Microscopic diffusion anisotropy in the human brain: reproducibility, normal values, and comparison with the fractional anisotropy

Abstract

Human neuroimaging of tissue microstructure, such as axonal density and integrity, is key in clinical and neuroscience research. Most studies rely on diffusion tensor imaging (DTI) and the measures derived from it, most prominently fractional anisotropy (FA). However, FA also depends on fiber orientation distribution, a more macroscopic tissue property. Recently introduced measures of so-called microscopic diffusion anisotropy, diffusion anisotropy on a cellular or microscopic level, overcome this limitation because they are independent of the orientation distributions of axons and fibers. In this study, we evaluate the feasibility of two measures of microscopic diffusion anisotropy I(MA) and MA indices, for human neuroscience and clinical research. Both indices reflect the eccentricity of the cells but while I(MA) also depends on the cell size, MA is independent of the cell size and, like FA, scaled between 0 and 1. In whole-brain measurements of a group of 19 healthy volunteers, we measured average values and variability, evaluated their reproducibility, both within and between sessions, and compared MA to FA values in selected regions-of-interest (ROIs). The within- and between-session comparison did not show substantial differences but the reproducibility was much better for the MA than I(MA) (coefficient of variation between sessions 10.5% vs. 28.9%). The reproducibility was less for MA than FA overall, but comparable in the defined ROIs and the average group sizes required for between-group comparisons was similar (about 60 participants for a relative difference of 5%). Group-averaged values of MA index were generally larger and showed less variation across white-matter brain ROIs than FA (mean ± standard deviation of seven ROIs 0.83 ± 0.10 vs. 0.58 ± 0.13). Even in some gray-matter ROIs, MA values comparable to those of white matter ROIs were observed. Furthermore, the within-group variation of the values in white matter ROIs was lower for the MA compared to the FA (mean standard deviation over volunteers 0.038 vs. 0.049) which could be due to significant variability in the distribution of fiber orientation contributing to FA. These results indicate that MA (i) should be preferred to I(MA), (ii) has a reproducibility and group-size requirements comparable to those of FA; (iii) is less sensitive to the fiber orientation distribution than FA; and (iv) could be more sensitive to differences or changes of the tissue microstructure than FA. R1.1.

Keywords: DWV; Double-wave-vector diffusion weighting; FA; I(MA) index; MA; Microscopic diffusion anisotropy; White matter integrity; d-PFG.