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1H MRS detection of glycine residue of reduced glutathione in vivo
Authors:Lana G Kaiser  Ma?gorzata Marjańska  Gerald B Matson  Isabelle Iltis  Seth D Bush  Brian J Soher  Susanne Mueller  Karl Young
Institution:1. Varian Incorporated, Palo Alto, CA, USA;2. Center for Magnetic Resonance Research and Department of Radiology, University of Minnesota, Minneapolis, MN 55455, USA;3. Center for Imaging of Neurodegenerative Diseases, Department of Veteran Affairs Medical Center, VA Medical Center (114M), 4150 Clement St., San Francisco, CA 94121, USA;4. Department of Pharmaceutical Chemistry, University of California, San Francisco, USA;5. California Polytechnic State University, San Luis Obispo, CA, USA;6. Department of Radiology, Duke University, Durham, NC, USA;7. Department of Radiology, University of California, San Francisco, USA
Abstract:Glutathione (GSH) is a powerful antioxidant found inside different kinds of cells, including those of the central nervous system. Detection of GSH in the human brain using 1H MR spectroscopy is hindered by low concentration and spectral overlap with other metabolites. Previous MRS methods focused mainly on the detection of the cysteine residue (GSH-Cys) via editing schemes. This study focuses on the detection of the glycine residue (GSH-Gly), which is overlapped by glutamate and glutamine (Glx) under physiological pH and temperature. The first goal of the study was to obtain the spectral parameters for characterization of the GSH-Gly signal under physiological conditions. The second goal was to investigate a new method of separating GSH-Gly from Glx in vivo. The characterization of the signal was carried out by utilization of numerical simulations as well as experiments over a wide range of magnetic fields (4.0–14 T). The proposed separation scheme utilizes J-difference editing to quantify the Glx contribution to separate it from the GSH-Gly signal. The presented method retains 100% of the GSH-Gly signal. The overall increase in signal to noise ratio of the targeted resonance is calculated to yield a significant SNR improvement compared to previously used methods that target GSH-Cys residue. This allows shorter acquisition times for in vivo human clinical studies.
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