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Grant Details

Grant Number: 5R01CA112182-06 Interpret this number
Primary Investigator: Ris, M
Organization: Baylor College Of Medicine
Project Title: Neurobehavioral Late-Effects in Pediatric Brain Tumors
Fiscal Year: 2010
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Abstract

DESCRIPTION (provided by applicant): Significant neurobehavioral sequelae of radiotherapy (RT) in children treated for brain tumors is well-documented and is of increasing concern as larger numbers of such children become long-term survivors. Research on long-term outcomes has promoted the development of RT techniques and protocols that attempt to reduce this morbidity. Further understanding of RT late-effects, though, requires improvements in how we characterized radiation delivered to the brain. Recent technical advances in radiation ontology that permit detailed examination of dose heterogeneity throughout the brain offer new possibilities for improving our models of outcome. One index that shows considerable promise is Integral Biologically effective Dose (IBED). IBED combines numerous RT parameters (dose, volume, fractionation, biological effect) into a Single index for the entire brain or for designated volumes/structures. In this proposal we describe a novel approach to studying outcome that improves upon existing research in three ways: (a) the use of IBED as a index of radiation insult, (b) an improved neurobehavioral measurement strategy that focuses on three crucial constructs (Attention, Processing Speed, and Working Memory), and (e) the use of sophisticated, multimodal imaging techniques (MR Volumetrics, Spectroscopy, and Diffusion Imaging) to measure late-effects on brain composition. This prospective study will be conducted at two sites (Cincinnati and Columbus) enrolling and following children for up to four yeas who have been treated for brain tumors. It will address neurobehavioral imaging changes for participants treated with RT compared to those treated without RT (Specific Aim 1), IBED as a predictor of neurobehavioral and imaging changes over time (Specific Aims 2 & 3), and the relationship between neurobehavioral and imaging changes (Specific Aim 4). The results of this study promise to improve our knowledge and prediction of radiation-related late-effects, which in turn will guide further improvements in RT techniques. It will also provide important information about the development of vulnerable neurobehavioral functions, how they might be protected/preserved, and where to focus early interventions to limit functional morbidity.

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Publications

Proton magnetic resonance spectroscopy: technique for the neuroradiologist.
Authors: Cecil KM
Source: Neuroimaging Clin N Am, 2013 Aug;23(3), p. 381-92.
EPub date: 2013 Jan 20.
PMID: 23928195
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Proton magnetic resonance spectroscopy in adults with childhood lead exposure.
Authors: Cecil KM, Dietrich KN, Altaye M, Egelhoff JC, Lindquist DM, Brubaker CJ, Lanphear BP
Source: Environ Health Perspect, 2011 Mar;119(3), p. 403-8.
EPub date: 2010 Oct 13.
PMID: 20947467
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The influence of age of lead exposure on adult gray matter volume.
Authors: Brubaker CJ, Dietrich KN, Lanphear BP, Cecil KM
Source: Neurotoxicology, 2010 Jun;31(3), p. 259-66.
EPub date: 2010 Mar 11.
PMID: 20226811
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Altered myelination and axonal integrity in adults with childhood lead exposure: a diffusion tensor imaging study.
Authors: Brubaker CJ, Schmithorst VJ, Haynes EN, Dietrich KN, Egelhoff JC, Lindquist DM, Lanphear BP, Cecil KM
Source: Neurotoxicology, 2009 Nov;30(6), p. 867-75.
EPub date: 2009 Jul 18.
PMID: 19619581
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Decreased brain volume in adults with childhood lead exposure.
Authors: Cecil KM, Brubaker CJ, Adler CM, Dietrich KN, Altaye M, Egelhoff JC, Wessel S, Elangovan I, Hornung R, Jarvis K, Lanphear BP
Source: PLoS Med, 2008 May 27;5(5), p. e112.
PMID: 18507499
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Lessons in pediatric neuropsycho-oncology: what we have learned since Johnny Gunther.
Authors: Ris MD
Source: J Pediatr Psychol, 2007 Oct;32(9), p. 1029-37.
EPub date: 2007 Apr 9.
PMID: 17426043
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Magnetic resonance spectroscopy and metabolic imaging in white matter diseases and pediatric disorders.
Authors: Cecil KM, Kos RS
Source: Top Magn Reson Imaging, 2006 Aug;17(4), p. 275-93.
PMID: 17415001
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The impact of early childhood lead exposure on brain organization: a functional magnetic resonance imaging study of language function.
Authors: Yuan W, Holland SK, Cecil KM, Dietrich KN, Wessel SD, Altaye M, Hornung RW, Ris MD, Egelhoff JC, Lanphear BP
Source: Pediatrics, 2006 Sep;118(3), p. 971-7.
PMID: 16950987
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