Principal Investigator: Jun Shen
Dr. Shen is chief of the Section on Magnetic Resonance Spectroscopy, Molecular Imaging Branch, Mood & Anxiety Disorders Program of the Intramural Research Program, National Institute of Mental Health, National Institutes of Health in Bethesda, Maryland. He attended college at Nankai University and graduate schools at Nankai University and University of Wisconsin at Madison. He did postdoctoral research in molecular biochemistry and biophysics at Yale University School of Medicine. He joined NIMH in 2002. His previous work involved in vivo magnetic resonance spectroscopy technology and applications with a focus on measuring glutamate and GABA. Prior to joining NIMH, he received a NARSAD Young Investigator Award.
We study brain chemistry and biophysics using, primarily, in vivo magnetic resonance spectroscopy and imaging. In vivo magnetic resonance spectroscopy (MRS) allows noninvasive detection of metabolic events and neurotransmitter cycling in the living human brain. It offers a unique window into brain chemistry by providing valuable biomarkers for brain disorders. We develop in vivo magnetic resonance spectroscopy and spectroscopic imaging techniques and apply them to study both animal models and patients with mental illnesses.
Whereas proton magnetic resonance spectroscopy measures static concentrations of important brain chemicals (e.g., GABA, the major inhibitory neurotransmitter in the CNS), 13C magnetic resonance spectroscopy allows determination of dynamic metabolic fluxes by introducing exogenous 13C-labeled substrates. For example, the flux between neuronal glutamate and astroglial glutamine can be determined by measuring the kinetics of 13C label incorporation into glutamate and glutamine from 13C labeled glucose or the glia-specific substrate acetate.
The phenomenon of in vivo enzyme-specific magnetization transfer was discovered for creatine kinase and ATP exchange reactions in the late 1970s using 31P magnetic resonance spectroscopy. No new enzyme-specific magnetization transfer effects had been found in vivo until our recent discovery of 13C magnetization transfer effects. Our discoveries have uncovered hidden rapid exchange reactions underneath commonplace magnetic resonance spectroscopy signals such as glutamate, aspartate and lactate and have extended the scope of in vivo 13C magnetic resonance spectroscopy to include specific enzymes.
In vivo 13C magnetic resonance spectroscopy of human brain on a clinical 3 T scanner using [2-13C]glucose infusion and low-power stochastic decoupling . Li S, Zhang Y, Wang S, Yang J, Ferraris Araneta M, Farris A, Johnson C, Fox S, Innis R, Shen J. Magn Reson Med. 2009 Sep;62(3):565-73. doi: 10.1002/mrm.22044. PMID: 19526500.
Prefrontal cortical gamma-aminobutyric Acid levels in panic disorder determined by proton magnetic resonance spectroscopy . Hasler G, van der Veen JW, Geraci M, Shen J, Pine D, Drevets WC. Biol Psychiatry. 2009 Feb 1;65(3):273-5. doi: 10.1016/j.biopsych.2008.06.023. Epub 2008 Aug 9. PMID: 18692172.
Determination of the glutamate-glutamine cycling flux using two-compartment dynamic metabolic modeling is sensitive to astroglial dilution . Shen J, Rothman DL, Behar KL, Xu S. J Cereb Blood Flow Metab. 2009 Jan;29(1):108-18. doi: 10.1038/jcbfm.2008.102. Epub 2008 Sep 3. PMID: 18766194.
Reduced prefrontal glutamate/glutamine and gamma-aminobutyric acid levels in major depression determined using proton magnetic resonance spectroscopyReduced prefrontal glutamate/glutamine and gamma-aminobutyric acid levels in major depression determined using proton magnetic resonance spectroscopy . Hasler G, van der Veen JW, Tumonis T, Meyers N, Shen J, Drevets WC. Arch Gen Psychiatry. 2007 Feb;64(2):193-200. PMID: 17283286.
Magnuson Clinical Center, Room 2D51A, MSC 1527
BETHESDA, MD 20814
Phone: +1 301 451 3408
Fax: +1 301 480 3610