The diagnostic efficiency of integration of 2HG MRS and IVIM versus individual parameters for predicting IDH mutation status in gliomas in clinical scenarios: A retrospective study.

Currently, there remains a scarcity of established preoperative tests to accurately predict the isocitrate dehydrogenase (IDH) mutation status in clinical scenarios, with limited research has explored the potential synergistic diagnostic performance among metabolite, perfusion, and diffusion parameters. To address this issue, we aimed to develop an imaging protocol that integrated 2-hydroxyglutarate (2HG) magnetic resonance spectroscopy (MRS) and intravoxel incoherent motion (IVIM) by comprehensively assessing metabolic, cellular, and angiogenic changes caused by IDH mutations, and explored the diagnostic efficiency of this imaging protocol for predicting IDH mutation status in clinical scenarios. Patients who met the inclusion criteria were categorized into two groups: IDH-wild type (IDH-WT) group and IDH-mutant (IDH-MT) group. Subsequently, we quantified the 2HG concentration, the relative apparent diffusion coefficient (rADC), the relative true diffusion coefficient value (rD), the relative pseudo-diffusion coefficient (rD*) and the relative perfusion fraction value (rf). Intergroup differences were estimated using t-test and Mann-Whitney U test. Finally, we performed receiver operating characteristic (ROC) curve and DeLong's test to evaluate and compare the diagnostic performance of individual parameters and their combinations. 64 patients (female, 21; male, 43; age, 47.0 ± 13.7 years) were enrolled. Compared with IDH-WT gliomas, IDH-MT gliomas had higher 2HG concentration, rADC and rD (P < 0.001), and lower rD* (P = 0.013). The ROC curve demonstrated that 2HG + rD + rD* exhibited the highest areas under curve (AUC) value (0.967, 95%CI 0.889-0.996) for discriminating IDH mutation status. Compared with each individual parameter, the predictive efficiency of 2HG + rADC + rD* and 2HG + rD + rD* shows a statistically significant enhancement (DeLong's test: P < 0.05). The integration of 2HG MRS and IVIM significantly improves the diagnostic efficiency for predicting IDH mutation status in clinical scenarios.

Yu M ，Ge Y ，Wang Z ，Zhang Y ，Hou X ，Chen H ，Chen X ，Ji N ，Li X ，Shen H ... -  《-》

Comparative Value of 2-Hydroxyglutarate-to-Lipid and Lactate Ratio versus 2-Hydroxyglutarate Concentration on MR Spectroscopic Images for Predicting Isocitrate Dehydrogenase Mutation Status in Gliomas.

To compare the ability of 2-hydroxyglutarate (2HG)-to-lipid and lactate (2HG/[lipid + lactate]) ratio with the ability of 2HG concentration alone to predict the isocitrate dehydrogenase (IDH) mutation status in patients with glioma. In this retrospective study, consecutive patients with histopathologically proven glioma were enrolled between July 2016 and February 2019. A total of 79 patients were enrolled (mean age, 44 years; 49 men). The 2HG concentration and other MR spectroscopic parameters were measured by single-voxel point-resolved spectroscopy before surgery. The diagnostic performance of the 2HG concentration and 2HG/(lipid + lactate) ratio were calculated. Internal validation was assessed by the bootstrap approach with 1000 bootstrap resamples. Differences in the predictive accuracy of 2HG/(lipid + lactate) ratio and 2HG concentration were determined by calculating the integrated discrimination improvement. The diagnostic accuracy (sensitivity, specificity, and area under the receiver operating characteristic curve [AUC]) of these measures was also compared separately in patients with glioblastomas and patients with lower-grade gliomas. Of the 79 enrolled patients, 28 had IDH mutations and 51 had wild-type IDH. The sensitivity, specificity, and AUC of 2HG concentration for predicting IDH-mutant gliomas were 89% (25 of 28), 67% (34 of 51), and 0.80 (95% confidence interval [CI]: 0.70, 0.88; C statistic, 0.80), respectively. The sensitivity, specificity, and AUC of the 2HG/(lipid + lactate) ratio for predicting IDH-mutant gliomas were 79% (22 of 28), 92% (47 of 51), and 0.90 (95% CI: 0.81, 0.96; C statistics, 0.90), respectively. The optimal cutoff value for the 2HG/(lipid + lactate) ratio was 0.63. The 2HG/(lipid + lactate) ratio was significantly better for predicting IDH mutation status than the 2HG concentration alone (P < .01). In glioblastoma, the 2HG/(lipid + lactate) ratio was also better for predicting IDH mutations than the 2HG concentration alone, with borderline significance (P = .052). In lower-grade glioma, the 2HG/(lipid + lactate) ratio and the 2HG concentration showed comparable diagnostic performance (P = .72). The 2HG/(lipid + lactate) ratio is more accurate for predicting IDH mutation status in patients with glioma than the 2HG concentration alone.Keywords: Brain/Brain Stem, CNS, MR-Imaging, MR-Spectroscopy, Neoplasms-Primary, Neuro-Oncology© RSNA, 2020.

Suh CH ，Kim HS ，Park JE ，Jung SC ，Choi CG ，Woo DC ，Lee HB ，Kim SJ ... -  《-》

Noninvasive assessment of isocitrate dehydrogenase mutation status in cerebral gliomas by magnetic resonance spectroscopy in a clinical setting.

Tietze A ，Choi C ，Mickey B ，Maher EA ，Parm Ulhøi B ，Sangill R ，Lassen-Ramshad Y ，Lukacova S ，Østergaard L ，von Oettingen G ... -  《-》

Treatment Response Assessment in IDH-Mutant Glioma Patients by Noninvasive 3D Functional Spectroscopic Mapping of 2-Hydroxyglutarate.

Measurements of objective response rates are critical to evaluate new glioma therapies. The hallmark metabolic alteration in gliomas with mutant isocitrate dehydrogenase (IDH) is the overproduction of oncometabolite 2-hydroxyglutarate (2HG), which plays a key role in malignant transformation. 2HG represents an ideal biomarker to probe treatment response in IDH-mutant glioma patients, and we hypothesized a decrease in 2HG levels would be measureable by in vivo magnetic resonance spectroscopy (MRS) as a result of antitumor therapy. We report a prospective longitudinal imaging study performed in 25 IDH-mutant glioma patients receiving adjuvant radiation and chemotherapy. A newly developed 3D MRS imaging was used to noninvasively image 2HG. Paired Student t test was used to compare pre- and posttreatment tumor 2HG values. Test-retest measurements were performed to determine the threshold for 2HG functional spectroscopic maps (fSM). Univariate and multivariate regression were performed to correlate 2HG changes with Karnofsky performance score (KPS). We found that mean 2HG (2HG/Cre) levels decreased significantly (median = 48.1%; 95% confidence interval = 27.3%-56.5%;P= 0.007) in the posttreatment scan. The volume of decreased 2HG correlates (R(2)= 0.88,P= 0.002) with clinical status evaluated by KPS. We demonstrate that dynamic measurements of 2HG are feasible by 3D fSM, and the decrease of 2HG levels can monitor treatment response in patients with IDH-mutant gliomas. Our results indicate that quantitative in vivo 2HG imaging may be used for precision medicine and early response assessment in clinical trials of therapies targeting IDH-mutant gliomas.

Andronesi OC ，Loebel F ，Bogner W ，Marjańska M ，Vander Heiden MG ，Iafrate AJ ，Dietrich J ，Batchelor TT ，Gerstner ER ，Kaelin WG ，Chi AS ，Rosen BR ，Cahill DP ... -  《-》

Accumulation of 2-hydroxyglutarate in gliomas correlates with survival: a study by 3.0-tesla magnetic resonance spectroscopy.

Natsumeda M ，Igarashi H ，Nomura T ，Ogura R ，Tsukamoto Y ，Kobayashi T ，Aoki H ，Okamoto K ，Kakita A ，Takahashi H ，Nakada T ，Fujii Y ... -  《Acta Neuropathologica Communications》