Diagnostics (Aug 2023)

The Correlation of In Vivo MR Spectroscopy and Ex Vivo 2-Hydroxyglutarate Concentration for the Prediction of Isocitrate Dehydrogenase Mutation Status in Diffuse Glioma

  • Bart R. J. van Dijken,
  • Hanne-Rinck Jeltema,
  • Justyna Kłos,
  • Peter Jan van Laar,
  • Roelien H. Enting,
  • Ronald G. H. J. Maatman,
  • Klaas Bijsterveld,
  • Wilfred F. A. Den Dunnen,
  • Rudi A. Dierckx,
  • Paul E. Sijens,
  • Anouk van der Hoorn

DOI
https://doi.org/10.3390/diagnostics13172791
Journal volume & issue
Vol. 13, no. 17
p. 2791

Abstract

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Isocitrate dehydrogenase (IDH) mutation status is an important biomarker in the glioma-defining subtype and corresponding prognosis. This study proposes a straightforward method for 2-hydroxyglutarate (2-HG) quantification by MR spectroscopy for IDH mutation status detection and directly compares in vivo 2-HG MR spectroscopy with ex vivo 2-HG concentration measured in resected tumor tissue. Eleven patients with suspected lower-grade glioma (ten IDH1; one IDHwt) were prospectively included. Preoperatively, 3T point-resolved spectroscopy (PRESS) was acquired; 2-HG was measured as the percentage elevation of Glx3 (the sum of 2-HG and Glx) compared to Glx4. IDH mutation status was assessed by immunochemistry or direct sequencing. The ex vivo 2-HG concentration was determined in surgically obtained tissue specimens using gas chromatography–mass spectrometry. Pearson correlation was used for assessing the correlation between in vivo MR spectroscopy and ex vivo 2-HG concentration. MR spectroscopy was positive for 2-HG in eight patients, all of whom had IDH1 tumors. A strong correlation (r = 0.80, p = 0.003) between 2-HG MR spectroscopy and the ex vivo 2-HG concentration was found. This study shows in vivo 2-HG MR spectroscopy can non-invasively determine IDH status in glioma and demonstrates a strong correlation with ex vivo 2-HG concentration in patients with lower-grade glioma.

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