Microstructural maturation of the adult mouse brain.

While lifespan studies have consistently shown changes in diffusion MRI (dMRI) metrics indicating gradual microstructural remodeling until middle age, the cellular sources remain unclear due to the lack of microstructural specificity of traditional dMRI measurements. To provide insight into the biophysical mechanisms of dMRI changes during aging, we employ advanced techniques with improved microstructural specificity to study healthy mouse brain maturation from 3-8 months of age. Agreeing with past studies, fractional anisotropy, diffusional kurtosis and myelin-specific MRI metrics increased with age. Our main finding is that kurtosis increases were driven by increases in its sub-component of "isotropic kurtosis" (sensitive to variance of compartmental mean diffusivities), while the remaining sub-component of "anisotropic kurtosis" (sensitive to microstructural anisotropy) remained stable. These observations were accompanied by increases in myelin content and oligodendrocyte density. Our findings suggest that diffusional kurtosis increases during adult mouse brain maturation are not driven by changes in anisotropic structures like axons, but by overall heterogeneity increases that are due, at least in part, to changing oligodendrocyte populations. This work gives further insight into microstructural changes occurring during brain maturation and new insight into the biological underpinnings of dMRI contrast.