Diffusion <scp>MRI</scp> Microstructure Markers of Changes in the Human Brain Across the Lifespan Using Constrained Spherical Deconvolution and Fixel‐Based Techniques

Understanding how the brain develops, matures, ages, and declines is one of the fundamental questions facing neuroscience. This study uses 3-tissue constrained spherical deconvolution (3T-CSD) and more recently developed fixel-based derivatives to examine the relationship between brain diffusion microstructure and chronological age. These metrics are able to quantify signal fraction measurements at the voxel-wise level from six different tissue microenvironments found in the brain: extracellular free water, intracellular isotropic, intracellular anisotropic, fiber density and cross-section, the g-ratio, and aggregate conduction velocity. This study analyzes the Nathanial Kline Institute's Rockland cohort, a large-scale community sample of brain MRI data across the lifespan (409 subjects, ages 5-85 years). 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 and g-ratio, a negative relationship between age and intracellular isotropic signal fraction, fiber density and cross-section, and conduction velocity, 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 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 and fixel-based metrics are 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 analysis of microstructure changes in the presence of pathology or with behavior. Finally, the detailed analysis of lateralized ROI results can inform diffusion microstructure studies examining cortical and subcortical regions.