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Accuracy of 2-hydroxyglutarate quantification by short-echo proton-MRS at 3 T: a phantom study
Nicola Bertolino1, Chiara Marchionni2, Francesco Ghielmetti1
1Neuroradiology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy.
Summary
Variable concentrations of N-acetyl-l-aspartate (NAA) and Glutamate (Glu) can confound measurements of the brain oncometabolite 2-hydroxyglutarate (2HG). This may mask low 2HG levels in patients, but is unlikely to cause false positives in IDH-wildtype gliomas.
Area of Science:
- Neuroimaging
- Biomarker Discovery
- Oncology
Background:
- 2-hydroxyglutarate (2HG) is a potential biomarker for IDH-mutant gliomas.
- Standard magnetic resonance spectroscopy (MRS) protocols may face challenges due to spectral overlap.
- N-acetyl-l-aspartate (NAA) and Glutamate (Glu) can interfere with 2HG measurements.
Purpose of the Study:
- To investigate the confounding effects of NAA and Glu concentrations on 2HG measurements using MRS.
- To assess the impact of these confounders on 2HG as a biomarker for IDH-mutant gliomas.
Main Methods:
- Acquired spectra from 25 phantoms with varying concentrations of 2HG, NAA, and Glu.
- Utilized a clinical 3 T scanner and a standard point-resolved spectroscopy sequence (TE = 30 ms).
- Estimated metabolite concentrations via linear combination analysis and simulated basis sets.
Main Results:
- NAA and Glu concentrations significantly confound 2HG measurements.
- Decreased NAA and Glu levels in perilesional areas can lead to underestimation of 2HG.
- This effect is concentration-dependent and can mask low 2HG levels.
Conclusions:
- The confounding effect of NAA and Glu on 2HG measurements must be considered.
- Low 2HG concentrations may be masked in patients, but false positives are unlikely.
- Caution is advised when interpreting 2HG data from standard short echo-time MRS protocols.

