Radiation-induced alterations in mouse brain development characterized by magnetic resonance imaging

Purpose: The purpose of this study was to identify regions of altered development in the mouse brain after cranial irradiation using longitudinal MRI. Methods and Materials: Female C57Bl/6 mice received a whole-brain radiation dose of 7Gy at an infant-equivalent age of 2.5 weeks. MRI was performed before irradiation, and at three time points following irradiation. Deformation-based morphometry was used to quantify volume and growth rate changes following irradiation. Results: Widespread developmental deficits were observed in both white and gray matter regions following irradiation. Most of the affected brain regions suffered an initial volume deficit followed by growth at a normal rate, remaining smaller in irradiated brains compared to controls at all time points examined. The one exception was the olfactory bulb, which in addition to an early volume deficit, grew at a slower rate thereafter, resulting in a progressive volume deficit relative to controls. Immunohistochemical assessment revealed demyelination in white matter and loss of neural progenitor cells in the subgranular zone of the dentate gyrus and subventricular zone. Conclusions: MRI can detect regional differences in neuroanatomy and brain growth after whole-brain irradiation in the developing mouse. Developmental deficits in neuroanatomy persist, or even progress, and may serve as useful markers of late effects in mouse models. The high-throughput evaluation of brain development enabled by these methods may allow testing of strategies to mitigate late effects after paediatric cranial irradiation.This study was conducted with the support of the Ontario Institute for Cancer Research through funding provided by the Government of Ontario and with funding from the Canadian Institutes of Health Research