4.5 Article

Detection of 2-hydroxyglutarate in brain tumors by triple-refocusing MR spectroscopy at 3T in vivo

Journal

MAGNETIC RESONANCE IN MEDICINE
Volume 78, Issue 1, Pages 40-48

Publisher

WILEY
DOI: 10.1002/mrm.26347

Keywords

2-hydroxyglutarate; 1H MRS; 3T; triple refocusing; human brain tumor; glioma; isocitrate dehydrogenase

Funding

  1. National Institutes of Health [CA184584]
  2. Cancer Prevention Research Institute of Texas [RP140021-P04, RP130427]

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PurposeTo test the efficacy of triple-refocusing MR spectroscopy (MRS) for improved detection of 2-hydroxyglutarate (2HG) in brain tumors at 3T in vivo. MethodsThe triple-refocusing sequence parameters were tailored at 3T, with density-matrix simulations and phantom validation, for enhancing the 2HG 2.25-ppm signal selectivity with respect to the adjacent resonances of glutamate (Glu), glutamine (Gln), and gamma-aminobutyric acid (GABA). In vivo MRS data were acquired from 15 glioma patients and analyzed with LCModel using calculated basis spectra. Metabolites were quantified with reference to water. ResultsA triple-refocusing sequence (echo time=137 ms) was obtained for 2HG detection. The 2HG 2.25-ppm signal was large and narrow while the Glu and Gln signals between 2.2 and 2.3 ppm were minimal. The optimized triple refocusing offered improved separation of 2HG from Glu, Gln and GABA when compared with published MRS methods. 2HG was detected in all 15 patients, the estimated 2HG concentrations ranging from 2.4 to 15.0 mM, with Cramer-Rao lower bounds of 2%-11%. The 2HG estimates did not show significant correlation with total choline. ConclusionThe optimized triple refocusing provides excellent 2HG signal discrimination from adjacent resonances and may confer reliable in vivo measurement of 2HG at relatively low concentrations. Magn Reson Med 78:40-48, 2017. (c) 2016 International Society for Magnetic Resonance in Medicine

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