White matter alterations in crossing fibres following traumatic brain injury

Following traumatic brain injury, the ability of conventional diffusion-weighted MRI analysis techniques to resolve tract-specific white matter damage, particularly in crossing fibre regions, is limited. Using fixel-based analysis, this study aimed to identify white matter abnormalities in chronic traumatic brain injury patients and to resolve the effects of traumatic brain injury on distinct white matter tracts, especially in crossing fibre regions. In this cross-sectional study, diffusion-weighted MRI were acquired from adults with chronic moderate-to-severe traumatic brain injury (N = 29; median time since injury 1.9 years) and matched healthy controls (N = 17). Whole-brain and tract-of-interest analyses compared differences in white matter connectivity represented by fixel-wise metrics (fibre density, fibre bundle cross-section and combined fibre density and bundle cross-section) between groups. Regions where crossing white matter fibres demonstrates differential damage were identified. Significant reductions were found in all corrected fixel-wise metrics in traumatic brain injury patients, with distinct spatial distributions between metrics. Combined fibre density and bundle cross-section demonstrated the highest sensitivity out of the fixel-wise metrics and fractional anisotropy, detecting abnormalities in 73.6% of examined tracts. Fixel-based analysis resolved the distinct effects of traumatic brain injuries on crossing fibres with 14% of tract pairings containing crossing fibres (131/927) demonstrating robust evidence of differential damage (i.e. significant difference between groups in the fixel-wise metric of one tract in the pair but not the other tract within the same voxel). Fixel-based analysis identified variabilities in white matter abnormalities in traumatic brain injury patients. Crucially, fixel-based analysis was able to resolve injury-related tract-specific alterations even in crossing fibre regions, supporting further exploration of fixel-wise metrics as more specific biomarkers of white matter alterations in traumatic brain injury.