Diffusion MRI Anisotropy in the Cerebral Cortex is Determined by Unmyelinated Tissue Features

Abstract

AbstractThe diffusion of water molecules through the brain is constrained by tissue and cellular substructure, which imposes an anisotropy that can be measured through diffusion magnetic resonance imaging (dMRI). In the white matter, myelinated axons strongly shape diffusion anisotropy; however, in gray matter the determinants of dMRI signals remain poorly understood. Here we investigated the histological tissue properties underlying dMRI anisotropy and diffusivity in the cerebral cortex of the marmoset monkey. We acquired whole brain ex vivo dMRI data designed for high signal-to-noise at ultra-high (150μm) resolution. We compared the MRI to myelin- and Nissl-stained histological sections obtained from the scanned brain. We found that dMRI anisotropy corresponds most strongly not with cortical myelin content, but rather with the microscale anisotropy of tissue features, most notably those unmyelinated features highlighted by Nissl staining. The results suggest that dMRI anisotropy in gray matter derives from the organization of unmyelinated neurites, which are known to be affected by neurodegenerative diseases.