MULIPLE QUANTUM SODIUM NMR SPECTROSCOPY AND IMAGING

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DESCRIPTION (Adapted from applicant's abstract): Myocardial ischemia is one of the most common causes of serious illness and early death in the developed world. Many studies have shown that alterations in intracellular sodium (Nai+) play a key role in cell dysfunction and damage after ischemia. The main goal of this research is to test the hypothesis that multiple-quantum-filter (MQF) 23Na magnetic resonance spectroscopy and imaging can quantitatively determine the extent and location of acute cardiac injury after an ischemic episode. MQF 23Na NMR has been suggested as a method to mainly observe Nai+. The overwhelming advantage of MQF 23Na magnetic resonance (MR) techniques is that they allow non-invasive measurement and can be applied to humans. Although some extracellular Na+ contributes to the MQF 23Na signal, the applicant's data from other groups, show that this signal does not change during ischemia and other physiological manipulations. Therefore, MQF MR techniques can provide a completely noninvasive method of detecting changes in Nai+. The applicant's first aim is to develop and validate MQF 23Na MR spectroscopy (MRS) for quantitation of changes in [Nai+] with the help of a 23Na shift reagent, TmDOPTP5-. The changes in MQF 23Na MRS during global ischemia and reperfusion will be correlated with phosphorus energy metabolism and cardiac performance in the isolated perfused rabbit heart. The second aim is to develop and validate quantitative MQF 23Na MR imaging (MRI) for mapping changes in [Nai+] and correlate the MRI results with tissue viability as measured by functional performance and triphenyltetrazolium chloride (TTC) MRI staining in the perfused heart during regional ischemia and reperfusion. The efficacy of MQF 23Na MRI to monitor ischemic damage will also be compared with diffusion weighted 1H imaging in the perfused heart during regional ischemia and reperfusion with and without a cardioprotective amiloride analog. The third aim is to develop a surface coil MAF 23Na MRI technique to obtain quantitative maps of changes in Nai+ and apply this technique to assess tissue viability in closed chest rabbit hearts. Finally, the feasibility of quantitative cardiac MQF 23Na MRI in humans at 4T will be demonstrated. The development of MQF 23Na MRI to assess and image post-ischemic myocardial injury and recovery may prove useful for identifying viable tissue and assessing the efficacy of therapeutic interventions aimed at preserving cellular viability.