Quantification of microscopic diffusion anisotropy disentangles effects of orientation dispersion from microstructure: Applications in healthy volunteers and in brain tumors

The anisotropy of water diffusion in brain tissue is affected by both disease and development. This change can be detected using diffusion MRI and is often quantified by the fractional anisotropy (FA) derived from diffusion tensor imaging (DTI). Although FA is sensitive to anisotropic cell structures, such as axons, it is also sensitive to their orientation dispersion. This is a major limitation to the use of FA as a biomarker for "tissue integrity", especially in regions of complex microarchitecture. In this work, we seek to circumvent this limitation by disentangling the effects of microscopic diffusion anisotropy from the orientation dispersion. The microscopic fractional anisotropy (mu FA) and the order parameter (OP) were calculated from the contrast between signal prepared with directional and isotropic diffusion encoding, where the latter was achieved by magic angle spinning of the q-vector (qMAS). These parameters were quantified in healthy volunteers and in two patients; one patient with meningioma and one with glioblastoma. Finally, we used simulations to elucidate the relation between FA and mu FA in various micro-architectures. Generally, mu FA was high in the white matter and low in the gray matter. In the white matter, the largest differences between mu FA and FA were found in crossing white matter and in interfaces between large white matter tracts, where mu FA was high while FA was low. Both tumor types exhibited a low FA, in contrast to the mu FA which was high in the meningioma and low in the glioblastoma, indicating that the meningioma contained disordered anisotropic structures, while the glioblastoma did not. This interpretation was confirmed by histological examination. We conclude that FA from DTI reflects both the amount of diffusion anisotropy and orientation dispersion. We suggest that the mu FA and OP may complement FA by independently quantifying the microscopic anisotropy and the level of orientation coherence. (C) 2014 The Authors. Published by Elsevier Inc.