动态对比增强及平均表观传播子磁共振成像在预测高级别胶质瘤MGMT启动子甲基化状态中的应用价值

The value of DCE and MAP-MRI in predicting the methylation status of MGMT promoter in high-grade glioma

目的 探讨应用平均表观传播子MRI(mean apparent propagator-magnetic resonance imaging, MAP-MRI)及动态对比增强MRI(dynamic contrast enhanced magnetic resonance imaging, DCE-MRI)预测3、4级胶质瘤患者O6-甲基鸟嘌呤-DNA-甲基转移酶(O6-methylguanine-DNA methyhransferase, MGMT)启动子甲基化状态的可行性。材料与方法 前瞻性纳入本院自2018年6月至2022年1月经病理证实的14例MGMT启动子甲基化和17例MGMT启动子非甲基化胶质瘤患者,进行了术前常规MRI、DCE-MRI及MAP-MRI扫描。通过手动勾画肿瘤实质区域为感兴趣区(region of interest, ROI)并提取ROI定量参数特征,测量DCE-MRI参数及MAP-MRI参数。参数与MGMT甲基化间的相关性采用Pearson相关分析。所有参数均采用两独立样本t检验,比较DCE-MRI和MAP-MRI对预测3、4级胶质瘤MGMT启动子甲基化状态的诊断效能。进一步建立单因素和多因素logistic回归模型,分析构建受试者工作特征(receiver operating characteristic, ROC)曲线,以DeLong检验比较DCE-MRI参数、MAP-MRI参数与多参数联合模型预测MGMT甲基化的诊断效果。结果 DCE-MRI参数容积转运常数(volume transfer constant,Ktrans)、血管外细胞外容积分数(fractional volume of the extravascular-extracellular space, Ve)以及MAP-MRI参数非高斯(non-Gaussianity, NG)、非高斯轴向(non-Gaussianity axial, NGAx)、Q空间逆方差(Q-space inverse variance,QIV)、返回原点概率(return to the origin probability, RTOP)、返回轴线概率(return to the axis probability,RTAP)与MGMT启动子甲基化间呈中等相关性,对预测3、4级胶质瘤MGMT启动子甲基化与非甲基化组间差异具有统计学意义(P<0.05);ROC曲线下面积(area under the curve, AUC)分别为0.803、0.815、0.807、0.803、0.765、0.790、0.739。多因素logistic分析显示Ve是预测MGMT启动子甲基化的最佳预测因子,其准确性最高,AUC为0.815(95%CI:0.659~0.971),比值比(odds ratio, OR)为0.891(95%CI:0.815~0.975)。DeLong检验结果表明DCE-MRI和MAP-MRI多参数联合后预测胶质瘤MGMT启动子甲基化状态的诊断效能最高,AUC为0.992。结论 DCE-MRI和MAP-MRI对于预测高级别胶质瘤MGMT启动子甲基化状态具有一定的应用价值,同时应用两者联合诊断将有助于进一步提高诊断的效能。

Objective:To investigate the feasibility of predicting the methylation status of O6-methylguanine-DNA-methyltransferase(MGMT)promoter in patients with grade 3 and 4 gliomas by mean apparent propagator-MRI(MAP-MRI)and dynamic contrast enhanced MRI(DCE-MRI).Materials and Methods:From June 2018 to January 2022,14 patients with MGMT promoter methylation and 17 patients with MGMT promoter non-methylated gliomas confirmed by pathology in our hospital were prospectively enrolled.Preoperative routine magnetic resonance imaging,DCE-MRI and MAP-MRI scans were performed.The tumor parenchymal region was manually delineated as region of interest(ROI)and the quantitative parameters of ROI were extracted to measure the parameters of DCE-MRI and MAP-MRI.Pearson correlation analysis was used to analyze the correlation between parameters.Two independent sample t-test was used to compare the diagnostic efficacy of DCE-MRI and MAP-MRI in predicting MGMT promoter methylation status of grade 3 and 4 gliomas.Univariate and multivariate logistic regression models were further established,and receiver operating characteristic(ROC)curves were analyzed and constructed.DeLong test was used to compare the diagnostic effects of DCE-MRI parameters,MAP-MRI parameters and multi-parameter combined model in predicting MGMT methylation.Results:The parameters volume transfer constant(Ktrans)and fractional volume of the extravascular-extracellular space(Ve)of DCE-MRI and non-Gaussianity(NG),non-Gaussianityaxial(NGAx),Q-spaceinversevariance(QIV),return to the origin probability(RTOP),return to the axis probability(RTAP)of MAP-MRI were moderately correlated with MGMT promoter methylation,and the differences between the two groups were statistically significant(P<0.05).The area under the ROC curve(AUC)was 0.803,0.815,0.807,0.803,0.765,0.790,0.739,respectively.Multivariate logistic analysis showed that Ve was the best predictor of MGMT promoter methylation,with the highest accuracy and AUC of 0.815(95%CI:0.659-0.971),odds ratio(OR)of 0.891(95%CI:0.815-0.975).The results of DeLong test showed that the combined multi-parameter model of DCE-MRI and MAP-MRI had the highest diagnostic efficiency in predicting the methylation status of the MGMT promoter in glioma,with an AUC of 0.992.Conclusions:DCE-MRI and MAP-MRI are valuable for predicting the methylation status of the MGMT promoter in high-grade gliomas,and the simultaneous application of the two combined diagnoses will help to further improve the diagnostic efficacy.