AbstractIn conventional diffusion tensor imaging (DTI), water diffusion distribution is described as a 2nd‐order three‐dimensional (3D) diffusivity tensor. It assumes that diffusion occurs in a free and unrestricted environment with a Gaussian distribution of diffusion displacement, and consequently that diffusion weighted (DW) signal decays with diffusion factor (b‐value) monoexponentially. In biological tissue, complex cellular microstructures make water diffusion a highly hindered or restricted process. Non‐monoexponential decays are experimentally observed in both white matter and gray matter. As a result, DTI quantitation is b‐value dependent and DTI fails to fully utilize the diffusion measurements that are inherent to tissue microstructure. Diffusion kurtosis imaging (DKI) characterizes restricted diffusion and can be readily implemented on most clinical scanners. It provides a higher‐order description of water diffusion process by a 2nd‐order 3D diffusivity tensor as in conventional DTI together with a 4th‐order 3D kurtosis tensor. Because kurtosis is a measure of the deviation of the diffusion displacement profile from a Gaussian distribution, DKI analyses quantify the degree of diffusion restriction or tissue complexity without any biophysical assumption. In this work, the theory of diffusion kurtosis and DKI including the directional kurtosis analysis is revisited. Several recent rodent DKI studies from our group are summarized, and DKI and DTI compared for their efficacy in detecting neural tissue alterations. They demonstrate that DKI offers a more comprehensive approach than DTI in describing the complex water diffusion process in vivo. By estimating both diffusivity and kurtosis, it may provide improved sensitivity and specificity in MR diffusion characterization of neural tissues. Copyright © 2010 John Wiley & Sons, Ltd.