Microstructural variation of hippocampal substructures across childhood and adolescence quantified with high-gradient diffusion MRI

The hippocampus plays a crucial role in cognition, yet its microstructural development during childhood and adolescence remains poorly understood. Here, we investigate age-related differences in hippocampal microstructure using diffusion MRI with ultra-strong gradients (300 mT/m) in a cohort of 88 participants aged 8-19 years. Surface-based hippocampal modelling was combined with established microstructural approaches, and a more advanced biophysical model (Soma and Neurite Density Imaging: SANDI) suited for studying cortical microstructure. Hippocampal volume, gyrification, and thickness remained stable across this developmental window, however we observed significant differences across age related to MR-derived neurite and soma parameters. Diffusion-derived changes across age were found to be correlated with adult microstructure maps related to myelin and iron content, synaptic density, and hippocampal interneurons derived from MRI, PET and histology. These findings highlight age-related differences of MR-derived neurite and soma parameters in the human hippocampus during late childhood and adolescence, offering insights into structural maturation during this critical period.