Reliable diagnosis of IDH-mutant glioblastoma by 2-hydroxyglutarate detection: a study by 3-T magnetic resonance spectroscopy

Abstract

We have previously reported that reliable detection of 2-hydroxyglutarate (2HG) in isocitrate dehydrogenase (IDH)-mutant WHO grade 2 and 3 gliomas is possible utilizing 3.0-T single-voxel magnetic resonance spectroscopy (SVMRS). We set out to determine whether the same method could be applied to detect 2HG in IDH-mutant glioblastoma. Forty-four patients harboring glioblastoma underwent pre-operative MRS evaluation to detect 2HG and other metabolites. Presence of IDH-mutations was determined by IDH1 R132H immunohistochemical analysis and DNA sequencing of surgically obtained tissues. Six out of 44 (13.6%) glioblastomas were IDH-mutant. IDH-mutant glioblastoma exhibited significantly higher accumulation of 2HG (median 3.191 vs. 0.000 mM, p < 0.0001, Mann-Whitney test). A cutoff of 2HG = 0.897 mM achieved high sensitivity (100.0%) and specificity (92.59%) in determining IDH-mutation in glioblastoma. Glioblastoma with high 2HG accumulation did not have significantly longer overall survival than glioblastoma with low 2HG accumulation (p = 0.107, log-rank test). Non-invasive and reliable detection of 2HG in IDH-mutant glioblastoma was possible by 3.0-T SVMRS.

In vivo characterization of physiological and metabolic changes related to isocitrate dehydrogenase 1 mutation expcression by multiparametric MRI and MRS in a rat model with orthotopically grafted human‐derived glioblastoma cell lines

“…Among the in vivo techniques, 1 H MRS appears to be the most promising tool for the identification of IDH1 mutant gliomas by highlighting higher levels of 2-HG in these tumors. [12][13][14] However, this method has demonstrated a relatively high incidence of false positive results, ranging from 18.5% to 26%. 15 Nowadays, a number of structural and functional parameters, such as vascular density, vessel size index (VSI), cerebral blood flow (CBF), blood volume fraction (BVf), tumor oxygenation (tissue oxygen saturation (StO 2 )), and cerebral metabolic rate of oxygen (CMRO 2 ), as well as blood-brain barrier integrity (using a dynamic contrast enhanced (DCE) approach with time to peak (TTP) and signal contrast enhancement), are accessible by MRI.…”

2-Hydroxyglutarate MR spectroscopy for prediction of isocitrate dehydrogenase mutant glioma: a systemic review and meta-analysis using individual patient data

“…Magnetic resonance imaging (MRI) may have such a role as an important noninvasive tool for prediction of IDH mutant glioma; however, no MRI techniques have shown impressive results for predicting IDH mutant glioma except for 2-hydroxyglutarate (2HG) MR spectroscopy (MRS). 2HG MRS was introduced to detect the oncometabolite 2HG, [6][7][8][9][10][11][12][13][14][15][16][17][18][19] which occurs as a direct consequence of an IDH mutation. In previous studies, 2HG MRS demonstrated higher diagnostic performance (high sensitivities of 89-100% and high specificities of 81-88%) 10,18 than conventional MRI (sensitivities of 71-100% and specificities of 51-100%) [20][21][22] and diffusionweighted imaging and perfusion-weighted imaging (sensitivities of 56-100% and specificities of 63-100%).…”

False-Positive Measurement at 2-Hydroxyglutarate MR Spectroscopy in Isocitrate Dehydrogenase Wild-Type Glioblastoma: A Multifactorial Analysis

“…This was the first report to describe the relationship between false-positive 2HG measurement and high lactate concentration (7). It is well-known that such high lactate concentrations are associated with necrosis (6,24); therefore, the interpretation of 2HG concentration in patients with .01 3.9 (1.6, 9.4) ,.01 ADC (3 10 23 mm 2 /sec) 0.2 (0.0, 1.4) .10 0.1 (0.0, 0.7)…”