Water exchange as measured by diffusion MRI with free gradient waveforms: A potential biomarker of dendritic spine morphology

Motivation: Time-dependent diffusion MRI reveals fast exchange in grey matter, but it remains unclear whether permeative or non-permeative exchange explains these findings. Goal(s): We set to investigate the effect of non-permeative exchange induced by dendritic spines on the time-dependence of the diffusion-weighted signal and the exchange estimates obtained from the signal. Approach: Monte Carlo simulations were performed in synthetic dendrites with varying spine densities and signals were generated using free gradient waveforms. The intracellular signals were analysed using a restriction-exchange framework from previous work. Results: Dendritic spines give the same signal time-dependence as permeative exchange. Estimated exchange rates increase with spine density. Impact: Dendritic spines may explain the exchange rates observed with diffusion MRI in grey matter. Furthermore, exchange measurements provide a potential biomarker of dendritic spine morphology, which is important because spine density is implicated in, for example, learning and psychiatric disorders.