Tina Young Poussaint

Harvard University, Cambridge, Massachusetts, United States

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Publications (103)350.88 Total impact

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    ABSTRACT: 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 mm2/s, vendor B was 1.0964 × 10-3 mm2/s, and vendor C was 1.110 × 10-3 mm2/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. Copyright © 2014 AUR. Published by Elsevier Inc. All rights reserved. KEYWORDS: Diffusion phantom; MRI; pediatric brain tumors; quality assurance
    Academic Radiology 11/2014; 22(3). DOI:10.1016/j.acra.2014.10.006 · 2.08 Impact Factor
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    ABSTRACT: 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).
    Journal of Nuclear Medicine 07/2014; 55(9). DOI:10.2967/jnumed.114.139626 · 5.56 Impact Factor
  • Radiology 07/2014; 272(1):301-302. DOI:10.1148/radiol.14140435 · 6.21 Impact Factor
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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.
    PEDIATRICS 02/2014; 133(3). DOI:10.1542/peds.2012-0973 · 5.30 Impact Factor
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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.
    Neuro-Oncology 12/2013; 16(2). DOI:10.1093/neuonc/not154 · 5.29 Impact Factor
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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.
    Cancer 12/2013; 119(23). DOI:10.1002/cncr.28343 · 4.90 Impact Factor
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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.
    Pediatric Blood & Cancer 09/2013; 60(9). DOI:10.1002/pbc.24562 · 2.56 Impact Factor
  • 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.
    Neuroimaging Clinics of North America 08/2013; 23(3):499-525. DOI:10.1016/j.nic.2013.03.003 · 1.29 Impact Factor
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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.
    Journal of Nuclear Medicine 06/2013; 54(8). DOI:10.2967/jnumed.112.115782 · 5.56 Impact Factor
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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.
    Neuro-Oncology 09/2012; 14(11):1404-12. DOI:10.1093/neuonc/nos213 · 5.29 Impact Factor
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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.
    Journal of Neuro-Oncology 02/2012; 106(3):643-9. DOI:10.1007/s11060-011-0709-z · 2.79 Impact Factor
  • Michael J Paldino, Eric N Faerber, Tina Young Poussaint
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    ABSTRACT: Primary tumors of the central nervous system (CNS) are the second most common neoplasms in children and the leading cause of death in this patient population. The primary objective of this article is to describe the most common pediatric brain tumors and to offer an overview of their respective imaging features, primarily on magnetic resonance imaging. Precise anatomic characterization is essential for developing an appropriate differential diagnosis. Once equipped with this critical information, physicians should be better able to make firm diagnoses, leading to improved disease management and patient outcomes in the setting of CNS tumors of childhood.
    Radiologic Clinics of North America 07/2011; 49(4):589-616, v. DOI:10.1016/j.rcl.2011.05.011 · 1.83 Impact Factor
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    ABSTRACT: The purpose of this study was to assess the conspicuity of brain cortical maturation with sonography and MRI of fetuses referred because of ventriculomegaly and to determine whether sulcal visualization can be used to predict postnatal outcome. Women with 374 fetuses referred because of ventriculomegaly underwent sonography and MRI. Four to six radiologists rated visualization of 19 fissures or sulci. Majority opinion regarding sulcal visualization was compared among fetuses categorized by CNS abnormality: normal, isolated ventriculomegaly, and ventriculomegaly with additional CNS abnormalities. Live-born infants were categorized as having normal or abnormal development. Logistic regression analysis was used to correlate sulcal visualization and postnatal development. A subanalysis was performed with fetuses who had been classified prenatally as having a normal brain or isolated ventriculomegaly. Cortical sulci were visualized more frequently and at an earlier gestational age with MRI than with ultrasound. In the entire cohort, the odds ratio of normal development ranged from 3.1 to 10.0 whenever the calcarine, parietooccipital, cingulate, superior temporal, precentral, or postcentral sulcus was seen on MR images. In fetuses categorized as having a normal brain or having isolated ventriculomegaly, the odds ratio of normal development ranged from 3.5 to 9.0 whenever the parietooccipital, cingulate, or superior temporal sulcus was seen. Visualization of the sulci in fetal brains depends on the imaging modality used and the gestational age at imaging. Information regarding sulcal visualization may aid in counseling patients carrying fetuses with ventriculomegaly.
    American Journal of Roentgenology 06/2011; 196(6):1457-67. DOI:10.2214/AJR.10.5422 · 2.74 Impact Factor
  • T Y Poussaint
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    ABSTRACT: SUMMARY: Advances in brain imaging technologies allow a more comprehensive means to investigate pediatric neurological disorders and diseases. This article highlights 5 unique projects in pediatric neuroradiology which may improve our understanding of these disorders.
    American Journal of Neuroradiology 06/2011; 32(6):993-7. DOI:10.3174/ajnr.A2663 · 3.68 Impact Factor
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    ABSTRACT: The purpose of this study was to correlate 2-dimensional magnetic resonance (MR) measurements of lateral ventricular width and 3-dimensional measurements of lateral ventricular and supratentorial parenchymal volumes to postnatal outcomes in fetuses with ventriculomegaly. A total of 307 fetuses (mean gestational age, 26.0 weeks; range, 15.7-39.4 weeks) had MR volumetry after referral for ventriculomegaly. Fetuses were grouped into those with (n = 114) and without (n = 193) other central nervous system (CNS) anomalies. Pregnancy and postnatal neurodevelopmental outcomes up to 3 years of age were obtained. A subgroup analysis was performed excluding fetuses with other CNS anomalies. Logistic regression analysis was performed to assess which measurement was most predictive of outcomes. There were 50 terminations, 2 stillbirths, and 255 live births. Seventy-five cases were lost to follow-up. Among 180 live-born neonates with follow-up, 140 had abnormal and 40 had normal outcomes. Atrial diameter (P < .0001), frontal horn diameter (P < .0001), and ventricular volume (P = .04) were predictive of live birth, with 92% specificity at 60% sensitivity. Among fetuses without other CNS anomalies, 180 of 193 pregnancies (93%) resulted in live deliveries, with atrial diameter (P < .0001), frontal horn diameter (P = .003), and ventricular volume (P = .008) associated with live birth and atrial diameter having the highest specificity (>99% at 60% sensitivity). Parenchymal volume was not associated with normal or abnormal outcomes (either live birth versus death or normal versus abnormal neurodevelopmental outcome). Among live-born neonates, no age-adjusted threshold for any of the measurements reliably distinguished between normal and abnormal neurodevelopmental outcomes. Ventricular volume and diameter, but not parenchymal volume, correlate with live birth in fetuses with ventriculomegaly. However, once live born, neither 2- nor 3-dimensional measurements can distinguish a fetus that will have a normal outcome.
    Journal of ultrasound in medicine: official journal of the American Institute of Ultrasound in Medicine 05/2011; 30(5):595-603. · 1.53 Impact Factor
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    ABSTRACT: This phase II study was designed to assess the safety and efficacy of gefitinib given with and following radiation therapy in children newly diagnosed with a poor prognosis brainstem glioma. Eligible patients were those with a previously untreated nondisseminated diffuse intrinsic brainstem glioma. Histological confirmation was not required, provided patients had a characteristic clinical history and MRI findings. Treatment consisted of gefitinib, administered orally, 250 mg/m(2)/day, during standard external beam radiotherapy, continuing for up to 13 monthly courses in the absence of disease progression or unacceptable toxicity. Toxicities, particularly intratumoral hemorrhage, were monitored. Pharmacokinetics and investigational imaging studies were performed in consenting patients. Forty-three eligible patients were included in the study. Therapy was well tolerated; only 4 patients were withdrawn from the study for dose-limiting toxicity after receiving therapy for 6, 9, 17, and 24 weeks. The 12- and 24-month progression-free survival rates were 20.9 ±5.6 % and 9.3 ±4%, respectively. Overall survival rates were 56.4 ±7.6% and 19.6 ±5.9%, respectively, which appear nominally superior to other contemporaneous Pediatric Brain Tumor Consortium trials. Three patients remain progression-free survivors with ≥36 months follow-up. The observation that a subset of children with this generally fatal tumor experienced long-term progression-free survival, coupled with recent observations regarding the molecular features of brainstem gliomas, raises the possibility that prospective molecular characterization may allow enrichment of treatment responders and improvement in outcome results in future studies of biologically targeted agents.
    Neuro-Oncology 03/2011; 13(3):290-7. DOI:10.1093/neuonc/noq199 · 5.29 Impact Factor
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    ABSTRACT: We performed a phase II study to assess the efficacy and toxicity of tipifarnib, a farnesyltransferase inhibitor, administered with radiation therapy (RT) in children with newly diagnosed diffuse intrinsic pontine gliomas. Children 3-21 years old with pontine gliomas (BSGs) were treated with concurrent tipifarnib and RT, followed by adjuvant tipifarnib. Tipifarnib was taken orally twice daily (125 mg/m(2)/dose) during RT; after RT, it was taken at 200 mg/m(2) twice daily for 21 days, in 28-day cycles. Initial and follow-up neuroimaging was centrally reviewed. Forty eligible patients (median age, 5.5 years; range, 3.3-16.5 years) had a median progression-free survival of 6.8 months (range, 0.2-18.6 months) and median overall survival of 8.3 months (range, 0.2-18.6 months). Kaplan-Meier estimates (± standard error) of 1-year progression-free and overall survival were 12.9% ±4.9% and 34.3% ±7.4%, respectively. A single patient remained on tipifarnib without progression at the completion of the study, two years after initiation of treatment. Seven patients were without disease progression for at least six months, three of whom remained controlled for more than a year. The most frequent toxicity was grade 3 lymphopenia. We documented a single instance of "pseudoprogression" by neuroimaging review. We found no discordance among 3 approaches to defining disease progression: as interpreted by treating institutions (based on clinical status and/or imaging) and by central review (using bi-dimensional tumor "area" versus volumetric measurements). For children with diffuse BSGs, tipifarnib administered with irradiation offered no clinical advantage over historical controls. Biopsies and molecular analyses of pediatric BSGs are vital for identification of new agents and for rational use of targeted agents.
    Neuro-Oncology 03/2011; 13(3):298-306. DOI:10.1093/neuonc/noq202 · 5.29 Impact Factor
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    ABSTRACT: The purpose of this study was to assess (18)F-FDG uptake in children with a newly diagnosed diffuse intrinsic brain stem glioma (BSG) and to investigate associations with progression-free survival (PFS), overall survival (OS), and MRI indices. Two Pediatric Brain Tumor Consortium (PBTC) therapeutic trials in children with newly diagnosed BSG were designed to test radiation therapy combined with molecularly targeted agents (PBTC-007: phase I/II study of gefitinib; PBTC-014: phase I/II study of tipifarnib). Baseline brain (18)F-FDG PET scans were obtained in 40 children in these trials. Images were evaluated by consensus between 2 PET experts for intensity and uniformity of tracer uptake. Associations of (18)F-FDG uptake intensity and uniformity with both PFS and OS, as well as associations with tumor MRI indices at baseline (tumor volume on fluid-attenuated inversion recovery, baseline intratumoral enhancement, diffusion and perfusion values), were evaluated. In most of the children, BSG (18)F-FDG uptake was less than gray-matter uptake. Survival was poor, irrespective of intensity of (18)F-FDG uptake, with no association between intensity of (18)F-FDG uptake and PFS or OS. However, hyperintense (18)F-FDG uptake in the tumor, compared with gray matter, suggested poorer survival rates. Patients with (18)F-FDG uptake in 50% or more of the tumor had shorter PFS and OS than did patients with (18)F-FDG uptake in less than 50% of the tumor. There was some evidence that tumors with higher (18)F-FDG uptake were more likely to show enhancement, and when the diffusion ratio was lower, the uniformity of (18)F-FDG uptake appeared higher. Children with BSG for which (18)F-FDG uptake involves at least half the tumor appear to have poorer survival than children with uptake in less than 50% of the tumor. A larger independent study is needed to verify this hypothesis. Intense tracer uptake in the tumors, compared with gray matter, suggests decreased survival. Higher (18)F-FDG uptake within the tumor was associated with enhancement on MR images. Increased tumor cellularity as reflected by restricted MRI diffusion may be associated with increased (18)F-FDG uniformity throughout the tumor.
    Journal of Nuclear Medicine 02/2011; 52(2):188-95. DOI:10.2967/jnumed.110.081463 · 5.56 Impact Factor
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    ABSTRACT: We report MRI findings from 2 pediatric clinical trials of diffuse intrinsic brainstem glioma (BSG) incorporating concurrent radiation therapy (RT) with molecularly targeted agents (gefitinib and tipifarnib). We determined associations of MRI variables with progression-free survival and overall survival and investigated effects of treatment on these variables. MRI (including diffusion and perfusion) was done before treatment, every 8 weeks (first year), every 12 weeks (thereafter), and at the end of treatment or disease progression. Reduced tumor volume (P < .0001) and tumor diffusion values (P <.0001) were apparent on the first post-RT/drug studies. Decreases in tumor volume correlated with pre-RT volume (P < .0001) and pre-RT diffusion values (P < .0001); larger decreases were noted for tumors with higher volumes and diffusion values. Patients with larger pre-RT tumors had longer progression-free survival (P < .0001). Patients with ≥ 25% decrease in tumor volume and diffusion values after RT had longer progression-free survival (P = .028) and overall survival (P = .0009). Enhancement at baseline and over time was significantly associated with shorter survival. Tumor diffusion values with baseline enhancement were significantly lower than those without (P = .0002). RT of BSG is associated with decreased tumor volume and intralesional diffusion values; patients with ≥ 25% decrease in values post-RT had relatively longer survival intervals, apparently providing an early imaging-based surrogate for relative outcomes. Patients with larger tumors and greater decreases in tumor volume and diffusion values had longer survival intervals. Tumor enhancement was associated with shorter survival, lower tumor diffusion values (increased cellularity), and a smaller drop in diffusion values after RT (P = .006). These associations justify continued investigation in other large clinical trials of brainstem glioma patients.
    Neuro-Oncology 02/2011; 13(4):417-27. DOI:10.1093/neuonc/noq200 · 5.29 Impact Factor
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    ABSTRACT: The objective of this study was to assess the outcomes of the prenatal diagnosis of septal leaflet abnormalities in fetuses referred for prenatal imaging with a finding of ventriculomegaly. This study is a retrospective review of fetuses with a diagnostic code of septal leaflet abnormalities from a larger prospective study. Four hundred twenty-five pregnant women with 433 fetuses referred for ventriculomegaly were imaged with ultrasound and MRI between July 1, 2003, and May 15, 2009. Four to six radiologists independently reviewed sonographic and MR images and recorded lateral ventricular diameters at the atrium and frontal horns, ventricular configuration, and the presence of ventriculomegaly and of other CNS abnormalities. Final prenatal ultrasound, MRI, and overall diagnoses were decided by consensus. Fetuses with a diagnostic code of septal leaflet abnormalities were identified, and birth outcome, autopsy findings, postnatal imaging, and postnatal follow-up examinations were obtained. The analysis of covariance, controlling for gestational age, was used to compare ventricular dimensions between fetuses with septal leaflet abnormalities and fetuses with isolated ventriculomegaly. Interrater agreement for the detection of septal leaflet abnormalities was assessed with kappa statistics. Interrater agreement and intrarater agreement for frontal horn measurements were assessed by variance components analysis. Twenty-three fetuses had septal leaflet abnormalities and 229 had isolated ventriculomegaly. Atrial and frontal horn diameters, adjusted for gestational age, were 77% and 98% larger, respectively, in fetuses with septal leaflet abnormalities than in fetuses with isolated ventriculomegaly (p < 0.0001). Before the consensus conference, agreement among ultrasound readers was moderate (κ = 0.54) and among MR readers, good (κ = 0.69). Additional CNS findings were seen on MRI in 12 of 23 fetuses (52%). Eleven pregnancies with septal leaflet abnormalities underwent termination and 12 progressed to livebirth; of the 12 livebirths, three neonates died. Neurodevelopmental follow-up was abnormal in all surviving children. A septal leaflet abnormality in the setting of ventriculomegaly is most frequently associated with other CNS abnormalities and is associated with postnatal developmental delay.
    American Journal of Roentgenology 01/2011; 196(1):W83-92. DOI:10.2214/AJR.10.4434 · 2.74 Impact Factor

Publication Stats

2k Citations
350.88 Total Impact Points


  • 2008–2014
    • Harvard University
      Cambridge, Massachusetts, United States
  • 1993–2014
    • Boston Children's Hospital
      • Department of Radiology
      Boston, Massachusetts, United States
  • 2012
    • Duke University Medical Center
      Durham, North Carolina, 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
  • 2008–2011
    • University of California, San Francisco
      San Francisco, California, United States
  • 1996–2010
    • Harvard Medical School
      • Department of Radiology
      Boston, Massachusetts, United States
  • 2002–2008
    • The Children's Hospital of Philadelphia
      • Department of Radiology
      Filadelfia, Pennsylvania, United States
  • 2007
    • Childrens Hospital of Pittsburgh
      Pittsburgh, Pennsylvania, United States
  • 2003
    • Dana-Farber Cancer Institute
      • Department of Pediatric Oncology
      Boston, MA, United States
  • 2000
    • Duke University
      Durham, North Carolina, United States
  • 1998–1999
    • Cincinnati Children's Hospital Medical Center
      Cincinnati, Ohio, United States