Equilibrium water exchange between the intra- and extracellular spaces of mammalian brain

This report describes the measurement of water preexchange lifetimes and intra/extracellular content in intact, functioning mammalian brain. Intra- and extracellular water magnetic resonance (MR) signals from rat brain in vivo were quantitatively resolved in the longitudinal relaxation domain following administration of an MR relaxation agent into the extracellular space. The estimated intracellular water content fraction was 81% ± 8%, and the intra- to extracellular exchange rate constant was 1.81 ± 0.89 s ^-1 (mean ± SD, N = 9), corresponding to an intracellular water preexchange lifetime of ∼550 ms. These results provide a temporal framework for anticipating the water exchange regime (fast, intermediate, or slow) underlying a variety of compartment-sensitive measurements. The method also supplies a means by which to evaluate membrane water permeability and intra/extracellular water content serially in intact tissue. The data are obtained in an imaging mode that permits detection of regional variations in these parameters.