Machine learning-based radiomics analysis in predicting RAS mutational status using magnetic resonance imaging

Vincenza Granata, Roberta Fusco, Maria Chiara Brunese, Annabella Di Mauro, Antonio Avallone, Alessandro Ottaiano, Francesco Izzo, Nicola Normanno, Antonella Petrillo
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Abstract

Purpose

To assess the efficacy of radiomics features, obtained by magnetic resonance imaging (MRI) with hepatospecific contrast agent, in pre-surgical setting, to predict RAS mutational status in liver metastases.

Methods

Patients with MRI in pre-surgical setting were enrolled in a retrospective study. Manual segmentation was made by means 3D Slicer image computing, and 851 radiomics features were extracted as median values using the PyRadiomics Python package. The features were extracted considering the agreement with the Imaging Biomarker Standardization Initiative (IBSI). Balancing was performed through synthesis of samples for the underrepresented classes using the self-adaptive synthetic oversampling (SASYNO) approach. Inter- and intraclass correlation coefficients (ICC) were calculated to assess the between-observer and within-observer reproducibility of all radiomics characteristics. For continuous variables, nonparametric Wilcoxon–Mann–Whitney test was utilized. Benjamini and Hochberg's false discovery rate (FDR) adjustment for multiple testing was used. Receiver operating characteristics (ROC) analysis with the calculation of area under the ROC curve (AUC), sensitivity (SENS), specificity (SPEC), positive predictive value (PPV), negative predictive value (NPV) and accuracy (ACC) were assessed for each parameter. Linear and non-logistic regression model (LRM and NLRM) and different machine learning-based classifiers including decision tree (DT), k-nearest neighbor (KNN) and support vector machine (SVM) were considered. Moreover, features selection were performed before and after a normalized procedure using two different methods (3-sigma and z-score). McNemar test was used to assess differences statistically significant between dichotomic tables. All statistical procedures were done using MATLAB R2021b Statistics and Machine Toolbox (MathWorks, Natick, MA, USA).

Results

Seven normalized radiomics features, extracted from arterial phase, 11 normalized radiomics features, from portal phase, 12 normalized radiomics features from hepatobiliary phase and 12 normalized features from T2-W SPACE sequence were robust predictors of RAS mutational status. The multivariate analysis increased significantly the accuracy in RAS prediction when a LRM was used, combining 12 robust normalized features extracted by VIBE hepatobiliary phase reaching an accuracy of 99%, a sensitivity 97%, a specificity of 100%, a PPV of 100% and a NPV of 98%. No statistically significant increase was obtained, considering the tested classifiers DT, KNN and SVM, both without normalization and with normalization methods.

Conclusions

Normalized approach in MRI radiomics analysis allows to predict RAS mutational status.

Abstract Image

基于机器学习的放射组学分析利用磁共振成像预测 RAS 突变状态
目的 评估手术前使用肝脏特异性造影剂进行磁共振成像(MRI)获得的放射组学特征对预测肝转移瘤的RAS突变状态的有效性。通过 3D Slicer 图像计算进行手动分割,并使用 PyRadiomics Python 软件包提取 851 个放射组学特征的中值。提取特征时考虑了与成像生物标记标准化倡议(IBSI)的一致性。使用自适应合成过采样(SASYNO)方法,通过合成代表性不足类别的样本来实现平衡。通过计算类间和类内相关系数(ICC)来评估所有放射组学特征在观察者之间和观察者内部的重现性。对于连续变量,采用非参数 Wilcoxon-Mann-Whitney 检验。采用本杰明尼和霍赫伯格假发现率(FDR)调整多重检验。通过计算 ROC 曲线下面积 (AUC)、灵敏度 (SENS)、特异度 (SPEC)、阳性预测值 (PPV)、阴性预测值 (NPV) 和准确度 (ACC),对每个参数进行了受试者操作特征 (ROC) 分析。考虑了线性和非逻辑回归模型(LRM 和 NLRM)以及不同的基于机器学习的分类器,包括决策树(DT)、k-近邻(KNN)和支持向量机(SVM)。此外,在使用两种不同方法(3-sigma 和 z-score)进行归一化处理之前和之后,都进行了特征选择。McNemar 检验用于评估二分表之间在统计意义上的差异。结果从动脉期提取的 7 个归一化放射组学特征、从门静脉期提取的 11 个归一化放射组学特征、从肝胆期提取的 12 个归一化放射组学特征以及从 T2-W SPACE 序列提取的 12 个归一化特征是预测 RAS 突变状态的可靠指标。使用 LRM 时,多变量分析可显著提高 RAS 预测的准确性,结合 VIBE 肝胆期提取的 12 个稳健归一化特征,准确率达到 99%,灵敏度为 97%,特异性为 100%,PPV 为 100%,NPV 为 98%。在没有采用归一化方法和采用归一化方法的情况下,测试的分类器 DT、KNN 和 SVM 的准确率都没有明显提高。
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