Standard MRI methods are often inadequate for identifying mild traumatic brain injury (TBI). Advances in diffusion tensor imaging now provide potential biomarkers of TBI among white matter fascicles (tracts). However, it is still unclear which tracts are most pertinent to TBI diagnosis. This study ranked fiber tracts on their ability to discriminate patients with and without TBI. We acquired diffusion tensor imaging data from military veterans admitted to a polytrauma clinic (Overall n = 109; Age: M = 47.2, SD = 11.3; Male: 88%; TBI: 67%). TBI diagnosis was based on self-report and neurological examination. Fiber tractography analysis produced 20 fiber tracts per patient. Each tract yielded four clinically relevant measures (fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity). We applied receiver operating characteristic (ROC) analyses to identify the most diagnostic tract for each measure. The analyses produced an optimal cutpoint for each tract. We then used kappa coefficients to rate the agreement of each cutpoint with the neurologist's diagnosis. The tract with the highest kappa was most diagnostic. As a check on the ROC results, we performed a stepwise logistic regression on each measure using all 20 tracts as predictors. We also bootstrapped the ROC analyses to compute the 95% confidence intervals for sensitivity, specificity, and the highest kappa coefficients. The ROC analyses identified two fiber tracts as most diagnostic of TBI: the left cingulum (LCG) and the left inferior fronto-occipital fasciculus (LIF). Like ROC, logistic regression identified LCG as most predictive for the FA measure but identified the right anterior thalamic tract (RAT) for the MD, RD, and AD measures. These findings are potentially relevant to the development of TBI biomarkers. Our methods also demonstrate how ROC analysis may be used to identify clinically relevant variables in the TBI population.
Keywords: AD, axial diffusivity; Axon degeneration; CC, corpus callosum; Concussion; DAI, diffuse axonal injury; DTI, diffusion tensor imaging; FA, fractional anisotropy; GN, genu; Imaging; LAT, left anterior thalamic tract; LCG, left cingulum; LCH, left cingulum – hippocampus; LCS, left cortico-spinal tract; LIF, left inferior fronto-occipital fasciculus; LIL, left inferior longitudinal fasciculus; LSL, left superior longitudinal fasciculus; LST, left superior longitudinal fasciculus – temporal; LUN, left uncinate; MD, mean diffusivity; Neurodegeneration; PTSD, post-traumatic stress disorder; RAT, right anterior thalamic tract; RCG, right cingulum; RCH, right cingulum – Hippocampus; RCS, right cortico-spinal tract; RD, radial diffusivity; RIF, right inferior fronto-occipital fasciculus; RIL, right inferior longitudinal fasciculus; ROC, receiver operating characteristic; RSL, right superior longitudinal fasciculus; RST, right superior longitudinal fasciculus – temporal; RUN, right uncinate; SP, splenium; TBI, traumatic brain injury; Traumatic brain injury.