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Purpose: 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., Materials and Methods: 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., Results: 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)., Conclusion: 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., (2020 by the Radiological Society of North America, Inc.)

Objectives: A combination of T2/FLAIR mismatch sign and advanced imaging parameters may improve the determination of molecular subtypes of diffuse lower-grade glioma. We assessed the diagnostic value of adding the apparent diffusion coefficient (ADC) and cerebral blood volume (CBV) to the T2/FLAIR mismatch sign for differentiation of the IDH mutation or 1p/19q codeletion., Materials and Methods: Preoperative conventional, diffusion-weighted, and dynamic susceptibility contrast imaging were performed on 110 patients with diffuse lower-grade gliomas. The study population was classified into three groups using molecular subtype, namely IDH mutation and 1p/19q codeletion (IDHmut-Codel), IDH wild type (IDHwt) and IDH mutation and no 1p/19q codeletion (IDHmut-Noncodel). T2/FLAIR mismatch sign and the histogram parameters of apparent diffusion coefficient (ADC) and normalised cerebral blood volume (nCBV) values were assessed. A multivariate logistic regression model was constructed to distinguish IDHmut-Noncodel from IDHmut-Codel and IDHwt and from IDHwt, and the performance was compared with that of single parameters using the area under the receiver operating characteristics curve (AUC)., Results: Positive visual T2/FLAIR mismatch sign and higher nCBV skewness were significant variables to distinguish IDHmut-Noncodel from the other two groups (AUC, 0.88; 95% CI, 0.81-0.96). A lower ADC10 was a significant variable for distinguishing IDHmut-Noncodel from the IDHwt group (AUC, 0.75; 95% CI, 0.62-0.89). Adding ADC or CBV histogram parameters to T2/FLAIR mismatch sign improved performance in distinguishing IDHmut-Noncodel from the other two groups (AUC 0.882 vs. AUC 0.810) or from IDHwt (AUC 0.923 vs. AUC 0.868)., Conclusions: The combination of the T2/FLAIR mismatch sign with ADC or CBV histogram parameters can improve the identification of IDHmut-Noncodel diffuse lower-grade gliomas, which can be easily applied in clinical practice., Key Points: • The combination of the T2/FLAIR mismatch sign with the ADC or CBV histogram parameters can improve the identification of IDHmut-Noncodel diffuse lower-grade gliomas. • The multivariable model showed a significantly better performance for distinguishing the IDHmut-Noncodel group from other diffuse lower-grade gliomas than the T2/FLAIR mismatch sign alone or any single parameter. • The IDHmut-Noncodel type was associated with intermediate treatment outcomes; therefore, the identification of IDHmut-Noncodel diffuse lower-grade gliomas could be helpful for determining the clinical approach.

Objectives: To investigate whether clinical condition, imaging session, and locations affect repeatability of amide proton transfer-weighted (APTw) magnetic resonance imaging (MRI) in the brain., Materials and Methods: Three APTw MRI data sets were acquired, involving two intrasession scans and one intersession scan for 19 healthy, 15 glioma, and 12 acute stroke adult participants (mean age 53.8, 54.6, and 68.5, respectively) on a 3T MR scanner. The mean APTw signals from five locations in healthy brain (supratentorial and infratentorial locations) and from entire tumor and stroke lesions (supratentorial location) were calculated. The within-subject coefficient of variation (wCV) and intraclass correlation coefficient (ICC) were calculated for each clinical conditions, image sessions, and anatomic locations. Differences in APTw signals between sessions were analyzed using repeated-measures analysis of variance., Results: The ICC and wCV were 0.96 (95% confidence interval [CI], 0.91-0.99) and 16.1 (12.6-21.3) in glioma, 0.93 (0.82-0.98) and 15.0 (11.4-20.6) in stroke, and 0.84 (0.72-0.91) and 34.0 (28.7-41.0) in healthy brain. There were no significant differences in APTw signal between three sessions, irrespective of disease condition and location. The ICC and wCV were 0.85 (0.68-0.94) and 27.4 (21.8-35.6) in supratentorial, and 0.44 (- 0.18 to 0.76) and 32.7 (25.9 to 42.9) in infratentorial locations. There were significant differences in APTw signal between supra- (mean, 0.49%; 95% CI, 0.38-0.61) and infratentorial locations (1.09%, 0.98-1.20; p < 0.001)., Conclusion: The repeatability of APTw signal was excellent in supratentorial locations, while it was poor in infratentorial locations due to severe B0 inhomogeneity and susceptibility which affects MTR asymmetry., Key Points: • In supratentorial locations, APTw MRI showed excellent intrasession and intersession repeatability in brains of healthy controls and patients with glioma, as well as in stroke-affected regions. • APTw MRI showed excellent repeatability in supratentorial locations, but poor repeatability in infratentorial locations. • Considering poor repeatability in the infratentorial locations, the use of APTw MRI in longitudinal assessment in infratentorial locations is not indicated.

Purpose: Grading of brain gliomas is of clinical importance, and noninvasive molecular imaging may help differentiate low- and high-grade gliomas. We aimed to evaluate the diagnostic performance of amide proton transfer-weighted (APTw) MRI for differentiating low- and high-grade gliomas on 3-T scanners., Methods: A systematic literature search of Ovid-MEDLINE and EMBASE was performed up to March 28, 2018. Original articles evaluating the diagnostic performance of APTw MRI for differentiating low- and high-grade gliomas were selected. The pooled sensitivity and specificity were calculated using a bivariate random-effects model. A coupled forest plot and a hierarchical summary receiver operating characteristic curve were obtained. Heterogeneity was investigated using Higgins inconsistency index (I 2 ) test. Meta-regression was performed., Results: Ten original articles with a total of 353 patients were included. High-grade gliomas showed significantly higher APT signal intensity than low-grade gliomas. The pooled sensitivity and specificity for the diagnostic performance of APTw MRI for differentiating low-grade and high-grade gliomas were 88% (95% CI, 77-94%) and 91% (95% CI, 82-96%), respectively. Higgins I 2 statistic demonstrated heterogeneity in the sensitivity (I 2  = 68.17%), whereas no heterogeneity was noted in the specificity (I 2  = 44.84%). In meta-regression, RF saturation power was associated with study heterogeneity. Correlation coefficients between APT signal intensity and Ki-67 cellular proliferation index ranged from 0.430 to 0.597, indicating moderate correlation. All studies showed excellent interobserver agreement., Conclusions: Although heterogeneous protocols were used, APTw MRI demonstrated excellent diagnostic performance for differentiating low- and high-grade gliomas. APTw MRI could be a reliable technique for glioma grading in clinical practice.

Objectives: To evaluate the imaging features of isocitrate dehydrogenase (IDH) mutant glioma and to assess the diagnostic performance of magnetic resonance imaging (MRI) for prediction of IDH mutation in patients with glioma., Methods: A systematic search of Ovid-MEDLINE and EMBASE up to 10 October 2017 was conducted to find relevant studies. The search terms combined synonyms for 'glioma', 'IDH mutation' and 'MRI'. Studies evaluating the imaging features of IDH mutant glioma and the diagnostic performance of MRI for prediction of IDH mutation in patients with glioma were selected. The pooled summary estimates of sensitivity and specificity and their 95% confidence intervals (CIs) were calculated using a bivariate random-effects model. The results of multiple subgroup analyses are reported., Results: Twenty-eight original articles in a total of 2,146 patients with glioma were included. IDH mutant glioma showed frontal lobe predominance, less contrast enhancement, well-defined border, high apparent diffusion coefficient (ADC) value and low relative cerebral blood volume (rCBV) value. For the meta-analysis that included 18 original articles, the summary sensitivity was 86% (95% CI, 79%-91%) and the summary specificity was 87% (95% CI, 78-92%). In a subgroup analysis, the summary sensitivity of 2-hydroxyglutarate magnetic resonance spectroscopy (MRS) [96% (95% CI, 91-100%)] was higher than the summary sensitivities of other imaging modalities., Conclusions: IDH mutant glioma consistently demonstrated less aggressive imaging features than IDH wild-type glioma. Despite the variety of different MRI techniques used, MRI showed the potential to non-invasively predict IDH mutation in patients with glioma. 2-Hydroxyglutarate MRS shows higher pooled sensitivity than other imaging modalities., Key Points: • IDH mutant glioma showed frontal lobe predominance, less contrast enhancement, well-defined border, high ADC value, and low rCBV value. • The diagnostic performance of MRI for prediction of IDH mutation in patients with glioma is within a clinically acceptable range, the summary sensitivity was 86% (95% CI, 79-91%) and the summary specificity was 87% (95% CI, 78-92%). • In a subgroup analysis, the summary sensitivity of 2-hydroxyglutarate MRS [96% (95% CI, 91-100%)] was higher than the summary sensitivities of other imaging modalities.

Background: Noninvasive and accurate modality to predict isocitrate dehydrogenase (IDH) mutant glioma may have great potential in routine clinical practice. We aimed to investigate the diagnostic performance of 2-hydroxyglutarate (2HG) magnetic resonance spectroscopy (MRS) for prediction of IDH mutant glioma and provide an optimal cutoff value for 2HG., Methods: A systematic literature search of Ovid-MEDLINE and EMBASE was performed to identify original articles investigating the diagnostic performance of 2HG MRS up to March 20, 2018. Pooled sensitivity and specificity were calculated using a bivariate random-effects model. Subgroup analysis and meta-regression were performed to explain heterogeneity effects. An optimal cutoff value for 2HG was calculated from studies providing individual patient data., Results: Fourteen original articles with 460 patients were included. The pooled sensitivity and specificity for the diagnostic performance of 2HG MRS for prediction of IDH mutant glioma were 95% (95% CI, 85-98%) and 91% (95% CI, 83-96%), respectively. The Higgins I2 statistic demonstrated that heterogeneity was present in the sensitivity (I2 = 50.69%), but not in the specificity (I2 = 30.37%). In the meta-regression, echo time (TE) was associated with study heterogeneity. Among the studies using point-resolved spectroscopy (PRESS), a long TE (97 ms) resulted in higher sensitivity (92%) and specificity (97%) than a short TE (30-35 ms; sensitivity of 90%, specificity of 88%; P < 0.01). The optimal 2HG cutoff value of 2HG using individual patient data was 1.76 mM., Conclusion: 2HG MRS demonstrated excellent specificity for prediction of IDH mutant glioma, with TE being associated with heterogeneity in the sensitivity., Key Points: 1. HG MRS has excellent diagnostic performance in the prediction of IDH mutant glioma. 2. The pooled sensitivity was 95% and the pooled specificity was 91%. 3. Echo time was associated with study heterogeneity in the meta-regression.

Objectives: Differentiation of glioma from brain metastasis is clinically crucial because it affects the clinical outcome of patients and alters patient management. Here, we present a systematic review and meta-analysis of the currently available data on perfusion magnetic resonance imaging (MRI) for differentiating glioma from brain metastasis, assessing MRI protocols and parameters., Methods: A computerised search of Ovid-MEDLINE and EMBASE databases was performed up to 3 October 2017, to find studies on the diagnostic performance of perfusion MRI for differentiating glioma from brain metastasis. Pooled summary estimates of sensitivity and specificity were obtained using hierarchical logistic regression modelling. We conducted meta-regression and subgroup analyses to explain the effects of the study heterogeneity., Results: Eighteen studies with 900 patients were included. The pooled sensitivity and specificity were 90% (95% CI, 84-94%) and 91% (95% CI, 84-95%), respectively. The area under the hierarchical summary receiver operating characteristic curve was 0.96 (95% CI, 0.94-0.98). The meta-regression showed that the percentage of glioma in the study population and the study design were significant factors affecting study heterogeneity. In a subgroup analysis including patients with glioblastoma only, the pooled sensitivity was 92% (95% CI, 84-97%) and the pooled specificity was 94% (95% CI, 85-98%)., Conclusions: Although various perfusion MRI techniques were used, the current evidence supports the use of perfusion MRI to differentiate glioma from brain metastasis. In particular, perfusion MRI showed excellent diagnostic performance for differentiating glioblastoma from brain metastasis., Key Points: • Perfusion MRI shows high diagnostic performance for differentiating glioma from brain metastasis. • The pooled sensitivity was 90% and pooled specificity was 91%. • Peritumoral rCBV derived from DSC is a relatively well-validated.

Objectives: To compare the diagnostic performance of amide proton transfer (APT) imaging and 11-C methionine positron emission tomography (MET-PET) for in vivo molecular imaging of protein metabolism in post-treatment gliomas., Materials and Methods: This study included 43 patients (12 low and 31 high grade) with post-treatment gliomas who underwent both APT and MET-PET imaging within 3 weeks. APT-weighted voxel values and semi-quantitative tumour-to-normal ratios (TNR) were obtained from tumour portions. The voxel-wise relationships between TNR and APT were assessed. The diagnostic performance for recurrence of high-grade gliomas was calculated, using the area under the receiver operating characteristic curve (AUC) with maximum (TNR max and APT max ) and 90% histogram values (TNR90 and APT90)., Results: A moderate positive correlation between TNR and APT was found in low-grade recurrences (r = 0.47, p < 0.001), but not in high-grade ones (r = -0.24, p < 0.001). For distinguishing recurrence in post-treatment high-grade gliomas, APT max (AUC, 0.88) and APT90 (AUC, 0.78-0.83) had a similar to better diagnostic performance than TNR max (AUC, 0.71, p = 0.08) or TNR90 (AUC, 0.53-0.59, p = 0.01-0.05)., Conclusions: In post-treatment high-grade gliomas, APT provides different regional information to MET-PET and provides higher diagnostic performance. This difference needs to be considered when using APT or MET-PET as a surrogate marker for tumour protein metabolism., Key Points: • APT and TNR values in low-grade recurrence showed a moderate voxel-wise correlation. • APT and TNR demonstrated regional differences in post-treatment high-grade gliomas. • APT90 showed better diagnostic performance than TNR90 in high-grade recurrence.

Introduction: The need for information regarding functional alterations in patients with brain gliomas is increasing, but little is known about the functional consequences of focal brain tumors throughout the entire brain. Using resting-state functional MR imaging (rs-fMRI), this study assessed functional connectivity in patients with supratentorial brain gliomas with possible alterations in long-distance connectivity and network topology., Methods: Data from 36 patients with supratentorial brain gliomas and 12 healthy subjects were acquired using rs-fMRI. The functional connectivity matrix (FCM) was created using 32 pairs of cortical seeds on Talairach coordinates in each individual subject. Local and distant connectivity were calculated using z-scores in the individual patient's FCM, and the averaged FCM of patients was compared with that of healthy subjects. Weighted network analysis was performed by calculating local efficiency, global efficiency, clustering coefficient, and small-world topology, and compared between patients and healthy controls., Results: When comparing the averaged FCM of patients with that of healthy controls, the patients showed decreased long-distance, inter-hemispheric connectivity (0.32 ± 0.16 in patients vs. 0. 42 ± 0.15 in healthy controls, p = 0.04). In network analysis, patients showed increased local efficiency (p < 0.05), but global efficiency, clustering coefficient, and small-world topology were relatively preserved compared to healthy subjects., Conclusion: Patients with supratentorial brain gliomas showed decreased long-distance connectivity while increased local efficiency and preserved small-world topology. The results of this small case series may provide a better understanding of the alterations of functional connectivity in patients with brain gliomas across the whole brain scale.

Purpose: To correlate and compare diagnostic performance with amide proton transfer (APT) imaging as a tumor proliferation index with that with magnetic resonance (MR) spectroscopy in subgroups of patients with pre- and posttreatment glioma., Materials and Methods: This retrospective study was approved by the institutional review board. In 40 patients with pretreatment glioma and 25 patients with posttreatment glioma, correlation between APT asymmetry and the choline-to-creatine and choline-to-N-acetylaspartate ratios in corresponding voxels of interest was determined, and the 90% histogram cutoff of APT asymmetry values (APT90) for the entire solid portion of gliomas was calculated for diagnostic performance. Area under the receiver operating characteristic curve (AUC), leave-one-out cross validation, and intraclass correlation coefficients were analyzed., Results: The APT asymmetry values showed a moderate correlation (r = 0.49, P < .001) with the choline-to-creatine ratios and a mild correlation with the choline-to-N-acetyl-aspartate ratios (r = 0.32, P = .011) in the corresponding lesions. The APT90 showed comparable diagnostic accuracy for grading of gliomas (AUC, 0.81-0.84 vs 0.86; P = .582-.864) and superior accuracy for differentiation of tumor progression from treatment-related change (AUC, 0.89-0.90 vs 0.60; P = .031-.046) compared with those with MR spectroscopy. The cross-validated area under the curve and accuracy of the APT90 in posttreatment gliomas were 0.89-0.90 and 72%, respectively. The interreader agreement for APT90 was excellent in both pretreatment and posttreatment gliomas (intraclass correlation coefficient, 0.95 and 0.96, respectively)., Conclusion: APT imaging used as a tumor proliferation index showed moderate correlation with MR spectroscopic values and is a superior imaging method to MR spectroscopy, particularly for assessment of posttreatment gliomas., (© RSNA, 2015.)