The goals of this research are to develop advanced magnetic resonance spectroscopy (MRS) and imaging techniques and to apply them and other complementary methods to studying brain metabolism, neurotransmission and enzyme activity. MRS allows measurement of neurotransmission of glutamate and GABA in vivo, which play important roles in many major psychiatric diseases including depression and schizophrenia. During 2010-2011, significant progress has been made in the development and applications of novel spectroscopic techniques for studying metabolism and neurotransmission in vivo in the brain. From our previous work, we have found that 13C labeling of glutamate and glutamine can be measured from human subjects by low power proton stochastic decoupling in the carboxylic/amide spectral region (Li, et al, NMR Biomed, 2010). Since then, we have devised a novel windowed stochastic decoupling technique that allows for a 50% additional reduction in radiofrequency power deposition into the brain, making it feasible to perform 13C MRS at very high magnetic field strength (Yang et al, J. Magn Reson Imaging, in press). We have also validated that the carboxylic/amide 13C isotopomers can be used for simultaneous detection of the metabolic action of two different substrates (Yang et al, J Neurosci Methods, 2011). A novel 13C homonuclear spectral editing method has been developed to spectrally resolve glutamine from overlapping aspartate. Using our GABA method, Marenco et al found that anterior cingulate cortex GABA concentration is modulated by GAD1 and COMT (Marenco et al, Neuropsychopharmacology, 2010). A significant association of GABA level with ErbB4 was identified recently (Marenco et al, J. Neurosci, 2011). In addition, collaborations with Dr. Gregor Hasler have led to novel findings of genetic effects on variations in MRS measures of N-acetylaspartate and GABA (BDNF bipolar disorder risk allele on prefrontal N-acetylaspartate and TPH2 panic disorder risk allele on GABA). By introducing numerical regularization methods into MRS we have also succeeded in quantifying N-acetylaspartyl glutamate (Zhang et al, Magn Reson Med, 2011). Finally, we proposed and tested a novel method for extracting MRS signals from irregularly shaped region of interest using the sensitivity heterogeneity of multichannel phased array receive coils (An et al, Magn Reson Med, 2011).

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U.S. National Institute of Mental Health
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Evans, Jennifer W; Lally, Níall; An, Li et al. (2018) 7T 1H-MRS in major depressive disorder: a Ketamine Treatment Study. Neuropsychopharmacology 43:1908-1914
Li, Shizhe; An, Li; Duan, Qi et al. (2018) Determining the Rate of Carbonic Anhydrase Reaction in the Human Brain. Sci Rep 8:2328
An, Li; Araneta, Maria Ferraris; Johnson, Christopher et al. (2018) Simultaneous measurement of glutamate, glutamine, GABA, and glutathione by spectral editing without subtraction. Magn Reson Med 80:1776-1786
Marenco, Stefano; Meyer, Christian; van der Veen, Jan Willem et al. (2018) Role of gamma-amino-butyric acid in the dorsal anterior cingulate in age-associated changes in cognition. Neuropsychopharmacology 43:2285-2291
Li, Ningzhi; Li, Shizhe; Shen, Jun (2017) Reconstruction of randomly under-sampled spectra for in vivo13C magnetic resonance spectroscopy. Magn Reson Imaging 37:216-221
Li, Ningzhi; Li, Shizhe; Shen, Jun (2017) High Field In vivo13C Magnetic Resonance Spectroscopy of Brain by Random Radiofrequency Heteronuclear Decoupling and Data Undersampling. Front Phys 5:
van der Veen, Jan Willem; Marenco, Stefano; Berman, Karen F et al. (2017) Retrospective correction of frequency drift in spectral editing: The GABA editing example. NMR Biomed 30:
An, Li; Li, Shizhe; Shen, Jun (2017) Simultaneous determination of metabolite concentrations, T1 and T2 relaxation times. Magn Reson Med 78:2072-2081
Zhang, Yan; An, Li; Shen, Jun (2017) Fast computation of full density matrix of multispin systems for spatially localized in vivo magnetic resonance spectroscopy. Med Phys 44:4169-4178
Marenco, Stefano; Meyer, Christian; Kuo, Susan et al. (2016) Prefrontal GABA Levels Measured With Magnetic Resonance Spectroscopy in Patients With Psychosis and Unaffected Siblings. Am J Psychiatry 173:527-34

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