White Matter Tract Integrity: An Indicator of Axonal Pathology after Mild Traumatic Brain Injury

We seek to elucidate the underlying pathophysiology of injury sustained after mild traumatic brain injury (mTBI) using multi-shell diffusion magnetic resonance imaging, deriving compartment-specific white matter tract integrity (WMTI) metrics. WMTI allows a more biophysical interpretation of white matter (WM) changes by describing microstructural characteristics in both intra- and extra-axonal environments. Thirty-two patients with mTBI within 30 days of injury and 21 age- and sex-matched controls were imaged on a 3 Tesla magnetic resonance scanner. Multi-shell diffusion acquisition was performed with five b-values (250-2500 sec/mm²) along 6-60 diffusion encoding directions. Tract-based spatial statistics (TBSS) was used with family-wise error (FWE) correction for multiple comparisons. TBSS results demonstrated focally lower intra-axonal diffusivity (D_axon) in mTBI patients in the splenium of the corpus callosum (sCC; p < 0.05, FWE-corrected). The area under the curve value for D_axon was 0.76 with a low sensitivity of 46.9% but 100% specificity. These results indicate that D_axon may be a useful imaging biomarker highly specific for mTBI-related WM injury. The observed decrease in D_axon suggests restriction of the diffusion along the axons occurring shortly after injury.