John C Gore

Vanderbilt University, Nashville, Michigan, United States

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Publications (658)2546.73 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Chemical exchange saturation transfer (CEST) potentially provides the ability to detect small solute pools through indirect measurements of attenuated water signals. However, CEST effects may be diluted by various competing effects, such as non-specific magnetization transfer (MT) and asymmetric MT effects, water longitudinal relaxation (T1 ) and direct water saturation (radiofrequency spillover). In the current study, CEST images were acquired in rats following ischemic stroke and analyzed by comparing the reciprocals of the CEST signals at three different saturation offsets. This combined approach corrects the above competing effects and provides a more robust signal metric sensitive specifically to the proton exchange rate constant. The corrected amide proton transfer (APT) data show greater differences between the ischemic and contralateral (non-ischemic) hemispheres. By contrast, corrected nuclear Overhauser enhancements (NOEs) around -3.5 ppm from water change over time in both hemispheres, indicating whole-brain changes that have not been reported previously. This study may help us to better understand the contrast mechanisms of APT and NOE imaging in ischemic stroke, and may also establish a framework for future stroke measurements using CEST imaging with spillover, MT and T1 corrections. Copyright © 2014 John Wiley & Sons, Ltd. Copyright © 2014 John Wiley & Sons, Ltd.
    NMR in Biomedicine 12/2014; · 3.45 Impact Factor
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    ABSTRACT: Off-resonant RF irradiation in tissue indirectly lowers the water signal by saturation transfer processes: on the one hand, there are selective chemical exchange saturation transfer (CEST) effects originating from exchanging endogenous protons resonating a few parts per million from water; on the other hand, there is the broad semi-solid magnetization transfer (MT) originating from immobile protons associated with the tissue matrix with kilohertz linewidths. Recently it was shown that endogenous CEST contrasts can be strongly affected by the MT background, so corrections are needed to derive accurate estimates of CEST effects. Herein we show that a full analytical solution of the underlying Bloch–McConnell equations for both MT and CEST provides insights into their interaction and suggests a simple means to isolate their effects. The presented analytical solution, based on the eigenspace solution of the Bloch–McConnell equations, extends previous treatments by allowing arbitrary lineshapes for the semi-solid MT effects and simultaneously describing multiple CEST pools in the presence of a large MT pool for arbitrary irradiation. The structure of the model indicates that semi-solid MT and CEST effects basically add up inversely in determining the steady-state Z-spectrum, as previously shown for direct saturation and CEST effects. Implications for existing previous CEST analyses in the presence of a semi-solid MT are studied and discussed. It turns out that, to accurately quantify CEST contrast, a good reference Z-value, the observed longitudinal relaxation rate of water, and the semi-solid MT pool size fraction must all be known. Copyright © 2014 John Wiley & Sons, Ltd.
    NMR in Biomedicine 12/2014; · 3.45 Impact Factor
  • John C. Gore
    Magnetic Resonance Imaging 11/2014; · 2.06 Impact Factor
  • John T. Spear, John C. Gore
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    ABSTRACT: Diffusion in non-uniform fields causes dispersion of spin-lock relaxation rates.•Spin-lock dispersions can be used to estimate the sizes of susceptibility variations.•Simulations relate dispersions to the spatial frequency content of non-uniform fields.•Spin-lock dispersions can characterize inhomogeneous media and biological tissues.
    Journal of Magnetic Resonance. 10/2014;
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    ABSTRACT: PurposeTo monitor the spontaneous recovery of cervical spinal cord injury (SCI) using longitudinal multiparametric MRI methods.Methods Quantitative MRI imaging including diffusion tensor imaging, magnetization transfer (MT), and chemical exchange saturation transfer (CEST) were conducted in anesthetized squirrel monkeys at 9.4T. The structural, cellular, and molecular features of the spinal cord were examined before and at different time points after a dorsal column lesion in each monkey.ResultsImages with MT contrast enhanced visualization of the gray and white matter boundaries and the lesion and permitted differentiation of core and rim compartments within an abnormal volume (AV). In the early weeks after SCI, both core and rim exhibited low cellular density and low protein content, with high levels of exchanging hydroxyl, amine, and amide protons, as evidenced by increased apparent diffusion coefficient, decreased fractional anisotropy, decreased MT ratio, decreased nuclear Overhauser effect, and large CEST effects. Over time, cellular density and fiber density increased, whereas amide, amine, and hydroxyl levels dropped significantly, but at differing rates. Histology confirmed the nature of the AV to be a cyst.Conclusion Multiparametric MRI offers a novel method to quantify the spontaneous changes in structure and cellular and molecular compositions of SC during spontaneous recovery from injury. Magn Reson Med, 2014. © 2014 Wiley Periodicals, Inc.
    Magnetic Resonance in Medicine 10/2014; · 3.27 Impact Factor
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    ABSTRACT: The objectives of this study were (1) to develop a novel magnetization transfer ratio (MTR) MRI assay of the proximal sciatic nerve (SN), which is inaccessible via current tools for assessing peripheral nerves, and (2) to evaluate the resulting MTR values as a potential biomarker of myelin content changes in patients with Charcot-Marie-Tooth (CMT) diseases.
    Neurology 09/2014; · 8.30 Impact Factor
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    ABSTRACT: Curcumin is a promising compound that can be used as a theranostic agent to aid research in Alzheimer's disease. Beyond its ability to bind to amyloid plaques, the compound can also cross the blood-brain barrier. Presently, curcumin can be applied only to animal models, as the formulation needed for iv injection renders it unfit for human use. Here, we describe a novel technique to aerosolize a curcumin derivative, FMeC1, and facilitate its safe delivery to the brain. Aside from the translational applicability of this approach, a study in the 5XFAD mouse model suggested that inhalation exposure to an aerosolized FMeC1 modestly improved the distribution of the compound in the brain. Additionally, immunohistochemistry data confirms that following aerosol delivery, FMeC1 binds amyloid plaques expressed in the hippocampal areas and cortex.
    Journal of Alzheimer's disease: JAD 09/2014; · 4.17 Impact Factor
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    ABSTRACT: Mapping mean axon diameter and intra-axonal volume fraction may have significant clinical potential because nerve conduction velocity is directly dependent on axon diameter, and several neurodegenerative diseases affect axons of specific sizes and alter axon counts. Diffusion-weighted MRI methods based on the pulsed gradient spin echo (PGSE) sequence have been reported to be able to assess axon diameter and volume fraction non-invasively. However, due to the relatively long diffusion times used, e.g. > 20ms, the sensitivity to small axons (diameter<2μm) is low, and the derived mean axon diameter has been reported to be overestimated. In the current study, oscillating gradient spin echo (OGSE) diffusion sequences with variable frequency gradients were used to assess rat spinal white matter tracts with relatively short effective diffusion times (1 - 5ms). In contrast to previous PGSE-based methods, the extra-axonal diffusion cannot be modeled as hindered (Gaussian) diffusion when short diffusion times are used. Appropriate frequency-dependent rates are therefore incorporated into our analysis and validated by histology-based computer simulation of water diffusion. OGSE data were analyzed to derive mean axon diameters and intra-axonal volume fractions of rat spinal white matter tracts (mean axon diameter~1.27 - 5.54μm). The estimated values were in good agreement with histology, including the small axon diameters (<2.5μm). This study establishes a framework for quantification of nerve morphology using the OGSE method with high sensitivity to small axons.
    NeuroImage 09/2014; · 6.25 Impact Factor
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    ABSTRACT: The fusiform face area (FFA) is one of several areas in occipito-temporal cortex whose activity is correlated with perceptual expertise for objects. Here, we investigate the robustness of expertise effects in FFA and other areas to a strong task manipulation that increases both perceptual and attentional demands. With high-resolution fMRI at 7Telsa, we measured responses to images of cars, faces and a category globally visually similar to cars (sofas) in 26 subjects who varied in expertise with cars, in (a) a low load 1-back task with a single object category and (b) a high load task in which objects from two categories rapidly alternated and attention was required to both categories. The low load condition revealed several areas more active as a function of expertise, including both posterior and anterior portions of FFA bilaterally (FFA1/FFA2 respectively). Under high load, fewer areas were positively correlated with expertise and several areas were even negatively correlated, but the expertise effect in face-selective voxels in the anterior portion of FFA (FFA2) remained robust. Finally, we found that behavioral car expertise also predicted increased responses to sofa images but no behavioral advantages in sofa discrimination, suggesting that global shape similarity to a category of expertise is enough to elicit a response in FFA and other areas sensitive to experience, even when the category itself is not of special interest. The robustness of expertise effects in right FFA2 and the expertise effects driven by visual similarity both argue against attention being the sole determinant of expertise effects in extrastriate areas.
    Neuropsychologia 09/2014; · 3.48 Impact Factor
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    ABSTRACT: PurposeA diffusion-weighted multishot echo-planar imaging approach combined with SENSE and a two-dimensional (2D) navigated motion correction was investigated as an alternative to conventional single-shot counterpart to obtain optic nerve images at higher spatial resolution with reduced artifacts.Methods Fifteen healthy subjects were enrolled in the study. Six of these subjects underwent a repeated acquisition at least 2 weeks after the initial scan session to address reproducibility. Both single-shot and multishot diffusion tensor imaging studies of the human optic nerve were performed with matched scan time. Effect of subject motions were corrected using 2D phase navigator during multishot image reconstruction. Tensor-derived indices from proposed multishot were compared against conventional single-shot approach. Image resolution difference, right–left optic nerve asymmetry, and test–retest reproducibility were also assessed.ResultsIn vivo results of acquired multishot images and quantitative maps of diffusion properties of the optic nerve showed significantly reduced image artifacts (e.g., distortions and blurring), and the derived diffusion indices were comparable to those from other studies. Single-shot scans presented larger variability between right and left optic nerves than multishot scans. Multishot scans also presented smaller variations across scans at different time points when compared with single-shot counterparts.Conclusion The multishot technique has considerable potential for providing improved information on optic nerve pathology and may also be translated to higher fields. Magn Reson Med, 2014. © 2014 Wiley Periodicals, Inc.
    Magnetic Resonance in Medicine 09/2014; · 3.27 Impact Factor
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    ABSTRACT: Functional magnetic resonance imaging using blood oxygenation level dependent (BOLD) contrast is well established as one of the most powerful methods for mapping human brain function. Numerous studies have measured how low-frequency BOLD signal fluctuations from the brain are correlated between voxels in a resting state, and have exploited these signals to infer functional connectivity within specific neural circuits. However, to date there have been no previous substantiated reports of resting state correlations in the spinal cord. In a cohort of healthy volunteers, we observed robust functional connectivity between left and right ventral (motor) horns, and between left and right dorsal (sensory) horns. Our results demonstrate that low-frequency BOLD fluctuations are inherent in the spinal cord as well as the brain, and by analogy to cortical circuits, we hypothesize that these correlations may offer insight into the execution and maintenance of sensory and motor functions both locally and within the cerebrum.DOI:
    eLife Sciences 08/2014; 3:e02812. · 8.52 Impact Factor
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    ABSTRACT: The purpose of this study is to evaluate the utility of high-resolution non-invasive endogenous high-field MRI methods for the longitudinal structural and quantitative assessments of mouse kidney disease using the model of unilateral ureter obstruction (UUO). T1-weighted, T2-weighted and magnetization transfer (MT) imaging protocols were optimized to improve the regional contrast in mouse kidney. Conventional T1 and T2 weighted images were collected in UUO mice on day 0 (~3 h), day 1, day 3 and day 6 after injury, on a 7 T small animal MRI system. Cortical and medullary thickness, corticomedullary contrast and Magnetization Transfer Ratio (MTR) were assessed longitudinally. Masson trichrome staining was used to histologically assess changes in tissue microstructure. Over the course of UUO progression there were significant (p b 0.05) changes in thickness of cortex and outer medulla, and regional changes in T2 signal intensity and MTR values. Histological changes included tubular cell death, tubular dilation, urine retention, and interstitial fibrosis, assessed by histology. The MRI measures of renal cortical and medullary atrophy, cortical–medullary differentiation and MTR changes provide an endogenous, non-invasive and quantitative evaluation of renal morphology and tissue composition during UUO progression.
    Magnetic Resonance Imaging 08/2014; 32:1125-1132. · 2.06 Impact Factor
  • Ping Wang, Jake Block, John C Gore
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    ABSTRACT: To quantify the characteristics of proton chemical exchange in knee cartilage in vivo by R1ρ dispersion analysis.
    Magnetic resonance imaging. 08/2014;
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    ABSTRACT: Thomsen-Friedenreich (TF) antigen belongs to the mucin-type tumor-associated carbohydrate antigen. Notably, TF antigen is overexpressed in colorectal cancer (CRC) but is rarely expressed in normal colonic tissue. Increased TF antigen expression is associated with tumor invasion and metastasis. In this work, we sought to validate a novel nanobeacon for imaging TF-associated CRC in a preclinical animal model. We developed and characterized the nanobeacon for use with fluorescence colonoscopy. In vivo imaging was performed on an orthotopic rat model of colorectal cancer. Both white light and fluorescence colonoscopy methods were utilized to establish the ratio-imaging index for the probe. The nanobeacon exhibited specificity for TF-associated cancer. Fluorescence colonoscopy using the probe can detect lesions at the stage which is not readily confirmed by conventional visualization methods. Further, the probe can report the dynamic change of TF expression as tumor regresses during chemotherapy.Data from this work suggests that fluorescence colonoscopy can improve early CRC detection. Supplemented by the established ratio-imaging index, the probe can be used not only for early detection, but also for reporting tumor response during chemotherapy. Furthermore, since the data obtained through in vivo imaging confirmed that the probe was not absorbed by the colonic mucosa, no registered toxicity is associated with this nanobeacon. Taken together, these data demonstrate the potential of this novel probe for imaging TF antigen as a biomarker for the early detection and prediction of the progression of CRC at the molecular level. © 2014 Wiley Periodicals, Inc.
    International Journal of Cancer 07/2014; · 6.20 Impact Factor
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    ABSTRACT: We have been investigating an imaging agent that enables real-time and accurate diagnosis of early colorectal cancer at the intestinal mucosa by colonoscopy. The imaging agent is peanut agglutinin-immobilized polystyrene nanospheres with surface poly(N-vinylacetamide) chains encapsulating coumarin 6. Intracolonically-administered lectin-immobilized fluorescent nanospheres detect tumor-derived changes through molecular recognition of lectin for the terminal sugar of cancer-specific antigens on the mucosal surface. The focus of the present study was to evaluate imaging abilities of the nanospheres in animal models that reflect clinical environments. We previously developed an orthotopic mouse model with human colorectal tumors growing on the mucosa of the descending colon to better resemble the clinical disease. The entire colon of the mice in the exposed abdomen was monitored in real time with an in vivo imaging apparatus. Fluorescence from the nanospheres was observed along the entire descending colon after intracolonical administration from the anus. When the luminal side of the colon was washed with phosphate-buffered saline, most of the nanospheres were flushed. However, fluorescence persisted in areas where cancer cells were implanted. Histological evaluation demonstrated that tumors were present in the mucosal epithelia where the nanospheres fluoresced. In contrast, no fluorescence was observed when control mice, without tumors were tested. The lectin-immobilized fluorescent nanospheres were tumor-specific and remained bound to tumors even after vigorous washing. The nanospheres nonspecifically bound to normal mucosa were easily removed through mild washing. These results indicate that the nanospheres combined with colonoscopy, will be a clinically-valuable diagnostic tool for early-stage primary colon carcinoma. Copyright © 2014 John Wiley & Sons, Ltd.
    Contrast Media & Molecular Imaging 06/2014; · 2.87 Impact Factor
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    ABSTRACT: The regional uptake of glucose in rat brain in vivo was measured at high resolution using spin-lock magnetic resonance imaging after infusion of the glucose analogue 2-deoxy-D-glucose (2DG). Previous studies of glucose metabolism have used (13)C-labeled 2DG and NMR spectroscopy, (18)F-labeled fluorodeoxyglucose (FDG) and PET, or chemical exchange saturation transfer (CEST) MRI, all of which have practical limitations. Our goal was to explore the ability of spin-lock sequences to detect specific chemically-exchanging species in vivo and to compare the effects of 2DG in brain tissue on CEST images.
    Magnetic Resonance Imaging 06/2014; · 2.06 Impact Factor
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    ABSTRACT: Diffusion measurements derived from breast MRI can be adversely affected by unwanted signals from abundant fatty tissues if they are not suppressed adequately. To minimize this undesired contribution, we designed and optimized a water-selective diffusion-weighted imaging (DWI) sequence, which relies on spectrally selective excitation on the water resonance, obviating the need for fat suppression. As this method is more complex than standard DWI methods, we also report a test–retest study to evaluate its reproducibility. In this study, a spectrally selective Gaussian pulse on water resonance was combined with a pair of slice-selective adiabatic refocusing pulses for water-only DWI. Field map-based shimming and manual determination of the center frequency were used for water selection. The selectivity of the excitation pulse was optimized by a spectrally selective spectroscopy sequence based on the same principles. A test–retest study of 10 volunteers in two separate visits was used to evaluate its reproducibility. Our results from all subjects showed high-quality diffusion-weighted images of the breast without fat contamination. Mean apparent diffusion coefficients for b = 0, 600 s/mm2 and b = 50, 600 s/mm2 all showed good reproducibility, as 95% confidence intervals of the apparent diffusion coefficients were 4 × 10–5 mm2/s and 5 × 10–5 mm2/s and repeatability values were 1.09 × 10–4 and 1.31 × 10–4, respectively. In conclusion, water-selective DWI is a feasible alternative to standard methods of DWI based on fat suppression. The added complexity of the method does not compromise the reproducibility of diffusion measurements in the breast. Copyright © 2014 John Wiley & Sons, Ltd.
    NMR in Biomedicine 06/2014; · 3.45 Impact Factor
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    ABSTRACT: Current radiologic methods for diagnosing breast cancer detect specific morphologic features of solid tumors or any associated calcium deposits. These deposits originate from an early molecular microcalcification process of 2 types: type 1 is calcium oxylate and type II is carbonated calcium hydroxyapatite. Type I microcalcifications are associated mainly with benign tumors, whereas type II microcalcifications are produced internally by malignant cells. No current noninvasive in vivo techniques are available for detecting intratumoral microcalcifications. Such a technique would have a significant impact on breast cancer diagnosis and prognosis in preclinical and clinical settings. (18)F-NaF PET has been used solely for bone imaging by targeting the bone hydroxyapatite. In this work, we provide preliminary evidence that (18)F-NaF PET imaging can be used to detect breast cancer by targeting the hydroxyapatite lattice within the tumor microenvironment with high specificity and soft-tissue contrast-to-background ratio while delineating tumors from inflammation. Mice were injected with approximately 10(6) MDA-MB-231 cells subcutaneously and imaged with (18)F-NaF PET/CT in a 120-min dynamic sequence when the tumors reached a size of 200-400 mm(3). Regions of interest were drawn around the tumor, muscle, and bone. The concentrations of radiotracer within those regions of interest were compared with one another. For comparison to inflammation, rats with inflamed paws were subjected to (18)F-NaF PET imaging. Tumor uptake of (18)F(-) was significantly higher (P < 0.05) than muscle uptake, with the tumor-to-muscle ratio being about 3.5. The presence of type II microcalcification in the MDA-MB-231 cell line was confirmed histologically using alizarin red S and von Kossa staining as well as Raman microspectroscopy. No uptake of (18)F(-) was observed in the inflamed tissue of the rats. Lack of hydroxyapatite in the inflamed tissue was verified histologically. This study provides preliminary evidence suggesting that specific targeting with (18)F(-) of hydroxyapatite within the tumor microenvironment may be able to distinguish between inflammation and cancer.
    Journal of Nuclear Medicine 05/2014; · 5.77 Impact Factor
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    ABSTRACT: This paper proposes a new energy minimization method called multiplicative intrinsic component optimization (MICO) for joint bias field estimation and segmentation of magnetic resonance (MR) images. The proposed method takes full advantage of the decomposition of MR images into two multiplicative components, namely, the true image that characterizes a physical property of the tissues and the bias field that accounts for the intensity inhomogeneity, and their respective spatial properties. Bias field estimation and tissue segmentation are simultaneously achieved by an energy minimization process aimed to optimize the estimates of the two multiplicative components of an MR image. The bias field is iteratively optimized by using efficient matrix computations, which are verified to be numerically stable by matrix analysis. More importantly, the energy in our formulation is convex in each of its variables, which leads to the robustness of the proposed energy minimization algorithm. The MICO formulation can be naturally extended to 3D/4D tissue segmentation with spatial/sptatiotemporal regularization. Quantitative evaluations and comparisons with some popular softwares have demonstrated superior performance of MICO in terms of robustness and accuracy.
    Magnetic resonance imaging. 04/2014;
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    ABSTRACT: Multifunctional nanoparticles are synthesized for both pH-triggered drug release and imaging with radioluminescence, upconversion luminescent, and magnetic resonance imaging (MRI). The particles have a yolk-in-shell morphology, with a radioluminescent core, an upconverting shell, and a hollow region between the core and shell for loading drugs. They are synthesized by controlled encapsulation of a radioluminescent nanophosphor yolk in a silica shell, partial etching of the yolk in acid, and encapsulation of the silica with an upconverting luminescent shell. Metroxantrone, a chemotherapy drug, was loaded into the hollow space between X-ray phosphor yolk and up-conversion phosphor shell through pores in the shell. To encapsulate the drug and control the release rate, the nanoparticles are coated with pH-responsive biocompatible polyelectrolyte layers of charged hyaluronic acid sodium salt and chitosan. The nanophosphors display bright luminescence under X-ray, blue light (480 nm), and near infrared light (980 nm). They also served as T1 and T2 MRI contrast agents with relaxivities of 3.5 mM−1 s−1 (r1) and 64 mM−1s−1 (r2). These multifunctional nanocapsules have applications in controlled drug delivery and multimodal imaging.
    Small 04/2014; · 7.82 Impact Factor

Publication Stats

28k Citations
2,546.73 Total Impact Points


  • 2000–2014
    • Vanderbilt University
      • • Vanderbilt University Institute of Imaging Science (VUIIS)
      • • Department of Radiology and Radiological Sciences
      • • Department of Psychology
      Nashville, Michigan, United States
  • 2013
    • University Medical Center Utrecht
      • Department of Radiology
      Utrecht, Provincie Utrecht, Netherlands
    • Clemson University
      • Department of Chemistry
      Anderson, IN, United States
    • SAS Institute
      North Carolina, United States
  • 2009–2013
    • Northwestern University
      • • Department of Radiology
      • • Department of Psychology
      Evanston, Illinois, United States
    • Memorial Sloan-Kettering Cancer Center
      New York City, New York, United States
    • The Chinese University of Hong Kong
      • Department of Psychology
      Hong Kong, Hong Kong
    • Vietnam National University, Hanoi
      Hà Nội, Ha Nội, Vietnam
  • 2012
    • Sichuan University
      • College of Electronics and Information Engineering
      Chengdu, Sichuan Sheng, China
  • 2011
    • Setsunan University
      • Faculty of Pharmaceutical Sciences
      Ōsaka-shi, Osaka-fu, Japan
  • 2008–2010
    • King's College
      • Department of Biology
      Wilkes-Barre, Pennsylvania, United States
    • Shaare Zedek Medical Center
      • Neurology and Toxicology Service and Unit
      Yerushalayim, Jerusalem District, Israel
  • 1986–2010
    • Yale University
      • • Department of Diagnostic Radiology and Pediatric Diagnostic Radiology
      • • Department of Biomedical Engineering
      • • Department of Electrical Engineering
      • • School of Engineering and Applied Science
      • • Department of Pediatrics
      • • Department of Therapeutic Radiology
      New Haven, CT, United States
  • 2005
    • State University of New York
      New York City, New York, United States
  • 1984–2005
    • Yale-New Haven Hospital
      • Department of Laboratory Medicine
      New Haven, Connecticut, United States
  • 2002–2003
    • Columbia University
      • • College of Physicians and Surgeons
      • • Department of Psychiatry
      New York City, NY, United States
    • Korea University
      • Department of Physics
      Seoul, Seoul, South Korea
  • 1991–2002
    • Albert Einstein College of Medicine
      • Department of Medicine
      New York City, NY, United States
  • 1999
    • Haskins Laboratories
      New Haven, Connecticut, United States
  • 1998
    • University of Rochester
      • School of Medicine and Dentistry
      Rochester, NY, United States
  • 1997
    • University of Kentucky
      • Department of Radiation Medicine
      Lexington, KY, United States
    • McGill University
      • Department of Physics
      Montréal, Quebec, Canada
  • 1995
    • University of Texas Health Science Center at San Antonio
      San Antonio, Texas, United States
  • 1994
    • Massachusetts Institute of Technology
      Cambridge, Massachusetts, United States
  • 1993
    • Massachusetts General Hospital
      Boston, Massachusetts, United States