Pitfalls in 2HG detection with TE-optimized MRS at 3T.

Area of Science:

• Neuroimaging
• Biomarkers
• Oncology

Background:

• In-vivo magnetic resonance spectroscopy (MRS) detects 2-hydroxyglutarate (2HG), a potential biomarker for isocitrate dehydrogenase (IDH)-mutated glioma.
• Previous studies show high diagnostic accuracy for IDH-mutated vs. IDH-wildtype glioma, but less is known about distinguishing from non-tumor tissue.

Purpose of the Study:

• To evaluate the accuracy of TE-optimized 2HG MRS in differentiating IDH-mutated glioma from normal-appearing brain tissue.
• To investigate the influence of spectral modeling strategies on 2HG detection.
• To identify factors contributing to false-positive 2HG signals.

Main Methods:

• 48 patients with suspected IDH-mutated glioma underwent 3T PRESS MRS (TE=97ms) targeting 2HG.
• MRS data from tumor and contralateral non-tumor tissue were analyzed using LCModel.
• Receiver operating characteristic (ROC) analysis assessed diagnostic performance; metabolite correlations were examined.

Main Results:

• TE-optimized PRESS showed lower sensitivity (0.62-0.76) and specificity (0.78-0.85) for IDH-mutated glioma vs. non-tumor tissue compared to previous literature.
• Strong negative correlations between gamma-aminobutyric acid (GABA) and 2HG were observed across modeling strategies.
• A case study highlighted interference from acetone (a ketone body) in a patient on a ketogenic diet.

Conclusions:

• Spectral overlap with GABA and acetone can lead to false-positive 2HG detection in non-tumor brain tissue.
• Clinicians must be aware of these potential pitfalls when interpreting 2HG MRS findings for glioma diagnosis.
• Further research may be needed to refine spectral analysis and improve diagnostic specificity.