High Resolution Ex Vivo Diffusion Tensor Distribution MRI of Neural Tissue

Neural tissue microstructure plays a key role in developmental, physiological and pathophysiological processes. In the continuing quest to characterize it at ever finer length scales, we use a novel diffusion tensor distribution (DTD) paradigm to probe microstructural features much smaller than the nominal MRI voxel size. We first assume the DTD is a normal tensor variate distribution constrained to lie on the manifold of positive definite matrices, characterized by a mean and covariance tensor. We then estimate the DTD using Monte Carlo signal inversion combined with parsimonious model selection framework that exploits a hierarchy of symmetries of mean and covariance tensors. High resolution multiple pulsed field gradient (mPFG) MRI measurements were performed on a homogeneous isotropic diffusion phantom (PDMS) for control, and excised visual cortex and spinal cord of macaque monkey to investigate the capabilities of DTD MRI in revealing neural tissue microstructural features using strong gradients not typically available in clinical MRI scanners. DTD-derived stains and glyphs, which disentangle size, shape, and orientation heterogeneities of microscopic diffusion tensors, are presented for all samples along with the distribution of the mean diffusivity (MD) within each voxel. We also present a new glyph to visualize the symmetric (kurtosis) and asymmetric parts of the fourth-order covariance tensor. An isotropic mean diffusion tensor and zero covariance tensor was found for the isotropic PDMS phantom, as expected, while the covariance tensor (both symmetric and asymmetric parts) for neural tissue was non-zero indicating that the kurtosis tensor may not be sufficient to fully describe the microstructure. Cortical layers were clearly delineated in the higher moments of the MD spectrum consistent with histology, and microscopic anisotropy was detected in both gray and white matter of neural tissue. DTD MRI captures crossing and splaying white matter fibers penetrating into the cortex, and skewed fiber diameter distributions in the white matter tracts within the cortex and spinal cord. DTD MRI was also shown to subsume diffusion tensor imaging (DTI) while providing additional microstructural information about tissue heterogeneity and microscopic anisotropy within each voxel.