Both noise-floor and tissue compartment difference in diffusivity contribute to FA dependence on b-value in diffusion MRI.

Noninvasive diffusion magnetic resonance imaging (dMRI) has been widely employed in both clinical and research settings to investigate brain tissue microstructure. Despite the evidence that dMRI-derived fractional anisotropy (FA) correlates with white matter properties, the metric is not specific. Recent studies have reported that FA is dependent on the b-value, and its origin has primarily been attributed to either the influence of microstructure or the noise-floor effect. A systematic investigation into the inter-relationship of these two effects is however still lacking. This study aims to quantify contributions of the reported differences in intra- and extra-neurite diffusivity to the observed changes in FA, in addition to the noise in measurements. We used in-vivo and post-mortem human brain imaging, as well as numerical simulations and histological validation, for this purpose. Our investigations reveal that the percentage difference of FA between b-values (pdFA) has significant positive associations with neurite density index (NDI), which is derived from in-vivo neurite orientation dispersion and density imaging (NODDI), or Bielschowsky's silver impregnation (BIEL) staining sections of fixed post-mortem human brain samples. Furthermore, such an association is found to be varied with Signal-to-Noise Ratio (SNR) level, indicating a nonlinear interaction effect between tissue microstructure and noise. Finally, a multicompartment model simulation revealed that these findings can be driven by differing diffusivities of intra- and extra-neurite compartments in tissue, with the noise-floor further amplifying the effect. In conclusion, both the differences in intra- and extra-neurite diffusivity and noise-floor effects significantly contribute to the FA difference associated with the b-value.