Diffusion MRI: Pitfalls, literature review and future directions of research in mild traumatic brain injury.

Mild traumatic brain injury (mTBI) is a leading cause of disability in adults, many of whom report a distressing combination of physical, emotional and cognitive symptoms, collectively known as post-concussion syndrome, that persist after the injury. Significant developments in magnetic resonance diffusion imaging, involving voxel-based quantitative analysis through the measurement of fractional anisotropy or mean diffusivity, have enhanced our knowledge on the different stages of mTBI pathophysiology. Other diffusion imaging-derived techniques, including diffusion kurtosis imaging with multi-shell diffusion and high-order tractography models, have recently demonstrated their usefulness in mTBI. Our review starts by briefly outlining the physical basis of diffusion tensor imaging including the pitfalls for use in brain trauma, before discussing findings from diagnostic trials testing its usefulness in assessing brain structural changes in patients with mTBI. Use of different post-processing techniques for the diffusion imaging data, identified the corpus callosum as the most frequently injured structure in mTBI, particularly at sub-acute and chronic stages, and a crucial location for evaluating functional outcome. However, structural changes appear too subtle for identification using traditional diffusion biomarkers, thus disallowing expansion of these techniques into clinical practice. In this regard, more advanced diffusion techniques are promising in the assessment of this complex disease.