Diffusion Tensor Orientation as a Microstructural MRI Marker of Mossy Fiber Sprouting after TBI in Rats

Diffusion tensor imaging (DTI) metrics are highly sensitive to microstructural brain alterations and are potentially useful imaging biomarkers for underlying neuropathologic changes after experimental and human traumatic brain injury (TBI). As potential imaging biomarkers require direct correlation with neuropathologic alterations for validation and interpretation, this study systematically examined neuropathologic abnormalities underlying alterations in DTI metrics in the hippocampus and cortex following controlled cortical impact (CCI) in rats. Ex vivo DTI metrics were directly compared with a comprehensive histologic battery for neurodegeneration, microgliosis, astrocytosis, and mossy fiber sprouting by Timm histochemistry at carefully matched locations immediately, 48 hours, and 4 weeks after injury. DTI abnormalities corresponded to spatially overlapping but temporally distinct neuropathologic alterations representing an aggregate measure of dynamic tissue damage and reorganization. Prominent DTI alterations of were observed for both the immediate and acute intervals after injury and associated with neurodegeneration and inflammation. In the chronic period, diffusion tensor orientation in the hilus of the dentate gyrus became prominently abnormal and was identified as a reliable structural biomarker for mossy fiber sprouting after CCI in rats, suggesting potential application as a biomarker to follow secondary progression in experimental and human TBI.