Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.05.04.074856v1?rss=1 Authors: Benjamini, D., Hutchinson, E. B., Komlosh, M. E., Comrie, C. J., Schwerin, S. C., Zhang, G., Pierpaoli, C., Basser, P. J. Abstract: We describe a practical two-dimensional (2D) diffusion MRI framework to deliver specificity and improve sensitivity to axonal injury in the spinal cord. This approach provides intravoxel distributions of correlations of water mobilities in orthogonal directions, revealing sub-voxel diffusion components. Here we use it to investigate water diffusivities along axial and radial orientations within spinal cord specimens with confirmed, tract-specific axonal injury. First, we show using transmission electron microscopy (TEM) and immunohistochemistry that tract-specific axonal beading occurs following Wallerian degeneration in the cortico-spinal tract (CST) as direct sequelae to closed head injury (CHI). We demonstrate that although some voxel-averaged diffusion tensor imaging (DTI) metrics are sensitive to this axonal injury, they are non-specific, i.e., they do not reveal an underlying biophysical mechanism of injury. Then we employed 2D diffusion correlation imaging (DCI) to improve discrimination of different water microenvironments by measuring and mapping the joint water mobility distributions perpendicular and parallel to the spinal cord axis. We determined six distinct diffusion spectral components that differ according to their microscopic anisotropy and mobility. We further identified a distinct microenvironment that is specifically associated with the injury-induced axonal degeneration, with reduced and increased diffusivities parallel and perpendicular, respectively, hallmarks of axonal beading. An injury-specific MR image of the CHI spinal cord was then generated, and a radiological-pathological correlation with histological silver staining % area was performed. The resulting large and significant correlation (r = 0.79, p<0.0001) indicates the high specificity with which DCI detects injury-induced tissue alterations. We predict that the ability to selectively image microstructural changes following axonal injury in the spinal cord can be useful in clinical and research applications, by enabling specific detection and increased sensitivity to injury-induced microstructural alterations. These results also encourage us to translate DCI to higher spatial dimensions to enable assessment of traumatic axonal injury, and possibly other diseases and disorders in the brain. Copy rights belong to original authors. Visit the link for more info