In vivo targeted MRS detection of 2-hydroxyglutarate molecules in IDH-mutant gliomas via spin regulation

2-hydroxyglutarate (2-HG) is a key metabolic biomarker for identifying IDH-mutant gliomas. Non-invasive and accurate detection of 2-HG is of great significance for the early diagnosis of diseases and dynamic monitoring of therapeutic efficacy. However, conventional magnetic resonance spectroscopy (MRS) faces challenges in detecting 2-HG in vivo, mainly due to the overlap of its resonance peaks with those of metabolites such as glutamate (Glu) and N-acetylaspartate (NAA). Although the long echo time (TE) filtering method can separate signals to a certain extent, it is often accompanied by peak distortion and signal attenuation, which limits its clinical application. To address this problem, this study proposes a 2-HG-targeted detection sequence based on optimal control pulses. By applying optimal control pulses to regulate the state evolution of a 14-spin system composed of 2-HG, Glu, and NAA molecules, the study achieves selective retention of 2-HG signals and suppression of other molecular signals. In experimental verification conducted on phantoms and IDH-mutant glioma animal models, the targeted sequence exhibited excellent signal resolution performance: it efficiently retained 2-HG signals and achieved approximately 95% and 98% suppression of Glu and NAA signals, respectively. To further verify the quantitative reliability of the targeted sequence, the 2-HG concentrations measured by this sequence were compared with those obtained by liquid chromatography-tandem mass spectrometry (LC-MS/MS). A high linear correlation was found between the two sets of results, which fully confirms the accuracy of non-invasive quantitative detection of 2-HG using the targeted sequence.