Functional Imaging as a Biomaker for Neurotoxicity After Brain Irradiation

University Of Michigan At Ann Arbor, Ann Arbor MI

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Abstract

Radiation therapy (RT) is a major treatment modality for primary and metastatic brain neoplasms. Radiation-induced neurotoxicity is a limiting factor for brain RT. Clinical symptoms can occur acutely and subacutely after brain irradiation, but most devastated neurotoxicity manifests of late neurological sequelae, including neurocognitve dysfunction, and white matter degeneration and necrosis. Given the delayed nature of neurotoxicity, it would be important to develop biomarkers, including derived from in vivo functional and molecular imaging, for early assessment of individual sensitivity to radiation and prediction of late neurotoxicity. Radiation-induced cerebral tissue injury is a complex and dynamic process, and involves in multiple tissue compartments. Cerebral vascular injury, which has been long considered to be crucial important for the development of cerebral tissue toxicity, occurs early after irradiation. White matter degeneration, including demyelination and necrosis, is progressive over time after brain irradiation. In this study, using in vivo dynamic-contrast-enhanced magnetic resonance imaging and diffusion tensor imaging, we aim to detect early alternations in cerebral vasculature and white matter tissue in the patients who have low-grade glioma or benign tumors and undergo fractionated partial brain RT. Also, we aim to determine the bio-dosimetric effects, including total dose and dose-volume, on the alterations of cerebral vasculature and white matter. We aim to assess neurocognitve function in the patients from pre RT up to 2 years post RT, and to determine correlative relationships of early cerebral vascular injury and early delayed white matter degradation with late neurocognitive dysfunction. We hypothesize that early monitoring of changes in cerebral microvessels and tissue degeneration in response to fractionated RT would allow us to predict late neurocognitive deficits.