Estimation of free water-corrected microscopic fractional anisotropy

Water diffusion anisotropy MRI is sensitive to microstructural changes in the brain that are hallmarks of various neurological conditions. However, conventional metrics like fractional anisotropy are confounded by neuron fiber orientation dispersion, and the relatively low resolution of diffusion-weighted MRI gives rise to significant free water partial volume effects in many brain regions that are adjacent to cerebrospinal fluid. Microscopic fractional anisotropy is a recent metric that can report water diffusion anisotropy independent of neuron fiber orientation dispersion but is still susceptible to free water contamination. In this paper, we present a free water elimination (FWE) technique to estimate microscopic fractional anisotropy and other related diffusion indices by implementing a signal representation in which the MRI signal within a voxel is assumed to come from two distinct sources: a tissue compartment and a free water compartment. A two-part algorithm is proposed to rapidly fit a set of diffusion-weighted MRI volumes containing both linear- and spherical-tensor encoding acquisitions to the representation. Simulations and in vivo acquisitions with four healthy volunteers indicated that the FWE method may be a feasible technique for measuring microscopic fractional anisotropy and other indices with greater specificity to neural tissue characteristics than conventional methods.