In vivo Metabolic Profiles as Determined by 31P and short TE 1H MR-Spectroscopy : No Difference Between Patients with IDH Wildtype and IDH Mutant Gliomas

Clin Neuroradiol. 2019 Mar;29(1):27-36. doi: 10.1007/s00062-017-0630-8. Epub 2017 Oct 5.

Abstract

Purpose: Previous ex vivo spectroscopic data from tissue samples revealed differences in phospholipid metabolites between isocitrate dehydrogenase mutated (IDHmut) and IDH wildtype (IDHwt) gliomas. We investigated whether these changes can be found in vivo using 1H-decoupled 31P magnetic resonance spectroscopic imaging (MRSI) with 3D chemical shift imaging (CSI) at 3 T in patients with low and high-grade gliomas.

Methods: The study included 33 prospectively enrolled, mostly untreated patients who met spectral quality criteria according to the World Health Organization (WHO II n = 7, WHO III n = 17, WHO IV n = 9; 25 patients IDHmut, 8 patients IDHwt). The MRSI protocol included 1H decoupled 31P MRSI with 3D CSI (3D 31P CSI), 2D 1H CSI and a 1H single voxel spectroscopy sequence (TE 30 ms) from the tumor area. For 1H MRS, absolute metabolite concentration values were calculated (phantom replacement method). For 31P MRS, metabolite intensity ratios were calculated for the choline (C) and ethanolamine (E)-containing metabolites.

Results: In our patient cohort we did not find significant differences for the ratio of phosphocholine (PC) and phosphoethanolamine (PE), PC/PE, (p = 0.24) for IDHmut compared to IDHwt gliomas. Furthermore, we found no elevated ratios of glycerophosphocholine (GPC) and glycerophosphoethanolamine (GPE), GPC/GPE, (p = 0.68) or GPC/PE (p = 0.12) for IDHmut gliomas. Even the ratio (PC+GPC)/(PE+GPE) showed no significant differences with respect to mutation status (p = 0.16). Nonetheless, changes related to tumor grade regarding intracellular pH (pHi) and phospholipid metabolism as well as absolute metabolite concentrations of co-registered 2D 1H CSI data for tumor and control tissue showed the anticipated results.

Conclusion: Using 3D-CSI data acquisition, in vivo 31P MR spectroscopic measurement of phospholipid metabolites could not distinguish between IDHmut and IDHwt.

Keywords: Glioma; IDH1 and IDH2 genes; Indirect detection; MR Spectroscopy; Mutations.

MeSH terms

  • Adult
  • Aged
  • Analysis of Variance
  • Astrocytoma / enzymology
  • Astrocytoma / genetics
  • Astrocytoma / pathology
  • Astrocytoma / therapy
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism
  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology
  • Brain Neoplasms / therapy
  • Diagnosis, Differential
  • Ethanolamines / analysis
  • Ethanolamines / metabolism
  • Female
  • Glioblastoma / enzymology
  • Glioblastoma / genetics
  • Glioblastoma / pathology
  • Glioblastoma / therapy
  • Glioma / genetics
  • Glioma / metabolism*
  • Glioma / pathology
  • Glioma / therapy
  • Glutarates / analysis
  • Glutarates / metabolism
  • Glycerylphosphorylcholine / analysis
  • Humans
  • Hydrogen
  • Isocitrate Dehydrogenase / genetics*
  • Isocitrate Dehydrogenase / metabolism
  • Isoenzymes / analysis
  • Isoenzymes / metabolism
  • Magnetic Resonance Spectroscopy / methods*
  • Male
  • Middle Aged
  • Mutation
  • Neoplasm Grading
  • Oligodendroglioma / enzymology
  • Oligodendroglioma / genetics
  • Oligodendroglioma / pathology
  • Oligodendroglioma / therapy
  • Phosphatidylethanolamines / analysis
  • Phosphatidylethanolamines / metabolism
  • Phosphorus Isotopes
  • Phosphorylcholine / analysis
  • Phosphorylcholine / metabolism
  • Prospective Studies
  • Tumor Burden

Substances

  • Biomarkers, Tumor
  • Ethanolamines
  • Glutarates
  • Isoenzymes
  • Phosphatidylethanolamines
  • Phosphorus Isotopes
  • Phosphorylcholine
  • glycerophosphoethanolamine
  • alpha-hydroxyglutarate
  • Glycerylphosphorylcholine
  • phosphorylethanolamine
  • Hydrogen
  • Isocitrate Dehydrogenase