Water exchange rates measure active transport and homeostasis in neural tissue

Abstract

For its size, the brain is the most metabolically active organ in the body. Most of its energy demand is used to maintain stable homeostatic physiological conditions. Altered homeostasis and active states are hallmarks of many diseases and disorders. Yet there is currently no reliable method to assess homeostasis and absolute basal activity or activity-dependent changes noninvasively. We propose a novel, high temporal resolution low-field, high-gradient diffusion exchange NMR method capable of directly measuring cellular metabolic activity via the rate constant for water exchange across cell membranes. Using viable ex vivo neonatal mouse spinal cords, we measure a component of the water exchange rate which is active, i.e., coupled to metabolic activity. We show that this water exchange rate is sensitive primarily to tissue homeostasis and viability and provides distinct functional information in contrast to the Apparent Diffusion Coefficient (ADC), which is sensitive primarily to tissue microstructure but not activity.