Journal of neuroimaging : official journal of the American Society of Neuroimaging · 2026
Pitfalls in 2HG Detection With TE-Optimized MRS at 3T.
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Alcicek Seyma, Simicic Dunja, Blair Lindsay, Saint-Germain Max, Zöllner Helge J, Davies-Jenkins Christopher W, Holdhoff Matthias, Laterra John, Bettegowda Chetan, Schreck Karisa C, Lin Doris D, Barker Peter B, Kamson David O, Oeltzschner Georg
Аннотация
BACKGROUND AND PURPOSE: In vivo MRS of 2-hydroxyglutarate (2HG) may provide diagnostic and monitoring biomarkers in isocitrate dehydrogenase (IDH)-mutated glioma. A previous meta-analysis has shown good diagnostic accuracy of TE-optimized PRESS for IDH-mutated glioma, but most studies feature IDH-wildtype glioma as a comparison. However, when considering newly identified brain lesions that may mimic glioma, full characterization of its diagnostic utility should also consider the accuracy of 2HG measurement in nontumor tissue. Therefore, we tested how well TE-optimized 2HG levels distinguish between IDH-mutated glioma and nontumor tissue-here, normal-appearing brain. We further examined the impact of different spectral modeling strategies (baseline stiffness, macromolecule inclusion, and basis set composition).
METHODS: Forty-eight patients with diagnosed/suspected IDH-mutated glioma were enrolled. 3T MRS data were acquired from tumor and contralateral nontumor tissue with TE-optimized PRESS and analyzed with "LCModel" software. ROC analysis evaluated 2HG estimates' ability to distinguish IDH-mutated glioma from nontumor tissue. Modeling interactions between 2HG and other metabolites were evaluated to identify reasons for potential false-positive 2HG detection.
RESULTS: TE-optimized PRESS distinguished IDH-mutated glioma from nontumor tissue with lower sensitivity (range 0.76-0.62) and specificity (0.85-0.78) than the literature suggests for IDH-mutated versus IDH-wildtype glioma. Strong negative correlations between gamma-aminobutyric acid (GABA) and 2HG persisted across all modeling strategies and may lead to false-positive 2HG detection in nontumor tissue. We further present a cautionary example from a patient on a ketogenic diet, showing that ketone body acetone can interfere with 2HG detection.
CONCLUSIONS: Spectral overlap with GABA and acetone can lead to false-positive 2HG detection in nontumor tissue.
METHODS: Forty-eight patients with diagnosed/suspected IDH-mutated glioma were enrolled. 3T MRS data were acquired from tumor and contralateral nontumor tissue with TE-optimized PRESS and analyzed with "LCModel" software. ROC analysis evaluated 2HG estimates' ability to distinguish IDH-mutated glioma from nontumor tissue. Modeling interactions between 2HG and other metabolites were evaluated to identify reasons for potential false-positive 2HG detection.
RESULTS: TE-optimized PRESS distinguished IDH-mutated glioma from nontumor tissue with lower sensitivity (range 0.76-0.62) and specificity (0.85-0.78) than the literature suggests for IDH-mutated versus IDH-wildtype glioma. Strong negative correlations between gamma-aminobutyric acid (GABA) and 2HG persisted across all modeling strategies and may lead to false-positive 2HG detection in nontumor tissue. We further present a cautionary example from a patient on a ketogenic diet, showing that ketone body acetone can interfere with 2HG detection.
CONCLUSIONS: Spectral overlap with GABA and acetone can lead to false-positive 2HG detection in nontumor tissue.