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 ... -  《-》

Identifying Recurrent Malignant Glioma after Treatment Using Amide Proton Transfer-Weighted MR Imaging: A Validation Study with Image-Guided Stereotactic Biopsy.

To quantify the accuracy of amide proton transfer-weighted (APTw) MRI for identifying active glioma after treatment via radiographically guided stereotactic tissue validation.Experimental Design: Twenty-one patients who were referred for surgery for MRI features concerning for tumor progression versus treatment effect underwent preoperative APTw imaging. Stereotactic biopsy samples were taken from regions of interest with varying APTw signal intensities. The relationship between final clinical pathology and the histopathology of each of the 64 specimens was analyzed relative to APTw results. Analysis of confirmed recurrent tumor or treatment effect tissue was used to perform ROC analysis. Eighteen of 21 patients had recurrent tumor, and 3 had treatment effect on clinical pathology. In 12 patients, there were multiple histopathologic assignments confirmed within the same tumor. Of the 64 total specimens, 20 specimens were active glioma, 27 mixed active and quiescent glioma, and 17 quiescent/no identifiable tumor. APTw signal intensity and histopathologic assignment, cellularity, and proliferation index had significant positive correlations (R = 0.651, 0.580, and 0.458, respectively; all P < 0.001). ROC analysis with a 1.79% APTw intensity cutoff differentiated active from nonactive tumor (AUC of 0.881) with 85.1% sensitivity and 94.1% specificity. Analysis of clinical pathology showed the mean APTw intensity for each patient had 94.4% sensitivity and 100% positive predictive value for identifying recurrent glioma at this cutoff. APTw imaging hyperintensity may be a marker of active malignant glioma. It is able to distinguish between regions of heterogeneous abnormality on anatomic brain MRI with high sensitivity and specificity.

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

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 ... -  《-》

Differentiating the histologic grades of gliomas preoperatively using amide proton transfer-weighted (APTW) and intravoxel incoherent motion MRI.

The purpose of this work was to investigate the diagnostic performance of amide proton transfer-weighted (APTW) and intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) in the preoperative grading of gliomas. Fifty-one patients with suspected gliomas were recruited and underwent a preoperative MRI examination that included APTW and IVIM sequences. All cases were confirmed by postsurgical histopathology. APTW signal intensity, true diffusion coefficient (D), perfusion fraction (f) and pseudo-diffusion coefficient (D*) were applied to assess the solid tumor component and contralateral normal-appearing white matter. The relative APTW signal intensity (rAPTW) was also used. Independent-sample and paired-sample t-tests were used to compare differences in MRI parameters between low-grade glioma (LGG) and high-grade glioma (HGG) groups. The diagnostic performance was assessed with the receiver operating characteristic curve. Twenty-six patients were pathologically diagnosed with LGG and 25 were diagnosed with HGG. APTW, rAPTW and f values were significantly higher (all p < 0.001), whereas D values were significantly lower (p < 0.001) in the HGG group than in the LGG group. There was no significant difference between D* values for the two groups. rAPTW had an area under the curve (AUC) of 0.957, with a sensitivity of 100% and a specificity of 84.6%, followed by APTW, f, D and D*. The combined use of APTW and IVIM showed the best diagnostic performance, with an AUC of 0.986. In conclusion, APTW and IVIM, as two promising supplementary sequences for routine MRI, could be valuable in differentiating LGGs from HGGs.

Zou T ，Yu H ，Jiang C ，Wang X ，Jiang S ，Rui Q ，Mei Y ，Zhou J ，Wen Z ... -  《-》

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 ... -  《-》