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Badea, Cristian Tudorel

Overview:

Dr. Cristian T. Badea is an Associate Professor in the Department of Radiology and faculty in the Departments of Biomedical Engineering and Medical Physics. His research focuses on pre-clinical imaging. Dr. Badea has research interests in the physics and biomedical applications of computed tomography (CT), micro-CT, tomosynthesis, fluorecence tomography and image reconstruction algorithms.


Positions:

Associate Professor in Radiology

Radiology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

Ph.D. 2001

Ph.D. — University of Patras (Greece)

News:

Grants:

Development of a New Generation Micro-CT imaging for Functional and Molecular Imaging of Cancer

Administered By
Radiology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
July 01, 2015
End Date
June 30, 2020

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

An Activatable Nanoparticle Probe for Molecular Imaging of Protease Activity by Dual Energy CT

Administered By
Biomedical Engineering
AwardedBy
National Institutes of Health
Role
Co-Sponsor
Start Date
June 01, 2015
End Date
May 31, 2018

Defining the Cellular Target of Radiation Therapy

Administered By
Radiation Oncology
AwardedBy
National Institutes of Health
Role
Collaborating Investigator
Start Date
January 01, 2014
End Date
December 31, 2015

Dual energy CT molecular imaging of vulnerable atherosclerotic plaques using a novel nanoparticle contrast agent

Administered By
Biomedical Engineering
AwardedBy
American Heart Association
Role
Co-Sponsor
Start Date
July 01, 2014
End Date
May 31, 2015

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

Small Animal Imaging Resource Program

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

Tumor perfusion in small animals with tomographic digital subtraction angiography

Administered By
Radiology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
March 12, 2007
End Date
February 28, 2009

The Duke University Molecular Imaging Center

Administered By
Radiology
AwardedBy
National Institutes of Health
Role
Associate in Research
Start Date
August 30, 2001
End Date
December 31, 2006
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Publications:

A neural network-based method for spectral distortion correction in photon counting x-ray CT.

Spectral CT using a photon counting x-ray detector (PCXD) shows great potential for measuring material composition based on energy dependent x-ray attenuation. Spectral CT is especially suited for imaging with K-edge contrast agents to address the otherwise limited contrast in soft tissues. We have developed a micro-CT system based on a PCXD. This system enables both 4 energy bins acquisition, as well as full-spectrum mode in which the energy thresholds of the PCXD are swept to sample the full energy spectrum for each detector element and projection angle. Measurements provided by the PCXD, however, are distorted due to undesirable physical effects in the detector and can be very noisy due to photon starvation in narrow energy bins. To address spectral distortions, we propose and demonstrate a novel artificial neural network (ANN)-based spectral distortion correction mechanism, which learns to undo the distortion in spectral CT, resulting in improved material decomposition accuracy. To address noise, post-reconstruction denoising based on bilateral filtration, which jointly enforces intensity gradient sparsity between spectral samples, is used to further improve the robustness of ANN training and material decomposition accuracy. Our ANN-based distortion correction method is calibrated using 3D-printed phantoms and a model of our spectral CT system. To enable realistic simulations and validation of our method, we first modeled the spectral distortions using experimental data acquired from (109)Cd and (133)Ba radioactive sources measured with our PCXD. Next, we trained an ANN to learn the relationship between the distorted spectral CT projections and the ideal, distortion-free projections in a calibration step. This required knowledge of the ground truth, distortion-free spectral CT projections, which were obtained by simulating a spectral CT scan of the digital version of a 3D-printed phantom. Once the training was completed, the trained ANN was used to perform distortion correction on any subsequent scans of the same system with the same parameters. We used joint bilateral filtration to perform noise reduction by jointly enforcing intensity gradient sparsity between the reconstructed images for each energy bin. Following reconstruction and denoising, the CT data was spectrally decomposed using the photoelectric effect, Compton scattering, and a K-edge material (i.e. iodine). The ANN-based distortion correction approach was tested using both simulations and experimental data acquired in phantoms and a mouse with our PCXD-based micro-CT system for 4 bins and full-spectrum acquisition modes. The iodine detectability and decomposition accuracy were assessed using the contrast-to-noise ratio and relative error in iodine concentration estimation metrics in images with and without distortion correction. In simulation, the material decomposition accuracy in the reconstructed data was vastly improved following distortion correction and denoising, with 50% and 20% reductions in material concentration measurement error in full-spectrum and 4 energy bins cases, respectively. Overall, experimental data confirms that full-spectrum mode provides superior results to 4-energy mode when the distortion corrections are applied. The material decomposition accuracy in the reconstructed data was vastly improved following distortion correction and denoising, with as much as a 41% reduction in material concentration measurement error for full-spectrum mode, while also bringing the iodine detectability to 4-6 mg ml(-1). Distortion correction also improved the 4 bins mode data, but to a lesser extent. The results demonstrate the experimental feasibility and potential advantages of ANN-based distortion correction and joint bilateral filtration-based denoising for accurate K-edge imaging with a PCXD. Given the computational efficiency with which the ANN can be applied to projection data, the proposed scheme can be readily integrated into existing CT reconstruction pipelines.

Authors
Touch, M; Clark, DP; Barber, W; Badea, CT
MLA Citation
Touch, M, Clark, DP, Barber, W, and Badea, CT. "A neural network-based method for spectral distortion correction in photon counting x-ray CT." Physics in medicine and biology 61.16 (August 2016): 6132-6153.
PMID
27469292
Source
epmc
Published In
Physics in Medicine and Biology
Volume
61
Issue
16
Publish Date
2016
Start Page
6132
End Page
6153
DOI
10.1088/0031-9155/61/16/6132

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

A dual energy CT study on vascular effects of gold nanoparticles in radiation therapy

© 2016 SPIE.Gold nanoparticles (AuNPs) are emerging as promising agents for both cancer therapy and CT imaging. AuNPs are delivered to tumors via the enhanced permeability and retention effect and they preferentially accumulate in close proximity to the tumor blood vessels. AuNPs produce low-energy, short-range photoelectrons during external beam radiation therapy (RT), boosting dose. This work is focused on understanding how tumor vascular permeability is influenced by AuNP-augmented radiation therapy (RT), and how this knowledge can potentially improve the delivery of additional nanoparticle-based chemotherapeutics. We use dual energy (DE) CT to detect accumulation of AuNPs and increased vascular permeability to liposomal iodine (i.e. a surrogate for chemotherapeutics with liposome encapsulation) following RT. We used sarcoma tumors generated in LSL-KrasG12D; p53FL/FL conditional mutant mice. A total of n=37 mice were used in this study. The treated mice were injected with 20 mg AuNP (0.1 ml/25 g mouse) 24 hours before delivery of 5 Gy RT (n=5), 10 Gy RT (n=3) or 20 Gy RT (n=6). The control mice received no AuNP injection and either no RT (n=6), 5 Gy RT (n=3), 10 Gy RT (n=3), 20 Gy RT (n=11) . Twenty four hours post-RT, the mice were injected with liposomal iodine (0.3 ml/25 mouse) and imaged with DE-CT three days later. The results suggest that independent of any AuNP usage, RT levels of 10 Gy and 20 Gy increase the permeability of tumor vasculature to liposomal iodine and that the increase in permeability is dose-dependent. We found that the effect of RT on vasculature may already be at its maximum response i.e. saturated at 20 Gy, and therefore the addition of AuNPs had almost no added benefit. Similarly, at 5 Gy RT, our data suggests that there was no effect of AuNP augmentation on tumor vascular permeability. However, b y using AuNPs with 10 Gy RT, we observed an increase in the vascular permeability, however this is not yet statistically significant due to the small number of mice in these groups. Such an approach can be used together with a liposomal drug delivery system to increase specific tumor delivery of chemotherapeutics. Our method has the potential to significantly improve tumor therapy and reduce the side effects from both RT and chemotherapy.

Authors
Ashton, JR; Hoye, J; Deland, K; Whitley, M; Qi, Y; Moding, E; Kirsch, DG; West, J; Badea, CT
MLA Citation
Ashton, JR, Hoye, J, Deland, K, Whitley, M, Qi, Y, Moding, E, Kirsch, DG, West, J, and Badea, CT. "A dual energy CT study on vascular effects of gold nanoparticles in radiation therapy." January 1, 2016.
Source
scopus
Published In
Proceedings of SPIE
Volume
9788
Publish Date
2016
DOI
10.1117/12.2217012

Resolution-enhancing hybrid, spectral CT reconstruction

© 2016 SPIE.Spectral x-ray imaging based on photon-counting x-ray detectors (PCXD) is an area of growing interest. By measuring the energy of x-ray photons, a spectral CT system can better differentiate elements using a single scan. However, the spatial resolution achievable with most PCXDs limits their application, particularly in preclinical CT imaging. Consequently, our group is developing a hybrid micro-CT scanner based on a high-resolution, energy-integrating (EID) detector and a lower-resolution, PCXD. To complement this system, we propose and demonstrate a hybrid, spectral CT reconstruction algorithm which robustly combines the spectral contrast of the PCXD with the spatial resolution of the EID. Specifically, the high-resolution, spectrally resolved data (X) is recovered as the sum of two matrices: one with low column rank (XL) determined from the EID data and one with intensity gradient sparse columns (XS) corresponding to the upsampled spectral contrast obtained from the PCXD data. We test the proposed algorithm in a feasibility study focused on molecular imaging of atherosclerotic plaque using activatable iodine and gold nanoparticles. The results show accurate estimation of material concentrations at increased spatial resolution for a voxel size ratio between the PCXD and the EID of 500 μm3:100 μm3. Specifically, regularized, iterative reconstruction of the MOBY mouse phantom around the K-edges of iodine (33.2 keV) and gold (80.7 keV) reduces the reconstruction error by more than a factor of three relative to least-squares, algebraic reconstruction. Likewise, the material decomposition accuracy into iodine, gold, calcium, and water improves by more than a factor of two.

Authors
Clark, DP; Badea, CT
MLA Citation
Clark, DP, and Badea, CT. "Resolution-enhancing hybrid, spectral CT reconstruction." January 1, 2016.
Source
scopus
Published In
Proceedings of SPIE
Volume
9783
Publish Date
2016
DOI
10.1117/12.2216935

Joint regularization for spectrooral CT reconstruction

© 2016 SPIE.X-ray CT is widely used, both clinically and preclinically, for fast, high-resolution, anatomic imaging; however, compelling opportunities exist to expand its use in functional imaging applications. For instance, spectral information combined with nanoparticle contrast agents enables quantification of tissue perfusion levels, while temporal information details cardiac and respiratory dynamics. In previous work, we proposed and demonstrated a projection acquisition and reconstruction strategy for 5D CT (3D + dual-energy + time) which recovered spectral and temporal information without substantially increasing radiation dose or sampling time relative to anatomic imaging protocols. The approach relied on the approximate separability of the temporal and spectral reconstruction sub-problems, which enabled substantial projection undersampling and effective regularization. Here, we extend this previous work to more general, nonseparable 5D CT reconstruction cases (3D + muti-energy + time) with applicability to K-edge imaging of exogenous contrast agents. We apply the newly proposed algorithm in phantom simulations using a realistic system and noise model for a photon counting x-ray detector with six energy thresholds. The MOBY mouse phantom used contains realistic concentrations of iodine, gold, and calcium in water. Relative to weighted least-squares reconstruction, the proposed 5D reconstruction algorithm improved reconstruction and material decomposition accuracy by 3-18 times. Furthermore, by exploiting joint, low rank image structure between time points and energies, ∼80 HU of contrast associated with the Kedge of gold and ∼35 HU of contrast associated with the blood pool and myocardium were recovered from more than 400 HU of noise.

Authors
Clark, DP; Badea, CT
MLA Citation
Clark, DP, and Badea, CT. "Joint regularization for spectrooral CT reconstruction." January 1, 2016.
Source
scopus
Published In
Proceedings of SPIE
Volume
9783
Publish Date
2016
DOI
10.1117/12.2217091

Novel approaches to address spectral distortions in photon counting x-ray CT using artificial neural networks

© 2016 SPIE.Spectral CT using a photon-counting x-ray detector (PCXD) can potentially increase accuracy of measuring tissue composition. However, PCXD spectral measurements suffer from distortion due to charge sharing, pulse pileup, and Kescape energy loss. This study proposes two novel artificial neural network (ANN)-based algorithms: one to model and compensate for the distortion, and another one to directly correct for the distortion. The ANN-based distortion model was obtained by training to learn the distortion from a set of projections with a calibration scan. The ANN distortion was then applied in the forward statistical model to compensate for distortion in the projection decomposition. ANN was also used to learn to correct distortions directly in projections. The resulting corrected projections were used for reconstructing the image, denoising via joint bilateral filtration, and decomposition into three-material basis functions: Compton scattering, the photoelectric effect, and iodine. The ANN-based distortion model proved to be more robust to noise and worked better compared to using an imperfect parametric distortion model. In the presence of noise, the mean relative errors in iodine concentration estimation were 11.82% (ANN distortion model) and 16.72% (parametric model). With distortion correction, the mean relative error in iodine concentration estimation was improved by 50% over direct decomposition from distorted data. With our joint bilateral filtration, the resulting material image quality and iodine detectability as defined by the contrast-to-noise ratio were greatly enhanced allowing iodine concentrations as low as 2 mg/ml to be detected. Future work will be dedicated to experimental evaluation of our ANN-based methods using 3D-printed phantoms.

Authors
Touch, M; Clark, DP; Barber, W; Badea, CT
MLA Citation
Touch, M, Clark, DP, Barber, W, and Badea, CT. "Novel approaches to address spectral distortions in photon counting x-ray CT using artificial neural networks." January 1, 2016.
Source
scopus
Published In
Proceedings of SPIE
Volume
9783
Publish Date
2016
DOI
10.1117/12.2217037

Spectrotemporal CT data acquisition and reconstruction at low dose.

X-ray computed tomography (CT) is widely used, both clinically and preclinically, for fast, high-resolution anatomic imaging; however, compelling opportunities exist to expand its use in functional imaging applications. For instance, spectral information combined with nanoparticle contrast agents enables quantification of tissue perfusion levels, while temporal information details cardiac and respiratory dynamics. The authors propose and demonstrate a projection acquisition and reconstruction strategy for 5D CT (3D+dual energy+time) which recovers spectral and temporal information without substantially increasing radiation dose or sampling time relative to anatomic imaging protocols.The authors approach the 5D reconstruction problem within the framework of low-rank and sparse matrix decomposition. Unlike previous work on rank-sparsity constrained CT reconstruction, the authors establish an explicit rank-sparse signal model to describe the spectral and temporal dimensions. The spectral dimension is represented as a well-sampled time and energy averaged image plus regularly undersampled principal components describing the spectral contrast. The temporal dimension is represented as the same time and energy averaged reconstruction plus contiguous, spatially sparse, and irregularly sampled temporal contrast images. Using a nonlinear, image domain filtration approach, the authors refer to as rank-sparse kernel regression, the authors transfer image structure from the well-sampled time and energy averaged reconstruction to the spectral and temporal contrast images. This regularization strategy strictly constrains the reconstruction problem while approximately separating the temporal and spectral dimensions. Separability results in a highly compressed representation for the 5D data in which projections are shared between the temporal and spectral reconstruction subproblems, enabling substantial undersampling. The authors solved the 5D reconstruction problem using the split Bregman method and GPU-based implementations of backprojection, reprojection, and kernel regression. Using a preclinical mouse model, the authors apply the proposed algorithm to study myocardial injury following radiation treatment of breast cancer.Quantitative 5D simulations are performed using the MOBY mouse phantom. Twenty data sets (ten cardiac phases, two energies) are reconstructed with 88 μm, isotropic voxels from 450 total projections acquired over a single 360° rotation. In vivo 5D myocardial injury data sets acquired in two mice injected with gold and iodine nanoparticles are also reconstructed with 20 data sets per mouse using the same acquisition parameters (dose: ∼60 mGy). For both the simulations and the in vivo data, the reconstruction quality is sufficient to perform material decomposition into gold and iodine maps to localize the extent of myocardial injury (gold accumulation) and to measure cardiac functional metrics (vascular iodine). Their 5D CT imaging protocol represents a 95% reduction in radiation dose per cardiac phase and energy and a 40-fold decrease in projection sampling time relative to their standard imaging protocol.Their 5D CT data acquisition and reconstruction protocol efficiently exploits the rank-sparse nature of spectral and temporal CT data to provide high-fidelity reconstruction results without increased radiation dose or sampling time.

Authors
Clark, DP; Lee, C-L; Kirsch, DG; Badea, CT
MLA Citation
Clark, DP, Lee, C-L, Kirsch, DG, and Badea, CT. "Spectrotemporal CT data acquisition and reconstruction at low dose." Medical physics 42.11 (November 2015): 6317-6336.
Website
http://hdl.handle.net/10161/11181
PMID
26520724
Source
epmc
Published In
Medical physics
Volume
42
Issue
11
Publish Date
2015
Start Page
6317
End Page
6336
DOI
10.1118/1.4931407

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

Rank-sparsity constrained, spectro-temporal reconstruction for retrospectively gated, dynamic CT

© 2015 SPIE.Relative to prospective projection gating, retrospective projection gating for dynamic CT applications allows fast imaging times, minimizing the potential for physiological and anatomic variability. Preclinically, fast imaging is attractive due to the rapid clearance of low molecular weight contrast agents and the rapid heart rate of rodents. Clinically, retrospective gating is relevant for intraoperative C-arm CT. More generally, retrospective sampling provides an opportunity for significant reduction in x-ray dose within the framework of compressive sensing theory and sparsity-constrained iterative reconstruction. Even so, CT reconstruction from projections with random temporal sampling is a very poorly conditioned inverse problem, requiring high fidelity regularization to minimize variability in the reconstructed results. Here, we introduce a highly novel data acquisition and regularization strategy for spectro-temporal (5D) CT reconstruction from retrospectively gated projections. We show that by taking advantage of the rank-sparse structure and separability of the temporal and spectral reconstruction sub-problems, being able to solve each sub-problem independently effectively guarantees that we can solve both problems together. In this paper, we show 4D simulation results (2D + 2 energies + time) using the proposed technique and compare them with two competing techniques - spatio-temporal total variation minimization and prior image constrained compressed sensing. We also show in vivo, 5D (3D + 2 energies + time) myocardial injury data acquired in a mouse, reconstructing 20 data sets (10 phases, 2 energies) and performing material decomposition from data acquired over a single rotation (360°, dose: ∼60 mGy).

Authors
Clark, DP; Lee, CL; Kirsch, DG; Badea, CT
MLA Citation
Clark, DP, Lee, CL, Kirsch, DG, and Badea, CT. "Rank-sparsity constrained, spectro-temporal reconstruction for retrospectively gated, dynamic CT." January 1, 2015.
Source
scopus
Published In
Proceedings of SPIE
Volume
9412
Publish Date
2015
DOI
10.1117/12.2081379

Spectral deblurring: An algorithm for high-resolution, hybrid spectral CT

© 2015 SPIE.We are developing a hybrid, dual-source micro-CT system based on the combined use of an energy integrating (EID) x-ray detector and a photon counting x-ray detector (PCXD). Due to their superior spectral resolving power, PCXDs have the potential to reduce radiation dose and to enable functional and molecular imaging with CT. In most current PCXDs, however, spatial resolution and field of view are limited by hardware development and charge sharing effects. To address these problems, we propose spectral deblurring - a relatively simple algorithm for increasing the spatial resolution of hybrid, spectral CT data. At the heart of the algorithm is the assumption that the underlying CT data is piecewise constant, enabling robust recovery in the presence of noise and spatial blur by enforcing gradient sparsity. After describing the proposed algorithm, we summarize simulation experiments which assess the trade-offs between spatial resolution, contrast, and material decomposition accuracy given realistic levels of noise. When the spatial resolution between imaging chains has a ratio of 5:1, spectral deblurring results in a 52% increase in the material decomposition accuracy of iodine, gadolinium, barium, and water vs. linear interpolation. For a ratio of 10:1, a realistic representation of our hybrid imaging system, a 52% improvement was also seen. Overall, we conclude that the performance breaks down around high frequency and low contrast structures. Following the simulation experiments, we apply the algorithm to ex vivo data acquired in a mouse injected with an iodinated contrast agent and surrounded by vials of iodine, gadolinium, barium, and water.

Authors
Clark, DP; Badea, CT
MLA Citation
Clark, DP, and Badea, CT. "Spectral deblurring: An algorithm for high-resolution, hybrid spectral CT." January 1, 2015.
Source
scopus
Published In
Proceedings of SPIE
Volume
9412
Publish Date
2015
DOI
10.1117/12.2081249

Simultaneous imaging of multiple contrast agents using full-spectrum micro-CT

© 2015 SPIE.One of the major challenges for in vivo, micro-computed tomography (CT) imaging is poor soft tissue contrast. To increase contrast, exogenous contrast agents can be used as imaging probes. Combining these probes with a photon counting x-ray detector (PCXD) allows energy-sensitive CT and probe material decomposition from a series of images associated with different x-ray energies. We have implemented full-spectrum micro-CT using a PCXD and 2 keV energy sampling. We then decomposed multiple k-edge contrast materials present in an object (iodine, barium, and gadolinium) from water. Since the energy bins were quite narrow, the projection data was very noisy. This noise and further spectral distortions amplify errors in post-reconstruction material decompositions. Here, we propose and demonstrate a novel post-reconstruction denoising scheme which jointly enforces local and global gradient sparsity constraints, improving the contrast-to-noise ratio in full-spectrum micro-CT data and resultant material decompositions. We performed experiments using both calibration phantoms and ex vivo mouse data. Denoising increased the material contrast-to-noise ratio by an average of 13 times relative to filtered backprojection reconstructions. The relative decomposition error after denoising was 21%. To further improve material decomposition accuracy in future work, we also developed a model of the spectral distortions caused by PCXD imaging using known spectra from radioactive isotopes (109Cd, 133Ba). In future work, we plan to combine this model with the proposed denoising algorithm, enabling material decomposition with higher sensitivity and accuracy.

Authors
Clark, DP; Touch, M; Barber, W; Badea, CT
MLA Citation
Clark, DP, Touch, M, Barber, W, and Badea, CT. "Simultaneous imaging of multiple contrast agents using full-spectrum micro-CT." January 1, 2015.
Source
scopus
Published In
Proceedings of SPIE
Volume
9412
Publish Date
2015
DOI
10.1117/12.2081049

Rank-sparsity constrained atlas construction and phenotyping

© 2015 SPIE.Atlas construction is of great interest in the medical imaging community as a tool to visually and quantitatively characterize anatomic variability within a population. Because such atlases generally exhibit superior data fidelity relative to the individual data sets from which they are constructed, they have also proven invaluable in numerous informatics applications such as automated segmentation and classification, regularization of individual-specific reconstructions from undersampled data, and for characterizing physiologically relevant functional metrics. Perhaps the most valuable role of an anatomic atlas is not to define what is "normal," but, in fact, to recognize what is "abnormal." Here, we propose and demonstrate a novel anatomic atlas construction strategy that simultaneously recovers the average anatomy and the deviation from average in a visually meaningful way. The proposed approach treats the problem of atlas construction within the context of robust principal component analysis (RPCA) in which the redundant portion of the data (i.e. the low rank atlas) is separated from the spatially and gradient sparse portion of the data unique to each individual (i.e. the sparse variation). In this paper, we demonstrate the application of RPCA to the Shepp-Logan phantom, including several forms of variability encountered with in vivo data: population variability, class variability, contrast variability, and individual variability. We then present preliminary results produced by applying the proposed approach to in vivo, murine cardiac micro-CT data acquired in a model of right ventricle hypertrophy induced by pulmonary arteriole hypertension.

Authors
Clark, DP; Badea, CT
MLA Citation
Clark, DP, and Badea, CT. "Rank-sparsity constrained atlas construction and phenotyping." January 1, 2015.
Source
scopus
Published In
Proceedings of SPIE
Volume
9413
Publish Date
2015
DOI
10.1117/12.2081415

A Plasmonic Gold Nanostar Theranostic Probe for In Vivo Tumor Imaging and Photothermal Therapy.

Nanomedicine has attracted increasing attention in recent years, because it offers great promise to provide personalized diagnostics and therapy with improved treatment efficacy and specificity. In this study, we developed a gold nanostar (GNS) probe for multi-modality theranostics including surface-enhanced Raman scattering (SERS) detection, x-ray computed tomography (CT), two-photon luminescence (TPL) imaging, and photothermal therapy (PTT). We performed radiolabeling, as well as CT and optical imaging, to investigate the GNS probe's biodistribution and intratumoral uptake at both macroscopic and microscopic scales. We also characterized the performance of the GNS nanoprobe for in vitro photothermal heating and in vivo photothermal ablation of primary sarcomas in mice. The results showed that 30-nm GNS have higher tumor uptake, as well as deeper penetration into tumor interstitial space compared to 60-nm GNS. In addition, we found that a higher injection dose of GNS can increase the percentage of tumor uptake. We also demonstrated the GNS probe's superior photothermal conversion efficiency with a highly concentrated heating effect due to a tip-enhanced plasmonic effect. In vivo photothermal therapy with a near-infrared (NIR) laser under the maximum permissible exposure (MPE) led to ablation of aggressive tumors containing GNS, but had no effect in the absence of GNS. This multifunctional GNS probe has the potential to be used for in vivo biosensing, preoperative CT imaging, intraoperative detection with optical methods (SERS and TPL), as well as image-guided photothermal therapy.

Authors
Liu, Y; Ashton, JR; Moding, EJ; Yuan, H; Register, JK; Fales, AM; Choi, J; Whitley, MJ; Zhao, X; Qi, Y; Ma, Y; Vaidyanathan, G; Zalutsky, MR; Kirsch, DG; Badea, CT; Vo-Dinh, T
MLA Citation
Liu, Y, Ashton, JR, Moding, EJ, Yuan, H, Register, JK, Fales, AM, Choi, J, Whitley, MJ, Zhao, X, Qi, Y, Ma, Y, Vaidyanathan, G, Zalutsky, MR, Kirsch, DG, Badea, CT, and Vo-Dinh, T. "A Plasmonic Gold Nanostar Theranostic Probe for In Vivo Tumor Imaging and Photothermal Therapy." Theranostics 5.9 (January 2015): 946-960.
Website
http://hdl.handle.net/10161/11045
PMID
26155311
Source
epmc
Published In
Theranostics
Volume
5
Issue
9
Publish Date
2015
Start Page
946
End Page
960
DOI
10.7150/thno.11974

In vivo small animal micro-CT using nanoparticle contrast agents.

Computed tomography (CT) is one of the most valuable modalities for in vivo imaging because it is fast, high-resolution, cost-effective, and non-invasive. Moreover, CT is heavily used not only in the clinic (for both diagnostics and treatment planning) but also in preclinical research as micro-CT. Although CT is inherently effective for lung and bone imaging, soft tissue imaging requires the use of contrast agents. For small animal micro-CT, nanoparticle contrast agents are used in order to avoid rapid renal clearance. A variety of nanoparticles have been used for micro-CT imaging, but the majority of research has focused on the use of iodine-containing nanoparticles and gold nanoparticles. Both nanoparticle types can act as highly effective blood pool contrast agents or can be targeted using a wide variety of targeting mechanisms. CT imaging can be further enhanced by adding spectral capabilities to separate multiple co-injected nanoparticles in vivo. Spectral CT, using both energy-integrating and energy-resolving detectors, has been used with multiple contrast agents to enable functional and molecular imaging. This review focuses on new developments for in vivo small animal micro-CT using novel nanoparticle probes applied in preclinical research.

Authors
Ashton, JR; West, JL; Badea, CT
MLA Citation
Ashton, JR, West, JL, and Badea, CT. "In vivo small animal micro-CT using nanoparticle contrast agents." Frontiers in pharmacology 6 (January 2015): 256-. (Review)
Website
http://hdl.handle.net/10161/10945
PMID
26581654
Source
epmc
Published In
Frontiers in Pharmacology
Volume
6
Publish Date
2015
Start Page
256
DOI
10.3389/fphar.2015.00256

Spectral diffusion: an algorithm for robust material decomposition of spectral CT data.

Clinical successes with dual energy CT, aggressive development of energy discriminating x-ray detectors, and novel, target-specific, nanoparticle contrast agents promise to establish spectral CT as a powerful functional imaging modality. Common to all of these applications is the need for a material decomposition algorithm which is robust in the presence of noise. Here, we develop such an algorithm which uses spectrally joint, piecewise constant kernel regression and the split Bregman method to iteratively solve for a material decomposition which is gradient sparse, quantitatively accurate, and minimally biased. We call this algorithm spectral diffusion because it integrates structural information from multiple spectral channels and their corresponding material decompositions within the framework of diffusion-like denoising algorithms (e.g. anisotropic diffusion, total variation, bilateral filtration). 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(-1)), gold (0.9 mg mL(-1)), and gadolinium (2.9 mg mL(-1)) concentrations. We then apply spectral diffusion to the in vivo separation of these three materials in the mouse kidneys, liver, and spleen.

Authors
Clark, DP; Badea, CT
MLA Citation
Clark, DP, and Badea, CT. "Spectral diffusion: an algorithm for robust material decomposition of spectral CT data." Physics in medicine and biology 59.21 (November 2014): 6445-6466.
Website
http://hdl.handle.net/10161/11180
PMID
25296173
Source
epmc
Published In
Physics in Medicine and Biology
Volume
59
Issue
21
Publish Date
2014
Start Page
6445
End Page
6466
DOI
10.1088/0031-9155/59/21/6445

Micro-CT of rodents: state-of-the-art and future perspectives.

Micron-scale computed tomography (micro-CT) is an essential tool for phenotyping and for elucidating diseases and their therapies. This work is focused on preclinical micro-CT imaging, reviewing relevant principles, technologies, and applications. Commonly, micro-CT provides high-resolution anatomic information, either on its own or in conjunction with lower-resolution functional imaging modalities such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT). More recently, however, advanced applications of micro-CT produce functional information by translating clinical applications to model systems (e.g., measuring cardiac functional metrics) and by pioneering new ones (e.g. measuring tumor vascular permeability with nanoparticle contrast agents). The primary limitations of micro-CT imaging are the associated radiation dose and relatively poor soft tissue contrast. We review several image reconstruction strategies based on iterative, statistical, and gradient sparsity regularization, demonstrating that high image quality is achievable with low radiation dose given ever more powerful computational resources. We also review two contrast mechanisms under intense development. The first is spectral contrast for quantitative material discrimination in combination with passive or actively targeted nanoparticle contrast agents. The second is phase contrast which measures refraction in biological tissues for improved contrast and potentially reduced radiation dose relative to standard absorption imaging. These technological advancements promise to develop micro-CT into a commonplace, functional and even molecular imaging modality.

Authors
Clark, DP; Badea, CT
MLA Citation
Clark, DP, and Badea, CT. "Micro-CT of rodents: state-of-the-art and future perspectives." Physica medica : PM : an international journal devoted to the applications of physics to medicine and biology : official journal of the Italian Association of Biomedical Physics (AIFB) 30.6 (September 2014): 619-634. (Review)
Website
http://hdl.handle.net/10161/11179
PMID
24974176
Source
epmc
Published In
Physica Medica
Volume
30
Issue
6
Publish Date
2014
Start Page
619
End Page
634
DOI
10.1016/j.ejmp.2014.05.011

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

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

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

Micro-CT of rodents: State-of-the-art and future perspectives

Micron-scale computed tomography (micro-CT) is an essential tool for phenotyping and for elucidating diseases and their therapies. This work is focused on preclinical micro-CT imaging, reviewing relevant principles, technologies, and applications. Commonly, micro-CT provides high-resolution anatomic information, either on its own or in conjunction with lower-resolution functional imaging modalities such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT). More recently, however, advanced applications of micro-CT produce functional information by translating clinical applications to model systems (e.g. measuring cardiac functional metrics) and by pioneering new ones (e.g. measuring tumor vascular permeability with nanoparticle contrast agents). The primary limitations of micro-CT imaging are the associated radiation dose and relatively poor soft tissue contrast. We review several image reconstruction strategies based on iterative, statistical, and gradient sparsity regularization, demonstrating that high image quality is achievable with low radiation dose given ever more powerful computational resources. We also review two contrast mechanisms under intense development. The first is spectral contrast for quantitative material discrimination in combination with passive or actively targeted nanoparticle contrast agents. The second is phase contrast which measures refraction in biological tissues for improved contrast and potentially reduced radiation dose relative to standard absorption imaging. These technological advancements promise to develop micro-CT into a commonplace, functional and even molecular imaging modality. © 2014 Associazione Italiana di Fisica Medica.

Authors
Clark, DP; Badea, CT
MLA Citation
Clark, DP, and Badea, CT. "Micro-CT of rodents: State-of-the-art and future perspectives." Physica Medica 30.6 (January 1, 2014): 619-634. (Review)
Source
scopus
Published In
Physica Medica
Volume
30
Issue
6
Publish Date
2014
Start Page
619
End Page
634
DOI
10.1016/j.ejmp.2014.05.011

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

High-Resolution CT for Small-Animal Imaging Research

Authors
Badea, CT; Panetta, D
MLA Citation
Badea, CT, and Panetta, D. "High-Resolution CT for Small-Animal Imaging Research." Comprehensive Biomedical Physics. January 1, 2014. 221-242.
Website
http://hdl.handle.net/10161/11169
Source
scopus
Volume
2
Publish Date
2014
Start Page
221
End Page
242

Dual-energy micro-CT functional imaging of primary lung cancer in mice using gold and iodine nanoparticle contrast agents: a validation study.

To provide additional functional information for tumor characterization, we investigated the use of dual-energy computed tomography for imaging murine lung tumors. Tumor blood volume and vascular permeability were quantified using gold and iodine nanoparticles. This approach was compared with a single contrast agent/single-energy CT method. Ex vivo validation studies were performed to demonstrate the accuracy of in vivo contrast agent quantification by CT.Primary lung tumors were generated in LSL-Kras(G12D); p53(FL/FL) mice. Gold nanoparticles were injected, followed by iodine nanoparticles two days later. The gold accumulated in tumors, while the iodine provided intravascular contrast. Three dual-energy CT scans were performed-two for the single contrast agent method and one for the dual contrast agent method. Gold and iodine concentrations in each scan were calculated using a dual-energy decomposition. For each method, the tumor fractional blood volume was calculated based on iodine concentration, and tumor vascular permeability was estimated based on accumulated gold concentration. For validation, the CT-derived measurements were compared with histology and inductively-coupled plasma optical emission spectroscopy measurements of gold concentrations in tissues.Dual-energy CT enabled in vivo separation of gold and iodine contrast agents and showed uptake of gold nanoparticles in the spleen, liver, and tumors. The tumor fractional blood volume measurements determined from the two imaging methods were in agreement, and a high correlation (R(2) = 0.81) was found between measured fractional blood volume and histology-derived microvascular density. Vascular permeability measurements obtained from the two imaging methods agreed well with ex vivo measurements.Dual-energy CT using two types of nanoparticles is equivalent to the single nanoparticle method, but allows for measurement of fractional blood volume and permeability with a single scan. As confirmed by ex vivo methods, CT-derived nanoparticle concentrations are accurate. This method could play an important role in lung tumor characterization by CT.

Authors
Ashton, JR; Clark, DP; Moding, EJ; Ghaghada, K; Kirsch, DG; West, JL; Badea, CT
MLA Citation
Ashton, JR, Clark, DP, Moding, EJ, Ghaghada, K, Kirsch, DG, West, JL, and Badea, CT. "Dual-energy micro-CT functional imaging of primary lung cancer in mice using gold and iodine nanoparticle contrast agents: a validation study." PloS one 9.2 (January 2014): e88129-.
Website
http://hdl.handle.net/10161/11255
PMID
24520351
Source
epmc
Published In
PloS one
Volume
9
Issue
2
Publish Date
2014
Start Page
e88129
DOI
10.1371/journal.pone.0088129

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

In vivo characterization of tumor vasculature using iodine and gold nanoparticles and dual energy micro-CT.

Tumor blood volume and vascular permeability are well established indicators of tumor angiogenesis and important predictors in cancer diagnosis, planning and treatment. In this work, we establish a novel preclinical imaging protocol which allows quantitative measurement of both metrics simultaneously. First, gold nanoparticles are injected and allowed to extravasate into the tumor, and then liposomal iodine nanoparticles are injected. Combining a previously optimized dual energy micro-CT scan using high-flux polychromatic x-ray sources (energies: 40 kVp, 80 kVp) with a novel post-reconstruction spectral filtration scheme, we are able to decompose the results into 3D iodine and gold maps, allowing simultaneous measurement of extravasated gold and intravascular iodine concentrations. Using a digital resolution phantom, the mean limits of detectability (mean CNR = 5) for each element are determined to be 2.3 mg mL(-1) (18 mM) for iodine and 1.0 mg mL(-1) (5.1 mM) for gold, well within the observed in vivo concentrations of each element (I: 0-24 mg mL(-1), Au: 0-9 mg mL(-1)) and a factor of 10 improvement over the limits without post-reconstruction spectral filtration. Using a calibration phantom, these limits are validated and an optimal sensitivity matrix for performing decomposition using our micro-CT system is derived. Finally, using a primary mouse model of soft-tissue sarcoma, we demonstrate the in vivo application of the protocol to measure fractional blood volume and vascular permeability over the course of five days of active tumor growth.

Authors
Clark, DP; Ghaghada, K; Moding, EJ; Kirsch, DG; Badea, CT
MLA Citation
Clark, DP, Ghaghada, K, Moding, EJ, Kirsch, DG, and Badea, CT. "In vivo characterization of tumor vasculature using iodine and gold nanoparticles and dual energy micro-CT." Phys Med Biol 58.6 (March 21, 2013): 1683-1704.
PMID
23422321
Source
pubmed
Published In
Physics in Medicine and Biology
Volume
58
Issue
6
Publish Date
2013
Start Page
1683
End Page
1704
DOI
10.1088/0031-9155/58/6/1683

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

Assessing the radiation response of lung cancer with different gene mutations using genetically engineered mice.

PURPOSE: Non-small cell lung cancers (NSCLC) are a heterogeneous group of carcinomas harboring a variety of different gene mutations. We have utilized two distinct genetically engineered mouse models of human NSCLC (adenocarcinoma) to investigate how genetic factors within tumor parenchymal cells influence the in vivo tumor growth delay after one or two fractions of radiation therapy (RT). MATERIALS AND METHODS: Primary lung adenocarcinomas were generated in vivo in mice by intranasal delivery of an adenovirus expressing Cre-recombinase. Lung cancers expressed oncogenic Kras(G12D) and were also deficient in one of two tumor suppressor genes: p53 or Ink4a/ARF. Mice received no radiation treatment or whole lung irradiation in a single fraction (11.6 Gy) or in two 7.3 Gy fractions (14.6 Gy total) separated by 24 h. In each case, the biologically effective dose (BED) equaled 25 Gy10. Response to RT was assessed by micro-CT 2 weeks after treatment. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and immunohistochemical staining were performed to assess the integrity of the p53 pathway, the G1 cell-cycle checkpoint, and apoptosis. RESULTS: Tumor growth rates prior to RT were similar for the two genetic variants of lung adenocarcinoma. Lung cancers with wild-type (WT) p53 (LSL-Kras; Ink4a/ARF(FL/FL) mice) responded better to two daily fractions of 7.3 Gy compared to a single fraction of 11.6 Gy (P = 0.002). There was no statistically significant difference in the response of lung cancers deficient in p53 (LSL-Kras; p53(FL/FL) mice) to a single fraction (11.6 Gy) compared to 7.3 Gy × 2 (P = 0.23). Expression of the p53 target genes p21 and PUMA were higher and bromodeoxyuridine uptake was lower after RT in tumors with WT p53. CONCLUSION: Using an in vivo model of malignant lung cancer in mice, we demonstrate that the response of primary lung cancers to one or two fractions of RT can be influenced by specific gene mutations.

Authors
Perez, BA; Ghafoori, AP; Lee, C-L; Johnston, SM; Li, Y; Moroshek, JG; Ma, Y; Mukherjee, S; Kim, Y; Badea, CT; Kirsch, DG
MLA Citation
Perez, BA, Ghafoori, AP, Lee, C-L, Johnston, SM, Li, Y, Moroshek, JG, Ma, Y, Mukherjee, S, Kim, Y, Badea, CT, and Kirsch, DG. "Assessing the radiation response of lung cancer with different gene mutations using genetically engineered mice. (Published online)" Front Oncol 3 (2013): 72-.
PMID
23565506
Source
pubmed
Published In
Front Oncol
Volume
3
Publish Date
2013
Start Page
72
DOI
10.3389/fonc.2013.00072

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

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

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

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

Dual-energy micro-CT of the rodent lung.

The purpose of this work is to investigate the use of dual-energy micro-computed tomography (CT) for the estimation of vascular, tissue, and air fractions in rodent lungs using a postreconstruction three material decomposition method. Using simulations, we have estimated the accuracy limits of the decomposition for realistic micro-CT noise levels. Next, we performed experiments involving ex vivo lung imaging in which intact rat lungs were carefully removed from the thorax, injected with an iodine-based contrast agent, and then inflated with different volumes of air (n = 2). Finally, we performed in vivo imaging studies in C57BL/6 mice (n = 5) using fast prospective respiratory gating in end inspiration and end expiration for three different levels of positive end expiratory pressure (PEEP). Before imaging, mice were injected with a liposomal blood pool contrast agent. The three-dimensional air, tissue, and blood fraction maps were computed and analyzed. The results indicate that separation and volume estimation of the three material components of the lungs are possible. The mean accuracy values for air, blood, and tissue were 93, 93, and 90%, respectively. The absolute accuracy in determining all fraction materials was 91.6%. The coefficient of variation was small (2.5%) indicating good repeatability. The minimum difference that we could detect in material fractions was 15%. As expected, an increase in PEEP levels for the living mouse resulted in statistically significant increases in air fractions at end expiration but no significant changes at end inspiration. Our method has applicability in preclinical pulmonary studies where changes in lung structure and gas volume as a result of lung injury, environmental exposures, or drug bioactivity would have important physiological implications.

Authors
Badea, CT; Guo, X; Clark, D; Johnston, SM; Marshall, CD; Piantadosi, CA
MLA Citation
Badea, CT, Guo, X, Clark, D, Johnston, SM, Marshall, CD, and Piantadosi, CA. "Dual-energy micro-CT of the rodent lung." Am J Physiol Lung Cell Mol Physiol 302.10 (May 15, 2012): L1088-L1097.
PMID
22427526
Source
pubmed
Published In
American journal of physiology. Lung cellular and molecular physiology
Volume
302
Issue
10
Publish Date
2012
Start Page
L1088
End Page
L1097
DOI
10.1152/ajplung.00359.2011

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

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

Lung imaging in rodents using dual energy micro-CT

Dual energy CT imaging is expected to play a major role in the diagnostic arena as it provides material decomposition on an elemental basis. The purpose of this work is to investigate the use of dual energy micro-CT for the estimation of vascular, tissue, and air fractions in rodent lungs using a post-reconstruction three-material decomposition method. We have tested our method using both simulations and experimental work. Using simulations, we have estimated the accuracy limits of the decomposition for realistic micro-CT noise levels. Next, we performed experiments involving ex vivo lung imaging in which intact lungs were carefully removed from the thorax, were injected with an iodine-based contrast agent and inflated with air at different volume levels. Finally, we performed in vivo imaging studies in (n=5) C57BL/6 mice using fast prospective respiratory gating in endinspiration and end-expiration for three different levels of positive end-expiratory pressure (PEEP). Prior to imaging, mice were injected with a liposomal blood pool contrast agent. The mean accuracy values were for Air (95.5%), Blood (96%), and Tissue (92.4%). The absolute accuracy in determining all fraction materials was 94.6%. The minimum difference that we could detect in material fractions was 15%. As expected, an increase in PEEP levels for the living mouse resulted in statistically significant increases in air fractions at end-expiration, but no significant changes in end-inspiration. Our method has applicability in preclinical pulmonary studies where various physiological changes can occur as a result of genetic changes, lung disease, or drug effects. © 2012 SPIE.

Authors
Badea, CT; Guo, X; Clark, D; Johnston, SM; Marshall, C; Piantadosi, C
MLA Citation
Badea, CT, Guo, X, Clark, D, Johnston, SM, Marshall, C, and Piantadosi, C. "Lung imaging in rodents using dual energy micro-CT." Progress in Biomedical Optics and Imaging - Proceedings of SPIE 8317 (2012).
PMID
24027623
Source
scival
Published In
Proceedings of SPIE
Volume
8317
Publish Date
2012
DOI
10.1117/12.912155

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

A spectral calibration technique for x-ray CT

Spectral reconstruction algorithms for x-ray CT require an accurate spectral model of the system, including the spectrum of the photons emitted by the source and the spectral sensitivity of the detector. Although these components of the spectral model have been characterized in previous studies, there might be additional components that are unaccounted for, such as the inherent filtration of the x-ray source and the detector. In this study, we present a technique for measuring the inaccuracies in the spectral model and accounting for them. This technique entails the acquisition of photon measurements with several materials placed between the source and the detector, and the solution of a linear system of equations. We test the accuracy of this technique in simulations, and demonstrate its potential to improve the results of spectral reconstruction. © 2012 Copyright Society of Photo-Optical Instrumentation Engineers (SPIE).

Authors
Johnston, SM; Badea, CT
MLA Citation
Johnston, SM, and Badea, CT. "A spectral calibration technique for x-ray CT." Progress in Biomedical Optics and Imaging - Proceedings of SPIE 8313 (2012).
Source
scival
Published In
Proceedings of SPIE
Volume
8313
Publish Date
2012
DOI
10.1117/12.911532

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

Data analysis: evaluation of nanoscale contrast agent enhanced CT scan to differentiate between benign and malignant lung cancer in mouse model.

Proposed is a method for statistical analysis for a small sample size, repeated measure experiment with nesting factors. In the original experiment the Student t-test was used for analysis. Using the same data, we modeled the experiment into two groups of mice with benign and malignant primary lung tumors. 4 tumor nodules were selected from each mouse (N= 36). The dependent variables are the volume, diameter, and signal attenuation measured using computed tomography (CT). The measurements are made before injecting the contrast and at 0, 72, and 168 hours after injection. The contrast agent enhances tumor nodule volume and volume differences between benign and malignant tumor nodules measured across time (p < 0.05). The signal attenuation measured across time differentiates between benign and malignant groups (p < 0.05). There is significant correlation between rate of change of volume and diameter of tumor. The advantages of this statistical method are discussed.

Authors
Bell, RC; Rogith, D; Johnson, CW; Badea, CT; Athreya, KK; Espinosa, G; Clark, D; Ghafoori, AP; Li, Y; Kirsch, DG; Annapragada, A; Ghaghada, K
MLA Citation
Bell, RC, Rogith, D, Johnson, CW, Badea, CT, Athreya, KK, Espinosa, G, Clark, D, Ghafoori, AP, Li, Y, Kirsch, DG, Annapragada, A, and Ghaghada, K. "Data analysis: evaluation of nanoscale contrast agent enhanced CT scan to differentiate between benign and malignant lung cancer in mouse model." AMIA Annu Symp Proc 2012 (2012): 27-35.
PMID
23304269
Source
pubmed
Published In
AMIA ... Annual Symposium proceedings / AMIA Symposium. AMIA Symposium
Volume
2012
Publish Date
2012
Start Page
27
End Page
35

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

Highly efficient detection in fluorescence tomography of quantum dots using time-gated acquisition and ultrafast pulsed laser.

Quantum dots (QDs) are widely used in fluorescence tomography due to its unique advantages. Despite the very high quantum efficiency of the QDs, low fluorescent signal and autofluorescence are the most fundamental limitations in optical data acquisition. These limitations are particularly detrimental to image reconstruction for animal imaging, e.g., free-space in vivo fluorescence tomography. In animals studies, fluorescent emission from exogenous fluorescent probes (e.g. QDs) cannot be effectively differentiated from endogenous broad-spectral substances (mostly proteins) using optical filters. In addition, a barrow-band fluorescent filter blocks the majority of the fluorescent light and thus makes signal acquisition very inefficient. We made use of the long fluorescent lifetime of the QDs to reject the optical signal due to the excitation light pulse, and therefore eliminated the need for a fluorescent filter during acquisition. Fluorescent emission from the QDs was excited with an ultrafast pulsed laser, and was detected using a time-gated image intensifier. A tissue-simulating imaging phantom was used to validate the proposed method. Compared to the standard acquisition method that uses a narrow-band fluorescent filter, the proposed method is significantly more efficient in data acquisition (by a factor of >10 in terms of fluorescent signal intensity) and demonstrated reduction in autofluorescence. No additional imaging artifact was observed in the tomographic reconstruction.

Authors
Zhang, X; Badea, CT
MLA Citation
Zhang, X, and Badea, CT. "Highly efficient detection in fluorescence tomography of quantum dots using time-gated acquisition and ultrafast pulsed laser." Proc SPIE Int Soc Opt Eng 7896 (January 23, 2011).
Website
http://hdl.handle.net/10161/13278
PMID
21373380
Source
pubmed
Published In
Proceedings of SPIE - The International Society for Optical Engineering
Volume
7896
Publish Date
2011
DOI
10.1117/12.875502

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

Multi-modality PET-CT imaging of breast cancer in an animal model using nanoparticle x-ray contrast agent and 18F-FDG

Multi-modality PET-CT imaging is playing an important role in the field of oncology. While PET imaging facilitates functional interrogation of tumor status, the use of CT imaging is primarily limited to anatomical reference. In an attempt to extract comprehensive information about tumor cells and its microenvironment, we used a nanoparticle x-ray contrast agent to image tumor vasculature and vessel 'leakiness' and 18F-FDG to investigate the metabolic status of tumor cells. In vivo PET/CT studies were performed in mice implanted with 4T1 mammary breast cancer cells. Early-phase micro-CT imaging enabled visualization 3D vascular architecture of the tumors whereas delayed-phase micro-CT demonstrated highly permeable vessels as evident by nanoparticle accumulation within the tumor. Both imaging modalities demonstrated the presence of a necrotic core as indicated by a hypo-enhanced region in the center of the tumor. At early time-points, the CT-derived fractional blood volume did not correlate with 18F-FDG uptake. At delayed time-points, the tumor enhancement in 18F-FDG micro-PET images correlated with the delayed signal enhanced due to nanoparticle extravasation seen in CT images. The proposed hybrid imaging approach could be used to better understand tumor angiogenesis and to be the basis for monitoring and evaluating anti-angiogenic and nano-chemotherapies. © 2011 SPIE.

Authors
Badea, CT; Ghaghada, K; Espinosa, G; Strong, L; Annapragada, A
MLA Citation
Badea, CT, Ghaghada, K, Espinosa, G, Strong, L, and Annapragada, A. "Multi-modality PET-CT imaging of breast cancer in an animal model using nanoparticle x-ray contrast agent and 18F-FDG." Progress in Biomedical Optics and Imaging - Proceedings of SPIE 7965 (2011).
Source
scival
Published In
Proceedings of SPIE
Volume
7965
Publish Date
2011
DOI
10.1117/12.878024

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

Temporal and spectral reconstruction algorithms for x-ray CT

X-ray CT imaging of dynamic physiological processes entails the reconstruction of volumetric images of objects with x-ray attenuation properties that vary over time and energy. We show how the same algebraic model can be used to represent both temporal and spectral information. This model enables the formulation of algorithms capable of recovering information in either dimension. These dimensions can also be combined to develop algorithms that recover both dimensions simultaneously. We present such an algorithm, describe its implementation, and test it in simulations. © 2011 SPIE.

Authors
Johnston, SM; Badea, CT
MLA Citation
Johnston, SM, and Badea, CT. "Temporal and spectral reconstruction algorithms for x-ray CT." Progress in Biomedical Optics and Imaging - Proceedings of SPIE 7961 (2011).
Source
scival
Published In
Proceedings of SPIE
Volume
7961
Publish Date
2011
DOI
10.1117/12.878107

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

Phase-selective image reconstruction of the lungs in small animals using Micro-CT.

Gating in small animal imaging can compensate for artifacts due to physiological motion. This paper presents a strategy for sampling and image reconstruction in the rodent lung using micro-CT. The approach involves rapid sampling of free-breathing mice without any additional hardware to detect respiratory motion. The projection images are analyzed post-acquisition to derive a respiratory signal, which is used to provide weighting factors for each projection that favor a selected phase of the respiration (e.g. end-inspiration or end-expiration) for the reconstruction. Since the sampling cycle and the respiratory cycle are uncorrelated, the sets of projections corresponding to any of the selected respiratory phases do not have a regular angular distribution. This drastically affects the image quality of reconstructions based on simple filtered backprojection. To address this problem, we use an iterative reconstruction algorithm that combines the Simultaneous Algebraic Reconstruction Technique with Total Variation minimization (SART-TV). At each SART-TV iteration, backprojection is performed with a set of weighting factors that favor the desired respiratory phase. To reduce reconstruction time, the algorithm is implemented on a graphics processing unit. The performance of the proposed approach was investigated in simulations and in vivo scans of mice with primary lung cancers imaged with our in-house developed dual tube/detector micro-CT system. We note that if the ECG signal is acquired during sampling, the same approach could be used for phase-selective cardiac imaging.

Authors
Johnston, SM; Perez, BA; Kirsch, DG; Badea, CT
MLA Citation
Johnston, SM, Perez, BA, Kirsch, DG, and Badea, CT. "Phase-selective image reconstruction of the lungs in small animals using Micro-CT." Proc SPIE Int Soc Opt Eng 7622 (February 15, 2010): 76223G.1-76223G.9.
PMID
21243034
Source
pubmed
Published In
Proceedings of SPIE - The International Society for Optical Engineering
Volume
7622
Publish Date
2010
Start Page
76223G.1
End Page
76223G.9
DOI
10.1117/12.844359

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

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

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

Effects of sampling strategy on image quality in noncontact panoramic fluorescence diffuse optical tomography for small animal imaging.

Fluorescence diffuse optical tomography is an emerging technology for molecular imaging with recent technological advances in biomarkers and photonics. The introduction of noncontact imaging methods enables very large-scale data acquisition that is orders of magnitude larger than that from earlier systems. In this study, the effects of sampling strategy on image quality were investigated using an imaging phantom mimicking small animals and further analyzed using singular value analysis (SVA). The sampling strategy was represented in terms of a number of key acquisition parameters, namely the numbers of sources, detectors, and imaging angles. A number of metrics were defined to quantitatively evaluate image quality. The effects of acquisition parameters on image quality were subsequently studied by varying each of the parameters within a reasonable range while maintaining the other parameters constant, a method analogue to partial derivative in mathematical analysis. It was found that image quality improves at a much slower rate if the acquisition parameters are above certain critical values (approximately 5 sources, approximately 15 detectors, and approximately 20 angles for our system). These critical values remain virtually the same even if other acquisition parameters are doubled. It was also found that increasing different acquisition parameters improves image quality with different efficiencies in terms of the number of measurements: for a system characterized by a smaller threshold in SVA (less than 10(-5) in our study), the number of sources is the most efficient, followed by the number of detectors and subsequently the number of imaging angles. However, for systems characterized by a larger threshold, the numbers of sources and angles are equally more efficient than the number of detectors.

Authors
Zhang, X; Badea, C
MLA Citation
Zhang, X, and Badea, C. "Effects of sampling strategy on image quality in noncontact panoramic fluorescence diffuse optical tomography for small animal imaging." Opt Express 17.7 (March 30, 2009): 5125-5138.
PMID
19333276
Source
pubmed
Published In
Optics express
Volume
17
Issue
7
Publish Date
2009
Start Page
5125
End Page
5138

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

Micro-CT imaging of breast tumors in rodents using a liposomal, nanoparticle contrast agent.

A long circulating liposomal, nanoscale blood pool agent encapsulating traditional iodinated contrast agent (65 mg I/mL) was used for micro-computed tomography (CT) imaging of rats implanted with R3230AC mammary carcinoma. Three-dimensional vascular architecture of tumors was imaged at 100-micron isotropic resolution. The image data showed good qualitative correlation with pathologic findings. The approach holds promise for studying tumor angiogenesis and for evaluating anti-angiogenesis therapies.

Authors
Samei, E; Saunders, RS; Badea, CT; Ghaghada, KB; Hedlund, LW; Qi, Y; Yuan, H; Bentley, RC; Mukundan, S
MLA Citation
Samei, E, Saunders, RS, Badea, CT, Ghaghada, KB, Hedlund, LW, Qi, Y, Yuan, H, Bentley, RC, and Mukundan, S. "Micro-CT imaging of breast tumors in rodents using a liposomal, nanoparticle contrast agent." Int J Nanomedicine 4 (2009): 277-282.
PMID
20011244
Source
pubmed
Published In
International journal of nanomedicine
Volume
4
Publish Date
2009
Start Page
277
End Page
282

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

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

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

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

A registration based approach for 4D cardiac micro-CT using combined prospective and retrospective gating.

Recent advances in murine cardiac studies with three-dimensional cone beam micro-computed tomography (CT) have used either prospective or retrospective gating technique. While prospective gating ensures the best image quality and the highest resolution, it involves longer sampling times and higher radiation dose. Sampling is faster and the radiation dose can be reduced with retrospective gating but the image quality is affected by the limited number of projections with an irregular angular distribution which complicate the reconstruction process, causing significant streaking artifacts. This work involves both prospective and retrospective gating in sampling. Deformable registration is used between a high quality image set acquired with prospective gating with the multiple data sets during the cardiac cycle obtained using retrospective gating. Tests were conducted on a four-dimensional (4D) cardiac mouse phantom and after optimization, the method was applied to in vivo cardiac micro-CT data. Results indicate that, by using our method, the sampling time can be reduced by a factor of 2.5 and the radiation dose can be reduced 35% compared to the prospective sampling while the image quality can be maintained. In conclusion, we proposed a novel solution to 4D cine cardiac micro-CT based on a combined prospective with retrospective gating in sampling and deformable registration post reconstruction that mixed the advantages of both strategies.

Authors
Badea, CT; Schreibmann, E; Fox, T
MLA Citation
Badea, CT, Schreibmann, E, and Fox, T. "A registration based approach for 4D cardiac micro-CT using combined prospective and retrospective gating." Med Phys 35.4 (April 2008): 1170-1179.
PMID
18491508
Source
pubmed
Published In
Medical physics
Volume
35
Issue
4
Publish Date
2008
Start Page
1170
End Page
1179
DOI
10.1118/1.2868778

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

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

Utility of a prototype liposomal contrast agent for x-ray imaging of breast cancer: A proof of concept using micro-CT in small animals

Imaging tumor angiogenesis in small animals is extremely challenging due to the size of the tumor vessels. Consequently, both dedicated small animal imaging systems and specialized intravascular contrast agents are required. The goal of this study was to investigate the use of a liposomal contrast agent for high-resolution micro-CT imaging of breast tumors in small animals. A liposomal blood pool agent encapsulating iodine with a concentration of 65.5 mg/ml was used with a Duke Center for In Vivo Microscopy (CIVM) prototype micro-computed tomography (micro-CT) system to image the R3230AC mammary carcinoma implanted in rats. The animals were injected with equivalent volume doses (0.02 ml/kg) of contrast agent. Micro-CT with the liposomal blood pool contrast agent ensured a signal difference between the blood and the muscle higher than 450 HU allowing the visualization of the tumors 3D vascular architecture in exquisite detail at 100-micron resolution. The micro-CT data correlated well with the histological examination of tumor tissue. We also studied the ability to detect vascular enhancement with limited angle based reconstruction, i.e. tomosynthesis. Tumor volumes and their regional vascular percentage were estimated. This imaging approach could be used to better understand tumor angiogenesis and be the basis for evaluating anti-angiogenic therapies.

Authors
Badea, CT; Samei, E; Ghaghada, K; Saunders, R; Yuan, H; Qi, Y; Hedlund, LW; Mukundan, S
MLA Citation
Badea, CT, Samei, E, Ghaghada, K, Saunders, R, Yuan, H, Qi, Y, Hedlund, LW, and Mukundan, S. "Utility of a prototype liposomal contrast agent for x-ray imaging of breast cancer: A proof of concept using micro-CT in small animals." Progress in Biomedical Optics and Imaging - Proceedings of SPIE 6913 (2008).
Source
scival
Published In
Proceedings of SPIE
Volume
6913
Publish Date
2008
DOI
10.1117/12.772307

Optimization of dual energy contrast enhanced breast tomosynthesis for improved mammographic lesion detection and diagnosis

Dual-energy contrast-enhanced breast tomosynthesis has been proposed as a technique to improve the detection of early-stage cancer in young, high-risk women. This study focused on optimizing this technique using computer simulations. The computer simulation used analytical calculations to optimize the signal difference to noise ratio (SdNR) of resulting images from such a technique at constant dose. The optimization included the optimal radiographic technique, optimal distribution of dose between the two single-energy projection images, and the optimal weighting factor for the dual energy subtraction. Importantly, the SdNR included both anatomical and quantum noise sources, as dual energy imaging reduces anatomical noise at the expense of increases in quantum noise. Assuming a tungsten anode, the maximum SdNR at constant dose was achieved for a high energy beam at 49 kVp with 92.5 μm copper filtration and a low energy beam at 49 kVp with 95 μm tin filtration. These analytical calculations were followed by Monte Carlo simulations that included the effects of scattered radiation and detector properties. Finally, the feasibility of this technique was tested in a small animal imaging experiment using a novel iodinated liposomal contrast agent. The results illustrated the utility of dual energy imaging and determined the optimal acquisition parameters for this technique. This work was supported in part by grants from the Komen Foundation (PDF55806), the Cancer Research and Prevention Foundation, and the NIH (NCI R21 CA124584-01). CIVM is a NCRR/NCI National Resource under P41-05959/U24-CA092656.

Authors
Saunders, R; Samei, E; Badea, C; Yuan, H; Ghaghada, K; Qi, Y; Hedlund, LW; Mukundan, S
MLA Citation
Saunders, R, Samei, E, Badea, C, Yuan, H, Ghaghada, K, Qi, Y, Hedlund, LW, and Mukundan, S. "Optimization of dual energy contrast enhanced breast tomosynthesis for improved mammographic lesion detection and diagnosis." Progress in Biomedical Optics and Imaging - Proceedings of SPIE 6913 (2008).
Source
scival
Published In
Proceedings of SPIE
Volume
6913
Publish Date
2008
DOI
10.1117/12.772042

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

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

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

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." Medical physics 34.5 (May 2007): 1546-1555.
PMID
17555236
Source
epmc
Published In
Medical physics
Volume
34
Issue
5
Publish Date
2007
Start Page
1546
End Page
1555
DOI
10.1118/1.2717384

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

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

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

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." Medical physics 33.9 (September 2006): 3193-3202.
PMID
17022212
Source
epmc
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

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

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

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

Experiments with the nonlinear and chaotic behaviour of the multiplicative algebraic reconstruction technique (MART) algorithm for computed tomography.

Among the iterative reconstruction algorithms for tomography, the multiplicative algebraic reconstruction technique (MART) has two advantages that make it stand out from other algorithms: it confines the image (and therefore the projection data) to the convex hull of the patient, and it maximizes entropy. In this paper, we have undertaken a series of experiments to determine the importance of MART nonlinearity to image quality. Variants of MART were implemented aiming to exploit and exaggerate the nonlinear properties of the algorithm. We introduce the Power MART, Boxcar Averaging MART and Bouncing MART algorithms. Power MART is linked to the relaxation concept. Its behaviour is similar to that of the chaos of a logistic equation. There appears to be an antagonism between increasing nonlinearity and noise in the projection data. The experiments confirm our general observation that regularization as a means of solving simultaneous linear equations that are underdetermined is suboptimal: it does not necessarily select the correct image from the hyperplane of solutions, and so does not maximize the image quality:x-ray dose ratio. Our investigations prove that there is scope to optimize CT algorithms and thereby achieve greater dose reduction.

Authors
Badea, C; Gordon, R
MLA Citation
Badea, C, and Gordon, R. "Experiments with the nonlinear and chaotic behaviour of the multiplicative algebraic reconstruction technique (MART) algorithm for computed tomography." Phys Med Biol 49.8 (April 21, 2004): 1455-1474.
PMID
15152685
Source
pubmed
Published In
Physics in Medicine and Biology
Volume
49
Issue
8
Publish Date
2004
Start Page
1455
End Page
1474

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

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." 2004.
Source
scival
Published In
2004 2nd IEEE International Symposium on Biomedical Imaging: Macro to Nano
Volume
2
Publish Date
2004
Start Page
1377
End Page
1380

Estimation of the heart respiratory motion with applications for cone beam computed tomography imaging: a simulation study.

Computed tomography (CT) reconstruction methods assume imaging of static objects; object movement during projection data acquisition causes tomogram artifacts. The continuously moving heart, therefore, represents a complicated imaging case. The associated problems due to the heart beating can be overcome either by using very short projection acquisition times, during which the heart may be considered static, or by ECG-gated acquisition. In the latter case, however, the acquisition of a large number of projections may not be completed in a single breath hold, thus heart displacement occurs as an additional problem. This problem has been addressed by applying heart motion models in various respiratory motion compensation algorithms. Our paper focuses on cone beam computed tomography (CBCT), performed in conjunction with isocentric, fluoroscopic equipment, and continuous ECG and respiratory monitoring. Such equipment is used primarily for in-theater three-dimensional (3-D) imaging and benefits particularly from the recent developments in flat panel detector technologies. The objectives of this paper are: i) to develop a model for the motion of the heart due to respiration during the respiratory cycle; ii) to apply this model to the tomographic reconstruction algorithm, in order to account for heart movement due to respiration in the reconstruction; and iii) to initially evaluate this method by means of simulation studies. Based on simulation studies, we were able to demonstrate that heart displacement due to respiration can be estimated from the same projection data, required for a CBCT reconstruction. Our paper includes semiautomatic segmentation of the heart on the X-ray projections and reconstruction of a convex 3-D-heart object that performs the same motion as the heart during respiration, and use of this information into the CBCT reconstruction algorithm. The results reveal significant image quality improvements in cardiac image reconstruction.

Authors
Buliev, IG; Badea, CT; Kolitsi, Z; Pallikarakis, N
MLA Citation
Buliev, IG, Badea, CT, Kolitsi, Z, and Pallikarakis, N. "Estimation of the heart respiratory motion with applications for cone beam computed tomography imaging: a simulation study." IEEE Trans Inf Technol Biomed 7.4 (December 2003): 404-411.
PMID
15000366
Source
pubmed
Published In
IEEE Transactions on Information Technology in Biomedicine
Volume
7
Issue
4
Publish Date
2003
Start Page
404
End Page
411

A novel approach for distortion correction for X-ray image intensifiers.

Applications of X-ray image intensifiers in medical imaging, include the use of fluoroscopic projection images to generate three-dimensional tomographic reconstructions. Unfortunately, the inherent distortions on the acquired projections deteriorate the quality of the reconstructed tomograms. Distortion correction can be performed using algorithms that can be classified as global or local according to the method used, both having specific advantages and disadvantages. In this work, a novel approach for distortion correction is proposed which, by combining both global and local correction methods allows good image quality in relatively acceptable time. Correction parameters were obtained using a calibration phantom specially designed for this purpose.

Authors
Soimu, D; Badea, C; Pallikarakis, N
MLA Citation
Soimu, D, Badea, C, and Pallikarakis, N. "A novel approach for distortion correction for X-ray image intensifiers." Comput Med Imaging Graph 27.1 (2003): 79-85.
PMID
12573892
Source
pubmed
Published In
Computerized Medical Imaging and Graphics
Volume
27
Issue
1
Publish Date
2003
Start Page
79
End Page
85

Respiratory displacement modelling in cone beam computed tomography

Any organ motion during the projection acquisition causes blurring artefacts in the Computed Tomography (CT) reconstructions. It is a drawback in applications of Cone Beam CT (CBCT) for which, the complete scanning cannot be performed during a single breath hold. Our study proposes a new approach for estimation of the organ's respiratory displacement, from the same projection data, required for the CBCT with sampling over a circular trajectory. The processing includes semiautomatic outlining of the organ's boundaries on the X-ray projections, creating approximate shadow images, and constructing, from them, of a convex 3D organ-like structure, with the property to perform the same respiratory displacement as the one of the organ of interest. The motion is derived as a function of the respiration and can be used for respiratory motion correction in the following CBCT algorithm. Simulation results reveal significant improvements of the image quality in a cardiac tomogram reconstruction.

Authors
Buliev, IG; Badea, CT; Pallikarakis, N
MLA Citation
Buliev, IG, Badea, CT, and Pallikarakis, N. "Respiratory displacement modelling in cone beam computed tomography." Computers in Cardiology 30 (2003): 617-620.
Source
scival
Published In
Computers in Cardiology
Volume
30
Publish Date
2003
Start Page
617
End Page
620

Logarithmic amplifier for computed tomography tasks using fluoroscopic projections.

The image intensifier (II)-based imaging systems, as radiotherapy simulators or C-arm X-ray units, have also been used for image acquisition in computed tomography. When analogue-to-digital conversion is performed on the output signal of the television camera, the accuracy for low-amplitude video signals, corresponding to X-ray pathways crossing high attenuation structures, is limited. To deal with this lack of accuracy, we investigated the benefits of using a logarithmic amplifier (LOGAMP) inserted between the television camera output and the analogue-to-digital converter (ADC) in the image acquisition chain. Such a device was intended to provide better use of the available ADCs of a given resolution and actually to reduce the quantization noise. Simulated data were used in this study, and cases with and without logarithmic amplifier were compared. Based on the simulation results, we formulate requirements for several signal and acquisition system parameters where the use of such a circuit is recommended.

Authors
Buliev, I; Badea, C; Pallikarakis, N
MLA Citation
Buliev, I, Badea, C, and Pallikarakis, N. "Logarithmic amplifier for computed tomography tasks using fluoroscopic projections." J Med Eng Technol 26.6 (November 2002): 247-252.
PMID
12490030
Source
pubmed
Published In
Journal of Medical Engineering & Technology
Volume
26
Issue
6
Publish Date
2002
Start Page
247
End Page
252
DOI
10.1080/03091900210156832

Image quality in extended arc filtered digital tomosynthesis.

PURPOSE: To study image quality in filtered digital tomosynthesis (FDTS) tomograms as a function of their reconstruction arc, using isocentrically acquired, fluoroscopic projection data. MATERIAL AND METHODS: Both digital tomosynthesis (DTS) and cone beam CT (CBCT) reconstruction algorithms are based on backprojection and use cone beam projection data as input. Under limited angle conditions, CBCT is reduced to FDTS, where only a subset of projection data are used for reconstruction. The effect of the reconstruction arc on the spatial resolution, slice thickness, contrast sensitivity, shape distortion and artifacts, was also experimentally studied. The investigation was performed using both simulated and actual fluoroscopic images. RESULTS AND CONCLUSION: Image quality in terms of spatial resolution, slice thickness, shape distortion and artifacts, improved with increasing reconstruction arc and was optimized at 180 degrees, while contrast continued to improve as the arc was increased to 360 degrees. However, DTS was determined to be the technique of choice when reconstruction arcs of less than 40 degrees were used. Consequently, FDTS may be successfully implemented in applications involving extended arc reconstructions, in the range between 40 degrees delimiting the DTS domain and 360 degrees corresponding to CBCT.

Authors
Badea, C; Kolitsi, Z; Pallikarakis, N
MLA Citation
Badea, C, Kolitsi, Z, and Pallikarakis, N. "Image quality in extended arc filtered digital tomosynthesis." Acta Radiol 42.2 (March 2001): 244-248.
PMID
11259956
Source
pubmed
Published In
Acta Radiologica (Informa)
Volume
42
Issue
2
Publish Date
2001
Start Page
244
End Page
248

A 3-D imaging system for in-theatre orthopedic applications based on Digital Tomosynthesis

Authors
Badea, C; Kolitsi, Z; Pallikarakis, N
MLA Citation
Badea, C, Kolitsi, Z, and Pallikarakis, N. "A 3-D imaging system for in-theatre orthopedic applications based on Digital Tomosynthesis." 2001.
Source
wos-lite
Published In
International Congress Series
Volume
1230
Publish Date
2001
Start Page
1138
End Page
1138

A 3D imaging system for dental imaging based on digital tomosynthesis and cone beam CT

Authors
Badea, C; Kolitsi, Z; Pallikarakis, N
MLA Citation
Badea, C, Kolitsi, Z, and Pallikarakis, N. "A 3D imaging system for dental imaging based on digital tomosynthesis and cone beam CT." 2001.
Source
wos-lite
Published In
MEDICON 2001: PROCEEDINGS OF THE INTERNATIONAL FEDERATION FOR MEDICAL & BIOLOGICAL ENGINEERING, PTS 1 AND 2
Publish Date
2001
Start Page
739
End Page
741

A 3D imaging system for in-theatre orthopedic applications based on Digital Tomosynthesis.

Authors
Badea, CT; Kolitsi, Z; Pallikarakis, N
MLA Citation
Badea, CT, Kolitsi, Z, and Pallikarakis, N. "A 3D imaging system for in-theatre orthopedic applications based on Digital Tomosynthesis." Elsevier, 2001.
Source
dblp
Published In
CARS
Volume
1230
Publish Date
2001
Start Page
1209
End Page
1210

Three-dimensional localisation based on projectional and tomographic image correlation: an application for digital tomosynthesis.

Accurate three-dimensional tumor localisation in Radiotherapy, is critical to the treatment outcome, particularly when high dose gradients are present. A number of techniques have been proposed for the localisation of anatomical structures or markers. The present study proposes an approach to a concurrent maximisation of localisation accuracy and efficiency by correlation of tomographic and projectional images. The method introduces an element of direct verification and interactive optimisation of the process. Tomographic images are used for the identification of a point of interest. Its position is computed within the treatment co-ordinate system and verification of this position is achieved by obtaining the beam's eye view of the identified point on two projection radiographs. The key element of the approach is that all images used should be part of one single image data set. The implementation of this localisation method, as part of the functionality of a Digital Tomosynthesis prototype, has provided an integrated facility for localisation, of optimised accuracy and precision, while easy and efficient to use. The considerations are general and apply in principle to any imaging system that can augment tomographic images with projections.

Authors
Messaris, G; Kolitsi, Z; Badea, C; Pallikarakis, N
MLA Citation
Messaris, G, Kolitsi, Z, Badea, C, and Pallikarakis, N. "Three-dimensional localisation based on projectional and tomographic image correlation: an application for digital tomosynthesis." Med Eng Phys 21.2 (March 1999): 101-109.
PMID
10426510
Source
pubmed
Published In
Medical Engineering & Physics
Volume
21
Issue
2
Publish Date
1999
Start Page
101
End Page
109

A software tool to assist the planning of electrophysiological experiments on rat brain slices

We propose an interactive software tool for finding the plane which can be cut through the rat brain so as to contain maximum cross-section with a selected brain structure or combination of structures, i.e. a path of nerve fibers and the area they are known to connect to. A set of digitized coronal images from a stereotactic rat brain atlas is preprocessed: the images are registered, and the structures of interest plus the bulk of the brain are assigned specific gray levels. The Interactive Data Language (IDL) computing environment is used for volume reconstruction, visualization, and implementing the search procedure. Selected rat brain structures can be analyzed with our method, provided that the preprocessing of the atlas images is performed. As a first application of this method we have identified a set of parameters for which a plane (0.4 mm slice thickness) cut through the rat brain includes as many as possible intact connections between the fornix fibers and the mammilary bodies. Further development of the application will focus on automating the process and extending it to visualization of histochemical and autoradiographic data.

Authors
Bocioaca, A; Badea, C; Papatheodoropoulos, C; Kostopoulos, G
MLA Citation
Bocioaca, A, Badea, C, Papatheodoropoulos, C, and Kostopoulos, G. "A software tool to assist the planning of electrophysiological experiments on rat brain slices." Studies in Health Technology and Informatics 68 (1999): 976-979.
Source
scival
Published In
Studies in health technology and informatics
Volume
68
Publish Date
1999
Start Page
976
End Page
979
DOI
10.3233/978-1-60750-912-7-976

A wavelet-based method for removal of out-of-plane structures in digital tomosynthesis.

Reconstructed images in digital tomosynthesis (DTS) are affected by artifacts due to blur from planes other than the fulcrum plane. A wavelet-based method has been developed for the discrimination and subsequent removal of unrelated structures from the reconstructed plane. The approach exploits both the specific pattern of noise in DTS and the spatial locality of the wavelet transformation. The technique was implemented on a DTS clinical protoype system. Experimental evaluation on angiographic types of images demonstrated excellent noise differentiation and elimination. The method is therefore particularly useful for certain medical imaging applications such as vascular DTS imaging.

Authors
Badea, C; Kolitsi, Z; Pallikarakis, N
MLA Citation
Badea, C, Kolitsi, Z, and Pallikarakis, N. "A wavelet-based method for removal of out-of-plane structures in digital tomosynthesis." Comput Med Imaging Graph 22.4 (July 1998): 309-315.
PMID
9840661
Source
pubmed
Published In
Computerized Medical Imaging and Graphics
Volume
22
Issue
4
Publish Date
1998
Start Page
309
End Page
315

Medical device surveillance world-wide.

Authors
Badea, C; Kolitsi, Z; Pallikarakis, N; Papapanagiotou, A
MLA Citation
Badea, C, Kolitsi, Z, Pallikarakis, N, and Papapanagiotou, A. "Medical device surveillance world-wide." Stud Health Technol Inform 28 (1996): 157-174.
PMID
10184634
Source
pubmed
Published In
Studies in health technology and informatics
Volume
28
Publish Date
1996
Start Page
157
End Page
174
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Research Areas:

  • Algorithms
  • Ambulatory Care
  • Amplifiers, Electronic
  • Analog-Digital Conversion
  • Angiography
  • Angiography, Digital Subtraction
  • Animals
  • Antigens, CD31
  • Artifacts
  • Biological Markers
  • Blood Vessels
  • Blood Volume
  • Bone
  • Brachytherapy
  • Calibration
  • Capillary Permeability
  • Carcinoma, Non-Small-Cell Lung
  • Cardiac-Gated Imaging Techniques
  • Cardiovascular Physiological Phenomena
  • Cell Line, Tumor
  • Child Development
  • Cineradiography
  • Colonic Neoplasms
  • Computer Graphics
  • Computer Simulation
  • Computers
  • Contrast Media
  • Coronary Vessels
  • Diagnosis, Differential
  • Diagnostic Imaging
  • Diaphragm
  • Disease Models, Animal
  • Electrocardiography
  • Equipment Design
  • Equipment Failure Analysis
  • Equipment Safety
  • Equipment and Supplies
  • European Union
  • Evaluation Studies as Topic
  • Feasibility Studies
  • Female
  • Fibrosarcoma
  • Fluorescent Antibody Technique
  • Fluoroscopy
  • Four-Dimensional Computed Tomography
  • Gold
  • Heart
  • Heart Ventricles
  • Humans
  • Image Enhancement
  • Image Interpretation, Computer-Assisted
  • Image Processing, Computer-Assisted
  • Imaging, Three-Dimensional
  • Infant
  • Iodine
  • Iopamidol
  • Least-Squares Analysis
  • Liposomes
  • Lung
  • Lung Compliance
  • Lung Diseases
  • Lung Neoplasms
  • Magnetic Resonance Imaging
  • Male
  • Mammary Neoplasms, Animal
  • Mammary Neoplasms, Experimental
  • Mammography
  • Metal Nanoparticles
  • Metals
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Nude
  • Mice, Transgenic
  • Microinjections
  • Microscopy
  • Microscopy, Fluorescence
  • Microvessels
  • Models, Biological
  • Models, Statistical
  • Models, Theoretical
  • Molecular Imaging
  • Movement
  • Myocardial Contraction
  • Myocardial Infarction
  • Myocardium
  • Nanoparticles
  • Neovascularization, Pathologic
  • Nonlinear Dynamics
  • Normal Distribution
  • Organophosphorus Compounds
  • Organotechnetium Compounds
  • Perfusion
  • Perfusion Imaging
  • Permeability
  • Phantoms, Imaging
  • Phenotype
  • Positive-Pressure Respiration
  • Product Surveillance, Postmarketing
  • Proto-Oncogene Proteins p21(ras)
  • Pulmonary Alveoli
  • Pulmonary Fibrosis
  • Quality Control
  • Radiation Dosage
  • Radiation Injuries, Experimental
  • Radiographic Image Enhancement
  • Radiographic Image Interpretation, Computer-Assisted
  • Radiography, Thoracic
  • Rats
  • Rats, Inbred F344
  • Rats, Sprague-Dawley
  • Regression Analysis
  • Reproducibility of Results
  • Respiration
  • Respiratory Mechanics
  • Respiratory-Gated Imaging Techniques
  • Retrospective Studies
  • Reverse Transcriptase Polymerase Chain Reaction
  • Rodents
  • Sample Size
  • Sarcoma
  • Scattering, Radiation
  • Sensitivity and Specificity
  • Sheep
  • Spectrometry, Fluorescence
  • Spectrometry, X-Ray Emission
  • Stochastic Processes
  • Stress, Physiological
  • Subtraction Technique
  • Thermodilution
  • Thermography
  • Tidal Volume
  • Time Factors
  • Tomography
  • Tomography Scanners, X-Ray Computed
  • Tomography, Emission-Computed, Single-Photon
  • Tomography, Optical
  • Tomography, X-Ray
  • Tomography, X-Ray Computed
  • Triiodobenzoic Acids
  • Tumor Burden
  • Tumor Markers, Biological
  • Tumor Microenvironment
  • Tumor Suppressor Protein p53
  • Tumors
  • Tungsten
  • Ventricular Function, Left
  • Ventricular Remodeling
  • Video Recording
  • Water
  • Whole Body Imaging
  • X-Ray Intensifying Screens
  • X-Ray Microtomography
  • X-Rays