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 N, Li L, Zhang Y, Ferraris Araneta M, Johnson C, Shen J (2019). Quantification of in vivo transverse relaxation of glutamate in the frontal cortex of human brain by radio frequency pulse-driven longitudinal steady state. PLoS One 14, e0215210. https://doi.org/10.1371/journal.pone.0215210. [Pubmed Link]
Marenco S, Meyer C, van der Veen JW, Zhang Y, Kelly R, Shen J, Weinberger DR, Dickinson D, Berman KF (2018). Role of gamma-amino-butyric acid in the dorsal anterior cingulate in age-associated changes in cognition. Neuropsychopharmacology 43, 2285-2291. https://doi.org/10.1038/s41386-018-0134-5. [Pubmed Link]
Evans JW, Lally N, An L, Li N, Nugent AC, Banerjee D, Snider SL, Shen J, Roiser JP, Zarate CA (2018). 7T 1H-MRS in major depressive disorder: a Ketamine Treatment Study. Neuropsychopharmacology 43, 1908-1914. https://doi.org/10.1038/s41386-018-0057-1. [Pubmed Link]
An L, Araneta MF, Victorino M, Shen J (2020) Determination of Brain Metabolite T1 Without Interference From Macromolecule Relaxation. J Magn Reson Imaging, in press (e-pub ahead of print) https://doi.org/10.1002/jmri.27259. [Pubmed Link]
An L, Araneta MF, Johnson C, Shen J (2018). Simultaneous measurement of glutamate, glutamine, GABA, and glutathione by spectral editing without subtraction. Magn Reson Med 80, 1776-1786. https://doi.org/10.1002/mrm.27172. [Pubmed Link]
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