DataSheet_1_Sex-specific radiomic features of L-[S-methyl-11C] methionine PET in patients with newly-diagnosed gliomas in relation to IDH1 predictability.docx

IntroductionAmino-acid positron emission tomography (PET) is a validated metabolic imaging approach for the diagnostic work-up of gliomas. This study aimed to evaluate sex-specific radiomic characteristics of L-[S-methyl-11Cmethionine (MET)-PET images of glioma patients in consideration of the prognostically relevant biomarker isocitrate dehydrogenase (IDH) mutation status.
MethodsMET-PET of 35 astrocytic gliomas (13 females, mean age 41 ± 13 yrs. and 22 males, mean age 46 ± 17 yrs.) and known IDH mutation status were included. All patients underwent radiomic analysis following imaging biomarker standardization initiative (IBSI)-conform guidelines both from standardized uptake value (SUV) and tumor-to-background ratio (TBR) PET values. Aligned Monte Carlo (MC) 100-fold split was utilized for SUV and TBR dataset pairs for both sex and IDH-specific analysis. Borderline and outlier scores were calculated for both sex and IDH-specific MC folds. Feature ranking was performed by R-squared ranking and Mann-Whitney U-test together with Bonferroni correction. Correlation of SUV and TBR radiomics in relation to IDH mutational status in male and female patients were also investigated.
ResultsThere were no significant features in either SUV or TBR radiomics to distinguish female and male patients. In contrast, intensity histogram coefficient of variation (ih.cov) and intensity skewness (stat.skew) were identified as significant to predict IDH +/-. In addition, IDH+ females had significant ih.cov deviation (0.031) and mean stat.skew (-0.327) differences compared to IDH+ male patients (0.068 and -0.123, respectively) with two-times higher standard deviations of the normal brain background MET uptake as well.
DiscussionWe demonstrated that female and male glioma patients have significantly different radiomic profiles in MET PET imaging data. Future IDH prediction models shall not be built on mixed female-male cohorts, but shall rely on sex-specific cohorts and radiomic imaging biomarkers.

引言：氨基酸正电子发射断层扫描（Positron Emission Tomography, PET）是一种经过验证的代谢成像手段，用于胶质瘤的诊断评估。本研究旨在结合与预后相关的生物标志物异柠檬酸脱氢酶（Isocitrate Dehydrogenase, IDH）突变状态，评估胶质瘤患者的L-[甲基-¹¹C]甲硫氨酸（MET）-PET影像的性别特异性放射组学特征。

方法：本研究纳入35例星形细胞胶质瘤患者的MET-PET影像及已知的IDH突变状态信息，其中女性13例，平均年龄41±13岁；男性22例，平均年龄46±17岁。所有患者均按照影像生物标志物标准化倡议（Imaging Biomarker Standardization Initiative, IBSI）的指南要求，对标准化摄取值（Standardized Uptake Value, SUV）和肿瘤本底比（Tumor-to-Background Ratio, TBR）两类PET参数开展放射组学分析。本研究采用对齐式蒙特卡洛（Monte Carlo, MC）100折划分法，针对SUV与TBR的数据集对分别开展性别特异性及IDH特异性分析。针对性别特异性及IDH特异性的MC折，分别计算边界值与异常值评分。特征排序采用R平方排序法结合Mann-Whitney U检验，并进行Bonferroni校正。此外还分析了男性及女性患者中，SUV与TBR放射组学特征与IDH突变状态的相关性。

结果：SUV及TBR放射组学特征均无显著差异可用于区分女性与男性患者。与之相反，强度直方图变异系数（ih.cov）与强度偏度（stat.skew）被证实可显著预测IDH突变状态（IDH+/-）。此外，与IDH突变阳性的男性患者（ih.cov为0.068，stat.skew为-0.123）相比，IDH突变阳性的女性患者的ih.cov（0.031）与平均stat.skew（-0.327）均存在显著差异，且其正常脑组织本底MET摄取的标准差亦为男性患者的2倍。

讨论：本研究证实，在MET-PET影像数据中，女性与男性胶质瘤患者的放射组学特征存在显著差异。未来的IDH预测模型不应基于混合性别的队列构建，而应依托性别特异性队列及放射组学影像生物标志物。