RBIO-07. Longitudinal assessment of radiation effects on white matter and neuronal activity in mice using 9.4 T MRI

Abstract Cranial radiotherapy is a life-saving treatment for people with primary or metastatic brain tumors. Unfortunately, it can also damage healthy brain tissue, often resulting in memory problems, slowed thinking, and other cognitive impairments that reduce quality of life. It has been shown to be mediated by white matter injury and synaptic dysfunction. A better understanding of these effects is needed to develop early imaging biomarkers and guide therapeutic strategies. In this preliminary study, we used longitudinal high-field 9.4 Tesla magnetic resonance imaging (MRI) to evaluate structural and functional brain changes that follow cranial irradiation in a mouse model. Six adult male C57BL/6 mice underwent baseline resting-state functional MRI (rsfMRI) and diffusion MRI (dMRI) one week before irradiation. Mice were then randomized into gamma-irradiated (20 Gray, n=3) or sham control (n=3) groups, followed by imaging at 1-month post-treatment. rsfMRI data (400 volumes) were acquired using a T2*-weighted, single-shot, gradient-echo echo-planar imaging sequence. Multi-shell dMRI data were acquired using a four-shot diffusion tensor imaging echo planar imaging (DTI-EPI) sequence (b = 800 and 2000 s/mm², 45 directions). Fractional anisotropy (FA) maps were generated to assess white matter integrity, and amplitude of low-frequency fluctuations (ALFF) was computed to quantify spontaneous brain activity. Compared to baseline, irradiated mice showed reduced FA in the corpus callosum, corticospinal tract, hippocampus, amygdala, and sensorimotor cortices, indicating widespread white matter disruption. ALFF was suppressed throughout the brain, reflecting decreased spontaneous neural activity. Sham-irradiated mice showed no noticeable changes. Additional scans at 6 and 18 months are planned to assess long-term trajectories of white matter and functional alterations. Histological analyses will complement imaging findings. These preliminary results demonstrate that 9.4 T MRI can sensitively detect early structural and functional changes following cranial irradiation. Ongoing longitudinal assessments will enhance our understanding of the durability and progression of radiation-induced brain injury.