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Although concussions can result in persistent neurological post-concussion symptoms, they are typically invisible on routine magnetic resonance imaging (MRI) scans. Our study aimed to investigate the use of ultra-high-field diffusion tensor imaging (UHF-DTI) in discerning severity-dependent microstructural changes in the mouse brain following a concussion. Twenty-three C57BL/6 mice were randomly allocated into three groups: the low concussive (LC, n = 9) injury group, the high concussive (HC, n = 6) injury group, and the sham control (SC, n = 7) group. Mice were perfused on day 2 post-injury, and the brains were scanned on a 16.4T MRI scanner with UHF-DTI and neurite orientation dispersion imaging (NODDI). Finite element analysis (FEA) was performed to determine the pattern and extent of the physical impact on the brain tissue. MRI findings were correlated with histopathological analysis in a subset of mice. In the LC group, increased fractional anisotropy (FA) and decreased orientation dispersion index (ODI) but limited neurite density index (NDI) changes were found in the gray matter, and minimal changes to white matter (WM) were observed. The HC group presented increased mean diffusivity (MD), decreased NDI, and decreased ODI in the WM and gray matter (GM); decreased FA was also found in a small area of the WM. WM changes were associated with WM degeneration and neuroinflammation. FEA showed varying region-dependent degrees of stress, in line with the different imaging findings. This study provides evidence that UHF-DTI combined with NODDI can detect concussions of variable intensities. This has significant implications for the diagnosis of concussion in humans. [ABSTRACT FROM AUTHOR]

Due to the unmet need for a means to study chronic traumatic encephalopathy (CTE) in vivo, there have been numerous efforts to develop an animal model of this progressive tauopathy. However, there is currently no consensus in the field on an injury model that consistently reproduces the neuropathological and behavioral features of CTE. We have implemented a repetitive Closed-Head Impact Model of Engineered Rotational Acceleration (CHIMERA) injury paradigm in human transgenic (hTau) mice. Animals were subjected to daily subconcussive or concussive injuries for 20 days and tested acutely, 3 months, and 12 months post-injury for deficits in social behavior, anxiety, spatial learning and memory, and depressive behavior. Animals also were assessed for chronic tau pathology, astrogliosis, and white matter degeneration. Repetitive concussive injury caused acute deficits in Morris water maze performance, including reduced swimming speed and increased distance to the platform during visible and hidden platform phases that persisted during the subacute and chronic time-points following injury. We found evidence of white matter disruption in animals injured with subconcussive and concussive injuries, with the most severe disruption occurring in the repetitive concussive injury group. Severity of white matter disruption in the corpus callosum was moderately correlated with swimming speed, while white matter disruption in the fimbria showed weak but significant correlation with worse performance during probe trial. There was no evidence of tau pathology or astrogliosis in sham or injured animals. In summary, we show that repetitive brain injury produces persistent behavioral abnormalities as late as 1 year post-injury that may be related to chronic white matter disruption, although the relationship with CTE remains to be determined. [ABSTRACT FROM AUTHOR]