Evaluating backscattering polarized light imaging microstructural mapping capabilities through neural tissue and analogous phantom imaging.

Significance: Knowledge of fiber microstructure and orientation in the brain is critical for many applications. Polarized light imaging (PLI) has been shown to have potential for better understanding neural fiber microstructure and directionality due to the anisotropy in myelin sheaths surrounding nerve fibers of the brain. Continuing to advance backscattering based PLI systems could provide a valuable avenue for in vivo neural imaging. Aim: To assess the potential of backscattering PLI systems, the ability to resolve crossing fibers, and the sensitivity to fiber inclination and curvature are considered across different imaging wavelengths. Approach: Investigation of these areas of relative uncertainty is undergone through imaging potential phantoms alongside analogous regions of interest in fixed ferret brain samples with a five-wavelength backscattering Mueller matrix polarimeter. Results: Promising phantoms are discovered for which the retardance, diattenuation and depolarization mappings are derived from the Mueller matrix and studied to assess the sensitivity of this polarimeter configuration to fiber orientations and tissue structures. Conclusions: Rich avenues for future study include further classifying this polarimeter's sensitivity to fiber inclination and fiber direction to accurately produce microstructural maps of neural tissue.

Direct and specific assessment of axonal injury and spinal cord microenvironments using diffusion correlation imaging.

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 and immunohistochemistry that tract-specific axonal beading occurs following Wallerian degeneration in the cortico-spinal tract as direct sequelae to closed head injury. 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 employ 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 determine six distinct diffusion spectral components that differ according to their microscopic anisotropy and mobility. We show that at the injury site a highly anisotropic diffusion component completely disappears and instead becomes more isotropic. Based on these findings, an injury-specific MR image of the spinal cord was generated, and a radiological-pathological correlation with histological silver staining % area was performed. The resulting strong and significant correlation (r=0.70,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.