John C Gore

Vanderbilt University, Нашвилл, Michigan, United States

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Publications (692)2779.56 Total impact

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    ABSTRACT: The clinical course of multiple sclerosis (MS) is mainly attributable to cervical and upper thoracic spinal cord dysfunction. High-resolution, 7T anatomical imaging of the cervical spinal cord is presented. Image contrast between gray/white matter and lesions surpasses conventional, clinical T1- and T2-weighted sequences at lower field strengths. To study the spinal cord of healthy controls and patients with MS using magnetic resonance imaging at 7T. Axial (C2-C5) T1- and T2*-weighted and sagittal T2*-/spin-density-weighted images were acquired at 7T in 13 healthy volunteers (age 22-40 years), and 15 clinically diagnosed MS patients (age 19-53 years, Extended Disability Status Scale, (EDSS) 0-3) in addition to clinical 3T scans. In healthy volunteers, a high-resolution multi-echo gradient echo scan was obtained over the same geometry at 3T. Evaluation included signal and contrast to noise ratios and lesion counts for healthy and patient volunteers, respectively. High-resolution images at 7T exceeded resolutions reported at lower field strengths. Gray and white matter were sharply demarcated and MS lesions were more readily visualized at 7T compared to clinical acquisitions, with lesions apparent at both fields. Nerve roots were clearly visualized. White matter lesion counts averaged 4.7 vs 3.1 (52% increase) per patient at 7T vs 3T, respectively (p=0.05). © The Author(s), 2015.
    Multiple Sclerosis 07/2015; DOI:10.1177/1352458515591070 · 4.86 Impact Factor
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    ABSTRACT: Diffusion MRI provides a non-invasive means to characterize tissue microstructure at varying length scales. Temporal diffusion spectra reveal how the apparent diffusion coefficient (ADC) varies with frequency. When measured using oscillating gradient spin echo sequences, the manner in which ADC disperses with gradient frequency (which is related to the reciprocal of diffusion time) provides information on the characteristic dimensions of restricting structures within the medium. For example, the dispersion of ADC with oscillating gradient frequency (ΔfADC) has been shown to correlate with axon sizes in white matter and provide novel tissue contrast in images of mouse hippocampus and cerebellum. However, despite increasing interest in applying frequency-dependent ADC to derive novel information on tissue, the interpretations of ADC spectra are not always clear. In this study, the relation between ADC spectra and restricting dimensions are further elucidated and used to derive novel image contrast related to the sizes of intrinsic microstructures. Copyright © 2015. Published by Elsevier Inc.
    Magnetic Resonance Imaging 06/2015; DOI:10.1016/j.mri.2015.06.009 · 2.02 Impact Factor
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    ABSTRACT: To investigate the influence of cell membrane permeability on diffusion measurements over a broad range of diffusion times. Human myelogenous leukemia K562 cells were cultured and treated with saponin to selectively alter cell membrane permeability, resulting in a broad physiologically relevant range of 0.011-0.044 μm/ms. Apparent diffusion coefficient (ADC) values were acquired with the effective diffusion time (Δeff ) ranging from 0.42 to 3000 ms. Cosine-modulated oscillating gradient spin echo (OGSE) measurements were performed to achieve short Δeff from 0.42 to 5 ms, while stimulated echo acquisitions were used to achieve long Δeff from 11 to 2999 ms. Computer simulations were also performed to support the experimental results. Both computer simulations and experiments in vitro showed that the influence of membrane permeability on diffusion MR measurements is highly dependent on the choice of diffusion time, and it is negligible only when the diffusion time is at least one order of magnitude smaller than the intracellular exchange lifetime. The influence of cell membrane permeability on the measured ADCs is negligible in OGSE measurements at moderately high frequencies. By contrast, cell membrane permeability has a significant influence on ADC and quantitative diffusion measurements at low frequencies such as those sampled using conventional pulsed gradient methods. Magn Reson Med, 2015. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
    Magnetic Resonance in Medicine 06/2015; DOI:10.1002/mrm.25724 · 3.40 Impact Factor
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    ABSTRACT: This study aimed to evaluate the reproducibility and specificity of quantitative magnetization transfer (qMT) imaging for monitoring spinal cord injuries (SCIs). MRI scans were performed in anesthetized monkeys at 9.4T, before and serially after a unilateral lesion of the cervical spinal cord. A two-pool fitting model was used to derive qMT parameters. qMT measures were reproducible across normal subjects, with an average pool size ratio (PSR) of 0.086 ± 0.003 (mean ± SD) for gray matter, and 0.120 ± 0.005 for white matter, respectively. Compared with normal gray matter, the PSR of abnormal tissues rostral and caudal to the injury site decreased by 19.5% (P < 0.05), while the PSR of the cyst-like volume decreased drastically weeks after SCI. Strong correlations in cyst-like regions were observed between PSR and other MRI measures including longitudinal relaxation rate (R1 ), apparent diffusion coefficient and fractional anisotropy (FA). Decreased PSR and FA values correlated well with demyelination in abnormal tissues. The qMT parameters provide robust and specific information about the molecular and cellular changes produced by SCI. PSR detected demyelination and loss of macromolecules in abnormal tissue regions rostral and caudal to the cyst/lesion sites. Magn Reson Med, 2015. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
    Magnetic Resonance in Medicine 05/2015; DOI:10.1002/mrm.25725 · 3.40 Impact Factor
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    ABSTRACT: Liver glycogen represents an important physiological form of energy storage. It plays a key role in the regulation of blood glucose concentrations and dysregulations in hepatic glycogen metabolism are linked to many diseases including diabetes and insulin resistance. In this work we develop, optimize, and validate a non-invasive protocol to measure glycogen levels in isolated perfused mouse livers using Chemical Exchange Saturation Transfer (CEST) NMR spectroscopy. Model glycogen solutions were used to determine optimal saturation pulse parameters which were then applied to intact perfused mouse livers of varying glycogen content. Glycogen measurements from serially acquired CEST Z-spectra of livers were compared with measurements from interleaved natural abundance 13C NMR spectra. Experimental data revealed that CEST-based glycogen measurements were highly correlated with 13C NMR glycogen spectra. Monte Carlo simulations were then used to investigate the inherent (i.e. signal to noise based) errors in the quantification of glycogen with each technique. This revealed that CEST was intrinsically more precise than 13C NMR, although in practice may be prone to other errors induced by variations in experimental conditions. We also observed that the CEST signal from glycogen in liver was significantly less than that observed from identical amounts in solution. Our results demonstrate that CEST provides an accurate, precise, and readily accessible method to non-invasively measure liver glycogen levels and their changes. Furthermore this technique can be used to map glycogen distributions via conventional proton magnetic resonance imaging - a capability universally available on clinical and pre-clinical MRI scanners vs. 13C detection, which is limited to a small fraction of clinical-scale MRI scanners.
    Analytical Chemistry 05/2015; 87(11). DOI:10.1021/acs.analchem.5b01296 · 5.83 Impact Factor
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    ABSTRACT: Several studies have shown strong correlations between myelin content and T1 within the brain, and have even suggested that T1 can be used to estimate myelin content. However, other micro-anatomical features such as compartment size are known to affect longitudinal relaxation rates, similar to compartment size effects in porous media. T1 measurements were compared with measured or otherwise published axon size measurements in white matter tracts of the rat spinal cord, rat brain, and human brain. In both ex vivo and in vivo studies, correlations were present between the relaxation rate 1/T1 and axon size across regions of rat spinal cord with nearly equal myelin content. While myelination is likely the dominant determinant of T1 in white matter, variations in white matter microstructure, independent of myelin volume fraction, may also be reflected in T1 differences between regions or subjects. Magn Reson Med, 2015. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
    Magnetic Resonance in Medicine 04/2015; DOI:10.1002/mrm.25709 · 3.40 Impact Factor
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    ABSTRACT: Recent demonstrations of correlated low-frequency MRI signal variations between subregions of the spinal cord at rest in humans, similar to those found in the brain, suggest that such resting-state functional connectivity constitutes a common feature of the intrinsic organization of the entire central nervous system. We report our detection of functional connectivity within the spinal cords of anesthetized squirrel monkeys at rest and show that the strength of connectivity within these networks is altered by the effects of injuries. By quantifying the low-frequency MRI signal correlations between different horns within spinal cord gray matter, we found distinct functional connectivity relationships between the different sensory and motor horns, a pattern that was similar to activation patterns evoked by nociceptive heat or tactile stimulation of digits. All horns within a single spinal segment were functionally connected, with the strongest connectivity occurring between ipsilateral dorsal and ventral horns. Each horn was strongly connected to the same horn on neighboring segments, but this connectivity reduced drastically along the spinal cord. Unilateral injury to the spinal cord significantly weakened the strength of the intrasegment horn-to-horn connectivity only on the injury side and in slices below the lesion. These findings suggest resting-state functional connectivity may be a useful biomarker of functional integrity in injured and recovering spinal cords.
    Proceedings of the National Academy of Sciences 04/2015; 112(19). DOI:10.1073/pnas.1424106112 · 9.81 Impact Factor
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    ABSTRACT: The high value of the specific absorption rate (SAR) of radio-frequency (RF) energy arising from the series of RF refocusing pulses in T2-weighted (T2-w) turbo spin echo (TSE) MRI hampers its clinical application at 7.0 Tesla (7T). T2-w gradient and spin echo (GRASE) uses the speed from gradient refocusing in combination with the chemical-shift/static magnetic field (B0) inhomogeneity insensitivity from spin-echo refocusing to acquire T2-w images with a limited number of refocusing RF pulses, thus reducing SAR. To investigate whether low SAR T2-w GRASE could replace T2-w TSE in detecting white matter (WM) disease in MS patients imaged at 7T. The .7 mm(3) isotropic T2-w TSE and T2-w GRASE images with variable echo times (TEs) and echo planar imaging (EPI) factors were obtained on a 7T scanner from postmortem samples of MS brains. These samples were derived from brains of 3 female MS patients. WM lesions (WM-Ls) and normal-appearing WM (NAWM) signal intensity, WM-Ls/NAWM contrast-to-noise ratio (CNR) and MRI/myelin staining sections comparisons were obtained. GRASE sequences with EPI factor/TE = 3/50 and 3/75 ms were comparable to the SE technique for measures of CNR in WM-Ls and NAWM and for detection of WM-Ls. In all sequences, however, identification of areas with remyelination, Wallerian degeneration, and gray matter demyelination, as depicted by myelin staining, was not possible. T2-w GRASE images may replace T2-w TSE for clinical use. However, even at 7T, both sequences fail in detecting and characterizing MS disease beyond visible WM-Ls. Copyright © 2015 by the American Society of Neuroimaging.
    Journal of neuroimaging: official journal of the American Society of Neuroimaging 04/2015; 25(3). DOI:10.1111/jon.12238 · 1.82 Impact Factor
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    ABSTRACT: Neuroimaging studies have provided compelling evidence for abnormal hippocampal activity in schizophrenia. Most studies made inferences about baseline hippocampal activity using a single hemodynamic parameter (e.g., blood volume or blood flow). Here we studied several hemodynamic measures in the same cohort to test the hypothesis of increased hippocampal activity in schizophrenia. We used dynamic susceptibility contrast- (DSC-) magnetic resonance imaging (MRI) to assess blood volume, blood flow, and mean transit time in the hippocampus of 15 patients with chronic schizophrenia and 15 healthy controls. Left and right hippocampal measurements were combined for absolute measures of cerebral blood volume (CBV), cerebral blood flow (CBF), and mean transit time (MTT). We found significantly increased hippocampal CBV, but normal CBF and MTT, in schizophrenia. The uncoupling of CBV and CBF could be due to several factors, including antipsychotic medication, loss of cerebral perfusion pressure, or angiogenesis. Further studies need to incorporate several complementary imaging modalities to better characterize hippocampal dysfunction in schizophrenia. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    Psychiatry Research Neuroimaging 04/2015; 232(3). DOI:10.1016/j.pscychresns.2015.03.007 · 2.83 Impact Factor
  • Journal of Pain 04/2015; 16(4):S62. DOI:10.1016/j.jpain.2015.01.265 · 4.22 Impact Factor
  • Journal of Pain 04/2015; 16(4):S62. DOI:10.1016/j.jpain.2015.01.264 · 4.22 Impact Factor
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    ABSTRACT: PurposeA new approach has been developed to quantify cell sizes and intracellular volume fractions using temporal diffusion spectroscopy with diffusion-weighted acquisitions.Methods Temporal diffusion spectra may be used to characterize tissue microstructure by measuring the effects of restrictions over a range of diffusion times. Oscillating gradients have been used previously to probe variations on cellular and subcellular scales, but their ability to accurately measure cell sizes larger than 10 μm is limited. By combining measurements made using oscillating gradient spin echo (OGSE) and a conventional pulsed gradient spin echo (PGSE) acquisition with a single, relatively long diffusion time, we can accurately quantify cell sizes and intracellular volume fractions.ResultsBased on a two compartment model (incorporating intra- and extracellular spaces), accurate estimates of cell sizes and intracellular volume fractions were obtained in vitro for (i) different cell types with sizes ranging from 10 to 20 μm, (ii) different cell densities, and (iii) before and after anticancer treatment.Conclusion Hybrid OGSE-PGSE acquisitions sample a larger region of temporal diffusion spectra and can accurately quantify cell sizes over a wide range. Moreover, the maximum gradient strength used was lower than 15 G/cm, suggesting that this approach is translatable to practical MR imaging. Magn Reson Med, 2015. © 2015 Wiley Periodicals, Inc.
    Magnetic Resonance in Medicine 04/2015; DOI:10.1002/mrm.25684 · 3.40 Impact Factor
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    ABSTRACT: To develop and evaluate a new method for detecting calcium deposits using their characteristic magnetic susceptibility effects on magnetic resonance (MR) images at high fields and demonstrate its potential in practice for detecting breast microcalcifications. Characteristic dipole signatures of calcium deposits were detected in magnetic resonance phase images by computing the cross-correlation between the acquired data and a library of templates containing simulated phase patterns of spherical deposits. The influence of signal-to-noise ratio and various other MR parameters on the results were assessed using simulations and validated experimentally. The method was tested experimentally for detection of calcium fragments within gel phantoms and calcium-like inhomogeneities within chicken tissue at 7 T with optimized MR acquisition parameters. The method was also evaluated for detection of simulated microcalcifications, modeled from biopsy samples of malignant breast cancer, inserted in silico into breast magnetic resonance imaging (MRIs) of healthy subjects at 7 T. For both assessments of calcium fragments in phantoms and biopsy-based simulated microcalcifications in breast MRIs, receiver operator characteristic curve analyses were performed to determine the cross-correlation index cutoff, for achieving optimal sensitivity and specificity, and the area under the curve (AUC), for measuring the method's performance. The method detected calcium fragments with sizes of 0.14-0.79 mm, 1 mm calcium-like deposits, and simulated microcalcifications with sizes of 0.4-1.0 mm in images with voxel sizes between (0.2 mm)(3) and (0.6 mm)(3). In images acquired at 7 T with voxel sizes of (0.2 mm)(3)-(0.4 mm)(3), calcium fragments (size 0.3-0.4 mm) were detected with a sensitivity, specificity, and AUC of 78%-90%, 51%-68%, and 0.77%-0.88%, respectively. In images acquired with a human 7 T scanner, acquisition times below 12 min, and voxel sizes of (0.4 mm)(3)-(0.6 mm)(3), simulated microcalcifications with sizes of 0.6-1.0 mm were detected with a sensitivity, specificity, and AUC of 75%-87%, 54%-87%, and 0.76%-0.90%, respectively. However, different microcalcification shapes were indistinguishable. The new method is promising for detecting relatively large microcalcifications (i.e., 0.6-0.9 mm) within the breast at 7 T in reasonable times. Detection of smaller deposits at high field may be possible with higher spatial resolution, but such images require relatively long scan times. Although mammography can detect and distinguish the shape of smaller microcalcifications with superior sensitivity and specificity, this alternative method does not expose tissue to ionizing radiation, is not affected by breast density, and can be combined with other MRI methods (e.g., dynamic contrast-enhanced MRI and diffusion weighted MRI), to potentially improve diagnostic performance.
    Medical Physics 03/2015; 42(3):1436. DOI:10.1118/1.4908009 · 3.01 Impact Factor
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    ABSTRACT: We are investigating an imaging agent that detects early-stage primary colorectal cancer on the mucosal surface in real time under colonoscopic observation. The imaging agent, which is named the nanobeacon, is fluorescent nanospheres conjugated with peanut agglutinin and poly(N-vinylacetamide). Its potential use as an imaging tool for colorectal cancer has been thoroughly validated in numerous studies. Here, toxicities of the nanobeacon were assessed in rats. The nanobeacon was prepared according to the synthetic manner which is being established as the Good Manufacturing Practice-guided production. The rat study was performed in accordance with Good Laboratory Practice regulations. No nanobeacon treatment-related toxicity was observed. The no observable adverse effect levels (NOAEL) of the nanobeacon in 7-day consecutive oral administration and single intrarectal administration were estimated to be more than 1000 mg/kg/day and 50 mg/kg/day, respectively. We concluded that the nanobeacon could be developed as a safe diagnostic agent for colonoscopy applications. Copyright © 2015. Published by Elsevier Inc.
    Nanomedicine Nanotechnology Biology and Medicine 02/2015; 11(5). DOI:10.1016/j.nano.2015.02.003 · 5.98 Impact Factor
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    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 02/2015; 28(2). DOI:10.1002/nbm.3243 · 3.56 Impact Factor
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    ABSTRACT: We undertook this pilot prospective cohort investigation to examine the feasibility of functional magnetic resonance imaging (fMRI) assessments in survivors of critical illness and to analyze potential associations between delirium and brain activation patterns observed during a working memory task (N-back) at hospital discharge and 3-month follow-up. At hospital discharge and 3 months later, fMRI assessed subjects' functional activity during an N-back task. Multiple linear regression was used to examine associations between duration of delirium and brain activity, and elastic net regression was used to assess the relationship between brain activation patterns at 3 months and cognitive outcomes at 12 months. Of 47 patients who underwent fMRI at discharge, 38 (80%) completed the protocol; of 37 who underwent fMRI at 3 months, 34 (91%) completed the protocol. At discharge, the mean (SD) percentage of correct responses on the most challenging version (the N2 version) of the N-back task was 70.4 (23.2; range of 20-100) compared with 76 (23.4; range of 33-100) at 3 months. No association was observed between delirium duration in the hospital and brain region activity in any brain region at discharge or 3 months after adjusting for relevant covariates (P values across all 11 brain regions of interest were >.25). Our data support the feasibility of using fMRI in survivors of critical illness at 3-month follow-up but not at discharge. In this small study, delirium was not associated with distinct or abnormal brain activation patterns, although overall performance on a cognitive task of working memory was poorer than observed in other cohorts of individuals with medically related executive dysfunction, mild cognitive impairment, and mild traumatic brain injury. Copyright © 2015. Published by Elsevier Inc.
    Journal of Critical Care 01/2015; 30(3). DOI:10.1016/j.jcrc.2015.01.017 · 2.19 Impact Factor
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    ABSTRACT: In previous work, we demonstrated the presence of hydroxyapetite (type II microcalcification), HAP, in triple negative MDA-MB-231 breast cancer cells. We used 18F-NaF to detect these types of cancers in mouse models as the free fluorine, 18F−, binds to HAP similar to bone uptake. In this work, we investigate other bone targeting agents and techniques including 99mTc-MDP SPECT and Osteosense 750EX FMT imaging as alternatives for breast cancer diagnosis via targeting HAP within the tumor microenvironment.
    Nuclear Medicine and Biology 12/2014; 42(3). DOI:10.1016/j.nucmedbio.2014.11.010 · 2.41 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; 28(2). DOI:10.1002/nbm.3237 · 3.56 Impact Factor
  • John C. Gore
    Magnetic Resonance Imaging 11/2014; DOI:10.1016/j.mri.2014.08.003 · 2.02 Impact Factor

Publication Stats

35k Citations
2,779.56 Total Impact Points

Institutions

  • 2000–2015
    • Vanderbilt University
      • • Vanderbilt Institute of Imaging Science
      • • Department of Radiology and Radiological Sciences
      • • Department of Psychology
      Нашвилл, Michigan, United States
    • CUNY Graduate Center
      New York City, New York, United States
  • 2009
    • Northwestern University
      • Department of Psychology
      Evanston, IL, United States
    • Vietnam National University, Hanoi
      Hà Nội, Ha Nội, Vietnam
  • 2008
    • Shaare Zedek Medical Center
      • Neurology and Toxicology Service and Unit
      Yerushalayim, Jerusalem District, Israel
    • Columbia University
      • Department of Psychiatry
      New York, New York, United States
    • The King's College
      Charlotte, North Carolina, United States
  • 1–2008
    • Yale University
      • • Department of Electrical Engineering
      • • Department of Applied Physics
      • • Department of Diagnostic Radiology and Pediatric Diagnostic Radiology
      • • Department of Physics
      New Haven, CT, United States
  • 1984–2003
    • Yale-New Haven Hospital
      • Department of Laboratory Medicine
      New Haven, Connecticut, United States
  • 2002
    • Korea University
      • Department of Physics
      Seoul, Seoul, South Korea
  • 1999
    • Haskins Laboratories
      New Haven, Connecticut, United States
  • 1997
    • University of Kentucky
      • Department of Radiation Medicine
      Lexington, KY, United States
    • McGill University
      • Department of Physics
      Montréal, Quebec, Canada
  • 1996
    • University of New Haven
      New Haven, Connecticut, United States
  • 1995
    • University of Texas Health Science Center at San Antonio
      San Antonio, Texas, United States
  • 1994
    • Massachusetts Institute of Technology
      Cambridge, Massachusetts, United States
  • 1992
    • Albert Einstein College of Medicine
      • Department of Medicine
      New York City, NY, United States