High Resolution Diffusion Tensor Imaging of the Human Cortex Reveals Non-linear Trajectories over the Healthy Lifespan

The human cortex undergoes significant macrostructural and microstructural changes across the lifespan, which can be assessed using high-resolution diffusion tensor imaging (DTI). In healthy individuals, diffusion is typically greater perpendicular to the cortical surface, aligning with neuronal bodies and apical dendrites. This study examined DTI metrics in 190 healthy individuals (ages 5-74 years) to characterize normative cortical changes across neurodevelopment and aging. Whole-brain DTI data were acquired with 1.5 mm isotropic resolution and a b-value of 1000 s/mm² acquired in only 3:36 minutes at 3T. Cortical segmentation was performed exclusively on diffusion images to yield thickness, radiality, fractional anisotropy (FA), mean (MD), axial (AD), and radial diffusivity (RD) in total cortex as well as five lobes and were compared versus age. Cortical thickness decreased exponentially which differed from the diffusion metric cross-sectional age trajectories. FA, MD, AD, and RD exhibited u-shaped trajectories reaching minimum values in adulthood (~20-40 years). In contrast, radiality showed a cubic pattern, declining in childhood, stabilizing from 20-55 years, then decreasing again after 55, with the largest early-life changes in the temporal and occipital lobes and later-life declines in the frontal and parietal lobes. Steeper childhood DTI changes may reflect increased myelination of tangential fibers, as well as the growth of neuronal axons, somata, and dendrites, while elderly changes likely indicate reduced cell body density and radius. This study provides a baseline for future research into neurodevelopment and neurodegenerative diseases across the lifespan.