23Na chemical-shift imaging

Abstract

The maintenance of a sodium gradient across the plasma membrane is of crucial importance to living systems. Short-term changes in the sodium gradient are essential to nerve impulse transmission and cell excitability, while long-term changes in the gradient occur as the cells’ high-energy phosphate metabolites become depleted and/ or cell death occurs. The study of sodium and sodium gradients in biological systems is thus critical for an understanding of their physiology. Over the past few years advances in 23Na NMR spectroscopy have made it an increasingly useful tool for the study of sodium in biological tissue. In particular, the development of paramagnetic shift reagents for cations has provided the means to distinguish intracellular and extracellular sodium pools and to track the breakdown of the sodium gradient as a function of ischemia or cell death (1-8). The success of spectroscopic studies using cationic shift reagents to differentiate intraand extracellular sodium pools and track changes in the sodium gradient on a global basis in vivo has led us to develop a chemical-shift-imaging technique for sodium so that spectroscopic information may be obtained on a regional basis. Although common for ‘H imaging studies, CSI experiments for 23Na have not been performed previously due to the difficulties created by the extremely short relaxation times and low concentrations of sodium in vivo. A recent preliminary report describes microimaging experiments using the shift reagent dysprosium tripolyphosphate (9). Using frequency-selective RF pulses to excite the well-resolved resonances of shifted and unshifted sodium, two images of the different sodium pools were sequentially produced. This technique depends upon the complete resolution of the sodium resonances, rarely obtainable with shift reagents other than the toxic tripolyphosphate, and requires separate experiments for each sodium species. We have developed CSI techniques for sodium to be used in conjunction with nontoxic paramagnetic shift reagents such as DyTTHA3-. These experiments allow the simultaneous generation of separate images of the intracellular and extracellular sodium pools, and therefore the direct monitoring of the distribution of sodium on a regional basis. The technique does not require complete resolution of the shifted and unshifted sodium species