MR hydrophysiology reveals multiple exchange pathways in neural tissue

Motivation: Understand the sensitivity of diffusion MRI to microstructure and function of living neural tissue. Goal(s): Determine dominant exchange pathways and whether they are active or passive. Approach: Realtime MR hydrophysiology was used to study steady-state water exchange and diffusion in live ex vivo neural tissue. Results: Water exchange is not active per se but is linked to tonicity maintained by active transport. Tonicity modulates the apparent exchange rate between fast transmembrane and slow intracellular pathways. The transmembrane pathway has a high activation energy and does not require ions, suggesting it is not through channels or cotransporters but is likely through lipid bilayers. Impact: A multisite exchange mechanism involving passive transmembrane and geometric pathways can explain connections to activity. Most of the transmembrane water exchange occurs through lipid bilayers in gray matter. This knowledge should inform the development of novel quantitative MRI biomarkers.