G. Johnson

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 Distinguished Professor of Radiology

Radiology
School of Medicine

Professor of Radiology

Radiology
School of Medicine

Professor of Biomedical Engineering

Biomedical Engineering
Pratt School of Engineering

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

Duke University

Grants:

Small Animal Imaging Resource Program

Administered By
Radiology
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

The Duke University Molecular Imaging Center

Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

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

Administered By
Duke-UNC Center for Brain Imaging and Analysis
Awarded By
National Institutes of Health
Role
Co Investigator
Start Date
End Date

Whole brain multimodal microscopy of an apoptosis reporter mouse

Administered By
Psychiatry & Behavioral Sciences
Awarded By
National Institutes of Health
Role
Collaborator
Start Date
End Date

Waxholm Space for Rodent Neuroinformatics

Administered By
Radiology
Awarded By
University of Pennsylvania
Role
Principal Investigator
Start Date
End Date

Publications:

Identifying Vulnerable Brain Networks in Mouse Models of Genetic Risk Factors for Late Onset Alzheimer's Disease.

The major genetic risk for late onset Alzheimer's disease has been associated with the presence of APOE4 alleles. However, the impact of different APOE alleles on the brain aging trajectory, and how they interact with the brain local environment in a sex specific manner is not entirely clear. We sought to identify vulnerable brain circuits in novel mouse models with homozygous targeted replacement of the mouse ApoE gene with either human APOE3 or APOE4 gene alleles. These genes are expressed in mice that also model the human immune response to age and disease-associated challenges by expressing the human NOS2 gene in place of the mouse mNos2 gene. These mice had impaired learning and memory when assessed with the Morris water maze (MWM) and novel object recognition (NOR) tests. Ex vivo MRI-DTI analyses revealed global and local atrophy, and areas of reduced fractional anisotropy (FA). Using tensor network principal component analyses for structural connectomes, we inferred the pairwise connections which best separate APOE4 from APOE3 carriers. These involved primarily interhemispheric connections among regions of olfactory areas, the hippocampus, and the cerebellum. Our results also suggest that pairwise connections may be subdivided and clustered spatially to reveal local changes on a finer scale. These analyses revealed not just genotype, but also sex specific differences. Identifying vulnerable networks may provide targets for interventions, and a means to stratify patients.
Authors
Badea, A; Wu, W; Shuff, J; Wang, M; Anderson, RJ; Qi, Y; Johnson, GA; Wilson, JG; Koudoro, S; Garyfallidis, E; Colton, CA; Dunson, DB
MLA Citation
Badea, Alexandra, et al. “Identifying Vulnerable Brain Networks in Mouse Models of Genetic Risk Factors for Late Onset Alzheimer's Disease.Front Neuroinform, vol. 13, 2019, p. 72. Pubmed, doi:10.3389/fninf.2019.00072.
URI
https://scholars.duke.edu/individual/pub1426827
PMID
31920610
Source
pubmed
Published In
Frontiers in Neuroinformatics
Volume
13
Published Date
Start Page
72
DOI
10.3389/fninf.2019.00072

Qualitative and Quantitative Neuropathology Approaches Using Magnetic Resonance Microscopy (Diffusion Tensor Imaging) and Stereology in a Hexachlorophene Model of Myelinopathy in Sprague-Dawley Rats.

It is well established that hexachlorophene, which is used as an antibacterial agent, causes intramyelinic edema in humans and animal models. The hexachlorophene myelinopathy model, in which male Sprague-Dawley rats received 25 to 30 mg/kg hexachlorophene by gavage for up to 5 days, provided an opportunity to compare traditional neuropathology evaluations with magnetic resonance microscopy (MRM) findings. In addition, stereology assessments of 3 neuroanatomical sites were compared to quantitative measurements of similar structures by MRM. There were positive correlations between hematoxylin and eosin and luxol fast blue stains and MRM for identifying intramyelinic edema in the cingulum of corpus callosum, optic chiasm, anterior commissure (aca), lateral olfactory tracts, pyramidal tracts (py), and white matter tracts in the cerebellum. Stereology assessments were focused on the aca, longitudinal fasciculus of the pons, and py and demonstrated differences between control and treated rats, as was observed using MRM. The added value of MRM assessments was the ability to acquire qualitative 3-dimensional (3-D) images and obtain quantitative measurements of intramyelinic edema in 26 neuroanatomical sites in the intact brain. Also, diffusion tensor imaging (fractional anisotropy [FA]) indicated that there were changes in the cytoarchitecture of the white matter as detected by decreases in the FA in the treated compared to the control rats. This study demonstrates creative strategies that are possible using qualitative and quantitative assessments of potential white matter neurotoxicants in nonclinical toxicity studies. Our results lead us to the conclusion that volumetric analysis by MRM and stereology adds significant value to the standard 2-D microscopic evaluations.
Authors
Sills, RC; Johnson, GA; Anderson, RJ; Johnson, CL; Staup, M; Brown, DL; Churchill, SR; Kurtz, DM; Cushman, JD; Waidyanatha, S; Robinson, VG; Cesta, MF; Andrews, DMK; Behl, M; Shockley, KR; Little, PB
MLA Citation
URI
https://scholars.duke.edu/individual/pub1467010
PMID
33334257
Source
pubmed
Published In
Toxicol Pathol
Volume
48
Published Date
Start Page
965
End Page
980
DOI
10.1177/0192623320968210

TBR-760, a Dopamine-Somatostatin Compound, Arrests Growth of Aggressive Nonfunctioning Pituitary Adenomas in Mice.

TBR-760 (formerly BIM-23A760) is a chimeric dopamine (DA)-somatostatin (SST) compound with potent agonist activity at both DA type 2 (D2R) and SST type 2 (SSTR2) receptors. Studies have shown that chimeric DA-SST compounds are more efficacious than individual DA and/or SST analogues, either alone or combined, in inhibiting secretion from primary cultures of human somatotroph and lactotroph tumor cells. Nonfunctioning pituitary adenomas (NFPAs) express both D2R and SSTR2 and, consequently, may respond to TBR-760. We used a mouse model with the pro-opiomelanocortin (POMC) gene knocked out that spontaneously develops aggressive NFPAs. Genomic microarray and DA and SST receptor messenger RNA expression analysis indicate that POMC KO mouse tumors and human NFPAs have similar expression profiles, despite arising from different cell lineages, establishing POMC KO mice as a model for study of NFPAs. Treatment with TBR-760 for 8 weeks resulted in nearly complete inhibition of established tumor growth, whereas tumors from vehicle-treated mice increased in size by 890 ± 0.7%. Comparing TBR-760 with its individual DA and SST components, TBR-760 arrested tumor growth. Treatment with equimolar or 10×-higher doses of the individual SST or DA agonists, either alone or in combination, had no significant effect. One exception was the lower dose of DA agonist that induced modest suppression of tumor growth. Only the chimeric compound TBR-760 arrested tumor growth in this mouse model of NFPA. Further, significant tumor shrinkage was observed in 20% of the mice treated with TBR-760. These results support the development of TBR-760 as a therapy for patients with NFPA.
Authors
Halem, HA; Hochgeschwender, U; Rih, JK; Nelson, R; Johnson, GA; Thiagalingam, A; Culler, MD
MLA Citation
Halem, Heather A., et al. “TBR-760, a Dopamine-Somatostatin Compound, Arrests Growth of Aggressive Nonfunctioning Pituitary Adenomas in Mice.Endocrinology, vol. 161, no. 8, Aug. 2020. Pubmed, doi:10.1210/endocr/bqaa101.
URI
https://scholars.duke.edu/individual/pub1448996
PMID
32591776
Source
pubmed
Published In
Endocrinology
Volume
161
Published Date
DOI
10.1210/endocr/bqaa101

Characterization complex collagen fiber architecture in knee joint using high-resolution diffusion imaging.

PURPOSE: To evaluate the complex fiber orientations and 3D collagen fiber network of knee joint connective tissues, including ligaments, muscle, articular cartilage, and meniscus using high spatial and angular resolution diffusion imaging. METHODS: Two rat knee joints were scanned using a modified 3D diffusion-weighted spin echo pulse sequence with the isotropic spatial resolution of 45 μm at 9.4T. The b values varied from 250 to 1250 s/mm2 with 31 diffusion encoding directions for 1 rat knee. The b value was fixed to 1000 s/mm2 with 147 diffusion encoding directions for the second knee. Both the diffusion tensor imaging (DTI) model and generalized Q-sampling imaging (GQI) method were used to investigate the fiber orientation distributions and tractography with the validation of polarized light microscopy. RESULTS: To better resolve the crossing fibers, the b value should be great than or equal to 1000 s/mm2 . The tractography results were comparable between the DTI model and GQI method in ligament and muscle. However, the tractography exhibited apparent difference between DTI and GQI in connective tissues with more complex collagen fibers network, such as cartilage and meniscus. In articular cartilage, there were numerous crossing fibers found in superficial zone and transitional zone. Tractography generated with GQI also resulted in more intact tracts in articular cartilage than DTI. CONCLUSION: High-resolution diffusion imaging with GQI method can trace the complex collagen fiber orientations and architectures of the knee joint at microscopic resolution.
Authors
Wang, N; Mirando, AJ; Cofer, G; Qi, Y; Hilton, MJ; Johnson, GA
MLA Citation
Wang, Nian, et al. “Characterization complex collagen fiber architecture in knee joint using high-resolution diffusion imaging.Magn Reson Med, vol. 84, no. 2, Aug. 2020, pp. 908–19. Pubmed, doi:10.1002/mrm.28181.
URI
https://scholars.duke.edu/individual/pub1428325
PMID
31962373
Source
pubmed
Published In
Magn Reson Med
Volume
84
Published Date
Start Page
908
End Page
919
DOI
10.1002/mrm.28181

Optimizing Diffusion Imaging Protocols for Structural Connectomics in Mouse Models of Neurological Conditions.

Network approaches provide sensitive biomarkers for neurological conditions, such as Alzheimer's disease (AD). Mouse models can help advance our understanding of underlying pathologies, by dissecting vulnerable circuits. While the mouse brain contains less white matter compared to the human brain, axonal diameters compare relatively well (e.g., ~0.6 μm in the mouse and ~0.65-1.05 μm in the human corpus callosum). This makes the mouse an attractive test bed for novel diffusion models and imaging protocols. Remaining questions on the accuracy and uncertainty of connectomes have prompted us to evaluate diffusion imaging protocols with various spatial and angular resolutions. We have derived structural connectomes by extracting gradient subsets from a high-spatial, high-angular resolution diffusion acquisition (120 directions, 43-μm-size voxels). We have simulated protocols with 12, 15, 20, 30, 45, 60, 80, 100, and 120 angles and at 43, 86, or 172-μm voxel sizes. The rotational stability of these schemes increased with angular resolution. The minimum condition number was achieved for 120 directions, followed by 60 and 45 directions. The percentage of voxels containing one dyad was exceeded by those with two dyads after 45 directions, and for the highest spatial resolution protocols. For the 86- or 172-μm resolutions, these ratios converged toward 55% for one and 39% for two dyads, respectively, with <7% from voxels with three dyads. Tractography errors, estimated through dyad dispersion, decreased most with angular resolution. Spatial resolution effects became noticeable at 172 μm. Smaller tracts, e.g., the fornix, were affected more than larger ones, e.g., the fimbria. We observed an inflection point for 45 directions, and an asymptotic behavior after 60 directions, corresponding to similar projection density maps. Spatially downsampling to 86 μm, while maintaining the angular resolution, achieved a subgraph similarity of 96% relative to the reference. Using 60 directions with 86- or 172-μm voxels resulted in 94% similarity. Node similarity metrics indicated that major white matter tracts were more robust to downsampling relative to cortical regions. Our study provides guidelines for new protocols in mouse models of neurological conditions, so as to achieve similar connectomes, while increasing efficiency.
Authors
Anderson, RJ; Long, CM; Calabrese, ED; Robertson, SH; Johnson, GA; Cofer, GP; O'Brien, RJ; Badea, A
MLA Citation
Anderson, Robert J., et al. “Optimizing Diffusion Imaging Protocols for Structural Connectomics in Mouse Models of Neurological Conditions.Front Phys, vol. 8, Apr. 2020. Pubmed, doi:10.3389/fphy.2020.00088.
URI
https://scholars.duke.edu/individual/pub1441260
PMID
33928076
Source
pubmed
Published In
Frontiers in Physics
Volume
8
Published Date
DOI
10.3389/fphy.2020.00088

Research Areas:

Age Factors
Aging
Alzheimer Disease
Angiography, Digital Subtraction
Animals
Anisotropy
Aorta
Artifacts
Atlases as Topic
Bayes Theorem
Biological Markers
Blast Injuries
Blood Flow Velocity
Blood-Brain Barrier
Brain
Brain Diseases
Brain Injuries
Brain Mapping
Cardiac-Gated Imaging Techniques
Cardiovascular System
Cell Line, Tumor
Central Nervous System
Cerebellar Nuclei
Cerebral Cortex
Computer Graphics
Computer Simulation
Computer Systems
Computers
Contrast Media
Coronary Vessels
Databases, Factual
Diagnostic Imaging
Diffusion
Diffusion Tensor Imaging
Disease Models, Animal
Disease Susceptibility
Dose-Response Relationship, Drug
Drug Evaluation, Preclinical
Echo-Planar Imaging
Electromagnetic Fields
Electromagnetic Phenomena
Embryo, Mammalian
Equipment Design
Female
Fetal Alcohol Syndrome
Fiber Optic Technology
Fibrosis
Four-Dimensional Computed Tomography
Fourier Analysis
Gadolinium
Gadolinium DTPA
Genotype
Heart
Heart Rate
Helium
Histological Techniques
Histology
Humans
Image Enhancement
Image Interpretation, Computer-Assisted
Image Processing, Computer-Assisted
Imaging
Imaging, Three-Dimensional
Immunohistochemistry
Infarction, Middle Cerebral Artery
Informatics
Information Dissemination
Intubation
Iodine
Kidney
Kidney Cortex
Kidney Diseases
Kidney Glomerulus
Kidney Medulla
Least-Squares Analysis
Liposomes
Liver
Magnetic Resonance Angiography
Magnetic Resonance Imaging
Magnetic Resonance Spectroscopy
Magnetic susceptibility
Magnetics
Magnetite Nanoparticles
Manganese
Manganese Compounds
Methods
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Inbred Strains
Mice, Knockout
Mice, Neurologic Mutants
Mice, Nude
Microbubbles
Microcirculation
Microscopy
Microscopy, Confocal
Microscopy, Electron, Scanning
Models, Anatomic
Models, Animal
Models, Biological
Models, Cardiovascular
Models, Neurological
Models, Statistical
Molecular Imaging
Monitoring, Physiologic
Multiple Sclerosis
Myocardial Contraction
Myocardial Infarction
Nanoparticles
Nervous System
Neural Pathways
Noble Gases
Nuclear magnetic resonance
Optical Imaging
Pathology
Perfusion
Perfusion Imaging
Phantoms, Imaging
Phenotype
Protons
Pulmonary Artery
Pulmonary Circulation
Pulmonary Diffusing Capacity
Pulmonary Fibrosis
Pulmonary Gas Exchange
Putamen
Radiation Dosage
Radiation Injuries, Experimental
Radiographic Image Enhancement
Radiographic Image Interpretation, Computer-Assisted
Radiography, Thoracic
Rats
Rats, Inbred F344
Rats, Sprague-Dawley
Reference Standards
Respiration
Respiratory Mechanics
Retrospective Studies
Rubidium
Signal Processing, Computer-Assisted
Software
Spatio-Temporal Analysis
Specimen Handling
Spectrometry, Fluorescence
Staining and Labeling
Stereotaxic Techniques
Substantia Nigra
Subtraction Technique
Technology, Radiologic
Tissue Fixation
Tomography
Tomography Scanners, X-Ray Computed
Tomography, Emission-Computed, Single-Photon
Tomography, Optical
Tomography, X-Ray Computed
Toxicology
Tumor Burden
Tumor Microenvironment
Ultrasonics
Ultrasonography, Doppler, Transcranial
Ventilation-Perfusion Ratio
Ventilators, Mechanical
Ventricular Function, Left
X-Ray Microtomography
X-Rays
Xenon Isotopes
Xenon Radioisotopes