High-Resolution Diffusion Kurtosis Imaging of Hippocampus Subfields Across the Healthy Lifespan

Diffusion kurtosis imaging (DKI) is typically applied to white matter, but it may provide insight into age-related microstructural changes in gray matter tissue like the hippocampus. The goal was to assess neurodevelopment and aging changes in hippocampal subfields using 1 mm isotropic DKI across the healthy lifespan (5-90 years). Multi-shell, 1 mm³, diffusion imaging focused on the hippocampus, was acquired at 3 T in 363 healthy participants (5-90 years, 206 females). Automatic hippocampal subfield segmentation and unfolded maps were obtained using HippUnfold. Nonlinear lifespan trajectories, sex differences, and age-corrected residual correlations with cognitive scores and other demographics were assessed for volume, mean diffusivity (MD), fractional anisotropy (FA), mean kurtosis (MK), and kurtosis FA (KFA). Whole hippocampus yielded distinct age trajectories for the volume, diffusion tensor, and diffusion kurtosis parameters: volume-quadratic fit (maximum ~35-42 years); MD-negative Gamma variate (minimum ~35 years); FA-positive Gamma variate fit (maximum ~25 years); MK-exponential fit (steep increase during development that plateaus after ~25 years); and KFA-negative linear across the lifespan. There were sex differences in age trajectories for volume and MK that were not evident with DTI metrics. Males exhibited larger volume and larger MK than females. The subfields showed similar age trajectories as whole hippocampus albeit with regional variations in the values. The subiculum showed dramatically higher MK after age 20, with males exhibiting higher values than females. MK residuals in whole hippocampus correlated positively with body mass index residuals in three age groups (young, middle age, and older). In conclusion, high-resolution 1 mm isotropic DKI of hippocampus revealed linear and nonlinear patterns with development and aging over a wide age range of 5-90 years that differ from DTI. These results suggest that DKI can provide novel insight into age-related microstructural changes at the sub-hippocampal level.