The first nuclear magnetic resonance (NMR) images were produced in 1973; in the ensuing years significant advances have been made in instrumentation and technique. Concurrent with developments in imaging technology NMR spectroscopic techniques have been applied with increasing frequency to study biological systems. The goal of this grant is to further develop and evaluate techniques which acquire proton spectroscopic (chemical shift) information within an NMR image. Specifically, efforts will focus on two primary aims. First, the ability to measure signal intensity and relaxation times of the two primary contributors to the proton spectra, lipid and water, will be tested using three chemical shift imaging techniques. Phantom data will be used to verify theoretical predictions of S/N and technique bias. Rat models of hepatic steatosis with and without the concomitant hepatitis will be used to validate these observations in vivo, and to compare the sensitivity of conventional NMR techniques to the three chemical shift imaging methods using multicomponent relaxation time measurements. Studies will then be extended to the investigation of human liver pathology. In order to facilitate rapid transfer of information to the clinical environment, studies of human bone marrow will be made in parallel with animal liver studies. These will first focus on patterns of normal bone marrow development. A pilot study of bone marrow in human leukemias will then be carried out, testing the ability of multicomponent measurements to characterize normal and abnormal marrow elements. The second specific aim of this study is to use proton chemical shift imaging techniques to map cerebral lactate during global and focal hypoxic insult. The sensitivity, precision and accuracy of lactate measurements will be determined in phantoms, evaluating techniques of both water and lipid suppression. Non-imaging experiments in rats will be carried out to evaluate system linearity in vivo, and tissue lactate relaxation times will be determined over a range of concentrations. A cat brain model of global hypoxia, temporally stabalized, will be imaged, with brain lactate levels determined biochemically compared to lactate image signal intensity. This model wil be extended in studies of focal ischemic insult. Pilot studies of lactate accumulation in humans will also be carried out, investigating stroke and CNS tumor patients.
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