AbstractThe diffusion kurtosis observed with diffusion magnetic resonance imaging (dMRI) may vary with direction. This directional variation is summarized in the scalar kurtosis fractional anisotropy (KFA). Recent studies suggest that kurtosis anisotropy offers microstructural contrast not contained in other commonly used dMRI markers. We compare KFA to other dMRI contrasts in fixed rat brain and in human brain. We then investigate the observed contrast differences using data obtained in a physical phantom and simulations based on data from the phantom, rat spinal cord, and human brain. Lastly, we assess a strategy for rapid estimation of a computationally modest KFA proxy by evaluating its correlation to true KFA for varying number of sampling directions and signal-to-noise ratio (SNR) levels. We also map this proxy’s b-value dependency. We find that KFA supplements the contrast of other dMRI metrics – particularly fractional anisotropy (FA) which vanishes in near orthogonal fiber arrangements where KFA does not. Simulations and phantom data support this interpretation. KFA therefore supplements FA and could be useful for evaluation of complex tissue arrangements. The KFA proxy is strongly correlated to true KFA when sampling is performed along at least nine directions and SNR is high.