Intracellular water preexchange lifetime in neurons and astrocytes

Purpose: To determine the intracellular water preexchange lifetime, τ_i, the “average residence time” of water, in the intracellular milieu of neurons and astrocytes. The preexchange lifetime is important for modeling a variety of MR data sets, including relaxation, diffusion-sensitive, and dynamic contrast–enhanced data sets. Methods: Herein, τ_i in neurons and astrocytes is determined in a microbead-adherent, cultured cell system. In concert with thin-slice selection, rapid flow of extracellular media suppresses extracellular signal, allowing determination of the transcytolemmal-exchange-dominated, intracellular T₁. With this knowledge, and that of the intracellular T₁ in the absence of exchange, τ_i can be derived. Results: Under normal culture conditions, τ_i for neurons is 0.75 ± 0.05 s versus 0.57 ± 0.03 s for astrocytes. Both neuronal and astrocytic τ_is decrease within 30 min after the onset of oxygen-glucose deprivation, with the astrocytic τ_i showing a substantially greater decrease than the neuronal τ_i. Conclusions: Given an approximate intra- to extracellular volume ratio of 4:1 in the brain, these data imply that, under normal physiological conditions, an MR experimental characteristic time of less than 0.012 s is required for a nonexchanging, two-compartment (intra- and extracellular) model to be valid for MR studies. This characteristic time shortens significantly (i.e., 0.004 s) under injury conditions. Magn Reson Med 79:1616–1627, 2018.