Quantifying human gray matter microstructure using NEXI and 300 mT/m gradients

Biophysical models of diffusion tailored to quantify gray matter microstructure are gathering increasing interest. The two-compartment Neurite EXchange Imaging (NEXI) model has been proposed recently to account for neurites, extra-cellular space and exchange across the cell membrane. NEXI parameter estimation requires multi-shell multi-diffusion time data and has so far only been implemented experimentally on animal data collected on a preclinical MRI set-up. In this work, the first ever translation of NEXI to the human cortex in vivo was achieved using a 3T Connectom MRI system with 300 mT/m gradients, that enables the acquisition of a broad range of b-values (0 - 7.5 ms/μ m^2) with a window of diffusion times (20 - 49 ms) suitable for the expected characteristic exchange times (10 - 50 ms). Microstructure estimates of four model variants: NEXI, NEXI_dot (its extension with the addition of a dot compartment) and their respective versions that correct for the Rician noise floor (NEXI_RM and NEXI_dot,RM) that particularly impacts high b-value signal, were compared. The reliability of estimates in each model variant was evaluated in synthetic and human in vivo data. In the latter, the intra-subject (scan-rescan) vs between-subjects variability of microstructure estimates were compared in the cortex. The better performance of NEXI_RM highlights the importance of correcting for Rician bias in the NEXI model to obtain accurate estimates of microstructure parameters in the human cortex, and the sensitivity of the NEXI framework to individual differences in cortical microstructure. This groundbreaking application of NEXI in humans marks a pivotal moment, unlocking new avenues for studying neurodevelopment, ageing, and various neurodegenerative disorders.