Sean B Fain

University of Wisconsin–Madison, Madison, Wisconsin, United States

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Publications (97)299.44 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Rationale and Objectives Previous cross-sectional studies have demonstrated that airway wall thickness and air trapping are greater in subjects with severe asthma than in those with mild-to-moderate asthma. However, a better understanding of how airway remodeling and lung density change over time is needed. This study aimed to evaluate predictors of airway wall remodeling and change in lung function and lung density over time in severe asthma. Materials and methods Phenotypic characterization and quantitative multidetector-row computed tomography (MDCT) of the chest were performed at baseline and ∼2.6 years later in 38 participants with asthma (severe n = 24 and mild-to-moderate n = 14) and nine normal controls from the Severe Asthma Research Program. Results Subjects with severe asthma had a significant decline in postbronchodilator forced expiratory volume in 1 second percent (FEV1%) predicted over time (P < .001). Airway wall thickness measured by MDCT was increased at multiple airway generations in severe asthma compared to mild-to-moderate asthma (wall area percent [WA%]: P < .05) and normals (P < .05) at baseline and year 2. Over time, there was an increase in WA% and wall thickness percent (WT%) in all subjects (P = .030 and .009, respectively) with no change in emphysema-like lung or air trapping. Baseline prebronchodilator FEV1% inversely correlated with WA% and WT% (both P < .05). In a multivariable regression model, baseline WA%, race, and health care utilization were predictors of subsequent airway remodeling. Conclusions Severe asthma subjects have a greater decline in lung function over time than normal subjects or those with mild-to-moderate asthma. MDCT provides a noninvasive measure of airway wall thickness that may predict subsequent airway remodeling.
    Academic Radiology. 08/2014; 21(8):986–993.
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    ABSTRACT: The purpose of this work was to use 3D radial ultrashort echo time (UTE) MRI to perform whole-lung oxygen-enhanced (OE) imaging in humans. Eight healthy human subjects underwent two 3D radial UTE MRI acquisitions (TE = 0.08 ms): one while breathing 21% O2 and the other while breathing 100% O2 . Scans were each performed over 5 min of free breathing, using prospective respiratory gating. For comparison purposes, conventional echo time (TE = 2.1 ms) images were acquired simultaneously during each acquisition using a radial " outward-inward" k-space trajectory. 3D percent OE maps were generated from these images. 3D OE maps showing lung signal enhancement were generated successfully in seven subjects (technical failure in one subject). Mean percent signal enhancement was 6.6% ± 1.8%, near the value predicted by theory of 6.3%. No significant enhancement was seen using the conventional echo time data, confirming the importance of UTE for this acquisition strategy. 3D radial UTE MRI shows promise as a method for OE MRI that enables whole-lung coverage and isotropic spatial resolution, in comparison to existing 2D OE methods, which rely on a less time-efficient inversion recovery pulse sequence. These qualities may help OE MRI become a viable low-cost method for 3D imaging of lung function in human subjects. Copyright © 2014 John Wiley & Sons, Ltd.
    NMR in Biomedicine 07/2014; · 3.45 Impact Factor
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    ABSTRACT: PurposeTo assess the feasibility of spatial–temporal constrained reconstruction for accelerated regional lung perfusion using highly undersampled dynamic contrast-enhanced (DCE) three-dimensional (3D) radial MRI with ultrashort echo time (UTE). MethodsA combined strategy was used to accelerate DCE MRI for 3D pulmonary perfusion with whole lung coverage. A highly undersampled 3D radial UTE MRI acquisition was combined with an iterative constrained reconstruction exploiting principal component analysis and wavelet soft-thresholding for dimensionality reduction in space and time. The performance of the method was evaluated using a 3D fractal-based DCE digital lung phantom. Simulated perfusion maps and contrast enhancement curves were compared with ground truth using the structural similarity index (SSIM) to determine robust threshold and regularization levels. Feasibility studies were then performed in a canine and a human subject with 3D radial UTE (TE = 0.08 ms) acquisition to assess feasibility of mapping regional 3D perfusion. ResultsThe method was able to accurately recover perfusion maps in the phantom with a nominal isotropic spatial resolution of 1.5 mm (SSIM of 0.949). The canine and human subject studies demonstrated feasibility for providing artifact-free perfusion maps in a simple 3D breath-held acquisition. Conclusion The proposed method is promising for fast and flexible 3D pulmonary perfusion imaging. Magn Reson Med, 2014. © 2014 Wiley Periodicals, Inc.
    Magnetic Resonance in Medicine 03/2014; · 3.27 Impact Factor
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    ABSTRACT: Pulmonary hypertension is a condition of varied etiology, commonly associated with poor clinical outcome. Patients are categorized on the basis of pathophysiological, clinical, radiologic, and therapeutic similarities. Pulmonary arterial hypertension (PAH) is often diagnosed late in its disease course, with outcome dependent on etiology, disease severity, and response to treatment. Recent advances in quantitative magnetic resonance imaging (MRI) allow for better initial characterization and measurement of the morphologic and flow-related changes that accompany the response of the heart-lung axis to prolonged elevation of pulmonary arterial pressure and resistance and provide a reproducible, comprehensive, and noninvasive means of assessing the course of the disease and response to treatment. Typical features of PAH occur primarily as a result of increased pulmonary vascular resistance and the resultant increased right ventricular (RV) afterload. Several MRI-derived diagnostic markers have emerged, such as ventricular mass index, interventricular septal configuration, and average pulmonary artery velocity, with diagnostic accuracy similar to that of Doppler echocardiography. Furthermore, prognostic markers have been identified with independent predictive value for identification of treatment failure. Such markers include large RV end-diastolic volume index, low left ventricular end-diastolic volume index, low RV ejection fraction, and relative area change of the pulmonary trunk. MRI is ideally suited for longitudinal follow-up of patients with PAH because of its noninvasive nature and high reproducibility and is advantageous over other biomarkers in the study of PAH because of its sensitivity to change in morphologic, functional, and flow-related parameters. Further study on the role of MRI image based biomarkers in the clinical environment is warranted.
    Journal of thoracic imaging 03/2014; 29(2):68-79. · 1.42 Impact Factor
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    ABSTRACT: To develop and demonstrate a breathheld 3D radial ultrashort echo time (UTE) acquisition to visualize co-registered lung perfusion and vascular structure. Nine healthy dogs were scanned twice at 3 Tesla (T). Contrast-enhanced pulmonary perfusion scans were acquired with a temporally interleaved three-dimensional (3D) radial UTE (TE = 0.08 ms) sequence in a breathhold (1 s time frames over a 33 s breathhold). The 3D breathheld volume was reconstructed into time-resolved perfusion datasets, and a composite vascular structure dataset. For structural comparison, a 5 min respiratory-gated 3D radial UTE scan was acquired. Data were analyzed by quantitative metrics and radiologist scoring. Appropriate time-course of contrast was seen in all subjects. Right ventricle to aorta transit times were 7.4 ± 2.0 s. Relative lung enhancement was a factor of 8.4 ± 1.5. Radiologist scoring showed similarly excellent visualization of the pulmonary arteries to the subsegmental level in breathheld (94% of cases) and respiratory-gated (100% of cases) acquisitions (P = 0.33) despite the aggressive under sampling in the breathheld scan. Similarly, differentiation of lung tissue and airways was achieved by both acquisition methods. A time-resolved 3D radial UTE sequence for simultaneous imaging of pulmonary perfusion and co-registered vascular structure is feasible.J. Magn. Reson. Imaging 2013. © 2013 Wiley Periodicals, Inc.
    Journal of Magnetic Resonance Imaging 12/2013; · 2.57 Impact Factor
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    ABSTRACT: Established as a method to study anatomic changes, such as renal tumors or atherosclerotic vascular disease, magnetic resonance imaging (MRI) to interrogate renal function has only recently begun to come of age. In this review, we briefly introduce some of the most important MRI techniques for renal functional imaging, and then review current findings on their use for diagnosis and monitoring of major kidney diseases. Specific applications include renovascular disease, diabetic nephropathy, renal transplants, renal masses, acute kidney injury, and pediatric anomalies. With this review, we hope to encourage more collaboration between nephrologists and radiologists to accelerate the development and application of modern MRI tools in nephrology clinics.Kidney International advance online publication, 25 September 2013; doi:10.1038/ki.2013.361.
    Kidney International 09/2013; · 8.52 Impact Factor
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    ABSTRACT: To investigate the utility of hyperpolarized He-3 MRI for detecting regional lung ventilated volume (VV ) changes in response to exercise challenge and leukotriene inhibitor montelukast, human subjects with exercise induced bronchoconstriction (EIB) were recruited. This condition is described by airway constriction following exercise leading to reduced forced expiratory volume in 1 second (FEV1) coinciding with ventilation defects on hyperpolarized He-3 MRI. Thirteen EIB subjects underwent spirometry and He-3 MRI at baseline, postexercise, and postrecovery at multiple visits. On one visit montelukast was given and on two visits placebo was given. Regional VV was calculated in the apical/basilar dimension, in the anterior/posterior dimension, and for the entire lung volume. The whole lung VV was used as an end-point and compared with spirometry. Postchallenge FEV1 dropped with placebo but not with treatment, while postchallenge VV dropped more with placebo than treatment. Sources of variability for VV included region (anterior/posterior), scan, and treatment. VV correlated with FEV1/ forced vital capacity (FVC) and forced expiratory flow between 25 and 75% of FVC and showed gravitational dependence after exercise challenge. A paradigm testing the response of ventilation to montelukast revealed both a whole-lung and regional response to exercise challenge and therapy in EIB subjects. J. Magn. Reson. Imaging 2013. © 2013 Wiley Periodicals, Inc.
    Journal of Magnetic Resonance Imaging 09/2013; · 2.57 Impact Factor
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    ABSTRACT: Rationale: Air trapping and ventilation defects on imaging are characteristics of asthma. Airway wall thickening occurs in asthma and is associated with increased bronchial vascularity and vascular permeability. Vascular endothelial cell products have not been explored as a surrogate to mark structural airway changes in asthma. Objectives: Determine whether reporters of vascular endothelial cell perturbation correlate with airway imaging metrics in patients with asthma of varying severity. Methods: Plasma from Severe Asthma Research Program subjects was analyzed by ELISAs for soluble von Willebrand factor mature protein (VWF:Ag) and propeptide (VWFpp), P-selectin, and platelet factor 4. Additional subjects were analyzed over 48 hours after whole-lung antigen challenge. We calculated ventilation defect volume by hyperpolarized helium-3 magnetic resonance imaging and areas of low signal density by multidetector computed tomography (less than -856 Hounsfield units [HU] at functional residual capacity and -950 HU at total lung capacity [TLC]). Measurements and Main Results: VWFpp and VWFpp/Ag ratio correlated with and predicted greater percentage defect volume on hyperpolarized helium-3 magnetic resonance imaging. P-selectin correlated with and predicted greater area of low density on chest multidetector computed tomography less than -950 HU at TLC. Platelet factor 4 did not correlate. Following whole-lung antigen challenge, variation in VWFpp, VWFpp/Ag, and P-selectin among time-points was less than that among subjects, indicating stability and repeatability of the measurements. Conclusions: Plasma VWFpp and P-selectin may be useful as surrogates of functional and structural defects that are evident on imaging. The results raise important questions about why VWFpp and P-selectin are associated specifically with different imaging abnormalities.
    American Journal of Respiratory and Critical Care Medicine 07/2013; 188(2):167-78. · 11.04 Impact Factor
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    ABSTRACT: PURPOSE: To develop a novel imaging technique to reduce the number of excitations and required scan time for hyperpolarized (13) C imaging. METHODS: A least-squares based optimization and reconstruction is developed to simultaneously solve for both spatial and spectral encoding. By jointly solving both domains, spectral imaging can potentially be performed with a spatially oversampled single echo spiral acquisition. Digital simulations, phantom experiments, and initial in vivo hyperpolarized [1-(13) C]pyruvate experiments were performed to assess the performance of the algorithm as compared to a multi-echo approach. RESULTS: Simulations and phantom data indicate that accurate single echo imaging is possible when coupled with oversampling factors greater than six (corresponding to a worst case of pyruvate to metabolite ratio < 9%), even in situations of substantial T2* decay and B0 heterogeneity. With lower oversampling rates, two echoes are required for similar accuracy. These results were confirmed with in vivo data experiments, showing accurate single echo spectral imaging with an oversampling factor of 7 and two echo imaging with an oversampling factor of 4. CONCLUSION: The proposed k-t approach increases data acquisition efficiency by reducing the number of echoes required to generate spectroscopic images, thereby allowing accelerated acquisition speed, preserved polarization, and/or improved temporal or spatial resolution. Magn Reson Med, 2013. © 2013 Wiley Periodicals, Inc.
    Magnetic Resonance in Medicine 05/2013; · 3.27 Impact Factor
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    ABSTRACT: BACKGROUND: Magnetic resonance imaging (MRI) with (3)He does not require ionizing radiation and has been shown to detect regional abnormalities in lung ventilation and structure in adults with asthma, but the method has not been extended to children with asthma. Measurements of regional lung ventilation and microstructure in subjects with childhood asthma could advance our understanding of disease mechanisms. OBJECTIVE: We sought to determine whether (3)He MRI in children can identify abnormalities related to the diagnosis of asthma or prior history of respiratory illness. METHODS: Forty-four children aged 9 to 10 years were recruited from a birth cohort at increased risk of asthma and allergic diseases. For each subject, a time-resolved 3-dimensional image series and a 3-dimensional diffusion-weighted image were acquired in separate breathing maneuvers. The numbers and sizes of ventilation defects were scored, and regional maps and statistics of average (3)He diffusion lengths were calculated. RESULTS: Children with mild-to-moderate asthma had lower average root-mean-square diffusion length (X(rms)¯) values (P = .004), increased regional SD of diffusion length values (P = .03), and higher defect scores (P = .03) than those without asthma. Children with histories of wheezing illness with rhinovirus infection before the third birthday had lower X(rms)¯ values (P = .01) and higher defect scores (P = .05). CONCLUSION: MRI with (3)He detected more and larger regions of ventilation defect and a greater degree of restricted gas diffusion in children with asthma compared with those seen in children without asthma. These measures are consistent with regional obstruction and smaller and more regionally variable dimensions of the peripheral airways and alveolar spaces.
    The Journal of allergy and clinical immunology 12/2012; · 12.05 Impact Factor
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    ABSTRACT: PURPOSE: To optimize 3D radial ultrashort echo time MRI for high resolution whole-lung imaging. METHODS: 3D radial ultrashort echo time was implemented on a 3T scanner to investigate the effects of: (1) limited field-of-view excitation, (2) variable density readouts, and (3) radial oversampling. Improvements in noise performance and spatial resolution were assessed through simulation and phantom studies. Their effects on lung and airway visualization in five healthy male human subjects (mean age 32 years) were compared qualitatively through blinded ordinal scoring by two cardiothoracic radiologists using a nonparametric Friedman test (P < 0.05). Relative signal difference between endobronchial air and adjacent lung tissue, normalized to nearby vessel, was used as a surrogate for lung tissue signal. Quantitative measures were compared using the paired Student's t-test (P < 0.05). Finally, clinical feasibility was investigated in a patient with interstitial fibrosis. RESULTS: Simulation and phantom studies showed up to 67% improvement in SNR and reduced blurring for short T2* species using all three optimizations. In vivo images showed decreased artifacts and improved lung tissue and airway visualization both qualitatively and quantitatively. CONCLUSION: The use of limited field-of-view excitation, variable readout gradients, and radial oversampling significantly improve the technical quality of 3D radial ultrashort echo time lung images. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc.
    Magnetic Resonance in Medicine 12/2012; · 3.27 Impact Factor
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    ABSTRACT: Purpose:To quantitatively evaluate interday, interreader, and intersite agreement of readers of hyperpolarized helium 3 (HPHe) MR images in patients with exercise-induced bronchoconstriction.Materials and Methods:This HIPAA-compliant, institutional review board approved study included 13 patients with exercise-induced bronchoconstriction. On two separate days, HPHe MR imaging of the lungs was performed at baseline, immediately after a 10-minute exercise challenge (postchallenge), and 45 minutes after exercise (recovery). Patients were imaged at two sites, six at site A and seven at site B. Images were analyzed independently by multiple readers at each site. Lung volume, ventilation defect volume, ventilated volume, and the number of defects were measured quantitatively, and the location of defects was evaluated qualitatively at site A. Interday and interreader agreement were evaluated by using the intraclass correlation coefficient (ICC), and intersite agreement was evaluated by using a modified Bland-Altman analysis.Results:The ICC between days for ventilation defect volume, ventilated volume, and number of defects was at least 0.74 at both sites. The ICC for lung volume was greater at site B (0.83-0.86) than at site A (0.60-0.65). Defects seen in the same location in the lung on both days included 19.7% of those seen on baseline images and 29.2% and 18.6% of defects on postchallenge and recovery images, respectively. Interreader ICC for each measurement was at least 0.82 for each site. Analysis of intersite agreement showed biases of 612 mL for lung volume, -60.7 mL for ventilation defect volume, 2.91% for ventilated volume, and -6.56 for number of defects.Conclusion:The reported measures of reproducibility of HPHe MR imaging may help in the design and interpretation of single- and multicenter studies of patients with exercise-induced bronchoconstriction.© RSNA, 2012.
    Radiology 11/2012; · 6.34 Impact Factor
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    ABSTRACT: Background: Heat shock protein 27 (HSP27) is a small HSP up-regulated in response to stress in the kidney. The relationship between HSP27 and intrarenal oxygenation in patients with native and transplant kidney disease is unknown. Methods: We compared HSP27 levels, intrarenal oxygenation measured by blood oxygen-level dependent (BOLD) imaging using R2* values, and perfusion determined by arterial spin labeling (ASL) magnetic resonance imaging (MRI), between patients with native and transplant kidney disease (n=28). Results: There were no statistical differences in mean age (53.9 vs. 47.1 years), kidney function (63.6 vs. 50.7 ml/min per 1.73 m2), mean arterial blood pressure (91.6 vs. 91.1 mm Hg), hematocrit (40.6% vs. 39.3%), diuretic or angiotensin-converting enzyme inhibitor use, serum or urine levels of hydrogen peroxide, nitric oxide, F2 isoprostanes and HSP27 between native and transplant kidneys. BOLD-MRI studies demonstrated comparable patterns in intrarenal oxygen bioavailability (medullary R2* 18.1 vs. 18.3/s and cortical R2* 12 vs. 11.7/s, respectively). However, medullary perfusion was significantly lower in transplant kidneys (36.4 vs. 78.7 ml/100 g per minute, p=0.0002). There was a linear relationship between serum HSP27 concentrations and medullary perfusion in kidney allografts (HSP27 concentration [ng/mL] = 0.78 + 0.09 medullary perfusion, R2=0.43, p=0.01). Conclusions: Our study demonstrates that medullary perfusion is significantly lower in kidney allografts compared with native kidneys with comparable renal function. We further noted a direct association between serum HSP27 levels and medullary perfusion after transplantation. Additional studies are needed to examine the role of HSP27 as a biomarker of kidney disease progression.
    Journal of nephrology 02/2012; · 2.02 Impact Factor
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    ABSTRACT: In the dynamic nuclear polarization process, microwave irradiation facilitates exchange of polarization from a radical's unpaired electron to nuclear spins at cryogenic temperatures, increasing polarization by >10,000. Doping samples with Gd(3+) ions further increases the achievable solid-state polarization. However, on dissolution, paramagnetic lanthanide metals can be potent relaxation agents, decreasing liquid-state polarization. Here, the effects of lanthanide metals on the solid and liquid-state magnetic properties of [1-(13) C]pyruvate are studied. The results show that in addition to gadolinium, holmium increases not only the achievable polarization but also the rate of polarization. Liquid-state relaxation studies found that unlike gadolinium, holmium minimally affects T(1) . Additionally, results reveal that linear contrast agents dissociate in pyruvic acid, greatly reducing liquid-state T(1) . Although macrocyclic agents do not readily dissociate, they yield lower solid-state polarization. Results indicate that polarization with free lanthanides and subsequent chelation during dissolution produces the highest polarization enhancement while minimizing liquid-state relaxation. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc.
    Magnetic Resonance in Medicine 02/2012; · 3.27 Impact Factor
  • RSNA 98th Scientific Assembly and Annual MeetingRSNA 98th Scientific Assembly and Annual Meeting; 01/2012
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    IEEE Trans. Biomed. Engineering. 01/2012; 59:45-49.
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    ABSTRACT: Background/Aims: Hypercholesterolemia in midlife increases risk for Alzheimer's disease (AD) and contributes to cerebrovascular dysregulation - an early finding in preclinical AD pathology. Statins improve vascular reactivity, but it is unknown if they increase regional cerebral blood flow (CBF) in individuals at risk for AD. Methods: In a randomized, controlled, double-blind pilot study, 16 asymptomatic middle-aged adults with parental history of AD were randomized to atorvastatin or placebo daily for 4 months. At baseline and month 4, regional CBF was measured using arterial spin-labeling magnetic resonance imaging and endothelial function was measured using brachial artery ultrasound. Results: At baseline, participants with low HDL-cholesterol, higher global vascular risk, and greater endothelial dysfunction had reduced regional CBF in areas of the brain related to memory and learning (all p < 0.03). Using voxel-based analysis, 4 months of atorvastatin increased CBF in bilateral hippocampi, fusiform gyrus, putamen and insular cortices compared to placebo. Conclusion: In this pilot study, atorvastatin increased regional CBF in persons at risk for AD. Further research is warranted to confirm whether statins increase CBF in areas of the brain related to memory and learning and whether such perfusion changes are associated with a delay in the onset of AD. Clinical Trial Registration: Identifier: NCT00751907.
    Current Alzheimer research 11/2011; 9(8):990-7. · 4.97 Impact Factor
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    ABSTRACT: The National Heart, Lung, and Blood Institute Severe Asthma Research Program (SARP) has characterized over the past 10 years 1,644 patients with asthma, including 583 individuals with severe asthma. SARP collaboration has led to a rapid recruitment of subjects and efficient sharing of samples among participating sites to conduct independent mechanistic investigations of severe asthma. Enrolled SARP subjects underwent detailed clinical, physiologic, genomic, and radiological evaluations. In addition, SARP investigators developed safe procedures for bronchoscopy in participants with asthma, including those with severe disease. SARP studies revealed that severe asthma is a heterogeneous disease with varying molecular, biochemical, and cellular inflammatory features and unique structure-function abnormalities. Priorities for future studies include recruitment of a larger number of subjects with severe asthma, including children, to allow further characterization of anatomic, physiologic, biochemical, and genetic factors related to severe disease in a longitudinal assessment to identify factors that modulate the natural history of severe asthma and provide mechanistic rationale for management strategies.
    American Journal of Respiratory and Critical Care Medicine 11/2011; 185(4):356-62. · 11.04 Impact Factor

Publication Stats

1k Citations
299.44 Total Impact Points


  • 2001–2014
    • University of Wisconsin–Madison
      • • Department of Medical Physics
      • • Department of Radiology
      Madison, Wisconsin, United States
  • 2012
    • University of Illinois at Chicago
      Chicago, Illinois, United States
  • 2004
    • Palm Beach Atlantic University
      Palm Beach, Florida, United States
  • 2000–2001
    • Mayo Clinic - Rochester
      • Department of Radiology
      Rochester, Minnesota, United States
  • 1999–2001
    • Mayo Foundation for Medical Education and Research
      • Department of Diagnostic Radiology
      Scottsdale, AZ, United States