Diffusion MRI anisotropy in the cerebral cortex is determined by unmyelinated tissue features

In gray matter, the relative contributions of myelinated axons and other tissue features to diffusion MRI (dMRI) are poorly understood. Here the authors combine ex vivo high-resolution dMRI of marmoset brain with histological sections of the same brain, and their findings suggest that in cortex, dMRI does not match the spatial distribution of myelin in the gray matter. Diffusion magnetic resonance imaging (dMRI) is commonly used to assess the tissue and cellular substructure of the human brain. In the white matter, myelinated axons are the principal neural elements that shape dMRI through the restriction of water diffusion; however, in the gray matter the relative contributions of myelinated axons and other tissue features to dMRI are poorly understood. Here we investigate the determinants of diffusion in the cerebral cortex. Specifically, we ask whether myelinated axons significantly shape dMRI fractional anisotropy (dMRI-FA), a measure commonly used to characterize tissue properties in humans. We compared ultra-high resolution ex vivo dMRI data from the brain of a marmoset monkey with both myelin- and Nissl-stained histological sections obtained from the same brain after scanning. We found that the dMRI-FA did not match the spatial distribution of myelin in the gray matter. Instead dMRI-FA was more closely related to the anisotropy of stained tissue features, most prominently those revealed by Nissl staining and to a lesser extent those revealed by myelin staining. Our results suggest that unmyelinated neurites such as large caliber apical dendrites are the primary features shaping dMRI measures in the cerebral cortex.

Automated summary

In this study, the authors combined ex vivo high-resolution diffusion magnetic resonance imaging (dMRI) of marmoset brain with histological sections of the same brain to investigate the contributions of myelinated axons and other tissue features to dMRI in the gray matter. They found that dMRI fractional anisotropy (dMRI-FA) did not match the spatial distribution of myelin in the gray matter, but was more closely related to the anisotropy of stained tissue features, particularly those revealed by Nissl staining.