Predicting IDH mutation status in grade II gliomas using amide proton transfer-weighted (APTw) MRI.

To assess the amide proton transfer-weighted (APTw) MRI features of isocitrate dehydrogenase (IDH)-wildtype and IDH-mutant grade II gliomas and to test the hypothesis that the APTw signal is a surrogate imaging marker for identifying IDH mutation status preoperatively. Twenty-seven patients with pathologically confirmed low-grade glioma, who were previously scanned at 3T, were retrospectively analyzed. The Mann-Whitney test was used to evaluate relationships between APTw intensities for IDH-mutant and IDH-wildtype groups, and receiver operator characteristic (ROC) analysis was used to assess the diagnostic performance of APTw. Based on histopathology and molecular analysis, seven cases were diagnosed as IDH-wildtype grade II gliomas and 20 cases as IDH-mutant grade II gliomas. The maximum and minimum APTw values, based on multiple regions of interest, as well as the whole-tumor histogram-based mean and 50th percentile APTw values, were significantly higher in the IDH-wildtype gliomas than in the IDH-mutant groups. This corresponded to the areas under the ROC curves of 0.89, 0.76, 0.75, and 0.75, respectively, for the prediction of the IDH mutation status. IDH-wildtype lesions typically were associated with relatively high APTw signal intensities as compared with IDH-mutant lesions. The APTw signal could be a valuable imaging biomarker by which to identify IDH1 mutation status in grade II gliomas. Magn Reson Med 78:1100-1109, 2017. © 2017 International Society for Magnetic Resonance in Medicine.

Jiang S ，Zou T ，Eberhart CG ，Villalobos MAV ，Heo HY ，Zhang Y ，Wang Y ，Wang X ，Yu H ，Du Y ，van Zijl PCM ，Wen Z ，Zhou J ... -  《-》

Diagnostic performance of gliomas grading and IDH status decoding A comparison between 3D amide proton transfer APT and four diffusion-weighted MRI models.

The focus of neuro-oncology research has changed from histopathologic grading to molecular characteristics, and medical imaging routinely follows this change. To compare the diagnostic performance of amide proton transfer (APT) and four diffusion models in gliomas grading and isocitrate dehydrogenase (IDH) genotype. Prospective. A total of 62 participants (37 males, 25 females; mean age, 52 ± 13 years) whose IDH genotypes were mutant in 6 of 14 grade II gliomas, 8 of 20 of grade III gliomas, and 4 of 28 grade IV gliomas. APT imaging using sampling perfection with application optimized contrasts by using different flip angle evolutions (SPACE) and DWI with q-space Cartesian grid sampling were acquired at 3 T. The ability of diffusion kurtosis imaging, diffusion kurtosis imaging, neurite orientation dispersion and density imaging (NODDI), mean apparent propagator (MAP), and APT imaging for glioma grade and IDH status were assessed, with histopathological grade and genetic testing used as a reference standard. Regions of interest (ROIs) were drawn by two neuroradiologists after consensus. T-test and Mann-Whitney U test; one-way analysis of variance (ANOVA); receiver operating curve (ROC) and area under the curve (AUC); DeLong test. P value < 0.05 was considered statistically significant. Compared with IDH-mutant gliomas, IDH-wildtype gliomas showed a significantly higher mean, 5th-percentile (APT5 ), and 95th-percentile from APTw, the 95th-percentile value of axial, mean, and radial diffusivity from DKI, and 95th-percentile value of isotropic volume fraction from NODDI, and no significantly different parameters from DTI and MAP (P = 0.075-0.998). The combined APT model showed a significantly wider area under the curve (AUC 0.870) for IDH status, when compared with DKI and NODDI. APT5 was significantly different between two of the three groups (glioma II vs. glioma III vs. glioma IV: 1.35 ± 0.75 vs. 2.09 ± 0.93 vs. 2.71 ± 0.81). APT has higher diagnostic accuracy than DTI, DKI, MAP, and NODDI in glioma IDH genotype. APT5 can effectively identify both tumor grading and IDH genotyping, making it a promising biomarker for glioma classification. 1 TECHNICAL EFFICACY: Stage 2.

Guo H ，Liu J ，Hu J ，Zhang H ，Zhao W ，Gao M ，Zhang Y ，Yang G ，Cui Y ... -  《-》

Amide proton transfer-weighted imaging and derived radiomics in the classification of adult-type diffuse gliomas.

To evaluate the utility of amide proton transfer-weighted (APTw) MRI imaging and its derived radiomics in classifying adult-type diffuse glioma. In this prospective study, APTw imaging was performed on 129 patients with adult-type diffuse gliomas. The mean APTw-related metrics (chemical exchange saturation transfer ratio (CESTR), CESTR normalized with the reference value (CESTRnr), and relaxation-compensated inverse magnetization transfer ratio (MTRRex)) and radiomic features within 3D tumor masks were extracted. APTw-radiomics models were developed using a support vector machine (SVM) classifier. Sensitivity analysis with tumor area of interest, different histogram cutoff values, and other classifiers were conducted. CESTR, CESTRnr, and MTRRex in glioblastomas were all significantly higher (p < 0.0003) than those of oligodendrogliomas and astrocytomas, with no significant difference between oligodendrogliomas and astrocytomas. The APTw-related metrics for IDH-wildtype and high-grade gliomas were significantly higher (p < 0.001) than those for the IDH-mutant and low-grade gliomas, with area under the curve (AUCs) of 0.88 for CESTR. The CESTR-radiomics models demonstrated accuracies of 84% (AUC 0.87), 83% (AUC 0.83), 90% (AUC 0.95), and 84% (AUC 0.86) in predicting the IDH mutation status, differentiating glioblastomas from astrocytomas, distinguishing glioblastomas from oligodendrogliomas, and determining high/low grade prediction, respectively, but showed poor performance in distinguishing oligodendrogliomas from astrocytomas (accuracy 63%, AUC 0.63). The sensitivity analysis affirmed the robustness of the APTw signal and APTw-derived radiomics prediction models. APTw imaging, along with its derived radiomics, presents a promising quantitative approach for prediction IDH mutation and grading adult-type diffuse glioma. Amide proton transfer-weighted imaging, a quantitative imaging biomarker, coupled with its derived radiomics, offers a promising non-invasive approach for predicting IDH mutation status and grading adult-type diffuse gliomas, thereby informing individualized clinical diagnostics and treatment strategies. • This study evaluates the differences of different amide proton transfer-weighted metrics across three molecular subtypes and their efficacy in classifying adult-type diffuse glioma. • Chemical exchange saturation transfer ratio normalized with the reference value and relaxation-compensated inverse magnetization transfer ratio effectively predicts IDH mutation/grading, notably the first one. • Amide proton transfer-weighted imaging and its derived radiomics holds potential to be used as a diagnostic tool in routine clinical characterizing adult-type diffuse glioma.

Wu M ，Jiang T ，Guo M ，Duan Y ，Zhuo Z ，Weng J ，Xie C ，Sun J ，Li J ，Cheng D ，Liu X ，Du J ，Zhang X ，Zhang Y ，Liu Y ... -  《-》

Predicting O6-Methylguanine-DNA Methyltransferase Protein Expression in Primary Low- and High-Grade Gliomas Using Certain Qualitative Characteristics of Amide Proton Transfer-Weighted Magnetic Resonance Imaging.

To demonstrate that certain qualitative amide proton transfer-weighted (APTw) characteristics can provide practical imaging clues for predicting O6-methylguanine-DNA methyltransferase (MGMT) protein expression in primary low- and high-grade gliomas, preoperatively and noninvasively. Pathologically confirmed low- and high-grade gliomas with APT data and immunohistochemical (IHC) reports were recruited in this study. The MGMT protein expression status was classified by postsurgery specimen immunostaining. Subjects were divided into two groups, MGMT-positive and MGMT-negative group, according to the immunoreactivity of MGMT protein expression documented in IHC reports. APTw images scanned at 3T magnetic resonance preoperatively were retrospectively analyzed. Two neuroradiologists were trained to evaluate presence of certain APTw features. Kappa value was calculated to show the consistency between the 2 observers. The Mann-Whitney U test was used to evaluate relationships between the 2 groups on APTw features. Negative predictive value and positive predictive value was used to evaluate the ability of APTw characteristics in predicting MGMT protein expression. Receiver operating characteristic curve was used to evaluate the diagnostic performance of APTw characters. Two-tailed P < 0.05 was considered as statistically significant. Forty-two subjects were recruited in this study. Among them 38 specimens presented positive MGMT immunostaining (MGMT-positive group), 4 specimens were negative MGMT immunostaing (MGMT-negative group). There were, respectively, 37 and 5 APTw images appeared positive and negative APTw features. Differences between tumors of positive and negative MGMT expression on qualitative APTw features were significant (P = 0.020). The consistency coefficient of the 2 observers was 0.876 (kappa = 0.876). Three of five llgliomas with negative APTw features showed MGMT-negative immunostaining, leading to a negative predictive value of 60%, and 36 of 37 cases presenting positive APTw characteristics were tumors of MGMT-positive expression, generating a positive predictive value of 97.3%. The area under curve was 0.849. APTw characteristics could be promising imaging markers by which to predict IHC MGMT expression in primary low- and high-grade gliomas preoperatively and noninvasively.

Su L ，Gao P ，Lin S ，Wu B ，Qin W ，Lin Y ，Xue J ... -  《-》

Amide proton transfer-weighted magnetic resonance image-guided stereotactic biopsy in patients with newly diagnosed gliomas.

Pathological assessment using World Health Organization (WHO) criteria is the gold standard for diagnosis of gliomas. However, the accuracy of diagnosis is limited by tissue sampling, particularly for infiltrating, heterogeneous tumours. We assessed the accuracy of amide proton transfer-weighted (APTw) magnetic resonance imaging (MRI)-guided tissue sampling to identify regions of high-grade glioma via radiographic-histopathologic correlation in patients with newly suspected glioma. Twenty-four patients with previously undiagnosed gliomas underwent a volumetric APTw MRI prior to their first neurosurgical procedure. A total of 70 specimens were collected via APTw image-directed stereotactic biopsy. Cellularity, necrosis, proliferation and glioma WHO grade were analysed for all specimens and correlated with corresponding APTw signal intensities. Thirty-three specimens displayed grade-II pathology, 14 grade-III, 15 grade-IV, and eight specimens revealed only peritumoural oedema. Multiple glioma grades were found within a single lesion in six patients. APTw signal intensities of the biopsied sites and the maximum APTw values across all biopsied sites in each patient were significantly higher for high-grade versus low-grade specimens. APTw signal intensities were significantly positively correlated with cellularity (R = 0.757) and proliferation (R = 0.538). Multiple linear regression analysis showed that tumour cellularity and proliferation index were the best predictors of APTw signal intensities. APTw imaging identified tumour areas of higher cellularity and proliferation, allowing identification of high-grade regions within heterogeneous gliomas. APTw imaging can be readily translated for more widespread use and can assist diagnostic neurosurgical procedures by increasing the accuracy of tumour sampling in patients with infiltrating gliomas.

Jiang S ，Eberhart CG ，Zhang Y ，Heo HY ，Wen Z ，Blair L ，Qin H ，Lim M ，Quinones-Hinojosa A ，Weingart JD ，Barker PB ，Pomper MG ，Laterra J ，van Zijl PCM ，Blakeley JO ，Zhou J ... -  《-》