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

Motivation: Detection of D-2-hydroxyglutarate (2-HG) using in-vivo magnetic resonance spectroscopy (MRS) is a highly promising potential biomarker for diagnosis and treatment monitoring in IDH-mutated glioma. Goal(s): This study investigates how 2-HG estimates from unedited MRS (at optimized TE) depend on different modeling strategies. Approach: We analyzed MRS data from patients with IDH-mutated glioma with different modeling strategies, focusing on the effect of spectral overlap on 2-HG quantification. Results: Spectral overlap with metabolites like GABA and acetone can lead to false-positive 2-HG detections in normal-appearing contralateral brain tissue. Clinicians need to be mindful of these pitfalls when interpreting 2-HG estimates. Impact: This study highlights that false-positive 2-HG MRS detection can occur in normal-appearing brain tissue and identifies signal overlap (with GABA, acetone, etc.) as the primary reason. 2-HG estimates should be interpreted carefully in clinical context, including dietary preferences or interventions.