Volumetric relationship between 2-hydroxyglutarate and FLAIR hyperintensity has potential implications for radiotherapy planning of mutant IDH glioma patients

Neuro Oncol. 2016 Nov;18(11):1569-1578. doi: 10.1093/neuonc/now100. Epub 2016 Jul 5.


Background: Gliomas with mutant isocitrate dehydrogenase (IDH) produce high levels of 2-hydroxyglutarate (2HG) that can be quantitatively measured by 3D magnetic resonance spectroscopic imaging (MRSI). Current glioma MRI primarily relies upon fluid-attenuated inversion recovery (FLAIR) hyperintensity for treatment planning, although this lacks specificity for tumor cells. Here, we investigated the relationship between 2HG and FLAIR in mutant IDH glioma patients to determine whether 2HG mapping is valuable for radiotherapy planning.

Methods: Seventeen patients with mutant IDH1 gliomas were imaged by 3 T MRI. A 3D MRSI sequence was employed to specifically image 2HG. FLAIR imaging was performed using standard clinical protocol. Regions of interest (ROIs) were determined for FLAIR and optimally thresholded 2HG hyperintensities. The overlap, displacement, and volumes of 2HG and FLAIR ROIs were calculated.

Results: In 8 of 17 (47%) patients, the 2HG volume was larger than FLAIR volume. Across the entire cohort, the mean volume of 2HG was 35.3 cc (range, 5.3-92.7 cc), while the mean volume of FLAIR was 35.8 cc (range, 6.3-140.8 cc). FLAIR and 2HG ROIs had mean overlap of 0.28 (Dice coefficients range, 0.03-0.57) and mean displacement of 12.2 mm (range, 3.2-23.5 mm) between their centers of mass.

Conclusions: Our results indicate that for a substantial number of patients, the 2HG volumetric assessment of tumor burden is more extensive than FLAIR volume. In addition, there is only partial overlap and asymmetric displacement between the centers of FLAIR and 2HG ROIs. These results may have important implications for radiotherapy planning of IDH mutant glioma.

Keywords: 2-hydroxyglutarate (2HG); glioma; isocitrate dehydrogenase (IDH) mutation; magnetic resonance spectroscopic imaging (MRSI); radiotherapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged, 80 and over
  • Brain / diagnostic imaging
  • Brain / metabolism
  • Brain Neoplasms / diagnostic imaging*
  • Brain Neoplasms / metabolism
  • Female
  • Glioma / diagnostic imaging*
  • Glioma / metabolism
  • Glutarates / metabolism*
  • Humans
  • Isocitrate Dehydrogenase / genetics*
  • Magnetic Resonance Imaging / methods*
  • Magnetic Resonance Spectroscopy / methods*
  • Male
  • Middle Aged
  • Mutation
  • Radiotherapy Planning, Computer-Assisted / methods*
  • Young Adult


  • Glutarates
  • alpha-hydroxyglutarate
  • Isocitrate Dehydrogenase
  • IDH1 protein, human