Diffusion MRI microstructure markers of changes in the human brain across the lifespan

Understanding how the brain develops, matures, ages, and declines is one of the fundamental questions facing neuroscience. Recent advances in diffusion MRI microstructure analysis have allowed for detailed descriptions of neuronal change in humans. However, it is essential that findings from these studies are appropriately contextualized to general age-related changes in the brain. This study uses 3-tissue constrained spherical deconvolution (3T-CSD) to examine the relationship between brain diffusion microstructure and chronological age. 3T-CSD is able to quantify signal fraction measurements at the voxel-wise level from three different tissue microenvironments found in the brain: extracellular free water, intracellular isotropic, and intracellular anisotropic. This study applies 3T-CSD analysis to the Nathanial Kline Institutes Rockland cohort, a large-scale community sample of brain MRI data across the lifespan. Microstructural measurements were taken in a number of structures throughout the white matter, subcortical gray matter, and lobar cortical regions while additionally evaluating lateral differences in microstructural measurements. The general trajectory of signal fraction measurements was a positive relationship with age and extracellular signal fraction, a negative relationship between age and intracellular isotropic signal fraction, and an inverted U-shaped trajectory for the intracellular anisotropic signal fraction. In individual sub-areas these trends tended to still be present, with some notable exceptions. However there were large differences in 3T-CSD microstructure measurements between individual structures, including significant lateral differences between hemispheres for each of the subcortical gray matter structures and for each of the cortical regions. These results demonstrate that 3T-CSD is able to describe age-related change across the brain and lifespan. By using a healthy population cohort this study can be used as a point of comparison for 3T-CSD analysis of microstructure changes in the presence of pathology. Finally, the detailed analysis of lateralized ROI results can inform diffusion microstructure studies examining cortical and subcortical regions.