This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Aggressive radiation therapy (RT) has contributed positively to long term disease-free survival from childhood cancer. Despite its therapeutic benefit, RT has been associated with a spectrum of acute, early-delayed, and late-delayed toxicities to the central nervous system. As a consequence, pediatric patients treated with brain radiation often develop neurological and neurocognitive deficits manifesting as behavioral or learning disabilities. It is unclear whether the neurocognitive deficits are due mainly to damage to the subcortical structures or if cortical areas are also involved. We plan using non-invasive methods based on magnetic resonance (MR - magnetic resonance spectroscopy, volumetric MRI, and diffusion tensor imaging) to determine a) how brain function, as measured by MR techniques, can be correlated with total radiation dose delivered to the brain and b) whether changes in measured parameters (metabolite concentration, lobar tissue volumes, and water diffusion characteristics) can be used as surrogate markers to predict the neuropsychological outcome from RT. We plan to perform a longitudinal MR study with a 30 months follow-up to assess changes in brain metabolism (using proton MR spectroscopy), loss of brain tissue (using volumetric MRI), and damage to tissue microstructure (using diffusion tensor imaging). Concurrent neuropsychological assessments will be performed to evaluate the neuropsychological status. Linear mixed effects (LME) regression analyses will be applied to examine the effect of radiation doses on regional brain metabolite levels, changes in lobar brain volumes and diffusion properties of water in the brain tissue and to evaluate the relationship between neuropsychological test scores and parameters measured by the proposed MR methods.
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