We have developed a noninvasive technique for studying transmembrane ion gradients in various tissues. For nuclei such as 23Na and 39K, a multiple quantum NMR approach can select populations of ions which exhibit biexponential relaxation. This type of relaxation occurs for ions which associate with macromolecules. Our goal is to apply this technique clinically to study tissue pathology. First, we need to establish that this technique can be used to selectively monitor intracellular ions. Initially, double quantum filtered (DQF) 23Na and 39K NMR spectra were obtained from rat brain in vivo. Upon death, the DQF 23Na signal increased 3-fold, consistent with the well-known influx of sodium ions into the cell. This technique could distinguish sodium ions from at least two different compartments in the brain. Studies in the cat brain following death, established a temporal correlation between the increase in triple quantum filtered 23Na signal and the decrease in ATP levels (by 31P NMR). To test the hypothesis that the multiple quantum NMR approach can monitor intracellular sodium, two approaches were used. First in rat brain, the time course for the increase in DQF 23Na signal following death correlated with the time course for the decrease in extracellular sodium measured by ion-sensitive surface electrodes. The second approach utilized the perfused organs, liver and heart, which unlike the intact brain, can be successfully treated with shift reagents. Using shift reagents, DQF 23Na signals were separated into intracellular and extracellular components. In the liver, little signal was shifted, indicating that most of the DQF 23Na signal in the absence of shift reagent was due to intracellular sodium. Following ischemia, the time course for the increase in DQF 23Na signal (without reagent) correlated with the increase in intracellular sodium as measured by conventional 23Na NMR with shift reagent.
