The Diagnostic Value Of Diffusion Weighted Imaging For Coexisting Isocitrate Dehydrogenase Mutation And O6-methylguanine-DNA Methyltransferase Promoter Methylation In Glioma

Objective To predict the coexistence of isocitrate dehydrogenase（IDH）mutation and O6-methylguanine-DNA methyltransferase（MGMT）promoter methylation in adult-type diffuse gliomas using apparent diffusion coefficient（ADC）histogram and direct ADC measurements and compare the diagnostic performances of the two methods.Materials and Methods The clinical and imaging data of 118 patients with adult diffuse glioma confirmed by pathology in Affiliated Hospital of Qingdao University from January2017 to April 2022 were retrospectively analyzed.All patients underwent preoperative brain magnetic resonance imaging（MRI）and diffusion weighted imaging（DWI）and did not receive any brain therapy.Based on ADC histogram analysis,ADC histogram parameters were extracted by manually delineating the region of interest（ROI）in solid components of the tumor layer by layer on the ADC map using 3D Slicer software.Based on the direct ADC measurements,the minimum and mean ADC were calculated by placing three circular or elliptic ROIs in solid components of gliomas.When delineating or placing ROIs,the necrotic,hemorrhagic,and cystic regions were avoided with reference to T₁WI,T₂WI and T₂WI-FLAIR.IDH mutation and MGMT promoter methylation status were assessed by genomic sequence analysis using Sanger method and fluorescence quantitative PCR method,and the enrolled patients were divided into coexisting IDH mutation and MGMT promoter methylation group（40 cases）and other molecular status group（78 cases）.The t-test,Wilcoxon–Mann–Whitney test,X² test andX² correction test was used to compare clinical features and parameters of ADC between the two groups.The parameters of ADC that were statistically different between the two sets were included in the multivariate binary logistic regression analysis.Receiver operating characteristic（ROC）curve analysis were used to evaluate the diagnostic performances of the two methods.Results（1）Patients with the coexistence of IDH mutation and MGMT promoter methylation were younger than patients with other molecular status（age:49.03±11.77 years vs 55.53±11.44 years,P=0.005）.Lower grade gliomas were the majority in gliomas with IDH mutation and MGMT promoter methylation（90.0%vs 15.4%,P<0.001）.There was no statistically significant difference in sex between the two groups（P=0.995）.（2）ADC histogram parameters including 10^th percentile,median,mean,root mean squared,90^thpercentile,skewness,kurtosis and minimum were significantly different between the two groups（P<0.001 to P=0.003）.Among the ADC histogram parameters,the 10^th percentile had the highest diagnostic efficiency（AUC=0.860）,and the optimal cut-off value was937.50×10^-6mm²/s with 80.0%sensitivity and 83.3%specificity.（3）Compared with gliomas with other molecular status,the minimum ADC and mean ADC obtained by direct measurements were higher in gliomas with the coexistence of IDH mutation and MGMT promoter methylation,and the difference was statistically significant(971.63±226.79×10^-6mm²/s vs 719.32±162.30×10^-6mm²/s,P<0.001;1146.96±218.15×10^-6mm²/s vs870.15±157.31×10^-6mm²/s,P<0.001).The predictive value of mean ADC was higher（AUC=0.844）,and the optimal cut-off value was 1073.17×10^-6mm²/s with 67.5%sensitivity and 89.7%specificity.（4）Among the three logistic regression models,the logistic regression model combining ADC histogram parameters and direct measurements had the best diagnostic efficiency（AUC:0.938,sensitivity:87.5%,specificity:87.2%）,followed by the logistic regression model combining the ADC histogram parameters with statistically significant difference（AUC:0.916）and the logistic regression model combining minimum ADC and mean ADC obtained by direct measurements（AUC:0.851）.Conclusions DWI has potential value in predicting the coexistence of IDH mutation and MGMT promoter methylation in adult-type diffuse glioma.ADC histogram parameters include 10^th percentile,90^th percentile,median,mean,root mean squared,skewness,kurtosis and minimum,as well as minimum ADC and mean ADC obtained by direct measurements can distinguish gliomas with the coexistence of IDH mutation and MGMT promoter methylation and other molecular status.The diagnostic performance of ADC histogram analysis is better than that of direct ADC measurements.The combination of the two methods showed the best diagnostic performance.