NIMG-54PREOPERATIVE PREDICTION OF IDH1 MUTATION IN GLIOMA TISSUE BY MR SPECTROSCOPY

INTRODUCTION: Mutation in isocitrate dehydrogenase 1 (IDH1) are found in up to 80% of low-grade glioma and secondary glioblastoma. The 2-hydroxyglutaric acid (2HG) specifically produced by mutant IDH1 would be a target to detect IDH1 mutant glioma. Therefore, reliable measurements of 2HG with in vivo MR spectroscopy (MRS) are of clinical interest to develop a noninvasive detection of IDH mutant glioma. MATERIALS AND METHODS: Metabolic profiling including 2HG of tumor targets was assessed by in vivo MRS preoperatively and analyzed with LC-model post-processing. Stereotactic navigation-guided sampling was performed exactly of the corresponding area to the preoperative MRS sampling. Ex vivo 2HG of the samples was quantified by Gas Chromatography Mass spectrometer (GC/MS) and compared with 2HG detected by in vivo MRS. The diagnosis of IDH1 mutant gliomas was confirmed by the immunohistochemical staining and the DNA sequence. RESULTS: Of the 40 patients enrolled in this study, 16(40%) had histologically verified IDH1 mutation. 2HG was exactly measurable by MRS at higher concentration than 1.5mM in 8 of 16 IDH mutated cases (Sensitivity 57% and specificity 92%). Although there were no significantly differences in metabolites of the TCA cycle between IDH1 mutant and wild cases, glutamate and glutamine were significantly lower in the IDH1 mutant group. Additional measurement of glutamate reduced false-negative results to predictive IDH1 mutation. Sensitivity improved to 69% and specificity to 100% (AUC 0.89). CONCLUSIONS: A change of the glutamine metabolism is inferred with IDH1 mutation. Measurement of glutamate may support the potential clinical use of 2HG using MRS as a predictor for IDH1 mutation in glioma because of limiting ability to measure 2HG directly with preoperative MRS.