超声分子影像组学评估前列腺癌前列腺特异膜抗原表达:实验研究

Ultrasound molecular radiomics for evaluation of prostate specific membrane antigen expression in prostate cancer:Experimental study

目的 观察超声分子影像组学评估前列腺癌(PCa)前列腺特异膜抗原(PSMA)表达的价值。方法 分别于裸鼠皮下接种22RV1细胞(PSMA阳性表达,n=9)或PC-3细胞(PSMA阴性表达,n=10),构建不同PSMA表达水平人前列腺癌细胞移植瘤裸鼠模型。制备靶向PSMA的超声纳米泡(PSMA-NB),进行表征检测及体内、外超声分子成像。以7∶3比例将裸鼠随机分为训练集及测试集,提取训练集纹理特征,以组内相关系数、单因素分析、最小绝对收缩和选择算子等方法筛选特征,构建超声分子影像组学模型,并评估模型诊断PSMA阳性PCa的效能。结果 所制备PSMA-NB平均粒径为(392.2±31.56)nm, Zeta电位为(-29.3±0.95)mV,体外显像效果理想,稳定性好。共基于训练集数据提取1 561个纹理特征,最终筛选出3个特征,包括exponential_glszm_ZoneVariance、wavelet_HHH_gldm_SmallDependenceLowGrayLevelEmphasis及logarithm_gldm_DependenceVariance,以之构建的超声分子影像组学模型诊断训练集、测试集PSMA阳性表达PCa的曲线下面积分别为0.950、0.875。结论 基于靶向PSMA超声分子影像组学模型可用于评估PCa裸鼠PSMA表达。

Objective To observe the value of ultrasound molecular radiomics for evaluation of prostate specific membrane antigen(PSMA)expression in prostate cancer(PCa).Methods 22RV1 cells(PSMA positive expression,n=9)and PC-3 cells(PSMA negative expression,n=10)were inoculated subcutaneously in nude mice to construct human prostate cancer cell transplantation tumor models with different PSMA expression level.PSMA targeted ultrasound nanobubbles(PSMA-NB)were prepared,and the characterizations of PSMA-NB were detected,while in vivo and in vitro ultrasound molecular imaging were acquired.The nude mice were randomly divided into training set or test set at a ratio of 7∶3.The texture features were extracted in training set.Ultrasound molecular radiomics model was constructed after screening features using intra-class correlation coefficient,one-way analysis,least absolute shrinkage and selection operator,and its efficency for diagnosing PSMA positive PCa was evaluated.Results The average particle size of PSMA-NB was(392.2±31.56)nm,and the Zeta potential was(-29.3±0.95)mV.The targeted nanobubbles showed good stability on in vitro ultrasound imaging.A total of 1561 texture features were extracted in training set,and 3 features,i.e.exponential_glszm_ZoneVariance,wavelet_HHH_gldm_SmallDependenceLowGrayLevelEmphasis and logarithm_gldm_DependenceVariance were screened out.The area under the curve of this radiomics model was 0.950 and 0.875 in training set and test set,respectively.Conclusion Ultrasound molecular radiomics model based on targeted PSMA could be used to evaluate PSMA expression in nude mice PCa.