Diffusion tensor imaging quantifies the asymmetry (fractional anisotropy; FA) and amount of water diffusion (mean diffusivity/apparent diffusion coefficient; MD/ADC) and has been used to assess white matter damage following traumatic brain injury (TBI). In healthy brains, diffusion is constrained by the organization of axons, resulting in high FA and low MD/ADC. Following a TBI, diffusion may be altered; however the exact nature of these changes has yet to be determined. A meta-analysis was therefore conducted to determine the location and extent of changes in DTI following adult TBI. The data from 44 studies that compared the FA and/or MD/ADC data from TBI and Control participants in different regions of interest (ROIs) were analyzed. The impact of injury severity, post-injury interval (acute: ≤ 1 week, subacute: 1 week-3 months, chronic: > 3 months), scanner details and acquisition parameters were investigated in subgroup analyses, with the findings indicating that mild TBI should be examined separately to that of moderate to severe injuries. Lower FA values were found in 88% of brain regions following mild TBI and 92% following moderate-severe TBI, compared to Controls. MD/ADC was higher in 95% and 100% of brain regions following mild and moderate-severe TBI, respectively. Moderate to severe TBI resulted in larger changes in FA and MD/ADC than mild TBI. Overall, changes to FA and MD/ADC were widespread, reflecting more symmetric and a higher amount of diffusion, indicative of white matter damage.

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Diffusion tensor imaging is often used to assess white matter (WM) changes following traumatic brain injury (TBI), but is limited in voxels that contain multiple fibre tracts.Fixel-based analysis (FBA) addresses this limitation by using a novel method of analysing high angular resolution diffusion-weighted imaging (HARDI) data. FBA examines three aspects of each fibre tract within a voxel: tissue micro-structure (fibre density [FD]), tissue macro-structure (fibre-bundle cross section [FC]) and a combined measure of both (FD and fibre-bundle cross section [FDC]). This study used FBA to identify the location and extent of micro-and macro-structural changes in WM following TBI. A large TBI sample (N mild = 133, N moderate-severe = 29) and control group (healthy and orthopaedic; N = 107) underwent magnetic resonance imaging with HARDI and completed reaction time tasks approximately 7 months after their injury (range:98-338 days). The TBI group showed micro-structural differences (lower FD) in the corpus callosum and forceps minor, compared to controls. Subgroup analyses revealed that the mild TBI group did not differ from controls on any fixel metric, but the moderate to severe TBI group had significantly lower FD, FC and FDC in multiple WM tracts, including the corpus callosum, cerebral peduncle, internal and external capsule. The moderate to severe TBI group also had significantly slower reaction times than controls, but the mild TBI group did not. Reaction time was not related to fixel findings.Thus, the WM damage caused by moderate to severe TBI manifested as fewer axons and a reduction in the cross-sectional area of key WM tracts. K E Y W O R D Sadults, diffusion-weighted imaging, fixel-based analysis, neuroimaging, traumatic brain injury

Objective: White matter (WM) changes detected using diffusion tensor imaging (DTI) are reportedly related to cognitive outcomes following traumatic brain injury (TBI), but much existing research is underpowered or has only examined general outcomes, rather than cognitive functioning. Method: A large sample of adults who had sustained mild, moderate or severe TBIs seven months prior (N = 165) and a control group (N = 106) underwent DTI and cognitive testing. Fractional anisotropy and mean diffusivity were calculated for 5 regions (corpus callosum: genu, body, splenium; fornix; superior longitudinal fasciculus) that recent meta-analyses identified as being affected by TBI and related to cognition following TBI. Memory, attention and executive functioning, which are often affected by TBI, were assessed. Results: Overall, mild TBI did not show significant WM or cognitive changes, relative to controls, but moderate to severe TBI was associated with large WM alterations (all regions) and poorer cognitive performance. No significant correlations were found between DTI findings and cognition in the moderate to severe group. Conclusions: The findings have shown that moderate to severe TBI leads to considerable WM and cognitive changes. Early and ongoing examination of mild TBI is needed to determine whether WM and cognitive changes are initially present and, if so, when they resolve.