The overall goal of my group is to develop advanced magnetic resonance spectroscopy and imaging techniques and to apply them and related methods to studying brain metabolism and neurotransmission in both human subjects and in animal models. Magnetic resonance spectroscopy, in principle, allows measurement of neurotransmitter GABA, which plays an important role in many psychiatric diseases including depression and schizophrenia, and its metabolism. In reality, such measurement is fraught with technical difficulties. During 2003-2004, significant progress was made in the development of new spectroscopic techniques for single-voxel GABA measurement and for spectroscopic imaging of GABA, resulting in improved reliability and sensitivity (J Shen, J Yang, I-Y Choi, SS Li, and Z Chen, A new strategy for in vivo spectral editing. Application to GABA editing using selective homonuclear polarization transfer spectroscopy, J. Magn. Reson., 170:290-298 (2004); I-Y Choi, S-P Lee, and J Shen, In vivo single-shot three-dimensionally localized multiple quantum spectroscopy of GABA in the human brain with improved spectral selectivity, J. Magn. Reson., revised; I-Y Choi, S-P Lee, and J Shen, Selective homonuclear Hartmann-Hahn transfer method for in vivo spectral editing in the human brain, Magn. Reson. Med., revised.). We have also finished initial studies using GABA chemical shift imaging to map the distribution of GABA in brain. A manuscript (I-Y Choi, S-P Lee, H Merkle, and J Shen, In vivo measurement of GABA distribution in gray and white matters in the human brain using double quantum filtered spectroscopic imaging, in preparation) is being prepared to report our findings in in vivo tissue- and regional specific distribution of GABA in the human brain. Significant progress has also been made in studying GABA neurometabolism and neurotransmission in rat brain. Using state-of-the-art spectroscopy and imaging techniques, we have found that the extent and intensity of brain's response to focal activation correlates with the concentration of endogenous GABA (Z Chen, AC Silva, J Yang, and J Shen, Elevated endogenous GABA level correlates with decreased fMRI signals in the rat brain during acute inhibition of GABA-transaminase, submitted to J. Neurosci. Res.). Very recently, we have also succeeded in detecting in vivo kinetics of 13C-label incorporation from [1-13C]glucose into [2-13C]GABA, the direct metabolic product of the GAD during [1-13C]glucose infusion (J Yang, C Li, and J Shen, In vivo detection of [2-13C]GABA turnover from intravenously infused [1-13C]glucose in the rat brain using adiabatic 1H-observed, 13C-edited spectroscopy at 11.7 Tesla, in preparation). Characterization of GABA metabolism and transmission during focal cerebral functional activation is currently in progress.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Intramural Research (Z01)
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U.S. National Institute of Mental Health
United States
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Novikov, Alexander (2011) Advanced theory of driven birdcage resonator with losses for biomedical magnetic resonance imaging and spectroscopy. Magn Reson Imaging 29:260-71
Hasler, Gregor; van der Veen, Jan Willem; Geraci, Marilla et al. (2009) Prefrontal cortical gamma-aminobutyric Acid levels in panic disorder determined by proton magnetic resonance spectroscopy. Biol Psychiatry 65:273-5
Shen, Jun; Rothman, Douglas L; Behar, Kevin L et al. (2009) Determination of the glutamate-glutamine cycling flux using two-compartment dynamic metabolic modeling is sensitive to astroglial dilution. J Cereb Blood Flow Metab 29:108-18
Xu, Su; Yang, Jehoon; Shen, Jun (2008) Measuring N-acetylaspartate synthesis in vivo using proton magnetic resonance spectroscopy. J Neurosci Methods 172:8-12
Yang, Jehoon; Singh, Sujata; Shen, Jun (2008) 13C saturation transfer effect of carbon dioxide-bicarbonate exchange catalyzed by carbonic anhydrase in vivo. Magn Reson Med 59:492-8
Xu, Su; Yang, Jehoon; Shen, Jun (2008) Inverse polarization transfer for detecting in vivo 13C magnetization transfer effect of specific enzyme reactions in 1H spectra. Magn Reson Imaging 26:413-9
Yang, Jehoon; Shen, Jun (2007) Relayed (13)C magnetization transfer: detection of malate dehydrogenase reaction in vivo. J Magn Reson 184:344-9
Hasler, Gregor; van der Veen, Jan Willem; Tumonis, Toni et al. (2007) Reduced prefrontal glutamate/glutamine and gamma-aminobutyric acid levels in major depression determined using proton magnetic resonance spectroscopy. Arch Gen Psychiatry 64:193-200
Li, Shizhe; Yang, Jehoon; Shen, Jun (2007) Novel strategy for cerebral 13C MRS using very low RF power for proton decoupling. Magn Reson Med 57:265-71
Xu, Su; Yang, Jehoon; Shen, Jun (2007) In vivo 13C saturation transfer effect of the lactate dehydrogenase reaction. Magn Reson Med 57:258-64

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