High-dose single-fraction brain irradiation: MRI, cerebral blood flow, electrophysiological, and histological studies

Radiation-induced alterations in cerebrovascular and metabolic function form the basis for the radiosurgical treatment of selected intracranial vascular malformations and tumors in human patients. However, the underlying mechanisms, temporal progression, and modifying factors involved in the radiosurgical obliteration of these intracranial lesions as well as the risks of delayed radiation injury to surrounding normal brain remain poorly understood. In this report, the rabbit brain was used as an animal model to examine the effects of high-dose single-fraction X-irradiation on magnetic resonance imaging (MRI) appearance, neurophysiologic function, and histological integrity. At approximately 10 weeks following left-hemisphere irradiation with 60 Gy (225 kVp) X rays, MRI studies showed radiation-induced changes including blood-brain barrier (BBB) perturbations in the white matter regions and the hippocampus. Significant reductions in regional cerebral blood flow (rCBF) ratios were found in the hippocampus and certain regions of the cortex in irradiated animals. However, no changes in somatosensory evoked potentials (SEP) were observed. Histological studies demonstrated telangiectatic vessels, spreading edema in the white matter, and focal regions of necrosis and hemorrhage in the irradiated cortices and hippocampi. These results demonstrate that the irradiated rabbit brain may be used as an experimental model to correlate the spatiotemporal pattern of functional changes with radiologic and histological changes in delayed radiation injury.