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.
Li S, An L, Yu S, Ferraris Araneta M, Johnson CS, Wang S, Shen J (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. https://doi.org/10.1002/mrm.25721. [Pubmed Link]
Hasler G, van der Veen JW, Geraci M, Shen J, Pine D, Drevets WC (2009). Prefrontal cortical gamma-aminobutyric Acid levels in panic disorder determined by proton magnetic resonance spectroscopy. Biol Psychiatry 65, 273-5. https://doi.org/10.1016/j.biopsych.2008.06.023. [Pubmed Link]
Salehi B, Preuss N, van der Veen JW, Shen J, Neumeister A, Drevets WC, Hodgkinson C, Goldman D, Wendland JR, Singleton A, Gibbs JR, Cookson MR, Hasler G (2013). Age-modulated association between prefrontal NAA and the BDNF gene. Int J Neuropsychopharmacol 16, 1185-93. https://doi.org/10.1017/S1461145712001204. [Pubmed Link]
Hasler G, van der Veen JW, Tumonis T, Meyers N, Shen J, Drevets WC (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. https://doi.org/10.1001/archpsyc.64.2.193. [Pubmed Link]
Lally N, An L, Banerjee D, Niciu MJ, Luckenbaugh DA, Richards EM, Roiser JP, Shen J, Zarate CA, Nugent AC (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. https://doi.org/10.1002/jmri.24970. [Pubmed Link]
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