Evidence for Altered White Matter Organisation After Mild Traumatic Brain Injury: A Scoping Review on the Use of Diffusion MRI and Blood-Based Biomarkers to Investigate Acute Pathology and Relationship to Persistent Post-Concussion Symptoms.

Mild traumatic brain injury (mTBI) is the most common form of traumatic brain injury. Post-concussive symptoms typically resolve after a few weeks although up to 20% of people experience these symptoms for >3 months, termed persistent-post concussive symptoms (PPCS). Subtle white matter (WM) microstructural damage is thought to underlie neurological and cognitive deficits experienced post-mTBI. Evidence suggests that diffusion magnetic resonance imaging (dMRI) and blood-based biomarkers could be used as surrogate markers of WM organisation. We conducted a scoping review according to PRISMA-ScR guidelines, aiming to collate evidence for the use of dMRI and/or blood-based biomarkers of WM organisation, in mTBI and PPCS, and document relationships between WM biomarkers and symptoms. We focused specifically on biomarkers of axonal or myelin integrity post-mTBI. Biomarkers excluded from this review therefore included: astroglial, perivascular, endothelial and inflammatory markers. A literature search performed across four databases: EMBASE, Scopus, Google Scholar and ProQuest identified 100 records: 68 analysed dMRI, 28 assessed blood-based biomarkers and 4 used both. Blood biomarker studies commonly assessed axonal cytoskeleton proteins (i.e. tau); dMRI studies assessed measures of WM organisation (i.e. fractional anisotropy). Significant biomarker alterations were frequently associated with heightened symptom burden and prolonged recovery time post-injury. These data suggests that dMRI and blood-based biomarkers may be useful proxies of WM organisation, though few studies assessed these complementary measures in parallel and the relationship between modalities remains unclear. Further studies are warranted to assess the benefit of a combined biomarker approach in evaluating alterations to WM organisation after mTBI.