d-2-hydroxyglutarate

D-2-Hydroxyglutarate

Isocitrate dehydrogenase (IDH) mutations are highly frequent in glioma, producing high levels of the oncometabolite D-2-hydroxyglutarate (D-2HG). Hence, D-2HG represents a valuable imaging marker for IDH mutant glioma.


Li et al. developed and evaluated a super-resolution 3D MR spectroscopy strategy to map D-2HG and tumor metabolism in IDH-mutated human glioma.

Between March and September 2018, participants with IDH1-mutated gliomas and healthy participants were prospectively scanned with a 3-T whole-brain 3D MR spectroscopic imaging protocol optimized for D-2HG. The acquired D-2HG maps with a voxel size of 5.2 × 5.2 × 12 mm were upsampled to a voxel size of 1.7 × 1.7 × 3 mm using a super-resolution method that combined weighted total variation, feature-based nonlocal means, and high-spatial-resolution anatomic imaging priors. Validation with simulated healthy and patient data and phantom measurements was also performed. The Mann-Whitney U test was used to check that the proposed super-resolution technique yields the highest peak signal-to-noise ratio and structural similarity index. Three participants with IDH1-mutated gliomas (mean age, 50 years ± 21 [standard deviation]; two men) and three healthy participants (mean age, 32 years ± 3; two men) were scanned. Twenty healthy participants (mean age, 33 years ± 5; 16 men) underwent a simulation of upsampled MR spectroscopic imaging. Super-resolution upsampling improved peak signal-to-noise ratio and structural similarity index by 62% (P < .05) and 7.3% (P < .05), respectively, for simulated data when compared with spline interpolation. Correspondingly, the proposed method significantly improved tissue contrast and structural information for the acquired 3D MR spectroscopic imaging data.

High-spatial-resolution whole-brain D-2-hydroxyglutarate imaging is possible in isocitrate dehydrogenase 1-mutated human glioma by using a super-resolution framework to upsample three-dimensional MR spectroscopic images acquired at lower resolution 1).


A study showed some evidence that both IDH1 mutation and 2-HG can lead to EMT-like phenotype and proliferation and migration in glioma cells. EMT-like biomarkers changed in IDH1 mutation cells generated via lentiviral transduction technology or treated in 2-HG 2).


Gas chromatography time-of-flight mass spectrometry was applied to CSF samples collected from 15 consecutive high-grade aSAH patients (modified Fisher grade 3 or 4). Collected CSF samples were analyzed at two time points (admission and the anticipated vasospasm timeframe). Metabolite levels at both time points were compared and correlated with vasospasm status and Glasgow Outcome Scale (GOS) of patients at 1 year post-aSAH. Significance level was defined as p < 0.05 with false discovery rate correction for multiple comparisons.

Of 97 metabolites identified, 16 metabolites, primarily free amino acids, significantly changed between the two time points. These changes were magnified in modified Fisher grade 4 compared with grade 3. Six metabolites (2-hydroxyglutarate, tryptophan, glycine, proline, isoleucine, and alanine) correlated with GOS at 1 year post-aSAH independent of vasospasm status. When predicting patients who had low disability (GOS 5 vs. GOS ≤4), 2-hydroxyglutarate had a sensitivity and specificity of 0.89 and 0.83 respectively.

This preliminary study suggests that specific metabolite changes occur in the brain during the course of aSAH and that quantification of specific CSF metabolites may be used to predict long-term outcome in patients with aSAH. This is the first study to implicate 2-hydroxyglutarate, a known marker of tissue hypoxia, in aSAH pathogenesis 3).

Last update 09.01.2020

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1)
Li X, Strasser B, Jafari-Khouzani K, Thapa B, Small J, Cahill DP, Dietrich J, Batchelor TT, Andronesi OC. Super-Resolution Whole-Brain 3D MR Spectroscopic Imaging for Mapping D-2-Hydroxyglutarate and Tumor Metabolism in Isocitrate Dehydrogenase 1-mutated Human Gliomas. Radiology. 2020 Jan 7:191529. doi: 10.1148/radiol.2020191529. [Epub ahead of print] PubMed PMID: 31909698.
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Lu J, Li D, Zeng Y, Wang H, Feng W, Qi S, Yu L. IDH1 mutation promotes proliferation and migration of glioma cells via EMT induction. J BUON. 2019 Nov-Dec;24(6):2458-2464. PubMed PMID: 31983120.
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Lu AY, Damisah EC, Winkler EA, Grant RA, Eid T, Bulsara KR. Cerebrospinal fluid untargeted metabolomic profiling of aneurysmal subarachnoid hemorrhage: an exploratory study. Br J Neurosurg. 2018 Dec 26:1-5. doi: 10.1080/02688697.2018.1519107. [Epub ahead of print] PubMed PMID: 30585503.
  • d-2-hydroxyglutarate.txt
  • Last modified: 2020/01/27 17:50
  • by administrador