Diffusion MRI of white matter alterations in chronic traumatic brain injury: a systematic review and meta-analysis

Traumatic brain injury (TBI) in the chronic stage (≥ 3 months post-injury) is associated with long-term symptoms and secondary conditions, which have been linked to persistent white matter alterations. Although these changes can be detected using diffusion magnetic resonance imaging (dMRI), it remains unclear whether the findings are consistently reported in the chronic phase of injury. This review aims to summarise and quantify differences in diffusion metrics between individuals with chronic non-sports/non-combat-related TBI and controls.

This review followed PRISMA guidelines. Database searches were conducted in MEDLINE, Embase, PsycINFO, and Scopus to identify studies examining dMRI metric changes in chronic TBI. Fractional anisotropy (FA) and mean diffusivity (MD) values were extracted to compute the standardised mean difference for individual fibre pathways. Meta-regression was performed to investigate the effect of clinical-demographic and imaging variables on FA effect sizes.

Twenty-seven studies were included in the meta-analysis. Decreases in FA and increases in MD were found across multiple white matter pathways in chronic TBI, with more pronounced effects in moderate-to-severe TBI compared with mild injury. The overall largest and most consistent effects were observed in the corpus callosum. Changes in FA were influenced by age, sex, and magnetic field strength.

This meta-analysis provides quantitative evidence of widespread white matter alterations in the chronic stage of TBI. dMRI measures (FA and MD) are sensitive biomarkers of white matter disruptions and exhibit changes associated with injury severity. Future research should carefully control for confounding factors to enhance data comparability across studies.