MULTIPLE QUANTUM SODIUM NMR SPECTROSCOPY AND IMAGING

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A sodium gradient is critically important to many cell functions and is sensitive to disease; consequently there is a continuing interesting methods which differentiate between Na+ in various tissue compartments. At least two magnetic resonance (MR) methods have been proposed to differentiate between intra- and extracellular Na+, the use of anionic shift reagents (SR) and multiple quantum (MQ) filter techniques. Each approach has disadvantages, especially for in vivo applications. The primary disadvantage of SRs concerns possible toxicity while MQ filters do not accurately filter intra- versus extracellular signals. However, MQ techniques do discriminate between isotropic and transiently bound states of Na+, and can be applied to human studies noninvasively. The long term objective of this research is to characterize and evaluate the use of MQ filtered 23Na spectroscopy and imaging for detecting physiological abnormalities in intact animals and perfused heart so that the technique may be applied clinically. The central hypothesis in this project is that the MQ filtered intracellular Na+ (Na+i) signal is more sensitive to physiological perturbations than the single quantum (SQ) signal intensity. We have recently introduced a new SR, TmDOTP5, to the biomedical community for in vivo animal experiments. This reagent provides an excellent way of testing the performance of MQ filters in intact animal and perfused organ experiments. Our preliminary data with this reagent shows that upon death, the MQ filtered Na+i signal from the rat liver increases 3-4 times faster than the increase in SQ signal. This does not result from changes in the relaxation times of Na+ but is rather due to the amount of Na+i that can pass through a MQ filter and thus suggest significant changes in binding of Na+i which are not detectable by other techniques. The experiments outlined in this proposal are designed to address the following questions; 1) Are there more subtle changes in cell physiology that will produce this same increase in the MQ filtered Na+i signal? 2) Is this increase in MQ filtered signal specific to the liver, or does it occur in other organs as well? 3) Is this effect reversible and is it a more sensitive indicator of cell damage than SQ Na+i signal intensity? In addition, we will study the effects of ischemia and different pharmacological manipulations in the perfused guinea pig heart to understand the mechanism of these changes in MQ filtered 23Na spectra. Finally, for MQ techniques to be useful clinically, a MQ filtered 23Na imaging technique will be developed and tested which will use weighted signal averaging and coherent echo addition to enhance the signal-to noise ratio.