Water signal attenuation in diffusion-weighted 1H NMR experiments during cerebral ischemia: influence of intracellular restrictions, extracellular tortuosity, and exchange.

The "concept of restricted intracellular water diffusion at permeable boundaries", which was recently used to model diffusion-weighted 1H NMR experiments on glioma cells, was applied to measurements on the rat brain in vivo. Combined with the "concept of extracellular tortuosity", various physiological states of the brain were simulated. Hereby, a variable intracellular volume fraction, intracellular exchange time, and extracellular tortuosity factor were considered for young, adult, and ischemic rat brains. The model simulated the cytotoxic shift of extracellular water, changes in membrane permeability and tissue morphology, and was able to explain the diffusion time dependence as well as the non-monoexponentiality of the diffusion attenuation curves. Preliminary diffusion time dependent experiments on the healthy rat brain (1H NMR imaging) agreed well with the theoretical concept. Hereby, the intracellular water signal was separated from extracellular signal contributions by large diffusion weighting. It showed the characteristic of restricted diffusion as well as a signal decay due to the exchange of intracellular water across the plasma membrane. A map of the mean intracellular exchange time for water in living animal brain was determined, and the upper limit in rat brain was evaluated to 15 ms. The presented methods can be applied to correlate local differences in a map of exchange times with tissue morphology and to detect pathological deviations of the exchange time, e.g., during ischemia.