Multimodal diffusion MRI biomarkers of white matter alterations and clinical impairment in mTBI

Mild traumatic brain injury (mTBI), which includes concussion, often results in subtle white matter abnormalities that are not detectable with conventional neuroimaging. This study investigated microstructural brain changes in individuals with subacute mTBI using advanced diffusion MRI (dMRI) techniques, including multi-shell diffusion tensor imaging (DTI), free-water corrected DTI (fw-DTI), diffusion kurtosis imaging (DKI), and neurite orientation dispersion and density imaging (NODDI).

Twenty individuals with mTBI and 24 healthy controls (HCs) underwent dMRI and cognitive assessment with the Montreal Cognitive Assessment (MoCA); mTBI participants were also evaluated using the Extended Glasgow Outcome Scale (GOS-E). Test-retest reliability was assessed in a subset of HCs.

Compared to controls, the mTBI group showed significantly lower MoCA scores and exhibited widespread reductions in fractional anisotropy (FA), mean kurtosis (MK), and kurtosis fractional anisotropy (KFA), along with increased free-water fraction and orientation dispersion indices. NODDI metrics revealed more localized reductions in neurite density (NDI), particularly in the genu of the corpus callosum, where lower NDI was associated with poorer cognitive performance. Elevated extracellular water content and greater neurite orientation dispersion were linked to worse functional and cognitive outcomes, even in areas without notable NDI loss, suggesting that early microenvironmental changes may influence recovery. In 11 HCs, test-retest analysis showed that NODDI and fw-DTI metrics had superior reliability compared to conventional DTI.

These findings support the utility of advanced, multi-parametric dMRI techniques for the sensitive detection of white matter alterations related to mTBI, highlighting their potential as reliable imaging biomarkers for clinical outcomes in mTBI.