Diffusion kurtosis imaging, MAP-MRI and NODDI selectively track gray matter myelin density in the primate cerebral cortex.

Diffusion magnetic resonance imaging (dMRI) has been widely used to model the trajectory of myelinated fiber bundles in the white matter. Increasingly, it is also used to evaluate the microstructure of the cerebral cortex gray matter. For example, in diffusion tensor imaging (DTI) of the cortex, fractional anisotropy (FA) correlates strongly with the anisotropy of cellular anatomy, while radial diffusivity (RD) tracks the anisotropy of myelinated fibers. However, no DTI parameter shows specificity to gray matter myelin density. Here, we show that three higher-order diffusion parameters-the mean diffusion kurtosis (MK), the Neurite Density Index (NDI) from neurite orientation dispersion and density imaging (NODDI), and the Non-Gaussian (NG) parameter from mean apparent propagator (MAP)-MRI-each track the laminar and regional myelin density of the primate cerebral cortex in fine detail. We carried out ultra-high-resolution, multi-shelled dMRI in ex-vivo marmoset monkey brains. We compared the spatial mapping of the MK, NDI, and ND diffusion parameters to the cortical myelin distribution of these brains, with the latter obtained in two ways: First, using histological sections finely co-registered to the MRI, and second using magnetization transfer ratio MRI scans (MTR), an established non-diffusion method for imaging myelin density. We found that, in contrast to DTI parameters, each of these higher-order diffusion measures captured the spatial variation of myelin density in the cortex. The demonstration that diffusion parameters exhibit both sensitivity and specificity for gray matter myelin density will allow dMRI to more effectively track human disease, in which myelinated and non-myelinated tissue compartments are affected differentially.