Spatiotemporal changes in blood-brain barrier permeability, cerebral blood flow, T₂ and diffusion following mild traumatic brain injury

The blood-brain barrier (BBB) can be impaired following traumatic brain injury (TBI), however the spatiotemporal dynamics of BBB leakage remain incompletely understood. In this study, we evaluated the spatiotemporal evolution of BBB permeability using dynamic contrast-enhanced MRI and measured the volume transfer coefficient (K^trans), a quantitative measure of contrast agent leakage across the blood and extravascular compartment. Measurements were made in a controlled cortical impact (CCI) model of mild TBI in rats from 1 h to 7 days following TBI. The results were compared with cerebral blood flow, T₂ and diffusion MRI from the same animal. Spatially, K^trans changes were localized to superficial cortical layers within a 1 mm thickness, which was dramatically different from the changes in cerebral blood flow, T₂ and diffusion, which were localized to not only the superficial layers but also to brain regions up to 2.2 mm from the cortical surface. Temporally, K^trans changes peaked at day 3, similar to CBF and ADC changes, but differed from T₂ and FA, whose changes peaked on day 2. The pattern of superficial cortical layer localization of K^trans was consistent with patterns revealed by Evans Blue extravasation. Collectively, these results suggest that BBB disruption, edema formation, blood flow disturbance and diffusion changes are related to different components of the mechanical impact, and may play different roles in determining injury progression and tissue fate processes following TBI.