Detection of microscopic diffusion anisotropy in human cortical gray matter in vivo with double diffusion encoding

Purpose: To detect microscopic diffusion anisotropy in human cortical gray matter in vivo with double diffusion encoding experiments. Methods: Double diffusion encoding experiments were performed on a 3 T whole-body MR system using echo-planar imaging. Angular double diffusion encoding measurements were acquired with 8 x 8 and 12 x 12 planar direction combinations and were analyzed in three regions of interest containing white matter, mostly cortical gray matter, and one having significant contributions from cerebrospinal fluid. Inversion with variable recovery times served to estimate and eliminate white matter partial volume effects. To investigate the influence of magnetic field inhomogeneities, experiments with gradient offsets and cross-term compensated diffusion weightings were performed. The MA index, a rotationally invariant measure of the microscopic diffusion anisotropy, was determined from measurements with 96 direction combinations. Results: The angular signal modulation in the gray matter region of interest has two components, one being consistent, inter alia, with cross terms with field inhomogeneities while the other represents a signal difference between parallel/antiparallel and orthogonal direction combinations, ie, the fingerprint of microscopic diffusion anisotropy. Based on the amplitudes and their dependency on the inversion time, white matter partial volumes can be excluded as the sole source for this modulation, providing strong evidence for the detection of microscopic diffusion anisotropy in cortical gray matter. MA maps of healthy volunteers show considerably lower values in cortical gray matter compared with white matter. Conclusion: Microscopic diffusion anisotropy can be measured in human cortical brain matter, which could help to characterize the microstructure of healthy and pathological tissue.