We propose to study five interrelated themes in order to develop basic knowledge on relaxation in tissues with the aim of applying these findings to improve clinical and research use of in vivo NMR. The themes of our research are: 1) proton relaxation in lipids, 2) the effect of oxygen on proton relaxation, 3) use of nitroxide free radicals to modify proton relaxation rates 4) the detection and use of altered redo states in tissues to enhance contrast, 5) the use of liposomes to model tissue processes and deliver contrast agents. Our primary experimental approach is to measure proton relaxation by obtaining a full NMR dispersion profile of T1 values from .01MHz to 50MHz. The measurement and modification of relaxation in lipids should provide the basis to use relaxation data from lipid protons to follow physiological and pathological changes. The use of oxygen as a contrast agent will be studied with an emphasis on effects in lipids because of the 4-fold increased solubility of oxygen in lipids. The chemical versatility of nitroxides provides potential advantages as contrast agents, including the use of lipid seeking nitroxides and optimization of solubility and/or water binding properties of nitroxides to increase relaxation. Areas of altered redox states may be detected by virtue of their different oxygen tension and/or effects on the activity of nitroxides. Liposomes provide potential means to deliver contrast agents with reduced toxicity and increased specificity. The team that will carry out these studies have extensive experience in the technology needed to carry out this proposal, including magnetic resonance relaxation, electron spin resonance and nitroxides and liposomes. Preliminary experiments have demonstrated the feasibility of these studies.
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