Magnetic resonance spectroscopic imaging (MRS imaging) is a promising new approach for the in vivo study of degenerative brain disorders. The major MRS-visible components of a water-suppressed brain proton spectrum are N-acetyl aspartate (NAA) (observed primarily in living neurons), creatine (an energy metabolite), and choline (a precursor to acetylcholine and also a constituent of cell membrane synthesis). We have recently used proton MRS to produce axial images of regional brain distribution of NAA, choline and creatine. In this project, we propose to further develop a system for proton spectroscopic imaging of all parts of the human brain which will be robust to the problems of inhomogeneity and susceptibility and will produce metabolic images that can be readily interpreted. In addition we will develop a method for quantification of spectroscopic data which will provide reliable regional concentration measurements. MRS imaging will be used to develop normative values for NAA, choline and creatine concentrations and distributions found across the age range of 50-80 in healthy community members and to examine alterations in metabolite concentrations and distributions in Alzheimer's disease (AD) patients. All subjects will be retested after a 2-year interval to determine change with normal aging and disease progression. An age-regression model will be used to identify heterogeneity within the AD group based on age of disease onset. In addition, we will investigate hypothesized associations between metabolite concentrations, volumes of white and grey matter in defined regions of interest, and performance on tests of specific cognitive functions.
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