Tina Young Poussaint

Dana-Farber Cancer Institute, Boston, Massachusetts, United States

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Publications (114)390.83 Total impact

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    ABSTRACT: Background: Diffuse intrinsic pontine glioma (DIPG) is associated with poor survival regardless of therapy. We used volumetric apparent diffusion coefficient (ADC) histogram metrics to determine associations with progression-free survival (PFS) and overall survival (OS) at baseline and after radiation therapy (RT). Methods: Baseline and post-RT quantitative ADC histograms were generated from fluid-attenuated inversion recovery (FLAIR) images and enhancement regions of interest. Metrics assessed included number of peaks (ie, unimodal or bimodal), mean and median ADC, standard deviation, mode, skewness, and kurtosis. Results: Based on FLAIR images, the majority of tumors had unimodal peaks with significantly shorter average survival. Pre-RT FLAIR mean, mode, and median values were significantly associated with decreased risk of progression; higher pre-RT ADC values had longer PFS on average. Pre-RT FLAIR skewness and standard deviation were significantly associated with increased risk of progression; higher pre-RT FLAIR skewness and standard deviation had shorter PFS. Nonenhancing tumors at baseline showed higher ADC FLAIR mean values, lower kurtosis, and higher PFS. For enhancing tumors at baseline, bimodal enhancement histograms had much worse PFS and OS than unimodal cases and significantly lower mean peak values. Enhancement in tumors only after RT led to significantly shorter PFS and OS than in patients with baseline or no baseline enhancement. Conclusions: ADC histogram metrics in DIPG demonstrate significant correlations between diffusion metrics and survival, with lower diffusion values (increased cellularity), increased skewness, and enhancement associated with shorter survival, requiring future investigations in large DIPG clinical trials.
    No preview · Article · Oct 2015 · Neuro-Oncology
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    Tina Young Poussaint · Thierry A G M Huisman

    Preview · Article · Sep 2015 · Pediatric Radiology
  • Tina Y Poussaint · Ashok Panigrahy · Thierry A G M Huisman
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    ABSTRACT: Among all causes of death in children from solid tumors, pediatric brain tumors are the most common. This article includes an overview of a subset of infratentorial and supratentorial tumors with a focus on tumor imaging features and molecular advances and treatments of these tumors. Key to understanding the imaging features of brain tumors is a firm grasp of other disease processes that can mimic tumor on imaging. We also review imaging features of a common subset of tumor mimics.
    No preview · Article · Sep 2015 · Pediatric Radiology
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    ABSTRACT: Cediranib (AZD2171), an oral pan-vascular endothelial growth factor (VEGF) inhibitor, was evaluated in this phase I study to determine its toxicity profile, dose-limiting toxicities (DLTs), maximum-tolerated dose (MTD), pharmacokinetics, and pharmacodynamics in children and adolescents with recurrent or refractory primary central nervous system (CNS) tumors. Children and adolescents <22 years were enrolled into one of two strata: stratum I-those not receiving enzyme-inducing anticonvulsant drugs (EIACD) and stratum II-those receiving EIACDs. Dose-level selection was based on the continual reassessment method (CRM). Thirty-six eligible patients with median age of 12.7 years (range, 5.4-21.7 years) in stratum I (24 males) and 12 patients (7 males) in stratum II with median age of 13.4 years (range, 8.9-19.5 years) were initially assessed over a 4-week DLT evaluation period, modified to 6 weeks during the study. An MTD of 32 mg/m(2)/day was declared; however, excessive toxicities (transaminitis, proteinuria, diarrhea, hemorrhage, palmer-planter syndrome, reversible posterior leukoencephalopathy) in the expansion cohort treated at this dose suggested that it might not be tolerated over a longer time period. An expansion cohort at 20 mg/m(2)/day also demonstrated poor longer-term tolerability. Diffusion and perfusion MRI and PET imaging variables as well as biomarker analysis were performed and correlated with outcome. At 20 mg/m(2)/day, the median plasma area under the concentration-time curve at steady state was lower than that observed in adults at similar dosages. While the MTD of once daily oral cediranib in children with recurrent or progressive CNS tumors was initially defined as 32 mg/m(2)/day, this dose and 20 mg/m(2)/day were not considered tolerable over a protracted time period.
    No preview · Article · Jul 2015 · Child s Nervous System

  • No preview · Article · Apr 2015 · Neuro-Oncology
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    ABSTRACT: Rationale and objectives: Magnetic resonance diffusion imaging can characterize physiologic characteristics of pediatric brain tumors used to assess therapy response. The purpose of this study was to assess the variability of the apparent diffusion coefficient (ADC) along z-axis of scanners in the multicenter Pediatric Brain Tumor Consortium (PBTC). Materials and methods: Ice-water diffusion phantoms for each PBTC site were distributed with a specific diffusion imaging protocol. The phantom was scanned four successive times to 1) confirm water in the tube reached thermal equilibrium and 2) allow for assessment of intra-examination ADC repeatability. ADC profiles across slice positions for each vendor and institution combination were characterized using linear regression modeling with a quadratic fit. Results: Eleven sites collected data with a high degree of compliance to the diffusion protocol for each scanner. The mean ADC value at slice position zero for vendor A was 1.123 × 10(-3) mm(2)/s, vendor B was 1.0964 × 10(-3) mm(2)/s, and vendor C was 1.110 × 10(-3) mm(2)/s. The percentage coefficient of variation across all sites was 0.309% (standard deviation = 0.322). The ADC values conformed well to a second-order polynomial along the z-axis, (ie, following a linear model pattern with quadratic fit) for vendor-institution combinations and across vendor-institution combinations as shown in the longitudinal model. Conclusions: Assessment of the variability of diffusion metrics is essential for establishing the validity of using these quantitative metrics in multicenter trials. The low variability in ADC values across vendors and institutions and validates the use of ADC as a quantitative tumor marker in pediatric multicenter trials.
    No preview · Article · Nov 2014 · Academic Radiology
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    ABSTRACT: Unlabelled: The purpose of this study was to describe (18)F-FDG uptake across a spectrum of pediatric brain tumors and correlate (18)F-FDG PET with MR imaging variables, progression-free survival (PFS), and overall survival (OS). Methods: A retrospective analysis was conducted of children enrolled in phase I/II clinical trials through the Pediatric Brain Tumor Consortium from August 2000 to June 2010. PET variables were summarized within diagnostic categories using descriptive statistics. Associations of PET with MR imaging variables and PFS and OS by tumor types were evaluated. Results: Baseline (18)F-FDG PET was available in 203 children; 66 had newly diagnosed brain tumors, and 137 had recurrent/refractory brain tumors before enrolling in a Pediatric Brain Tumor Consortium trial. MR imaging was performed within 2 wk of PET and before therapy in all cases. The (18)F-FDG uptake pattern and MR imaging contrast enhancement (CE) varied by tumor type. On average, glioblastoma multiforme and medulloblastoma had uniform, intense uptake throughout the tumor, whereas brain stem gliomas (BSGs) had low uptake in less than 50% of the tumor and ependymoma had low uptake throughout the tumor. For newly diagnosed BSG, correlation of (18)F-FDG uptake with CE portended reduced OS (P = 0.032); in refractory/recurrent BSG, lack of correlation between (18)F-FDG uptake and CE suggested decreased PFS (P = 0.023). In newly diagnosed BSG for which more than 50% of the tumor had (18)F-FDG uptake, there was a suggestion of lower apparent diffusion coefficient (P = 0.061) and decreased PFS (P = 0.065). Conclusion: (18)F-FDG PET and MR imaging showed a spectrum of patterns depending on tumor type. In newly diagnosed BSG, the correlation of (18)F-FDG uptake and CE suggested decreased OS, likely related to more aggressive disease. When more than 50% of the tumor had (18)F-FDG uptake, the apparent diffusion coefficient was lower, consistent with increased cellularity. In refractory/recurrent BSG, poor correlation between (18)F-FDG uptake and CE was associated with decreased PFS, which may reflect concurrent tissue breakdown at sites of treated disease and development of new sites of (18)F-FDG-avid malignancy.
    Full-text · Article · Jul 2014 · Journal of Nuclear Medicine
  • Sharon Byrd · Bonnie Davis · Iris Gibbs · Tina Young Poussaint · Virginia J Simmons

    No preview · Article · Jul 2014 · Radiology
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    ABSTRACT: We report on 6 infants who underwent elective surgery and developed postoperative encephalopathy, which had features most consistent with intraoperative cerebral hypoperfusion. All infants were <48 weeks' postmenstrual age and underwent procedures lasting 120 to 185 minutes. Intraoperative records revealed that most of the measured systolic blood pressure (SBP) values were <60 mm Hg (the threshold for hypotension in awake infants according to the Pediatric Advanced Life Support guidelines) but that only 11% of the measured SBP values were <1 SD of the mean definition of hypotension (<45 mm Hg) as reported in a survey of members of the Society for Pediatric Anesthesia in 2009. Four infants also exhibited prolonged periods of mild hypocapnia (<35 mm Hg). One infant did not receive intraoperative dextrose. All infants developed new-onset seizures within 25 hours of administration of the anesthetic, with a predominant cerebral pathology of supratentorial watershed infarction in the border zone between the anterior, middle, and posterior cerebral arteries. Follow-up of these infants found that 1 died, 1 had profound developmental delays, 1 had minor motor delays, 2 were normal, and 1 was lost to follow-up. Although the precise cause of encephalopathy cannot be determined, it is important to consider the role that SBP hypotension (as well as hypoglycemia, hyperthermia, hyperoxia, and hypocapnia) plays during general anesthesia in young infants in the development of infantile postoperative encephalopathy. Our observations highlight the lack of evidence-based recommendations for the lower limits of adequate SBP and end-tidal carbon dioxide in anesthetized infants.
    Preview · Article · Feb 2014 · PEDIATRICS
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    ABSTRACT: BackgroundA phase II study of bevacizumab (BVZ) plus irinotecan (CPT-11) was conducted in children with recurrent low-grade glioma to measure sustained response and/or stable disease lasting ≥6 months and progression-free survival.Methods Thirty-five evaluable patients received 2 doses (10 mg/kg each) of single-agent BVZ intravenously 2 weeks apart and then BVZ + CPT-11 every 2 weeks until progressive disease, unacceptable toxicity, or a maximum of 2 years of therapy. Correlative studies included neuroimaging and expression of tumor angiogenic markers (vascular endothelial growth factor [VEGF], VEGF receptor 2, hypoxia-inducible factor 2α, and carbonic anhydrase 9).ResultsThirty-five evaluable patients (median age 8.4 y [range, 0.6-17.6]) received a median of 12 courses of BVZ + CPT-11 (range, 2-26). Twenty-nine of 35 patients (83%) received treatment for at least 6 months. Eight patients progressed on treatment at a median time of 5.4 months (range, 1-17.8). Six patients (17.7%) still in follow-up have had stable disease without receiving additional treatment for a median of 40.1 months (range, 30.6-49.3) from initiating therapy. The 6-month and 2-year progression-free survivals were 85.4% (SE ± 5.96%) and 47.8% (SE ± 9.27%), respectively. The commonest toxicities related to BVZ included grades 1-2 hypertension in 24, grades 1-2 fatigue in 23, grades 1-2 epistaxis in 18, and grades 1-4 proteinuria in 15. The median volume of enhancement decreased significantly between baseline and day 15 (P < .0001) and over the duration of treatment (P < .037).Conclusion The combination of BVZ + CPT-11 appears to produce sustained disease control in some children with recurrent low-grade gliomas.
    No preview · Article · Dec 2013 · Neuro-Oncology
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    ABSTRACT: The incidence and spectrum of acute toxicities related to the use of bevacizumab (BVZ)-containing regimens in children are largely unknown. This report describes the adverse events in a recently completed large phase 2 trial of BVZ plus irinotecan (CPT-11) in children with recurrent central nervous system tumors. Pediatric Brain Tumor Consortium trial-022 evaluated the efficacy and toxicity of BVZ (10 mg/kg administered intravenously) as a single agent for 2 doses given 2 weeks apart and then combined with CPT-11 every 2 weeks (1 course = 4 weeks) in children with recurrent central nervous system tumors. Children were treated until they experienced progressive disease, unacceptable toxicity or completed up to a maximum of 2 years of therapy. Toxicities were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0. Patients who received at least 1 dose of BVZ were included for toxicity assessment. Between October 2006 and June 2010, 92 patients evaluable for toxicity were enrolled and received 687 treatment courses. The most common toxicities attributable to BVZ included grade I-III hypertension (38% of patients), grade I-III fatigue (30%), grade I-II epistaxis (24%), and grade I-IV proteinuria (22%). Twenty-two patients (24%) stopped therapy due to toxicity. The combination of BVZ and CPT-11 was fairly well-tolerated, and most severe BVZ-related toxicities were rare, self-limiting, and manageable. Cancer 2013;. © 2013 American Cancer Society.
    No preview · Article · Dec 2013 · Cancer
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    ABSTRACT: OBJECTIVE: Neurofibromatosis (NF)-related benign tumors such as plexiform neurofibromas (PN) and vestibular schwannomas (VS) can cause substantial morbidity. Clinical trials directed at these tumors have become available. Due to differences in disease manifestations and the natural history of NF-related tumors, response criteria used for solid cancers (1-dimensional/RECIST [Response Evaluation Criteria in Solid Tumors] and bidimensional/World Health Organization) have limited applicability. No standardized response criteria for benign NF tumors exist. The goal of the Tumor Measurement Working Group of the REiNS (Response Evaluation in Neurofibromatosis and Schwannomatosis) committee is to propose consensus guidelines for the evaluation of imaging response in clinical trials for NF tumors. METHODS: Currently used imaging endpoints, designs of NF clinical trials, and knowledge of the natural history of NF-related tumors, in particular PN and VS, were reviewed. Consensus recommendations for response evaluation for future studies were developed based on this review and the expertise of group members. RESULTS: MRI with volumetric analysis is recommended to sensitively and reproducibly evaluate changes in tumor size in clinical trials. Volumetric analysis requires adherence to specific imaging recommendations. A 20% volume change was chosen to indicate a decrease or increase in tumor size. Use of these criteria in future trials will enable meaningful comparison of results across studies. CONCLUSIONS: The proposed imaging response evaluation guidelines, along with validated clinical outcome measures, will maximize the ability to identify potentially active agents for patients with NF and benign tumors.
    Full-text · Article · Nov 2013 · Neurology
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    ABSTRACT: Criteria for new drug approval include demonstration of efficacy. In neuro-oncology, this is determined radiographically utilizing tumor measurements on MRI scans. Limitations of this method have been identified where drug activity is not reflected in decreased tumor size. The RANO (Response Assessment in Neuro-Oncology) working group was established to address limitations in defining endpoints for clinical trials in adult neuro-oncology and to develop standardized response criteria. RAPNO was subsequently established to address unique issues in pediatric neuro-oncology. The aim of this paper is to delineate response criteria issues in pediatric clinical trials as a basis for subsequent recommendations. Pediatr Blood Cancer 2013;9999:XX-XX. © 2013 Wiley Periodicals, Inc.
    No preview · Article · Sep 2013 · Pediatric Blood & Cancer
  • Lara A Brandão · Tina Young Poussaint
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    ABSTRACT: Pediatric brain tumors are the most common solid tumor of childhood. This article focuses on the metabolic signature of common pediatric brain tumors using MR spectroscopic analyses.
    No preview · Article · Aug 2013 · Neuroimaging Clinics of North America
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    ABSTRACT: The purpose of this study was to develop a method of registering (18)F-FDG PET with MR permeability images for investigating the correlation of (18)F-FDG uptake, permeability, and cerebral blood volume (CBV) in children with pediatric brain tumors and their relationship with outcome. Twenty-four children with brain tumors in a phase II study of bevacizumab and irinotecan underwent brain MR and (18)F-FDG PET within 2 wk. Tumor types included supratentorial high-grade astrocytoma (n = 7), low-grade glioma (n = 9), brain stem glioma (n = 4), medulloblastoma (n = 2), and ependymoma (n = 2). There were 33 cases (pretreatment only [n = 12], posttreatment only [n = 3], and both pretreatment [n = 9] and posttreatment [n = 9]). (18)F-FDG PET images were registered to MR images from the last time point of the T1 perfusion time series using mutual information. Three-dimensional regions of interest (ROIs) drawn on permeability images were automatically transferred to registered PET images. The quality of ROI registration was graded (1, excellent; 2, very good; 3, good; 4, fair; and 5, poor) by 3 independent experts. Spearman rank correlations were used to assess correlation of maximum tumor permeability (Kpsmax), maximum CBV (CBVmax), and maximum (18)F-FDG uptake normalized to white matter (T/Wmax). Cox proportional hazards models were used to investigate associations of these parameters with progression-free survival (PFS). The quality of ROI registration between PET and MR was good to excellent in 31 of 33 cases. There was no correlation of baseline Kpsmax with CBVmax (Spearman rank correlation = 0.018 [P = 0.94]) or T/Wmax (Spearman rank correlation = 0.07 [P = 0.76]). Baseline CBVmax was correlated with T/Wmax (Spearman rank correlation = 0.47 [P = 0.036]). Baseline Kpsmax, CBVmax, and T/Wmax were not significantly associated with PFS (P = 0.42, hazard ratio [HR] = 0.97, 95% confidence interval [CI] = 0.90-1.045, and number of events [nevents] = 15 for Kpsmax; P = 0.41, HR = 0.989, 95% CI = 0.963-1.015, and nevents = 14 for CBVmax; and P = 0.17, HR = 1.49, 95% CI = 0.856-2.378, and nevents = 15 for T/Wmax). (18)F-FDG PET and MR permeability images were successfully registered and compared across a spectrum of pediatric brain tumors. The lack of correlation between metabolism and permeability may be expected because these parameters characterize different molecular processes. The correlation of CBV and tumor metabolism may be related to an association with tumor grade. More patients are needed for a covariate analysis of these parameters and PFS by tumor histology.
    Preview · Article · Jun 2013 · Journal of Nuclear Medicine
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    ABSTRACT: Spinal dysraphism or neural tube defects encompass a heterogeneous group of congenital spinal anomalies that result from the defective closure of the neural tube early in gestation with anomalous development of the caudal cell mass. A clinical neuroradiologic classification system has been developed by Tortori-Donati et al. to help organize the various forms of spinal dysraphism [1]. This system was devised based on a large series of patients seen and imaged at their spina bifida center over a 24-year period. This classification system divides spinal dysraphism into open or closed forms. An open spinal dysraphism (OSD) is present when the neural elements and/or their coverings are exposed through a bone defect and not covered by skin. OSD can then be subdivided into two major diagnoses: myelomeningocele and myelocele, based on the position of the neural placode with respect to the level of the skin surface. When there is elevation because of expansion of the subarachnoid space, the lesion is referred to as a myelomeningocele (MMC). A closed spinal dysraphism (CSD) is skin-covered but frequently suspected clinically due to a subcutaneous mass, hemangioma, or an overlying hairy patch.
    No preview · Chapter · Jan 2013
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    ABSTRACT: A phase II study of bevacizumab (BVZ) plus irinotecan (CPT-11) was conducted in cases of pediatric recurrent ependymoma (EPN) to estimate sustained objective response rate and progression-free survival (PFS). Eligible patients received 2 doses of single-agent BVZ intravenously (10 mg/kg) 2 weeks apart and then BVZ + CPT-11 every 2 weeks until progressive disease, unacceptable toxicity, or a maximum of 2 years of therapy. Correlative studies included diffusion-weighted and T1 dynamic contrast enhanced permeability imaging and tumor immunohistochemistry for vascular endothelial growth factor (VEGF)-A and -B, hypoxia inducible factor-2α, VEGF receptor (R)-2, and carbonic anhydrase (CA)-9. Thirteen evaluable patients received a median of 3 courses (range, 2-12) of BVZ + CPT-11. No sustained response was observed in any patient. Median time to progression in 10 patients was 2.2 months (range, 1.9-6.3). Two patients had stable disease for 10 months and 12 months, respectively. Six-month PFS was 25.7% (SE = 11.1%). Grades I-III toxicities related to BVZ treatment included fatigue in 4 patients, systemic hypertension in 2, epistaxis in 1, headache in 1, and avascular necrosis of bone in 1. Although there was a decrease in the mean diffusion ratio following 2 doses of BVZ, it did not correlate with PFS. BVZ + CPT-11 was well tolerated but had minimal efficacy in cases of recurrent EPN.
    Preview · Article · Sep 2012 · Neuro-Oncology
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    ABSTRACT: To estimate the sustained (≥8 weeks) objective response rate in pediatric patients with recurrent or progressive high-grade gliomas (HGG, Stratum A) or brainstem gliomas (BSG, Stratum B) treated with the combination of O6-benzylguanine (O6BG) and temozolomide(®) (TMZ). Patients received O6BG 120 mg/m(2)/d IV followed by TMZ 75 mg/m(2)/d orally daily for 5 consecutive days of each 28-day course. The target objective response rate to consider the combination active was 17%. A two-stage design was employed. Forty-three patients were enrolled; 41 were evaluable for response, including 25 patients with HGG and 16 patients with BSG. The combination of O6BG and TMZ was tolerable, and the primary toxicities were myelosuppression and gastrointestinal symptoms. One sustained (≥8 weeks) partial response was observed in the HGG cohort; no sustained objective responses were observed in the BSG cohort. Long-term (≥6 courses) stable disease (SD) was observed in 4 patients in Stratum A and 1 patient in Stratum B. Of the 5 patients with objective response or long-term SD, 3 underwent central review with 2 reclassified as low-grade gliomas. The combination of O6BG and TMZ did not achieve the target response rate for activity in pediatric patients with recurrent or progressive HGG and BSG.
    Full-text · Article · Feb 2012 · Journal of Neuro-Oncology
  • Tina Young Poussaint · Andrea Rossi
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    ABSTRACT: Brain tumors are the most common solid pediatric tumors and are the leading cause of death in children from solid tumors [1]. The estimated incidence of all childhood primary brain and central nervous system (CNS) tumors is 4.8 per 100,000 person-years [2]. Approximately 4,150 new cases of childhood primary nonmalignant and malignant brain and CNS tumors will be diagnosed in the United States in 2011 [3]. In neonates, infants, and children up to the age of 3 years, supratentorial tumors are more common.
    No preview · Chapter · Jan 2012
  • Tina Young Poussaint
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    ABSTRACT: The phakomatoses, or neurocutaneous syndromes, are a group of disorders affecting structures of ectodermal origin
    No preview · Chapter · Jan 2012

Publication Stats

2k Citations
390.83 Total Impact Points

Institutions

  • 2003-2015
    • Dana-Farber Cancer Institute
      • Department of Pediatric Oncology
      Boston, Massachusetts, United States
  • 1999-2015
    • Harvard University
      Cambridge, Massachusetts, United States
  • 1993-2014
    • Boston Children's Hospital
      • Department of Radiology
      Boston, Massachusetts, United States
  • 2011
    • University of California, San Francisco
      San Francisco, California, United States
  • 2010-2011
    • St. Jude Children's Research Hospital
      Memphis, Tennessee, United States
    • Beth Israel Deaconess Medical Center
      • Department of Radiology
      Boston, Massachusetts, United States
  • 2005-2008
    • The Children's Hospital of Philadelphia
      Filadelfia, Pennsylvania, United States
  • 2007
    • Childrens Hospital of Pittsburgh
      Pittsburgh, Pennsylvania, United States
  • 1997-2006
    • Harvard Medical School
      • Department of Radiology
      Boston, Massachusetts, United States
  • 1998
    • Loma Linda University
      لوما ليندا، كاليفورنيا, California, United States