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The ability to characterize heterogeneous and anisotropic water diffusion processes within macroscopic MRI voxels non-invasively and in vivo is a desideratum in biology, neuroscience, and medicine. While an MRI voxel may contain approximately a microliter of tissue, our goal is to examine intravoxel diffusion processes on the order of picoliters. Here we propose a new theoretical framework and efficient experimental design to describe and measure such intravoxel structural heterogeneity and anisotropy. We assume that a constrained normal tensor-variate distribution (CNTVD) describes the variability of positive definite diffusion tensors within a voxel which extends its applicability to a wide range of b-values while preserving the richness of diffusion tensor distribution (DTD) paradigm unlike existing models. We introduce a new Monte Carlo (MC) scheme to synthesize realistic 6D DTD numerical phantoms and invert the MR signal. We show that the signal inversion is well-posed and estimate the CNTVD parameters parsimoniously by exploiting the different symmetries of the mean and covariance tensors of CNTVD. The robustness of the estimation pipeline is assessed by adding noise to calculated MR signals and compared with the ground truth. A family of invariant parameters and glyphs which characterize microscopic shape, size and orientation heterogeneity within a voxel are also presented.

A new framework for MR diffusion tensor distribution