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 (protocol no. 11-M-0045, NCT no. 01266577;protocol no. 05-M-0144, NCT no. 00109174). 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 2012-2013, we have made significant progress in the development and applications of novel spectroscopic and imaging 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 (Xiang, et al, NMR Biomed, 2011). We further extended this technique to acetate infusion with spectral editing (Xiang et al, J Magn Reson, 2012). Now we are able to distinguish 13C-glutamate C5 from 13C-labeled acetate, by using J coupling difference, although they resonant at the same frequency. Since acetaet is predominantly metabolized in astroglia this will allow us to measure the main metabolic flux from astroglia to neurons while taking advantage of the low decoupling power requirements (Shen, Front. Neuroenergetics, 2013). We are making progress in developing low decoupling power 13C MRS on a whole body 7 Tesla scanner for measuring glutamate in the prefrontal cortex. Preliminary validation of this method has been made on a 3 Tesla scanner (Li et al, J. Magn. Reson., 2012). For proton MRS, after overcoming daunting technical challenges, we have succeeded in obtaining high quality MRS data using the 7 Tesla whole body scanner. We developed our own methods for radio frquency pulse calibration, magnetic field correction, and multichannel data combination (An et al, J. Magn. Reson. Imaging, 2013). From this effort, we have developed 7 Tesla single-shot methods for measuring N-acetylaspartylglutamate (NAAG), glutamate, glutamine and glutathione (An et al, Magn Reson Med, under minor revision). Building on our previous collaborations with Dr. Zarate's group we are now measuring the effect of ketamine on glutamate at 7 Tesla. Collaborations with Dr. Hasler's group have led to understanding the genetic underpinning of amino acid GABA concentration in panic disorder (Preuss et al, Intl J. Neuropsychopharmacology, 2013) as well as age-modulated association between prefrontal NAA and the BDNF gene (Salehi et al, Intl J. Neuropsychopharmacology, 2013). Finally, we discovered a mechanism for restoring the magnetization excitation profile during rapid trasverse relaxation, which, we believe, will facilitate the forthcoming development of the NIH 11.7 Tesla whole body scanner.

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Project End
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Budget End
Support Year
11
Fiscal Year
2013
Total Cost
$882,597
Indirect Cost
Name
U.S. National Institute of Mental Health
Department
Type
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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
Li, Ningzhi; Li, Shizhe; Shen, Jun (2017) Reconstruction of randomly under-sampled spectra for in vivo(13)C magnetic resonance spectroscopy. Magn Reson Imaging 37:216-221
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
Zhang, Yan; Shen, Jun (2016) Simultaneous quantification of glutamate and glutamine by J-modulated spectroscopy at 3 Tesla. Magn Reson Med 76:725-32
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
Lally, Níall; An, Li; Banerjee, Dipavo et al. (2016) Reliability of 7T (1) H-MRS measured human prefrontal cortex glutamate, glutamine, and glutathione signals using an adapted echo time optimized PRESS sequence: A between- and within-sessions investigation. J Magn Reson Imaging 43:88-98
Li, Shizhe; An, Li; Yu, Shao et al. (2016) (13)C MRS of human brain at 7 Tesla using [2-(13)C]glucose infusion and low power broadband stochastic proton decoupling. Magn Reson Med 75:954-61
An, Li; Shen, Jun (2015) Image-guided spatial localization of heterogeneous compartments for magnetic resonance. Med Phys 42:5278-86
An, Li; Li, Shizhe; Murdoch, James B et al. (2015) Detection of glutamate, glutamine, and glutathione by radiofrequency suppression and echo time optimization at 7 tesla. Magn Reson Med 73:451-8

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