The goal of this research is to refine the capacity of proton NMR to acquire images displaying chemical shift spectral information, and to assess the role of these methods in vivo in clinical and basic research. As in our initial submission, two areas of investigation will be studied in detail. First, quantitative techniques of lipid and water imaging, evaluated during the initial funding period, will be further extended to measure additional spectral characteristics. These will include spectral resonance line broadening measured using an asymmetric spin echo (ASE) method, and scalar coupled fraction (SCF) measured using multiple quantum techniques. Two applications are planned. Following on the success of pilots studies funded during the initial study period, the clinical utility of quantitative analysis of lipid and water resonance concentration, relaxation times, and newly developed measures of spectral line widths will be evaluated in disorders of bone marrow. This will include detailed longitudinal studies of myeloproliferative disorders, and pilot studies of chemical shift imaging (CSI) techniques to measure marrow iron stores. Research will also begin on quantitative spectral imaging of atherosclerotic plaque. Work will focus on characterization of fatty plaques with lipid- sensitive and multiple quantum pulse sequences, and atherosclerotic arterial thrombus with iron-sensitive line width mapping. These studies will be directed towards establishing quantitative CSI as a non-invasive tool for evaluating the response of arterial lesions to new interventions such as laser angioplasty. Second, mapping lactate in cerebral ischemia will form the cornerstone of studies of brain physiology. Technical issues to be addressed will include improved methods of lipid suppression (previous work having demonstrated solutions to the problem of in vivo water suppression), and comparison between field strengths. Physiologic correlates to lactate maps including MR and PET measures of cerebral blood flow, brain pH and oxygen metabolism, will be used in both global hypoxia and focal ischemia to address questions of brain energy metabolism and pH regulation.
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