White matter abnormalities characterise the acute stage of sports-related mild Traumatic Brain Injury

Abstract

AbstractSports-related concussion, a form of mild traumatic brain injury (mTBI), is characterised by transient disturbances of brain function. There is increasing evidence that subtle abnormalities drive functional brain changes in white matter microstructure, and diffusion MRI has been instrumental in demonstrating these white matter abnormalities in vivo. However, the reported location and direction of the observed white matter changes in mTBI are variable, likely attributable to the inherent limitations of the white matter models used. This cross-sectional study applies an advanced and robust technique known as fixel-based analysis to investigate fibre tract-specific abnormalities in professional Australian Football League players with a recent mTBI. We used the fixel-based analysis framework to identify common abnormalities found in specific fibre tracts in participants with an acute mTBI (≤ 12 days after injury; n = 14). We then assessed whether similar changes exist in subacute mTBI (> 12 days and < 3 months after injury; n = 15). The control group was 29 neurologically healthy control participants. We assessed microstructural differences in fibre density and fibre bundle morphology and performed whole-brain fixel-based analysis to compare groups. Subsequent tract-of-interest analyses were performed within five selected white matter tracts to investigate the relationship between the observed tract-specific abnormalities and days since injury and the relationship between these tract-specific changes with cognitive abnormalities. Our whole-brain analyses revealed significant increases in fibre density and bundle cross-section in acute mTBI when compared to controls. Acute mTBI showed even more extensive differences when compared to subacute mTBI than to controls. The fibre structures affected in acute mTBI included the corpus callosum, left prefrontal and left parahippocampal white matter. The fibre density and cross-sectional increases were independent of time since injury in acute mTBI, and were not associated with cognitive deficits. Overall, this study demonstrates that acute mTBI is characterised by specific white matter abnormalities, which are compatible with tract-specific cytotoxic oedema. These potential oedematous changes were absent in our subacute mTBI participants, suggesting that they may normalise within 12 days after injury, although subtle abnormalities may persist in the subacute stage. Future longitudinal studies are needed to elucidate individualised recovery after brain injury.