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.
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