Brain 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, children 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 white matter or if cortical areas are also involved. Are there markers that could be measured non-invasively that reflect the degree of brain injury? Could these markers predict early in the course of treatment if brain damage will occur? Could these markers be used to evaluate sensitivity of different brain regions to radiation? Can the temporal course of regional changes due to radiation be mapped in the brain, non-invasively? We intend to answer these questions using non-invasive methods based on magnetic resonance (MR): magnetic resonance spectroscopy, diffusion tensor imaging, and volumetric MRI. Methods using MR have been demonstrated to be promising tools for detection of radiation damage. However, their ability to explain neuropsychological deficits in children remains to be evaluated. We plan to perform a longitudinal MR study with a 30 months follow-up to assess changes in brain metabolism, damage to tissue microstructure, and loss of brain tissue. Concurrent neuropsychological assessments will further enhance our understanding of the relationship between neuropsychological status and parameters measured by the proposed MR methods. The broad objectives of our research are to determine a) how brain function and integrity, as measured by MR techniques, can be correlated with total radiation dose delivered to the brain and b) whether changes in measured parameters (metabolite concentrations, water diffusion characteristics, and lobar gray and white volumes) can be used as surrogate markers to predict the neuropsychological outcome from RT.
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