The major goals of this application are to evaluate a localized two-dimensional (2D) MR spectroscopic technique (MRS) and to detect cerebral metabolites unequivocally in hepatic encephalopathy (HE). Detection of early changes is very critical in the diagnosis of HE. Localized MR Spectroscopy is a major biochemical tool in characterizing noninvasively several metabolites in human tissues. Excellent one-dimensional (1D) MR spectra of HE and other pathologies have been reported with promising results. However, spectral overlap of various metabolites has been a major concern with the conventional 1D MRS. Spectral analysis of certain metabolites, namely glutamate, glutamine, GABA, myo-inositol, aspartate, glutathione, and the aspartyl groups of NAA and NAAG, has been complicated by severe overlap at 1.5T. 2D MRS seems well suited to address this problem of overlap. It has revolutionized the applications of NMR in biological macromolecules. Previous attempts by other researchers to implement the localized versions of the two-dimensional MR techniques mainly used phantom solutions, although some results were reported from animal brains using a non-localized 2D technique. In addition to the major metabolites successfully assigned and analyzed so far with 1D MRS, more metabolites are yet to be detected and their respective roles in different pathologiesare yet to be explored using 2D MRS. A major hypothesis to be tested in this work is whether the changes of glutamine/glutamate, myo-inositol, aspartate, GABA and other cerebral metabolites can be detected using the localized 2D COSY more unambiguously in HE than the conventional 1D MRS. Three specific goals of this project will be: 1) to acquire the single-voxel based 2D COSY spectra in the anterior cingulate and the basal ganglia regions of HE patients; 2) to record the global pallidal Mill changes in HE patients; 3) to perform the neuropsychiatric and neurocognitive assessment in HE patients, and to correlate the MR findings with the neuropsycho-logical, blood ammonia and liver function test results using multivariate regression analysis. AGE 1.5T MRI scanner with a bilateral surface """"""""receive"""""""" coil (MRI Devices Corp.) in combination with a body rf """"""""transmit"""""""" coil will be used to achieve improved signal detection. Minimal spectral overlap leading to less ambiguous assignment and better quantitation of glutamate/glutamine, GABA, myo-inositol, threonine, glucose, taurine and glutathione, will be a major outcome of this work.
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