Longitudinal Changes of Regional Myelin Water Fraction during First Year after Moderate-to-Severe Diffuse Traumatic Brain Injury

Traumatic brain injury (TBI) is a worldwide health issue with a highly heterogeneous disease characterization, including widespread white matter damage in the brain. Most non-invasive white matter imaging methods currently available, including diffusion tensor imaging (DTI), cannot reliably measure the degree of neurodegeneration due to various confounds, making it challenging to select an endpoint measure for neuroprotective clinical trials. The present study investigates longitudinal white matter changes, measured by a novel imaging metric, apparent myelin water fraction (aMWF), and its relationship with neuropsychological measures during the first year after TBI. Data from 15 adult patients with moderate-to-severe TBI and 30 matched healthy controls were analyzed in the study. Whole-brain aMWF from direct visualization of short transverse relaxation time component (ViSTa) myelin water imaging (MWI) was evaluated in patients with TBI at 3, 6 and 12 months post-injury. Longitudinal neuropsychological assessment was done in the domains of executive function (EF), verbal learning (VL), and processing speed (PS). Based on recent meta-analysis studies, we selected three regions known to have altered white matter DTI metrics in TBI—i.e., splenium of corpus callosum, fornix, and superior longitudinal fasciculus (SLF). Then aMWF values were extracted from these white matter regions at each time point. Among the three regions, we found that only the SLF showed a significant longitudinal variation of aMWF in TBI patients (2.89%, 2.35%, and 2.53% at 3, 6, and 12 months post-injury respectively; Friedman test P=5.748 X 10-6). A post hoc Wilcoxon signed-rank test revealed a significant decline in aMWF from 3 to 6 months post-injury (P=6.1 X 10-5), but not from 6 to 12 months. Our results indicate that 1) there are significant regional variations in the temporal dynamics of white matter degeneration after moderate-to-severe TBI and 2) the rate of degeneration is steeper during the first half of the first year post-injury. We did not find significant associations between regional aMWF and neuropsychological performance at any time points. Potential explanations of the observed null findings were discussed