac chambers. A three-dimensional view of the aorta shows an irregular surface in the vicinity of an adrenal tumor. 3D MR exams provide a non-invasive technique for assessing vascular morphology in a clinical setting.

Authors
Cline, HE; Lorensen, WE; Herfkens, RJ; Johnson, GA; Glover, GH
MLA Citation
Cline, HE, Lorensen, WE, Herfkens, RJ, Johnson, GA, and Glover, GH. "Vascular morphology by three-dimensional magnetic resonance imaging." Magn Reson Imaging 7.1 (January 1989): 45-54.
PMID
2918818
Source
pubmed
Published In
Magnetic Resonance Imaging
Volume
7
Issue
1
Publish Date
1989
Start Page
45
End Page
54

In Situ Observations of Root-gall Formation Using Nuclear Magnetic Resonance Imaging.

Authors
Matyac, CA; Cofer, GP; Bailey, JE; Johnson, GA
MLA Citation
Matyac, CA, Cofer, GP, Bailey, JE, and Johnson, GA. "In Situ Observations of Root-gall Formation Using Nuclear Magnetic Resonance Imaging." J Nematol 21.1 (January 1989): 131-134.
PMID
19287587
Source
pubmed
Published In
Journal of nematology
Volume
21
Issue
1
Publish Date
1989
Start Page
131
End Page
134

Chemical shift imaging of atherosclerosis at 7.0 Tesla.

Chemical shift imaging (CSI) was performed on cadaveric atherosclerotic fibrous plaques, periaortic adipose tissue, and cholesterol standards using a 7.0 Tesla horizontal bore prototype imaging spectrometer. Proton spectroscopy of intact tissue and deuterated chloroform extracted samples was done at the equivalent field strength of 7.0 Tesla on a vertical bore spectrometer, including studies of temperature dependence and T2 relaxation measurements. Spectra obtained using CSI on the imaging magnet were comparable with those from the conventional vertical spectrometer. Fibrous plaques and adipose tissue had unique spectral features, differing in the ratios of their water and various fat components. Chloroform extractions revealed a typical cholesteric ester spectrum for the fibrous plaque in contrast to the triglyceride spectrum of the adipose tissue. These two tissues also had different T2 relaxation measurements of their major fat resonances, with fibrous plaques having a short T2 compared to adipose tissue (15.9 milliseconds vs. 46.2 milliseconds). Temperature dependence studies showed that spectral signal intensity of the fat resonance of the fibrous plaque increased while linewidth decreased with increasing temperature from 24 degrees C to 37 degrees C. Atherosclerotic lesions may be studied at 7.0 Tesla, and NMR parameters defined in the present study may be used for further studies at other magnetic field strengths.

Authors
Maynor, CH; Charles, HC; Herfkens, RJ; Suddarth, SA; Johnson, GA
MLA Citation
Maynor, CH, Charles, HC, Herfkens, RJ, Suddarth, SA, and Johnson, GA. "Chemical shift imaging of atherosclerosis at 7.0 Tesla." Invest Radiol 24.1 (January 1989): 52-60.
PMID
2917823
Source
pubmed
Published In
Investigative Radiology
Volume
24
Issue
1
Publish Date
1989
Start Page
52
End Page
60

In vivo magnetic resonance microscopy at 5 μm

Authors
Cofer, GP; Brown, JM; Johnson, GA
MLA Citation
Cofer, GP, Brown, JM, and Johnson, GA. "In vivo magnetic resonance microscopy at 5 μm." Journal of Magnetic Resonance (1969) 83.3 (1989): 608-616.
Source
scival
Published In
Journal of Magnetic Resonance (1969)
Volume
83
Issue
3
Publish Date
1989
Start Page
608
End Page
616
DOI
10.1016/0022-2364(89)90354-5

Magnetic resonance microscopy of chemically-induced liver foci.

Magnetic resonance imaging (MRI) is a new imaging technique used in clinical diagnosis. This paper describes extension of the technique to basic research applications--specifically detecting and characterizing chemically-induced liver neoplasms and foci of cellular alteration. Two systems have been built that allow spatial microscopic resolution--more than 100,000 x greater than that of earlier efforts. Use of spin-lattice (T1) and spin-spin (T2) relaxation times permits detailed characterization of the tissue.

Authors
Johnson, GA; Maronpot, RR
MLA Citation
Johnson, GA, and Maronpot, RR. "Magnetic resonance microscopy of chemically-induced liver foci." Toxicol Pathol 17.4 Pt 1 (1989): 613-616.
PMID
2629098
Source
pubmed
Published In
Toxicologic Pathology (Sage)
Volume
17
Issue
4 Pt 1
Publish Date
1989
Start Page
613
End Page
616
DOI
10.1177/0192623389017004106

Magnetic resonance microscopy of chemically-induced liver foci

Magnetic resonance imaging (MRI) is a new imaging technique used in clinical diagnosis. This paper describes extension of the technique to basic research applications - specifically detecting and characterizing chemically-induced liver neoplasms and foci of cellular alteration. Two systems have been built that allow spatial microscopic resolution - more than 100,000x greater than that of earlier efforts. Use of spin-lattice (T1) and spin-spin (T2) relaxation times permits detailed characterization of the tissue.

Authors
Johnson, GA; Maronpont, RR
MLA Citation
Johnson, GA, and Maronpont, RR. "Magnetic resonance microscopy of chemically-induced liver foci." Toxicologic Pathology 17.4 I (1989): 613-616.
Source
scival
Published In
Toxicologic Pathology (Sage)
Volume
17
Issue
4 I
Publish Date
1989
Start Page
613
End Page
616

THE IMPACT OF INCREASED SPIN-LATTICE RELAXATION-TIME MICROSCOPY AT 7.0T

Authors
DOCKERY, S; SUDDARTH, SA; COFER, GP; JOHNSON, GA
MLA Citation
DOCKERY, S, SUDDARTH, SA, COFER, GP, and JOHNSON, GA. "THE IMPACT OF INCREASED SPIN-LATTICE RELAXATION-TIME MICROSCOPY AT 7.0T." INVESTIGATIVE RADIOLOGY 23.9 (September 1988): S20-S20.
Source
wos-lite
Published In
Investigative Radiology
Volume
23
Issue
9
Publish Date
1988
Start Page
S20
End Page
S20

MR MICROSCOPY OF NEPHROTOXIC ACUTE TUBULAR-NECROSIS IN THE RAT

Authors
FARMER, THR; JOHNSON, GA; COFER, GP; MARONPOT, RR; HEDLUND, LW
MLA Citation
FARMER, THR, JOHNSON, GA, COFER, GP, MARONPOT, RR, and HEDLUND, LW. "MR MICROSCOPY OF NEPHROTOXIC ACUTE TUBULAR-NECROSIS IN THE RAT." INVESTIGATIVE RADIOLOGY 23.9 (September 1988): S10-S10.
Source
wos-lite
Published In
Investigative Radiology
Volume
23
Issue
9
Publish Date
1988
Start Page
S10
End Page
S10

INVITRO CHEMICAL-SHIFT IMAGING OF ATHEROSCLEROSIS AT 7.0-TESLA

Authors
MAYNOR, CH; CHARLES, HC; HERFKENS, RJ; SUDDARTH, SA; JOHNSON, GA
MLA Citation
MAYNOR, CH, CHARLES, HC, HERFKENS, RJ, SUDDARTH, SA, and JOHNSON, GA. "INVITRO CHEMICAL-SHIFT IMAGING OF ATHEROSCLEROSIS AT 7.0-TESLA." INVESTIGATIVE RADIOLOGY 23.9 (September 1988): S3-S3.
Source
wos-lite
Published In
Investigative Radiology
Volume
23
Issue
9
Publish Date
1988
Start Page
S3
End Page
S3

MAGNETIC-RESONANCE MICROSCOPY OF STEM TISSUES OF PELARGONIUM HORTORUM

Authors
BROWN, JM; THOMAS, JF; COFER, GP; JOHNSON, GA
MLA Citation
BROWN, JM, THOMAS, JF, COFER, GP, and JOHNSON, GA. "MAGNETIC-RESONANCE MICROSCOPY OF STEM TISSUES OF PELARGONIUM HORTORUM." BOTANICAL GAZETTE 149.3 (September 1988): 253-259.
Source
wos-lite
Published In
Botanical Gazette
Volume
149
Issue
3
Publish Date
1988
Start Page
253
End Page
259
DOI
10.1086/337713

MR MICROSCOPY USING DRIVEN EQUILIBRIUM (DEFT)

Authors
MAKI, JH; COFER, GP; HEDLUND, LW; MACFALL, JR; JOHNSON, GA
MLA Citation
MAKI, JH, COFER, GP, HEDLUND, LW, MACFALL, JR, and JOHNSON, GA. "MR MICROSCOPY USING DRIVEN EQUILIBRIUM (DEFT)." INVESTIGATIVE RADIOLOGY 23.9 (September 1988): S21-S21.
Source
wos-lite
Published In
Investigative Radiology
Volume
23
Issue
9
Publish Date
1988
Start Page
S21
End Page
S21

DEVELOPMENT OF A 3D RECONSTRUCTED-IMAGE SURGICAL PLANNING STATION

Authors
STERN, RL; CLINE, HE; JOHNSON, GA; RAVIN, CE
MLA Citation
STERN, RL, CLINE, HE, JOHNSON, GA, and RAVIN, CE. "DEVELOPMENT OF A 3D RECONSTRUCTED-IMAGE SURGICAL PLANNING STATION." INVESTIGATIVE RADIOLOGY 23.9 (September 1988): S60-S60.
Source
wos-lite
Published In
Investigative Radiology
Volume
23
Issue
9
Publish Date
1988
Start Page
S60
End Page
S60

FILM-BASED DIGITAL TOMOSYNTHESIS OF THE CHEST

Authors
SHERRIER, RH; SUDDARTH, SA; JOHNSON, GA
MLA Citation
SHERRIER, RH, SUDDARTH, SA, and JOHNSON, GA. "FILM-BASED DIGITAL TOMOSYNTHESIS OF THE CHEST." OPTICAL ENGINEERING 27.8 (August 1988): 691-695.
Source
wos-lite
Published In
Optical Engineering
Volume
27
Issue
8
Publish Date
1988
Start Page
691
End Page
695
DOI
10.1117/12.7976742

Magnetic resonance microscopy of chick embryos in ovo.

Magnetic resonance imaging (MRI) of the live 11-day chick embryo with special radiofrequency coils and 3-D imaging methods has produced contiguous 1.25-mm-thick slices with 200-microns pixel resolution, permitting definition of cardiac chambers, cerebral ventricles, spinal cord, liver, and lungs. It was the objective of this study to image younger chick embryos in ovo with higher spatial resolution through the application of implanted radiofrequency coils. Fertilized Arbor Acre eggs were windowed at 9, 6, and 4 days. Circular coils 18 mm in diameter tuned to 85.5 MHz were suspended around the developing embryo. The eggs were sealed with tape and maintained at 37 degrees C during the imaging procedure. MRI was performed in a 2.0-Tesla GE system utilizing a 3-D Fourier transform acquisition in sagittal and axial planes with a partial saturation sequence (TR = 400 ms, TE = 27 ms). Approximately 1 hour of imaging time was required to obtain 16 contiguous 600-microns-thick slices with 50-microns pixel resolution. Embryos remained viable through the imaging procedure. Embryos were photographed, fixed, and cleared for correlative anatomical study. Vitelline vessels, dorsal aorta, aortic arches, cardinal veins, and cardiac chambers were identified as areas of decreased signal intensity. Cerebral ventricles and the vitreous portion of the eye have signal intensities that are less than adjacent neural, scleral, and lens tissue. Further refinements in MR instrumentation and imaging sequences promise improvements in resolution and offer the potential for sequential observations of the intact embryo.

Authors
Effmann, EL; Johnson, GA; Smith, BR; Talbott, GA; Cofer, G
MLA Citation
Effmann, EL, Johnson, GA, Smith, BR, Talbott, GA, and Cofer, G. "Magnetic resonance microscopy of chick embryos in ovo." Teratology 38.1 (July 1988): 59-65.
PMID
3175940
Source
pubmed
Published In
Teratology
Volume
38
Issue
1
Publish Date
1988
Start Page
59
End Page
65
DOI
10.1002/tera.1420380109

MR imaging of the knee: preliminary results with a 3DFT GRASS pulse sequence.

The knees of 17 patients (18 extremities) with possible meniscal, cruciate ligament, and articular cartilage abnormalities were examined with a three-dimensional Fourier transform (3DFT), gradient-refocused acquisition in a steady state (GRASS) pulse sequence. Arthroscopic confirmation was available in all cases and was the standard for comparison. Thirteen of these extremities were also examined by using a two-dimensional Fourier transform spin-echo pulse sequence with a 2000-msec repetition time and 20- and 80-msec echo time. In these 13 cases, both pulse sequences correctly identified seven of eight meniscal abnormalities. However, interpretation of the 3DFT GRASS images resulted in fewer false-positive meniscal tears (three vs six). Cruciate ligament tears were detected more readily on the 3DFT GRASS images (six vs three with two possible tears on the spin-echo images). These preliminary findings suggest that the overall accuracy of MR imaging of the knee could be improved by including 3DFT gradient-refocused pulse sequences.

Authors
Spritzer, CE; Vogler, JB; Martinez, S; Garrett, WE; Johnson, GA; McNamara, MJ; Lohnes, J; Herfkens, RJ
MLA Citation
Spritzer, CE, Vogler, JB, Martinez, S, Garrett, WE, Johnson, GA, McNamara, MJ, Lohnes, J, and Herfkens, RJ. "MR imaging of the knee: preliminary results with a 3DFT GRASS pulse sequence." AJR Am J Roentgenol 150.3 (March 1988): 597-603.
PMID
3257617
Source
pubmed
Published In
AJR. American journal of roentgenology
Volume
150
Issue
3
Publish Date
1988
Start Page
597
End Page
603
DOI
10.2214/ajr.150.3.597

Effects of image processing on nodule detection rates in digitized chest radiographs: ROC study of observer performance.

To evaluate the effects of image processing in digitized chest radiographs when high-resolution images are used, an examination was done in which the detection of pulmonary nodules in unprocessed digitized chest radiographs was compared with that in images that had undergone processing with two methods, adaptive filtration and histogram equalization. The processing techniques have been optimized in previous work to selectively enhance the retrocardiac and subdiaphragmatic areas without significant alteration of detail in the lung. Eight observers were shown 150 test radiographs (50 unprocessed, 50 processed with adaptive filtration, 50 processed with histogram equalization) containing 150 nodules. The results indicate a statistically significant (P less than .03) difference, with highest observer performance in the chest radiographs processed with adaptive filtration (median area under ROC curve = 0.78), compared with unprocessed images (median = 0.68) and chest radiographs processed with histogram equalization (median = 0.62). Performance in the lung was not significantly different. Adaptive filtration applied to selectively enhance underexposed areas of film images may improve nodule detection. Histogram equalization provided no improvement in performance.

Authors
Sherrier, RH; Chiles, C; Wilkinson, WE; Johnson, GA; Ravin, CE
MLA Citation
Sherrier, RH, Chiles, C, Wilkinson, WE, Johnson, GA, and Ravin, CE. "Effects of image processing on nodule detection rates in digitized chest radiographs: ROC study of observer performance." Radiology 166.2 (February 1988): 447-450.
PMID
3336719
Source
pubmed
Published In
Radiology
Volume
166
Issue
2
Publish Date
1988
Start Page
447
End Page
450
DOI
10.1148/radiology.166.2.3336719

Magnetic resonance microscopy: in vivo sectioning of a developing insect.

The utility of magnetic resonance imaging vis-a-vis insect morphology and development was investigated. MRI is a noninvasive technique that distinguishes between tissues based on proton content and proton 'environment'. At present a resolution of 100 micron is achievable. The technique avoids fixation artifacts and allows the detection of motion within the organism.

Authors
Conner, WE; Johnson, GA; Cofer, GP; Dittrich, K
MLA Citation
Conner, WE, Johnson, GA, Cofer, GP, and Dittrich, K. "Magnetic resonance microscopy: in vivo sectioning of a developing insect." Experientia 44.1 (January 15, 1988): 11-12.
PMID
3350110
Source
pubmed
Published In
Experientia
Volume
44
Issue
1
Publish Date
1988
Start Page
11
End Page
12

Magnetic resonance imaging (MRI): a new tool in experimental toxicologic pathology.

Magnetic Resonance Imaging (MRI) is a noninvasive imaging technique that provides multidimensional images of the soft tissues of the body. This imaging technique has proven to be an excellent diagnostic and experimental tool for the detection of pathologic alterations in soft tissues, as well as an adjunct screening method for following the genesis, progression, or regression of chemically induced lesions in the same live animal. Future applications of MRI technology in small animals include MRI microscopy, mapping of vascular or circulatory alterations, measurement of perfusion and diffusion rates of body fluids, and acquisition of cell metabolic states in combination with Nuclear Magnetic Resonance (NMR) spectroscopy, all of which will contribute immensely to the advancement of toxicologic and biomolecular research.

Authors
Dixon, D; Johnson, GA; Cofer, GP; Hedlund, LW; Maronpot, RR
MLA Citation
Dixon, D, Johnson, GA, Cofer, GP, Hedlund, LW, and Maronpot, RR. "Magnetic resonance imaging (MRI): a new tool in experimental toxicologic pathology." Toxicol Pathol 16.3 (1988): 386-391.
PMID
3194661
Source
pubmed
Published In
Toxicologic Pathology (Sage)
Volume
16
Issue
3
Publish Date
1988
Start Page
386
End Page
391
DOI
10.1177/019262338801600311

SNR improvement in NMR microscopy using DEFT

This paper examines the use of a driven equilibrium Fourier transform (DEFT) pulse sequence for improving the signal per unit time and hence image resolution in NMR microscopy. DEFT vs partial saturation (PS) is modeled and it is shown that DEFT is most useful in physiologic materials provided short TE values (TE ≪ T2) and short TR values (TR < T1) are used. Under these conditions, DEFT can yield up to a fourfold signal increase compared to PS. It is shown that DEFT can provide spin density and T1/T2-ratio-weighted images. DEFT is also shown to have SNR advantages as T1 increases-an important consideration at higher magnetic fields. Experimental data that verify the theoretical predictions and the functioning of a DEFT pulse sequence to produce high-quality 2D spin-warp images of a phantom are presented. Studies performed on small animals demonstrate the utility of the DEFT sequence in MR microscopy by providing increased SNR and new contrast mechanisms over limited fields of view. © 1988.

Authors
Maki, JH; Johnson, GA; Cofer, GP; MacFall, JR
MLA Citation
Maki, JH, Johnson, GA, Cofer, GP, and MacFall, JR. "SNR improvement in NMR microscopy using DEFT." Journal of Magnetic Resonance (1969) 80.3 (1988): 482-492.
Source
scival
Published In
Journal of Magnetic Resonance (1969)
Volume
80
Issue
3
Publish Date
1988
Start Page
482
End Page
492
DOI
10.1016/0022-2364(88)90243-0

Magnetic resonance imaging (MRI): A new tool in experimental toxicologic pathology

Magnetic Resonance Imaging (MRI) is a noninvasive imaging technique that provides multidimensional images of the soft tissues of the body. This imaging technique has proven to be an excellent diagnostic and experimental tool for the detection of pathologic alterations in soft tissues, as well as an adjunct screening method for following the genesis, progression, or regression of chemically induced lesions in the same live animal. Future applications of MRI technology in small animals include MRI microscopy, mapping of vascular or circulatory alterations, measurement of perfusion and diffusion rates of body fluids, and acquisition of cell metabolic states in combination with Nuclear Magnetic Resonance (NMR) spectroscopy, all of which will contribute immensely to the advancement of toxicologic and biomolecular research.

Authors
Dixon, D; Johnson, GA; Cofer, GP; Hedlund, LW; Maronpot, RR
MLA Citation
Dixon, D, Johnson, GA, Cofer, GP, Hedlund, LW, and Maronpot, RR. "Magnetic resonance imaging (MRI): A new tool in experimental toxicologic pathology." Toxicologic Pathology 16.3 (1988): 387-391.
Source
scival
Published In
Toxicologic Pathology
Volume
16
Issue
3
Publish Date
1988
Start Page
387
End Page
391

In situ magnetic resonance microscopy.

Recent developments in MR permit imaging at microscopic resolution. Efforts have focused on small samples that fit entirely in the imaging probe. Extension of the techniques to imaging of individual organs in small animals is complicated by both the need to acquire an excessive number of phase encodings and limited signal to noise. Implantable radiofrequency coils described in this work eliminate both problems, permitting MR microscopy in the kidney of a live 200-g rat with spatial resolution of 117 X 117 X 1250 mu (.02 mm3). Inductive coupling permits complete freedom from external leads. A phantom designed to evaluate dielectric losses is described. Both phantom and in vivo comparison of live kidney images demonstrate the tenfold improvement in signal to noise obtained with the implantable coil.

Authors
Hollett, MD; Cofer, GP; Johnson, GA
MLA Citation
Hollett, MD, Cofer, GP, and Johnson, GA. "In situ magnetic resonance microscopy." Invest Radiol 22.12 (December 1987): 965-968.
PMID
3440731
Source
pubmed
Published In
Investigative Radiology
Volume
22
Issue
12
Publish Date
1987
Start Page
965
End Page
968

MAGNETIC-RESONANCE-IMAGING OF ROOT-WATER DISTRIBUTION

Authors
BROWN, JM; KRAMER, PJ; COFER, GP; JOHNSON, GA
MLA Citation
BROWN, JM, KRAMER, PJ, COFER, GP, and JOHNSON, GA. "MAGNETIC-RESONANCE-IMAGING OF ROOT-WATER DISTRIBUTION." HORTSCIENCE 22.5 (October 1987): 1087-1087.
Source
wos-lite
Published In
HortScience : a publication of the American Society for Horticultural Science
Volume
22
Issue
5
Publish Date
1987
Start Page
1087
End Page
1087

Magnetic resonance imaging in multiple sclerosis: decreased signal in thalamus and putamen.

High-field strength (1.5 Tesla) magnetic resonance imaging in 15 patients with multiple and extensive white-matter lesions and clinically definite multiple sclerosis delineated a previously undescribed finding of abnormally decreased signal intensity on T2-weighted images in the thalamus and putamen. The decreased signal intensity (preferential decreased T2 relaxation time) is most likely to be related to abnormally increased iron accumulation causing local magnetic field heterogeneities.

Authors
Drayer, BP; Burger, P; Hurwitz, B; Dawson, D; Cain, J; Leong, J; Herfkens, R; Johnson, GA
MLA Citation
Drayer, BP, Burger, P, Hurwitz, B, Dawson, D, Cain, J, Leong, J, Herfkens, R, and Johnson, GA. "Magnetic resonance imaging in multiple sclerosis: decreased signal in thalamus and putamen." Ann Neurol 22.4 (October 1987): 546-550.
PMID
3435073
Source
pubmed
Published In
Annals of Neurology
Volume
22
Issue
4
Publish Date
1987
Start Page
546
End Page
550
DOI
10.1002/ana.410220418

SMALL ANIMAL ANESTHESIA AND MONITORING DURING EXTENDED MR MICROSCOPY

Authors
HEDLUND, L; COFER, G; SUDDARTH, S; JOHNSON, GA
MLA Citation
HEDLUND, L, COFER, G, SUDDARTH, S, and JOHNSON, GA. "SMALL ANIMAL ANESTHESIA AND MONITORING DURING EXTENDED MR MICROSCOPY." INVESTIGATIVE RADIOLOGY 22.9 (September 1987): S44-S44.
Source
wos-lite
Published In
Investigative Radiology
Volume
22
Issue
9
Publish Date
1987
Start Page
S44
End Page
S44
DOI
10.1097/00004424-198709000-00193

Magnetic resonance microscopy of changes in water content in stems of transpiring plants.

Differences in water content and degree of binding in the various stem tissues of Pelargonium hortorum were observed by magnetic resonance imaging. 1H images were obtained with a resolution of 100 microns in the transverse plane and a slice thickness of 1250 microns. It was possible to distinguish the principal tissues of the stem by differences in their proton density or apparent water content and spin lattice relaxation time (T1) or degree of water binding. Measurements were made while the plant was slowly and actively transpiring. In the slowly transpiring plant, T1 of various tissues ranged from an average of 659 to 865 ms with a proton density variation of from 72 to 100%. In the actively transpiring plant, T1 ranged from an average of 511 to 736 ms, and the proton density was reduced, ranging between 62 and 88% of the peak value found in the slowly transpiring plant. The fibrous sheath surrounding the vascular tissue and the epidermal region was found to have the highest spin density and T1. Both tissues are comprised of relatively small thick-walled cells. Cortical and pith parenchyma are composed of larger, thinner-walled cells with numerous intercellular spaces and lower spin density and T1. The differences are attributed to the higher water content by volume in the tissue composed of smaller, more compactly arranged cells. The resolution obtained in this work enables clear definition of tissues in the living plant and quantitative information concerning differences in the distribution and extent of binding of water.

Authors
Johnson, GA; Brown, J; Kramer, PJ
MLA Citation
Johnson, GA, Brown, J, and Kramer, PJ. "Magnetic resonance microscopy of changes in water content in stems of transpiring plants." Proc Natl Acad Sci U S A 84.9 (May 1987): 2752-2755.
PMID
3472235
Source
pubmed
Published In
Proceedings of the National Academy of Sciences of USA
Volume
84
Issue
9
Publish Date
1987
Start Page
2752
End Page
2755

3-DIMENSIONAL MRI MICROSCOPY OF THE NORMAL RAT-BRAIN

Authors
JOHNSON, GA; THOMPSON, MB; DRAYER, BP
MLA Citation
JOHNSON, GA, THOMPSON, MB, and DRAYER, BP. "3-DIMENSIONAL MRI MICROSCOPY OF THE NORMAL RAT-BRAIN." MAGNETIC RESONANCE IN MEDICINE 4.4 (April 1987): 351-365.
Source
wos-lite
Published In
Magnetic Resonance in Medicine
Volume
4
Issue
4
Publish Date
1987
Start Page
351
End Page
365
DOI
10.1002/mrm.1910040406

MAGNETIC-RESONANCE MICROSCOPY OF LIVE CHICK-EMBRYOS IN OVO

Authors
EFFMANN, EL; JOHNSON, GA; SMITH, BR; TALBOTT, GA; COFER, G
MLA Citation
EFFMANN, EL, JOHNSON, GA, SMITH, BR, TALBOTT, GA, and COFER, G. "MAGNETIC-RESONANCE MICROSCOPY OF LIVE CHICK-EMBRYOS IN OVO." TERATOLOGY 35.2 (April 1987): A44-A44.
Source
wos-lite
Published In
Teratology
Volume
35
Issue
2
Publish Date
1987
Start Page
A44
End Page
A44

2-SECOND MR IMAGES - COMPARISON WITH SPIN-ECHO IMAGES IN 29 PATIENTS

Authors
UTZ, JA; HERFKENS, RJ; JOHNSON, CD; SHIMAKAWA, A; PELC, N; GLOVER, G; JOHNSON, GA; SPRITZER, CE
MLA Citation
UTZ, JA, HERFKENS, RJ, JOHNSON, CD, SHIMAKAWA, A, PELC, N, GLOVER, G, JOHNSON, GA, and SPRITZER, CE. "2-SECOND MR IMAGES - COMPARISON WITH SPIN-ECHO IMAGES IN 29 PATIENTS." AMERICAN JOURNAL OF ROENTGENOLOGY 148.3 (March 1987): 629-633.
Source
wos-lite
Published In
AJR. American journal of roentgenology
Volume
148
Issue
3
Publish Date
1987
Start Page
629
End Page
633

Two-second MR images: comparison with spin-echo images in 29 patients.

MR images can be obtained with a 2-sec scan time when an extremely short repetition rate (22 msec), limited flip angle (30 degrees), and gradient refocused echoes are used. Comparison of 415 such images obtained in 29 patients with routine T1-weighted (TR 500, TE 25) and T2-weighted (TR 2000, TE 80) images showed that images free of respiratory artifacts could be obtained in all patients. Although abdominal organs were well seen with 2-sec scan time, overall evaluation of these organs was better on routine T1-weighted images. Vascular structures, however, were seen as well or better on the 2-sec images in 60% of cases. The images were extremely sensitive to field nonhomogeneity, and metallic artifact was exaggerated in five patients with surgical clips. Two-sec MR images provide a rapid method of localizing abdominal organs for further evaluation. The sensitivity to blood flow may assist in the assessment of vascular patency.

Authors
Utz, JA; Herfkens, RJ; Johnson, CD; Shimakawa, A; Pelc, N; Glover, G; Johnson, GA; Spritzer, CE
MLA Citation
Utz, JA, Herfkens, RJ, Johnson, CD, Shimakawa, A, Pelc, N, Glover, G, Johnson, GA, and Spritzer, CE. "Two-second MR images: comparison with spin-echo images in 29 patients." AJR Am J Roentgenol 148.3 (March 1987): 629-633.
PMID
3492897
Source
pubmed
Published In
AJR. American journal of roentgenology
Volume
148
Issue
3
Publish Date
1987
Start Page
629
End Page
633
DOI
10.2214/ajr.148.3.629

Differentiation of benign from malignant pulmonary nodules with digitized chest radiographs.

To assess whether it is possible to distinguish benign from malignant solitary pulmonary nodules with digital techniques, a retrospective study of 68 patients with proved solitary nodules was performed. The conventional chest radiograph for each patient was digitized to 2,048 X 2,048 X 12 bits, and changes in the optical density within the nodule were analyzed. A number (the corrected gradient number) was then generated that reflected this variation. Striking differences were noted between 26 malignant nodules and 21 calcified granulomas. The technique was then applied to 21 benign nodules that had initially required thoracotomy or further study for diagnosis. In nine of these 21 patients (43%), the corrected gradient number allowed correct classification as a benign lesion.

Authors
Sherrier, RH; Chiles, C; Johnson, GA; Ravin, CE
MLA Citation
Sherrier, RH, Chiles, C, Johnson, GA, and Ravin, CE. "Differentiation of benign from malignant pulmonary nodules with digitized chest radiographs." Radiology 162.3 (March 1987): 645-649.
PMID
3809476
Source
pubmed
Published In
Radiology
Volume
162
Issue
3
Publish Date
1987
Start Page
645
End Page
649
DOI
10.1148/radiology.162.3.3809476

Performance of high-resolution monitors for digital chest imaging.

High-resolution cathode-ray tubes (CRT's) are currently the most viable soft-copy display for digital radiography. We present here methods for measuring large-area contrast ratio and detail contrast ratio. A two-dimensional charge coupled device (ccd) array signal-averaged with a video frame buffer permits linear microradiometric measure of individual beam lines. Results from three different 1000-line monitors demonstrate the shift variance of resolution. The detail contrast ratio (or modulation depth) was found to vary from 100% to less than 10% across the face of one CRT. Dynamic focus in both the horizontal and vertical deflection circuitry proved effective in reducing this shift variance. Comparisons of three phosphors demonstrate the utility of long persistence phosphors (P164) for static display in producing brighter images with less flicker. Recommendations for CRT design and selection for high-resolution digital radiography are included.

Authors
Suddarth, SA; Johnson, GA; Sherrier, RH; Ravin, CE
MLA Citation
Suddarth, SA, Johnson, GA, Sherrier, RH, and Ravin, CE. "Performance of high-resolution monitors for digital chest imaging." Med Phys 14.2 (March 1987): 253-257.
PMID
3587149
Source
pubmed
Published In
Medical physics
Volume
14
Issue
2
Publish Date
1987
Start Page
253
End Page
257
DOI
10.1118/1.596079

Contrast enhancement of the liver. Evaluation by automated contiguous pixel search.

Eight dogs were infused with one of three different contrast agents: meglumine diatrizoate, iosulamide meglumine, or an ethiodized oil emulsion (EOE 13). Image intensity in the liver was evaluated globally and regionally by means of an automated pixel sampling method to determine differences in the rate of enhancement produced by the three agents. The results of the automated method were compared with those of the standard manual cursor method. The automated method showed that liver parenchyma was enhanced uniformly by all three contrast agents. The maximum degree of enhancement (Mean +/- SEM) for the three agents was diatrizoate, 12.0 +/- 3.5 Hounsfield units (HU); iosluamide, 21.3 +/- 3.5 HU; and EOE 13, 37.2 +/- 4.25 HU. With the manual cursor method, contrast enhancement was about 20% more than estimated by the automated method. The automated method is better for evaluating the magnitude and pattern of contrast agent enhancement of the entire liver, since the currently employed cursor technique requires multiple evaluations to evaluate the entire liver.

Authors
Stude, RA; Hedlund, LW; Johnson, GA; Thompson, WM
MLA Citation
Stude, RA, Hedlund, LW, Johnson, GA, and Thompson, WM. "Contrast enhancement of the liver. Evaluation by automated contiguous pixel search." Invest Radiol 22.2 (February 1987): 132-136.
PMID
3030962
Source
pubmed
Published In
Investigative Radiology
Volume
22
Issue
2
Publish Date
1987
Start Page
132
End Page
136

RESOLUTION LIMITS IN MR - MR MICROSCOPY

Authors
JOHNSON, GA
MLA Citation
JOHNSON, GA. "RESOLUTION LIMITS IN MR - MR MICROSCOPY." MEDICAL PHYSICS 14.3 (1987): 499-499.
Source
wos-lite
Published In
Medical physics
Volume
14
Issue
3
Publish Date
1987
Start Page
499
End Page
499

IMPLEMENTATION OF ADAPTIVE FILTRATION FOR DIGITAL CHEST IMAGING.

Previous work has demonstrated the potential for adaptive filtration in processing digital chest images. The technique uses the histogram of the image to determine the pixels (and regions) in which edge enhancement is applied. This paper extends that work by investigating the choice of parameters used in selectively enhancing the mediastinum. The image is separated into its low and high frequency components by convolution with a square kernel. The effect of kernel size was studied with a choice of 17 multiplied by 17 mm, which was found to be sufficient to include the frequencies of interest. A serious deficiency in previous implementations of this technique is the existence of ringing artifacts at the juncture of the lung and mediastinum. These result in part from the use of a step function to specify the low frequency image intensity above which high frequencies are amplified. By replacing this step with a smoother (cosine) function, the artifact can be removed.

Authors
McAdams, HP; Johnson, GA; Suddarth, SA; Sherrier, RH; Ravin, CE
MLA Citation
McAdams, HP, Johnson, GA, Suddarth, SA, Sherrier, RH, and Ravin, CE. "IMPLEMENTATION OF ADAPTIVE FILTRATION FOR DIGITAL CHEST IMAGING." Optical Engineering 26.7 (1987): 669-674.
Source
scival
Published In
Optical Engineering
Volume
26
Issue
7
Publish Date
1987
Start Page
669
End Page
674

COMPUTED TOMOGRAPHIC ANALYSES OF WATER DISTRIBUTION IN THREE POROUS FOAM MEDIA.

Computer Assisted Tomography (CAT) is commonly used in diagnostic radiology to make nondestructive images and analyses of cross sections of the human body. CAT scanning may also be useful in imaging and measuring spatial distribution and changes in water distribution in porous media. The purpose of this paper is to review some of the details of CAT scanning that are of importance to the application of CAT scanning to porous media and to evaluate the use of the CAT scanner to measure the spatial distribution of water in three different porous media. The scanner's response to changes in the spatial distribution of water in three different porous phenolic foam materials after draining for 16 h was investigated. Water content distributions were successfully detected with good resolution on the x-ray image.

Authors
Brown, JM; Fonteno, WC; Cassel, DK; Johnson, GA
MLA Citation
Brown, JM, Fonteno, WC, Cassel, DK, and Johnson, GA. "COMPUTED TOMOGRAPHIC ANALYSES OF WATER DISTRIBUTION IN THREE POROUS FOAM MEDIA." Soil Science Society of America Journal 51.5 (1987): 1121-1125.
Source
scival
Published In
Soil Science Society of America Journal
Volume
51
Issue
5
Publish Date
1987
Start Page
1121
End Page
1125

Signal-to-noise improvements in three-dimensional NMR microscopy using limited-angle excitation

The 3D FT variant of spin-echo imaging has previously been successfully used to yield images at microscopic resolution. In obtaining such high resolution, optimization of signal to noise for a given acquisition time is crucial. Using a limited-angle (<60) slice-selective pulse one can improve the effective signal to noise or reduce the experimental time. The spin echo is generated through gradient refocusing. A phantom with T1 of 800 and 1200 ms was used to simulate white and gray matter. Signal intensity was modeled by the expression M= M0sinθ[1-exp(- TR T1)] 1-exp(- TR T1)cosθ For TR < 200 ms, limited-angle excitation can yield improvements in signal to noise by greater than a factor of two. These results were experimentally verified on a 1.5 T prototype system (General Electric, Milwaukee, Wis.) configured with gradient and rf coils designed for NMR microscopy. In those cases where signal-to-noise concerns do not require signal averaging beyond that which is inherent in the 3D FT technique, the limited-angle approach can reduce the acquisition time by as much as a factor of four. These results were verified in small animal studies of the brain of a 200 g rat. © 1987.

Authors
Karis, JP; Johnson, GA; Glover, GH
MLA Citation
Karis, JP, Johnson, GA, and Glover, GH. "Signal-to-noise improvements in three-dimensional NMR microscopy using limited-angle excitation." Journal of Magnetic Resonance (1969) 71.1 (1987): 24-33.
Source
scival
Published In
Journal of Magnetic Resonance (1969)
Volume
71
Issue
1
Publish Date
1987
Start Page
24
End Page
33

Rapid calculation of T1 using variable flip angle gradient refocused imaging.

We present a method for rapid measurement of T1 relaxation times using gradient refocused images at limited flip angles and short repetition times. This "variable nutation" techniques was investigated using a T1 phantom. There was a high correlation between measurements obtained with the variable nutation and partial saturation techniques. The ability of this method to create calculated T1 images is also demonstrated. We conclude that the variable nutation method may allow measurement of T1 relaxation times with a significant reduction in acquisition time compared to partial saturation techniques.

Authors
Fram, EK; Herfkens, RJ; Johnson, GA; Glover, GH; Karis, JP; Shimakawa, A; Perkins, TG; Pelc, NJ
MLA Citation
Fram, EK, Herfkens, RJ, Johnson, GA, Glover, GH, Karis, JP, Shimakawa, A, Perkins, TG, and Pelc, NJ. "Rapid calculation of T1 using variable flip angle gradient refocused imaging." Magn Reson Imaging 5.3 (1987): 201-208.
PMID
3626789
Source
pubmed
Published In
Magnetic Resonance Imaging
Volume
5
Issue
3
Publish Date
1987
Start Page
201
End Page
208

Methodology for the measurement and analysis of relaxation times in proton imaging.

Measurements of proton T1 and T2 were performed on GdCl3 solutions (20 less than T2 less than 500 msec, 90 less than T1 less than 1000 msec) on large-bore NMR imaging systems operating at 1.0T and 1.5T. CPMG multi-echo (ME), multiple saturation recovery (MSR) and modified fast inversion recovery (MFIR) pulse sequences as well as a sequence that combines and interleaves T1 and T2 weighted data acquisition (which we call "multiple saturation-recovery multiple-echo" (MSRME) were used. The relaxation data are compared to those obtained on a small bore NMR spectrometer operated at 1.5T. T1 and T2 values for the solutions were found to be the same within 10% for the two fields. Reproducibility of measurements of T1, T2 and the unnormalized spin density of the solutions was better than 5%. Systematic errors, amenable to correction through calibration, are noted in the imager T1 and T2 values. T1 and T2 values for some typical neural tissues at 1.5T and body tissue at 1.0T for human volunteers were obtained and are tabulated.

Authors
MacFall, JR; Wehrli, FW; Breger, RK; Johnson, GA
MLA Citation
MacFall, JR, Wehrli, FW, Breger, RK, and Johnson, GA. "Methodology for the measurement and analysis of relaxation times in proton imaging." Magn Reson Imaging 5.3 (1987): 209-220.
PMID
3041152
Source
pubmed
Published In
Magnetic Resonance Imaging
Volume
5
Issue
3
Publish Date
1987
Start Page
209
End Page
220

Regionally adaptive histogram equalization of the chest.

Advances in the area of digital chest radiography have resulted in the acquisition of high-quality images of the human chest. With these advances, there arises a genuine need for image processing algorithms specific to the chest, in order to fully exploit this digital technology. We have implemented the well-known technique of histogram equalization, noting the problems encountered when it is adapted to chest images. These problems have been successfully solved with our regionally adaptive histogram equalization method. With this technique histograms are calculated locally and then modified according to both the mean pixel value of that region as well as certain characteristics of the cumulative distribution function. This process, which has allowed certain regions of the chest radiograph to be enhanced differentially, may also have broader implications for other image processing tasks.

Authors
Sherrier, RH; Johnson, GA
MLA Citation
Sherrier, RH, and Johnson, GA. "Regionally adaptive histogram equalization of the chest." IEEE Trans Med Imaging 6.1 (1987): 1-7.
PMID
18230420
Source
pubmed
Published In
IEEE Transactions on Medical Imaging
Volume
6
Issue
1
Publish Date
1987
Start Page
1
End Page
7
DOI
10.1109/TMI.1987.4307791

REGIONALLY ADAPTIVE HISTOGRAM EQUALIZATION OF THE CHEST.

The authors have implemented the well-known technique of histogram equalization, noting the problems encountered when it is adapted to chest images. These problems have been successfully solved with a regionally adaptive histogram equalization method. With this technique, histograms are calculated locally and then modified according to both the mean pixel value of that region as well as certain characteristics of the cumulative distribution function. This process, which has allowed certain regions of the chest radiograph to be enhanced differentially, may also have broader implications for other image processing tasks.

Authors
Sherrier, RH; Johnson, GA
MLA Citation
Sherrier, RH, and Johnson, GA. "REGIONALLY ADAPTIVE HISTOGRAM EQUALIZATION OF THE CHEST." IEEE Transactions on Medical Imaging MI-6.1 (1987): 1-7.
Source
scival
Published In
IEEE Transactions on Medical Imaging
Volume
MI-6
Issue
1
Publish Date
1987
Start Page
1
End Page
7

In Vivo Magnetic Resonance Microscopy of Changing Water Content in Pelargonium hortorum Roots.

Magnetic resonance imaging (MRI) was used to nondestructively observe changes in water content in roots of Pelargonium hortorum x Bailey during a period of relatively rapid transpiration. Anatomical regions of the root could be differentiated with a spatial resolution of 0.1 x 0.1 mm. MRI shows great potential for study of plant-water relations.

Authors
Brown, JM; Johnson, GA; Kramer, PJ
MLA Citation
Brown, JM, Johnson, GA, and Kramer, PJ. "In Vivo Magnetic Resonance Microscopy of Changing Water Content in Pelargonium hortorum Roots." Plant Physiol 82.4 (December 1986): 1158-1160.
PMID
16665154
Source
pubmed
Published In
Plant physiology
Volume
82
Issue
4
Publish Date
1986
Start Page
1158
End Page
1160

Magnetic resonance microscopy of the rat thorax and abdomen.

With magnetic resonance (MR) microscopy, high-resolution volumetric imaging (3DFT) of small animals is possible. Although these techniques are suitable for imaging the head and other small stationary objects, breathing and cardiac motion degrade the quality of body images. Scan synchronous ventilation and cardiac gating methods have been developed that permit acquisition of high-resolution images from anywhere in the body of small animals (150 to 400 g). Anesthetized rats were ventilated in synchrony with three-dimensional Fourier spin warp (3DFT) sequence (TR = 400 to 1000 ms, TE = 20 ms). Eight or 16 slices (1.2 or 2.5 mm thick) were acquired simultaneously. Effective pixel size was 200 X 200 mu. Imaging was performed in a 1.5 T, 1-m bore research system using a 28-cm diameter high field gradient coil and a 6-cm diameter radio frequency coil. For thoracic imaging, acquisitions were gated to the QRS of the ECG. Scan synchronous ventilation eliminated breathing motion artifacts and permitted visualization of peripheral vascular structures in the lung and liver. In images that were also cardiac gated, cardiac chambers and major thoracic vessels, including the coronary arteries, were well demonstrated. Thus, thoroughly characterized rodent models can now be studied with MR not only to explore noninvasively the intricacies of mammalian pathomorphology, but also to test the capabilities of MR and aid in interpreting MR data.

Authors
Hedlund, LW; Johnson, GA; Mills, GI
MLA Citation
Hedlund, LW, Johnson, GA, and Mills, GI. "Magnetic resonance microscopy of the rat thorax and abdomen." Invest Radiol 21.11 (November 1986): 843-846.
PMID
3781788
Source
pubmed
Published In
Investigative Radiology
Volume
21
Issue
11
Publish Date
1986
Start Page
843
End Page
846

MR "microscopy" of the rat thorax.

High resolution images can be obtained from anywhere in the body of small animals with magnetic resonance combined with cardiac gating and scan synchronous ventilation. We used these methods to examine the intrathoracic anatomy of the rat. Anesthetized rats were intubated and ventilated in synchrony with imaging acquisition. Images were obtained in a 1 m bore, 1.5 T system fitted with a 28 cm diameter high field gradient coil and a 5 cm radio-frequency coil. We used cardiac gated, three-dimensional spin warp acquisitions. Eight contiguous slices (2.5 mm thick) were obtained simultaneously. In addition to visualizing major vessels and cardiac chambers, cardiac valves and papillary muscles were clearly demonstrated. Major pulmonary vessels and peripheral parenchyma were also seen. These results demonstrate MR "microscopy" can be used to image all major cardiopulmonary structures in the rat with respect to selected times of the cardiac cycle. This capability for noninvasive "microscopy" opens new avenues for cardiopulmonary research using well characterized rodent models.

Authors
Hedlund, LW; Johnson, GA; Karis, JP; Effmann, EL
MLA Citation
Hedlund, LW, Johnson, GA, Karis, JP, and Effmann, EL. "MR "microscopy" of the rat thorax." J Comput Assist Tomogr 10.6 (November 1986): 948-952.
PMID
3782566
Source
pubmed
Published In
Journal of Computer Assisted Tomography
Volume
10
Issue
6
Publish Date
1986
Start Page
948
End Page
952

3-DIMENSIONAL MAGNETIC-RESONANCE MICROSCOPY OF THE DEVELOPING CHICK-EMBRYO

Authors
BONE, SN; JOHNSON, GA; THOMPSON, MB
MLA Citation
BONE, SN, JOHNSON, GA, and THOMPSON, MB. "3-DIMENSIONAL MAGNETIC-RESONANCE MICROSCOPY OF THE DEVELOPING CHICK-EMBRYO." INVESTIGATIVE RADIOLOGY 21.10 (October 1986): 782-787.
Source
wos-lite
Published In
Investigative Radiology
Volume
21
Issue
10
Publish Date
1986
Start Page
782
End Page
787
DOI
10.1097/00004424-198610000-00003

STUDIES OF DISEASED ROOT-TISSUE USING NUCLEAR-MAGNETIC-RESONANCE IMAGING

Authors
JOHNSON, GA; BAILEY, JE; BRUCK, RI; MATYAC, CA
MLA Citation
JOHNSON, GA, BAILEY, JE, BRUCK, RI, and MATYAC, CA. "STUDIES OF DISEASED ROOT-TISSUE USING NUCLEAR-MAGNETIC-RESONANCE IMAGING." PHYTOPATHOLOGY 76.10 (October 1986): 1067-1067.
Source
wos-lite
Published In
Phytopathology
Volume
76
Issue
10
Publish Date
1986
Start Page
1067
End Page
1067

Three-dimensional magnetic resonance microscopy of the developing chick embryo.

Magnetic resonance imaging microscopy was performed on live chick embryos. A combination of high gradient strength (0.47 mT/cm), special purpose radiofrequency coils and 3-dimensional Fourier imaging was used to obtain images with effective thickness of 1.25 mm and pixel dimensions as small as 200 mu in the live chick embryo. The signal-to-noise ratio was sufficient to allow unequivocal identification of the individual chambers of the heart, spinal cord, ventricles in the brain, and vascular structures in the liver of a live 11-day embryo. Anatomical assignment was accomplished with the aid of correlated histologic sections. Because there are no external landmarks, the plane of imaging is frequently oblique, making the 3-dimensional acquisition particularly useful.

Authors
Bone, SN; Johnson, GA; Thompson, MB
MLA Citation
Bone, SN, Johnson, GA, and Thompson, MB. "Three-dimensional magnetic resonance microscopy of the developing chick embryo." Invest Radiol 21.10 (October 1986): 782-787.
PMID
3771148
Source
pubmed
Published In
Investigative Radiology
Volume
21
Issue
10
Publish Date
1986
Start Page
782
End Page
787

MRI MICROSCOPY OF THE DEVELOPING CHICK-EMBRYO

Authors
BONE, SN; JOHNSON, GA; THOMPSON, MB
MLA Citation
BONE, SN, JOHNSON, GA, and THOMPSON, MB. "MRI MICROSCOPY OF THE DEVELOPING CHICK-EMBRYO." INVESTIGATIVE RADIOLOGY 21.9 (September 1986): S34-S34.
Source
wos-lite
Published In
Investigative Radiology
Volume
21
Issue
9
Publish Date
1986
Start Page
S34
End Page
S34

3-DIMENSIONAL MRI MICROSCOPY OF THE RAT-BRAIN

Authors
JOHNSON, GA; THOMPSON, MB; DRAYER, BP
MLA Citation
JOHNSON, GA, THOMPSON, MB, and DRAYER, BP. "3-DIMENSIONAL MRI MICROSCOPY OF THE RAT-BRAIN." INVESTIGATIVE RADIOLOGY 21.9 (September 1986): S25-S25.
Source
wos-lite
Published In
Investigative Radiology
Volume
21
Issue
9
Publish Date
1986
Start Page
S25
End Page
S25

VARIANT ANGLE GRADIENT REFOCUSING IN 3-DIMENSIONAL MRI MICROSCOPY

Authors
KARIS, JP; GLOVER, GH; JOHNSON, GA
MLA Citation
KARIS, JP, GLOVER, GH, and JOHNSON, GA. "VARIANT ANGLE GRADIENT REFOCUSING IN 3-DIMENSIONAL MRI MICROSCOPY." INVESTIGATIVE RADIOLOGY 21.9 (September 1986): S34-S34.
Source
wos-lite
Published In
Investigative Radiology
Volume
21
Issue
9
Publish Date
1986
Start Page
S34
End Page
S34

MAGNETIC-RESONANCE-IMAGING OF THE RAT THORAX AND ABDOMEN

Authors
HEDLUND, L; JOHNSON, GA
MLA Citation
HEDLUND, L, and JOHNSON, GA. "MAGNETIC-RESONANCE-IMAGING OF THE RAT THORAX AND ABDOMEN." INVESTIGATIVE RADIOLOGY 21.9 (September 1986): S14-S14.
Source
wos-lite
Published In
Investigative Radiology
Volume
21
Issue
9
Publish Date
1986
Start Page
S14
End Page
S14
DOI
10.1097/00004424-198609000-00071

MRI of brain iron.

A prominently decreased signal intensity in the globus pallidum, reticular substantia nigra, red nucleus, and dentate nucleus was routinely noted in 150 consecutive individuals on T2-weighted images (SE 2000/100) using a high field strength (1.5 T)MR system. This MR finding correlated closely with the decreased estimated T2 relaxation times and the sites of preferential accumulation of ferric iron using the Perls staining method on normal postmortem brains. The decreased signal intensity on T2-weighted images thus provides an accurate in vivo map of the normal distribution of brain iron. Perls stain and MR studies in normal brain also confirm an intermediate level of iron distribution in the striatum, and still lower levels in the cerebral gray and white matter. In the white matter, iron concentration is (a) absent in the most posterior portion of the internal capsule and optic radiations, (b) higher in the frontal than occipital regions, and (c) prominent in the subcortical "U" fibers, particularly in the temporal lobe. There is no iron in the brain at birth; it increases progressively with aging. Knowledge of the distribution of brain iron should assist in elucidating normal anatomic structures and in understanding neurodegenerative, demyelinating, and cerebrovascular disorders.

Authors
Drayer, B; Burger, P; Darwin, R; Riederer, S; Herfkens, R; Johnson, GA
MLA Citation
Drayer, B, Burger, P, Darwin, R, Riederer, S, Herfkens, R, and Johnson, GA. "MRI of brain iron." AJR Am J Roentgenol 147.1 (July 1986): 103-110.
PMID
3487201
Source
pubmed
Published In
AJR. American journal of roentgenology
Volume
147
Issue
1
Publish Date
1986
Start Page
103
End Page
110
DOI
10.2214/ajr.147.1.103

Parkinson plus syndrome: diagnosis using high field MR imaging of brain iron.

The distribution of iron in the brain was analyzed using high field strength (1.5 T) magnetic resonance (MR) imaging in 14 healthy control individuals and six patients with Parkinson plus syndromes (multisystem atrophy and progressive supranuclear palsy) who were unresponsive to antiparkinsonian therapy. The normal topographic distribution of iron in the brain as indicated by high field MR images coincided precisely with the distribution of iron in the brain as determined by Perls staining for ferric iron. In Parkinson plus syndromes, there were abnormally increased concentrations of iron (decreased T2 relaxation times) in the putamen, and less prominent increases in the caudate nucleus and lateral pars compacta of the substantia nigra. In high field strength MR images of normal patients, the decreased signal intensity in the globus pallidus is more prominent than that of the putamen. In MR images of patients with Parkinson plus syndromes, the decreased signal intensity of the putamen is more prominent than that of the globus pallidus.

Authors
Drayer, BP; Olanow, W; Burger, P; Johnson, GA; Herfkens, R; Riederer, S
MLA Citation
Drayer, BP, Olanow, W, Burger, P, Johnson, GA, Herfkens, R, and Riederer, S. "Parkinson plus syndrome: diagnosis using high field MR imaging of brain iron." Radiology 159.2 (May 1986): 493-498.
PMID
3961182
Source
pubmed
Published In
Radiology
Volume
159
Issue
2
Publish Date
1986
Start Page
493
End Page
498
DOI
10.1148/radiology.159.2.3961182

Histogram-directed processing of digital chest images.

One of the potential advantages of digital chest imaging is the ability to process these images. However, such processing, when uniformly applied to the entire image, is often unsatisfactory due to the different processing requirements of lung field and mediastinum. Therefore, a method to selectively process these regions based upon the histogram of the original image has been developed. Thirteen conventional chest films were digitized with a laser film scanner. Analysis of individual lung field and mediastinum histograms showed that the chest image histogram is essentially bimodal with significant lung field-mediastinum histogram peak separation; overlap between these peaks is small (9% of the total histogram) and insensitive to minor pathologic change or radiographic technique. Using these histograms, a gray level threshold distinguishing mediastinum from lung field was selected and used to direct the regionally-selective processing of several chest images. This technique may prove especially useful for digital enhancement of the underexposed mediastinum often encountered on conventional chest radiographs.

Authors
McAdams, HP; Johnson, GA; Suddarth, SA; Ravin, CE
MLA Citation
McAdams, HP, Johnson, GA, Suddarth, SA, and Ravin, CE. "Histogram-directed processing of digital chest images." Invest Radiol 21.3 (March 1986): 253-259.
PMID
3957599
Source
pubmed
Published In
Investigative Radiology
Volume
21
Issue
3
Publish Date
1986
Start Page
253
End Page
259

MR IMAGING AND PERLS STAIN OF BASAL GANGLIA IRON WITH NORMAL AGING

Authors
DRAYER, B; BURGER, P; CAIN, J; LEONG, J; JOHNSON, GA; HEINZ, ER; RIEDERER, S; DJANG, W; HERFKENS, R
MLA Citation
DRAYER, B, BURGER, P, CAIN, J, LEONG, J, JOHNSON, GA, HEINZ, ER, RIEDERER, S, DJANG, W, and HERFKENS, R. "MR IMAGING AND PERLS STAIN OF BASAL GANGLIA IRON WITH NORMAL AGING." AMERICAN JOURNAL OF NEURORADIOLOGY 7.3 (1986): 554-555.
Source
wos-lite
Published In
American Journal of Neuroradiology
Volume
7
Issue
3
Publish Date
1986
Start Page
554
End Page
555

Nuclear magnetic resonance imaging at microscopic resolution

Resolution limits in NMR imaging are imposed by bandwidth considerations, available magnetic gradients for spatial encoding, and signal to noise. This work reports modification of a clinical NMR imaging device with picture elements of 500 × 500 × 5000 μm to yield picture elements of 50 × 50 × 1000 μm. Resolution has been increased by using smaller gradient coils permitting gradient fields >0.4 mT/cm. Significant improvements in signal to noise are achieved with smaller rf coils, close attention to choice of bandwidth, and signal averaging. These improvements permit visualization of anatomical structures in the rat brain with an effective diameter of 1 cm with the same definition as is seen in human imaging. The techniques and instrumentation should open a number of basic sciences such as embryology, plant sciences, and teratology to the potentials of NMR imaging. © 1986.

Authors
Johnson, GA; Thompson, MB; Gewalt, SL; Hayes, CE
MLA Citation
Johnson, GA, Thompson, MB, Gewalt, SL, and Hayes, CE. "Nuclear magnetic resonance imaging at microscopic resolution." Journal of Magnetic Resonance (1969) 68.1 (1986): 129-137.
Source
scival
Published In
Journal of Magnetic Resonance (1969)
Volume
68
Issue
1
Publish Date
1986
Start Page
129
End Page
137

MAGNETIC-RESONANCE-IMAGING OF BRAIN IRON

Authors
DRAYER, B; BURGER, P; DARWIN, R; RIEDERER, S; HERFKENS, R; JOHNSON, GA
MLA Citation
DRAYER, B, BURGER, P, DARWIN, R, RIEDERER, S, HERFKENS, R, and JOHNSON, GA. "MAGNETIC-RESONANCE-IMAGING OF BRAIN IRON." AMERICAN JOURNAL OF NEURORADIOLOGY 7.3 (1986): 373-380.
Source
wos-lite
Published In
American Journal of Neuroradiology
Volume
7
Issue
3
Publish Date
1986
Start Page
373
End Page
380

Magnetic resonance microscopy in neurologic models.

Magnetic resonance imaging techniques have been developed to permit imaging with slice thickness less than 1 mm and pixels of 50 x 50 microns. Special purpose gradient and radiofrequency coils and three-dimensional imaging techniques enable acquisition of images with sufficient signal to noise to utilize these microscopic picture elements. Live 200 g rats were imaged enabling clear definition of gray and white matter structures. Examples include the Sylvian aqueduct and the substantia nigra. Three-dimensional microscopic images of live chick embryos enabled definition of ventricles and brain parenchyma as well as measurement of T1 over the set of 16 contiguous 1.2 mm slices.

Authors
Johnson, GA; Thompson, MB; Drayer, BP; Bone, SN
MLA Citation
Johnson, GA, Thompson, MB, Drayer, BP, and Bone, SN. "Magnetic resonance microscopy in neurologic models." Acta Radiol Suppl 369 (1986): 267-268.
PMID
2980471
Source
pubmed
Published In
Acta radiologica. Supplementum
Volume
369
Publish Date
1986
Start Page
267
End Page
268

Digital synthesis of lung nodules.

Studies evaluating observer accuracy and visual perception of pulmonary nodules usually are based upon test films obtained from clinical practice in patients with proven pulmonary nodules. Unfortunately, such nodules do not always occur in the optimal size and location to facilitate testing. Such studies would be enhanced by the ability to place nodules of desired size and location on chest radiographs. This report describes a method of placing a computer-generated (synthesized) nodule on a digitized chest radiograph. To demonstrate the similarity of these synthesized nodules to real nodules, each digitized radiograph with a computer-generated nodule was paired with a digitized chest radiograph of a patient with a clinically proven pulmonary nodule. A total of 22 pairs of chest radiographs were then shown to 13 radiologists, who were asked to distinguish the synthesized nodule from the real nodule. With this two alternative forced-choice test, the radiologists were only able to distinguish the synthesized nodule in 51% of the cases, strongly suggesting that computer generated nodules may be used to simulate real pulmonary nodules in future tests of nodule detection.

Authors
Sherrier, RH; Johnson, GA; Suddarth, SA; Chiles, C; Hulka, C; Ravin, CE
MLA Citation
Sherrier, RH, Johnson, GA, Suddarth, SA, Chiles, C, Hulka, C, and Ravin, CE. "Digital synthesis of lung nodules." Invest Radiol 20.9 (December 1985): 933-937.
PMID
3841098
Source
pubmed
Published In
Investigative Radiology
Volume
20
Issue
9
Publish Date
1985
Start Page
933
End Page
937

Tissue relaxation time: in vivo field dependence.

Relaxation times (T1 and T2) were measured in vivo in mongrel dogs at fields of 0.3, 0.5, 1.0, 1.35, and 1.5 tesla (T). T1 was measured using nine values of inversion time ranging from 10 to 1,280 msec. T2 was measured with a four-point multiple spin-echo sequence. Relaxation times were calculated for muscle, kidney cortex, spleen, and adipose tissue. T2 is independent of field. A linear fit to the field dependence of T1 yields slopes of 400-500 msec/T for tissues in which the primary source of protons is water. The lower slope of adipose (approximately 150 msec/T) reflects the different mechanism of spin-lattice relaxation of the -CH2 protons.

Authors
Johnson, GA; Herfkens, RJ; Brown, MA
MLA Citation
Johnson, GA, Herfkens, RJ, and Brown, MA. "Tissue relaxation time: in vivo field dependence." Radiology 156.3 (September 1985): 805-810.
PMID
2991980
Source
pubmed
Published In
Radiology
Volume
156
Issue
3
Publish Date
1985
Start Page
805
End Page
810
DOI
10.1148/radiology.156.3.2991980

Time course and mechanism of alterations in proton relaxation during liver regeneration in the rat.

We studied the proton T1 and T2, water and lipid content of regenerating rat liver from 1 to 7 days after 70% hepatectomy. Liver from normal and sham-operated animals and splenic tissue from all animals were studied as controls. In vivo proton spectroscopy and imaging of liver was performed in a separate group of control and posthepatectomy rats. The T2 of regenerating liver, but not of sham or normal control liver, was prolonged. Changes in T1, relative to normal tissue, were found in liver and spleen of both operated groups. Lipid content, assessed both by extraction of tissue samples and by in vivo spectroscopy, was increased in regenerating tissue but not in controls. Water content was similarly increased in regenerating liver tissue. Changes in water and lipid content appeared to contribute to the alterations in proton relaxation which we observed.

Authors
Sostman, HD; Gore, JC; Flye, MW; Johnson, GA; Herfkens, RJ
MLA Citation
Sostman, HD, Gore, JC, Flye, MW, Johnson, GA, and Herfkens, RJ. "Time course and mechanism of alterations in proton relaxation during liver regeneration in the rat." Hepatology 5.4 (July 1985): 538-543.
PMID
2991104
Source
pubmed
Published In
Hepatology
Volume
5
Issue
4
Publish Date
1985
Start Page
538
End Page
543

Processing alternatives for digital chest imaging.

Radiographic imaging of the chest remains one of the most important and most challenging problems in radiology. The wide range of information that results from the great variation of radiation behind the lungs compared with that behind the mediastinum creates a very difficult imaging problem. The introduction and continued investigation of digital techniques have presented a potential solution to this problem. In this article, the authors describe the image-processing techniques of histogram equalization and adaptive filtration in digital chest imaging.

Authors
Johnson, GA; Danieley, N; Ravin, CE
MLA Citation
Johnson, GA, Danieley, N, and Ravin, CE. "Processing alternatives for digital chest imaging." Radiol Clin North Am 23.2 (June 1985): 335-340.
PMID
3991890
Source
pubmed
Published In
Radiologic Clinics of North America
Volume
23
Issue
2
Publish Date
1985
Start Page
335
End Page
340

EVALUATION OF COMPUTER SYNTHESIZED PULMONARY NODULES

Authors
SHERRIER, RH; CHILES, C; SUDDARTH, SA; JOHNSON, GA; RAVIN, CE
MLA Citation
SHERRIER, RH, CHILES, C, SUDDARTH, SA, JOHNSON, GA, and RAVIN, CE. "EVALUATION OF COMPUTER SYNTHESIZED PULMONARY NODULES." INVESTIGATIVE RADIOLOGY 20.6 (1985): S27-S27.
Source
wos-lite
Published In
Investigative Radiology
Volume
20
Issue
6
Publish Date
1985
Start Page
S27
End Page
S27

HISTOGRAM DIRECTED PROCESSING OF DIGITAL CHEST IMAGES

Authors
MCADAMS, HP; JOHNSON, GA; SUDDARTH, SA; RAVIN, CE
MLA Citation
MCADAMS, HP, JOHNSON, GA, SUDDARTH, SA, and RAVIN, CE. "HISTOGRAM DIRECTED PROCESSING OF DIGITAL CHEST IMAGES." INVESTIGATIVE RADIOLOGY 20.6 (1985): S18-S18.
Source
wos-lite
Published In
Investigative Radiology
Volume
20
Issue
6
Publish Date
1985
Start Page
S18
End Page
S18
DOI
10.1097/00004424-198509000-00099

SURFACE COIL MOTION ARTIFACTS IN MR IMAGING

Authors
BLINDER, RA; HERFKENS, RJ; JOHNSON, GA; COLEMAN, RE
MLA Citation
BLINDER, RA, HERFKENS, RJ, JOHNSON, GA, and COLEMAN, RE. "SURFACE COIL MOTION ARTIFACTS IN MR IMAGING." INVESTIGATIVE RADIOLOGY 20.6 (1985): S31-S31.
Source
wos-lite
Published In
Investigative Radiology
Volume
20
Issue
6
Publish Date
1985
Start Page
S31
End Page
S31
DOI
10.1097/00004424-198509000-00149

HIGH-RESOLUTION MRI IMAGING AT 1.5T USING SURFACE COILS

Authors
BLINDER, RA; HERFKENS, RJ; COLEMAN, RE; JOHNSON, GA; SCHENCK, JF; HART, HR; FOSTER, TH; EDELSTEIN, WA
MLA Citation
BLINDER, RA, HERFKENS, RJ, COLEMAN, RE, JOHNSON, GA, SCHENCK, JF, HART, HR, FOSTER, TH, and EDELSTEIN, WA. "HIGH-RESOLUTION MRI IMAGING AT 1.5T USING SURFACE COILS." JOURNAL OF NUCLEAR MEDICINE 26.5 (1985): P8-P8.
Source
wos-lite
Published In
Journal of nuclear medicine : official publication, Society of Nuclear Medicine
Volume
26
Issue
5
Publish Date
1985
Start Page
P8
End Page
P8

AUTOMATED OBSERVER STUDIES ON A DIGITAL CHEST SYSTEM

Authors
SHERRIER, RH; SUDDARTH, SA; JOHNSON, GA; RAVIN, CE
MLA Citation
SHERRIER, RH, SUDDARTH, SA, JOHNSON, GA, and RAVIN, CE. "AUTOMATED OBSERVER STUDIES ON A DIGITAL CHEST SYSTEM." INVESTIGATIVE RADIOLOGY 20.6 (1985): S18-S18.
Source
wos-lite
Published In
Investigative Radiology
Volume
20
Issue
6
Publish Date
1985
Start Page
S18
End Page
S18

OPTIMIZATION OF ADAPTIVE FILTRATION FOR DIGITAL CHEST IMAGING

Authors
MCADAMS, HP; JOHNSON, GA; SUDDARTH, SA; RAVIN, CE
MLA Citation
MCADAMS, HP, JOHNSON, GA, SUDDARTH, SA, and RAVIN, CE. "OPTIMIZATION OF ADAPTIVE FILTRATION FOR DIGITAL CHEST IMAGING." INVESTIGATIVE RADIOLOGY 20.6 (1985): S27-S27.
Source
wos-lite
Published In
Investigative Radiology
Volume
20
Issue
6
Publish Date
1985
Start Page
S27
End Page
S27
DOI
10.1097/00004424-198509000-00133

PRECISION AND ACCURACY IN THE MEASUREMENT OF T1 ON AN IMAGING-SYSTEM

Authors
WINTER, TC; JOHNSON, GA; MACFALL, JR
MLA Citation
WINTER, TC, JOHNSON, GA, and MACFALL, JR. "PRECISION AND ACCURACY IN THE MEASUREMENT OF T1 ON AN IMAGING-SYSTEM." INVESTIGATIVE RADIOLOGY 20.6 (1985): S14-S14.
Source
wos-lite
Published In
Investigative Radiology
Volume
20
Issue
6
Publish Date
1985
Start Page
S14
End Page
S14

Magnetic resonance imaging at high-strength magnetic fields.

Authors
Herfkens, RJ; Johnson, GA
MLA Citation
Herfkens, RJ, and Johnson, GA. "Magnetic resonance imaging at high-strength magnetic fields." Magn Reson Annu (1985): 197-215. (Review)
PMID
3917235
Source
pubmed
Published In
Magnetic resonance annual
Publish Date
1985
Start Page
197
End Page
215

A phantom for testing ECG-gated computed tomography of the heart.

A mechanical phantom has been built to evaluate electrocardiographically gated computed tomography of the heart. The phantom simulates the heart in terms of cyclic changes in chamber dimensions and wall thickness. Rate and excursion are variable, and the cavity of the chamber can be filled with liquid contrast media of different degrees of radio-opacity. Preliminary experiments with a prototypic gating system are described.

Authors
Godwin, JD; Johnson, GA; Fram, EK
MLA Citation
Godwin, JD, Johnson, GA, and Fram, EK. "A phantom for testing ECG-gated computed tomography of the heart." Invest Radiol 19.4 (July 1984): 279-283.
PMID
6480305
Source
pubmed
Published In
Investigative Radiology
Volume
19
Issue
4
Publish Date
1984
Start Page
279
End Page
283

Transition metal-chelate complexes as relaxation modifiers in nuclear magnetic resonance.

Studies are reported of relaxation modifiers for use in nuclear magnetic resonance (NMR) imaging systems. Chelate complexes of transition metal salts are under investigation to determine their ability to reduce the spin-lattice relaxation time (T1) of the nucleus under observation and to reduce the toxicity of the metal ion. The ethylenediaminetetraacetate (EDTA) complexes of FeCl3, GdCl3, and MnCl2 are not as effective as the respective salts in reducing T1 of water protons at 90 MHz. For Mn, this diminution in ability is offset by a significant reduction in toxicity. Explanations for this loss of effectiveness are discussed.

Authors
Brown, MA; Johnson, GA
MLA Citation
Brown, MA, and Johnson, GA. "Transition metal-chelate complexes as relaxation modifiers in nuclear magnetic resonance." Med Phys 11.1 (January 1984): 67-72.
PMID
6422223
Source
pubmed
Published In
Medical physics
Volume
11
Issue
1
Publish Date
1984
Start Page
67
End Page
72
DOI
10.1118/1.595455

INVIVO CHEMICAL-SHIFT IMAGING OF HYDROGEN

Authors
HERFKENS, RJ; JOHNSON, GA; GLOVER, G
MLA Citation
HERFKENS, RJ, JOHNSON, GA, and GLOVER, G. "INVIVO CHEMICAL-SHIFT IMAGING OF HYDROGEN." INVESTIGATIVE RADIOLOGY 19.5 (1984): S42-S42.
Source
wos-lite
Published In
Investigative Radiology
Volume
19
Issue
5
Publish Date
1984
Start Page
S42
End Page
S42
DOI
10.1097/00004424-198409000-00191

INVIVO FIELD-DEPENDENCE OF TISSUE RELAXATION-TIMES

Authors
JOHNSON, GA; HERFKENS, RJ; MACFALL, JR
MLA Citation
JOHNSON, GA, HERFKENS, RJ, and MACFALL, JR. "INVIVO FIELD-DEPENDENCE OF TISSUE RELAXATION-TIMES." INVESTIGATIVE RADIOLOGY 19.5 (1984): S33-S33.
Source
wos-lite
Published In
Investigative Radiology
Volume
19
Issue
5
Publish Date
1984
Start Page
S33
End Page
S33
DOI
10.1097/00004424-198409000-00154

A CT-EVALUATION OF 3 HEPATOBILIARY CONTRAST AGENTS

Authors
STUDE, R; HEDLUND, L; JOHNSON, GA; THOMPSON, WM
MLA Citation
STUDE, R, HEDLUND, L, JOHNSON, GA, and THOMPSON, WM. "A CT-EVALUATION OF 3 HEPATOBILIARY CONTRAST AGENTS." INVESTIGATIVE RADIOLOGY 19.5 (1984): S40-S40.
Source
wos-lite
Published In
Investigative Radiology
Volume
19
Issue
5
Publish Date
1984
Start Page
S40
End Page
S40
DOI
10.1097/00004424-198409000-00184

DESIGN CONSIDERATIONS FOR SMALL ANIMAL IMAGING IN A LARGE BORE MRI SYSTEM

Authors
HAYES, CE; JOHNSON, GA; HERFKENS, RJ
MLA Citation
HAYES, CE, JOHNSON, GA, and HERFKENS, RJ. "DESIGN CONSIDERATIONS FOR SMALL ANIMAL IMAGING IN A LARGE BORE MRI SYSTEM." INVESTIGATIVE RADIOLOGY 19.5 (1984): S25-S25.
Source
wos-lite
Published In
Investigative Radiology
Volume
19
Issue
5
Publish Date
1984
Start Page
S25
End Page
S25

VARIABLE FIELD STUDIES OF POTENTIAL PARAMAGNETIC NMR CONTRAST AGENTS

Authors
BROWN, MA; JOHNSON, GA
MLA Citation
BROWN, MA, and JOHNSON, GA. "VARIABLE FIELD STUDIES OF POTENTIAL PARAMAGNETIC NMR CONTRAST AGENTS." MAGNETIC RESONANCE IN MEDICINE 1.2 (1984): 119-120.
Source
wos-lite
Published In
Magnetic Resonance in Medicine
Volume
1
Issue
2
Publish Date
1984
Start Page
119
End Page
120

PROGRESS IN ECG-GATED CT - TESTING WITH A MOTION PHANTOM AND COMPARISON WITH THE IMATRON 50-MSEC SCANNER

Authors
GODWIN, JD; PELC, NJ; JOHNSON, GA; FRAM, EK; GOULD, RG
MLA Citation
GODWIN, JD, PELC, NJ, JOHNSON, GA, FRAM, EK, and GOULD, RG. "PROGRESS IN ECG-GATED CT - TESTING WITH A MOTION PHANTOM AND COMPARISON WITH THE IMATRON 50-MSEC SCANNER." INVESTIGATIVE RADIOLOGY 19.5 (1984): S27-S27.
Source
wos-lite
Published In
Investigative Radiology
Volume
19
Issue
5
Publish Date
1984
Start Page
S27
End Page
S27
DOI
10.1097/00004424-198409000-00131

CAROTID-ARTERY IMAGING BY A 1.5-T MR SYSTEM

Authors
HEINZ, ER; HERFKINS, R; JOHNSON, GA; DRAYER, BP
MLA Citation
HEINZ, ER, HERFKINS, R, JOHNSON, GA, and DRAYER, BP. "CAROTID-ARTERY IMAGING BY A 1.5-T MR SYSTEM." AMERICAN JOURNAL OF NEURORADIOLOGY 5.5 (1984): 670-670.
Source
wos-lite
Published In
American Journal of Neuroradiology
Volume
5
Issue
5
Publish Date
1984
Start Page
670
End Page
670

HIGH-FIELD NMR IMAGING (1.5T) IN A HOSPITAL ENVIRONMENT

Authors
DRAYER, BP; HERFKENS, RJ; JOHNSON, GA; HEINZ, ER; YEATES, AE
MLA Citation
DRAYER, BP, HERFKENS, RJ, JOHNSON, GA, HEINZ, ER, and YEATES, AE. "HIGH-FIELD NMR IMAGING (1.5T) IN A HOSPITAL ENVIRONMENT." AMERICAN JOURNAL OF NEURORADIOLOGY 5.5 (1984): 669-669.
Source
wos-lite
Published In
American Journal of Neuroradiology
Volume
5
Issue
5
Publish Date
1984
Start Page
669
End Page
669

DIGITAL SYNTHESIS OF LUNG NODULES

Authors
SHERRIER, RH; JOHNSON, GA; RAVIN, CE; SUDDARTH, SA
MLA Citation
SHERRIER, RH, JOHNSON, GA, RAVIN, CE, and SUDDARTH, SA. "DIGITAL SYNTHESIS OF LUNG NODULES." INVESTIGATIVE RADIOLOGY 19.5 (1984): S49-S49.
Source
wos-lite
Published In
Investigative Radiology
Volume
19
Issue
5
Publish Date
1984
Start Page
S49
End Page
S49
DOI
10.1097/00004424-198409000-00219

A survey of digital chest radiography.

The problems of chest radiography as they relate to digital systems are described, the current approaches to these problems are reviewed, and the utility of digital chest radiography is demonstrated.

Authors
Johnson, GA; Ravin, CE
MLA Citation
Johnson, GA, and Ravin, CE. "A survey of digital chest radiography." Radiol Clin North Am 21.4 (December 1983): 655-664.
PMID
6361846
Source
pubmed
Published In
Radiologic Clinics of North America
Volume
21
Issue
4
Publish Date
1983
Start Page
655
End Page
664

High-resolution sagittal and coronal reformatted CT images of the larynx.

Authors
Silverman, PM; Johnson, GA; Korobkin, M
MLA Citation
Silverman, PM, Johnson, GA, and Korobkin, M. "High-resolution sagittal and coronal reformatted CT images of the larynx." AJR Am J Roentgenol 140.4 (April 1983): 819-822.
PMID
6601398
Source
pubmed
Published In
AJR. American journal of roentgenology
Volume
140
Issue
4
Publish Date
1983
Start Page
819
End Page
822
DOI
10.2214/ajr.140.4.819

High kVp vs. low kVp for T-tube and operative cholangiography.

Based on several considerations, high kVp and high contrast agent concentration should produce better-quality operative and T-tube cholangiograms than the currently recommended low kVp and low contrast agent concentration. To test this theory, two kinds of studies were performed. In a laboratory phantom, the influence of kVp and contrast agent concentration on detectability of different size phantom stones was evaluated. High kVp and high contrast agent concentration (110 kVp, 38% iodine) were also compared with low kVp and low contrast agent concentration (75 kVp, 15% iodine) in 62 patients undergoing operative or T-tube cholangiography. Almost all phantom stones were well shown with all kVps and iodine concentrations. As the kVp was raised there was a mild decrease in stone detectability but this decrease was partially corrected by raising the iodine concentration. Overall stone detectability with high kVp and high contrast agent concentration technique was better than or similar to the currently recommended low kVp and low contrast agent concentration technique. Evaluation of the direct cholangiograms by five radiologists revealed that the high kVp, high contrast agent concentration studies were superior or similar to the low kVp and low contrast agent concentration radiographs in 70% of the cases. Based on these results high kVp (100-110) and a high contrast agent concentration (38%) are recommended for direct cholangiography.

Authors
Thompson, WM; Halvorsen, RA; Gedgaudas, RK; Kelvin, FM; Rice, RP; Woodfield, S; Johnson, GA; Hedlund, LW; Jorgensen, DB
MLA Citation
Thompson, WM, Halvorsen, RA, Gedgaudas, RK, Kelvin, FM, Rice, RP, Woodfield, S, Johnson, GA, Hedlund, LW, and Jorgensen, DB. "High kVp vs. low kVp for T-tube and operative cholangiography." Radiology 146.3 (March 1983): 635-642.
PMID
6828675
Source
pubmed
Published In
Radiology
Volume
146
Issue
3
Publish Date
1983
Start Page
635
End Page
642
DOI
10.1148/radiology.146.3.6828675

The 'optimal' chest radiograph

Authors
Ravin, CE; Johnson, GA
MLA Citation
Ravin, CE, and Johnson, GA. "The 'optimal' chest radiograph." Seminars in Respiratory Medicine 5.1 (1983): 1-14.
Source
scival
Published In
Seminars in Respiratory Medicine
Volume
5
Issue
1
Publish Date
1983
Start Page
1
End Page
14

A SYSTEM FOR DIGITAL VIDEODENSITOMETRY

Authors
JOHNSON, GA; DANIELEY, N; SUDDARTH, S; DUNNICK, NR
MLA Citation
JOHNSON, GA, DANIELEY, N, SUDDARTH, S, and DUNNICK, NR. "A SYSTEM FOR DIGITAL VIDEODENSITOMETRY." AMERICAN JOURNAL OF ROENTGENOLOGY 141.6 (1983): 1360-1361.
Source
wos-lite
Published In
AJR. American journal of roentgenology
Volume
141
Issue
6
Publish Date
1983
Start Page
1360
End Page
1361

CONTRAST ENHANCEMENT OF THE LIVER DURING CT - A COMPARISON OF BILIARY, VASCULAR AND RETICULOENDOTHELIAL AGENTS

Authors
THOMPSON, WM; STUDE, R; BATES, M; HEDLUND, L; JOHNSON, GA
MLA Citation
THOMPSON, WM, STUDE, R, BATES, M, HEDLUND, L, and JOHNSON, GA. "CONTRAST ENHANCEMENT OF THE LIVER DURING CT - A COMPARISON OF BILIARY, VASCULAR AND RETICULOENDOTHELIAL AGENTS." INVESTIGATIVE RADIOLOGY 18.4 (1983): S11-S11.
Source
wos-lite
Published In
Investigative Radiology
Volume
18
Issue
4
Publish Date
1983
Start Page
S11
End Page
S11
DOI
10.1097/00004424-198307000-00064

Testing electrocardiographically-gated ct of the heart with a motion phantom

Authors
Godwin, JD; Johnson, GA; Fram, EK
MLA Citation
Godwin, JD, Johnson, GA, and Fram, EK. "Testing electrocardiographically-gated ct of the heart with a motion phantom." Investigative Radiology 18.4 (1983): S33-S33. (Academic Article)
Source
manual
Published In
Investigative Radiology
Volume
18
Issue
4
Publish Date
1983
Start Page
S33
End Page
S33

SYSTEM FOR DIGITAL VIDEODENSITOMETRY.

Authors
Johnson, GA; Danieley, N; Suddarth, S; Dunnick, NR
MLA Citation
Johnson, GA, Danieley, N, Suddarth, S, and Dunnick, NR. "SYSTEM FOR DIGITAL VIDEODENSITOMETRY." Proceedings of SPIE - The International Society for Optical Engineering 419 (1983): 222-227.
Source
scival
Published In
Proceedings of SPIE - The International Society for Optical Engineering
Volume
419
Publish Date
1983
Start Page
222
End Page
227

Work in progress: high-resolution, thin-section computed tomography of the larynx.

Authors
Silverman, PM; Korobkin, M; Thompson, WM; Johnson, GA; Cole, TB; Fisher, SR
MLA Citation
Silverman, PM, Korobkin, M, Thompson, WM, Johnson, GA, Cole, TB, and Fisher, SR. "Work in progress: high-resolution, thin-section computed tomography of the larynx." Radiology 145.3 (December 1982): 723-725.
PMID
7146403
Source
pubmed
Published In
Radiology
Volume
145
Issue
3
Publish Date
1982
Start Page
723
End Page
725
DOI
10.1148/radiology.145.3.7146403

High-resolution multiplanar CT images of the larynx.

The standard technique for computed tomographic evaluation of the larynx utilizes 5-mm contiguous transaxial sections. Multiplanar images reformatted with these sections have not been of clinical use. We have evaluated the practicality of utilizing coronal and sagittal reformatted images produced from contiguous 1.5-mm transaxial sections. The technique of rapid sequential scanning with automatic table incrementation allows 36 contiguous thin section scans to be acquired in less than 9 minutes. Phantom studies showed a marked improvement in spatial resolution with thin section reconstructions. Preliminary clinical evaluation shows visualization of smaller structures with improved edge definition of both low- and high-contrast structures.

Authors
Silverman, PM; Johnson, GA; Korobkin, M; Thompson, WM
MLA Citation
Silverman, PM, Johnson, GA, Korobkin, M, and Thompson, WM. "High-resolution multiplanar CT images of the larynx." Invest Radiol 17.6 (November 1982): 634-637.
PMID
7152866
Source
pubmed
Published In
Investigative Radiology
Volume
17
Issue
6
Publish Date
1982
Start Page
634
End Page
637

Gated multiplanar cardiac computed tomography.

Multiplanar reformatting was combined with electrocardiographically gated computed tomography (CT) to provide a three-dimensional assessment of the beating heart of a live dog. Separate systolic and diastolic images were made in transverse, sagittal, coronal, and paraxial views. Three-dimensional contour images that outlined the cardiac chambers and the myocardium were then made using a separate research computer. This three-dimensional appreciation of cardiac morphology could be extended to assess regional function. Practical problems that limit the application of these methods are discussed, along with the proposed solutions.

Authors
Johnson, GA; Godwin, JD; Fram, EK
MLA Citation
Johnson, GA, Godwin, JD, and Fram, EK. "Gated multiplanar cardiac computed tomography." Radiology 145.1 (October 1982): 195-197.
PMID
7122877
Source
pubmed
Published In
Radiology
Volume
145
Issue
1
Publish Date
1982
Start Page
195
End Page
197
DOI
10.1148/radiology.145.1.7122877

Image techniques for multiplanar computed tomography.

Hardware and software options of the GE 8800 CT scanner were analyzed with respect to their effect on image quality for multiplanar images. Phantom studies were undertaken to demonstrate the effect of collimation, thick pixel reconstruction, and interpolation of both high- and low-contrast multiplanar images. Noise and spatial resolution were measured. Thick pixel reconstruction was found to be most useful in aiding in the delineation of low-contrast lesion boundaries. In addition, this option permits use of lower techniques, thus speeding data acquisition and reducing patient dose. Clinical examples are included.

Authors
Johnson, GA; Korobkin, M
MLA Citation
Johnson, GA, and Korobkin, M. "Image techniques for multiplanar computed tomography." Radiology 144.4 (September 1982): 829-834.
PMID
7111733
Source
pubmed
Published In
Radiology
Volume
144
Issue
4
Publish Date
1982
Start Page
829
End Page
834
DOI
10.1148/radiology.144.4.7111733

Distinguishing benign from malignant pulmonary nodules by computed tomography.

Investigators have been able to distinguish benign pulmonary nodules from malignant ones in about two-thirds of the cases studied by detecting high computed tomography (CT) numbers (attributed to microscopic calcifications) within many benign nodules. This paper reports a similar analysis on a series of 22 benign and 14 malignant pulmonary nodules. Although about one-third of the benign nodules gave high CT numbers, all but one of the nodules diagnosed as benign by CT could also be diagnosed by detection of calcification on plain radiographs or conventional tomograms.

Authors
Godwin, JD; Speckman, JM; Fram, EK; Johnson, GA; Putman, CE; Korobkin, M; Breiman, RS
MLA Citation
Godwin, JD, Speckman, JM, Fram, EK, Johnson, GA, Putman, CE, Korobkin, M, and Breiman, RS. "Distinguishing benign from malignant pulmonary nodules by computed tomography." Radiology 144.2 (July 1982): 349-351.
PMID
7089288
Source
pubmed
Published In
Radiology
Volume
144
Issue
2
Publish Date
1982
Start Page
349
End Page
351
DOI
10.1148/radiology.144.2.7089288

Low-cost digital subtraction angiography.

Authors
Ford, KK; Heinz, ER; Johnson, GA; Drayer, BD; Dubois, PJ
MLA Citation
Ford, KK, Heinz, ER, Johnson, GA, Drayer, BD, and Dubois, PJ. "Low-cost digital subtraction angiography." AJNR Am J Neuroradiol 3.4 (July 1982): 448-451.
PMID
6810680
Source
pubmed
Published In
American Journal of Neuroradiology
Volume
3
Issue
4
Publish Date
1982
Start Page
448
End Page
451