MEDU-25. THE EFFECTS OF CRANIAL RADIOTHERAPY-INDUCED VASCULAR INJURY ON BRAIN TISSUE STRUCTURE AND COGNITIVE FUNCTION IN CHILDREN WITH MEDULLOBLASTOMA

Abstract

INTRODUCTION: Cranial radiation therapy (CRT) remains an integral role in the treatment of pediatric medulloblastomas, despite its association with significant long-term effects including CRT-induced vascular injury and cognitive impairments. Manifestation of CRT-induced vascular injury including size-varying hemosiderin deposits in the form of cerebral microbleeds (CMBs), and changes in white matter integrity and cortical thickness can be detected with MRI as early as 8 months following treatment. Although vascular injuries have been previously related to cognitive decline in stroke and dementia, the underlying mechanisms driving these and CRT-associated cognitive deficits remain unclear. As current treatment strategies are improving the prognosis for children with medulloblastoma, identifying a link between CRT-induced injury and cognition is an important consideration for this group in determining the impact of treatment on development. METHOD(S): Ten pediatric medulloblastoma patients (age:10-24 years) treated with uniform, whole-supratentorial brain CRT 0.75-15 years prior, and 5 nonirradiated control patients (age:14-23 years) with posterior fossa tumors were scanned on a 7-Tesla system. High resolution T1-weighted anatomical and susceptibility-weighted vascular imaging were acquired along with multi-directional, multi-shell diffusion tensor imaging. A computerized cognitive battery (Cogstate) was employed to assess multiple domains of cognitive function. The spatial distribution of CRT-induced vascular injury was related to white-matter and cortical integrity, cognitive performance, and connectivity within cerebral networks. RESULT(S): Patients in the control group did not develop any CMBs. The majority of CMBs in irradiated children were located in the frontal lobe. The level of injury was associated with deficits initially in working-and then in visual-memory as a function of time since CRT and poorer connectivity. CONCLUSION(S): This work suggests that certain brain regions may be more sensitive to CRT and CMB formation, although the down stream effects on brain structure and function may be more global, and is currently being validated in a larger cohort.