MRI-DTI contributes to evaluating diffuse neural injury following repetitive mild traumatic brain injury

Repetitive mild traumatic brain injury (rmTBI) is an important risk factor for neurodegeneration, with early blood-brain barrier (BBB) disruption playing a key role. Clinical outcome heterogeneity may stem from region-specific disparities in white matter integrity and metabolic homeostasis linked to BBB permeability. Using a controlled cortical impact mouse model, we observed marked BBB disruption (Evans blue leakage, downregulation of ZO-1/claudin-5), accompanied by microglial activation and a pro-inflammatory cytokine shift (elevated IL-6 and reduced IL-4/IL-10). Magnetic resonance imaging-diffusion tensor imaging (MRI-DTI) using tract-based spatial statistics (TBSS) and voxel-based analysis (VBA) analysis revealed diffuse white matter injury in regions like the olfactory bulb and hypothalamus, while ¹⁸F-FDG PET-CT detected hypometabolism in the thalamus and striatum. These findings position BBB disruption as an early event potentially driving diffuse neural injury, and the combination of TBSS and VBA for MRI-DTI analysis offers a robust quantitative framework for assessing acute rmTBI pathology.