White Matter Injury Susceptibility via Fiber Strain Evaluation Using Whole-Brain Tractography

Abstract

Microscale brain injury studies suggest axonal elongation as a potential mechanism for diffuse axonal injury (DAI). Recent studies have begun to incorporate white matter (WM) structural anisotropy in injury analysis, with initial evidence suggesting improved injury prediction performance. In this study, we further develop a tractography-based approach to analyze fiber strains along the entire lengths of fibers from voxel- or anatomically constrained whole-brain tractography. This technique potentially extends previous element- or voxel-based methods that instead utilize WM fiber orientations averaged from typically coarse elements or voxels. Perhaps more importantly, incorporating tractography-based axonal structural information enables assessment of the overall injury risks to functionally important neural pathways and the anatomical regions they connect, which is not possible with previous methods. A DAI susceptibility index was also established to quantify voxel-wise WM local structural integrity and tract-wise damage of individual neural pathways. This “graded” injury susceptibility potentially extends the commonly employed treatment of injury as a simple binary condition. As an illustration, we evaluate the DAI susceptibilities of WM voxels and transcallosal fiber tracts in three idealized head impacts. Findings suggest the potential importance of the tractography-based approach for injury prediction. These efforts may enable future studies to correlate WM mechanical responses with neuroimaging, cognitive alteration, and concussion, and to reveal the relative vulnerabilities of neural pathways and identify the most vulnerable ones in real-world head impacts.