中国寄生虫学与寄生虫病杂志 ›› 2024, Vol. 42 ›› Issue (5): 582-593.doi: 10.12140/j.issn.1000-7423.2024.05.004
汪占金1(), 陈志恒1, 李富源1, 蔡俊杰1, 薛张佗1, 周瀛2, 曹云太3, 王展4,*(
)
收稿日期:
2024-05-16
修回日期:
2024-09-04
出版日期:
2024-10-30
发布日期:
2024-10-24
通讯作者:
* 王展(1985—),男,博士,副主任医师,从事棘球蚴病人工智能诊治研究。E-mail:ufofu01@163.com作者简介:
汪占金(1999—),男,硕士研究生,从事棘球蚴病人工智能诊治研究。E-mail:18197256027@163.com
基金资助:
WANG Zhanjin1(), CHEN Zhiheng1, LI Fuyuan1, CAI Junjie1, XUE Zhangtuo1, ZHOU Ying2, CAO Yuntai3, WANG Zhan4,*(
)
Received:
2024-05-16
Revised:
2024-09-04
Online:
2024-10-30
Published:
2024-10-24
Contact:
* E-mail: Supported by:
摘要:
目的 开发影像组学和临床特征的机器学习模型,以精准鉴别肝细粒棘球蚴病(HCE)病灶的生物活性。 方法 收集2018—2022年就诊于青海大学附属医院肝胆胰外科的521例HCE患者和就诊于果洛州人民医院普外科和玉树州人民医院普外科的236例HCE患者的CT图像及临床资料,提取影像特征并进行筛选。对临床资料采用单因素及多因素Logistic回归分析,筛选构建模型的特征。采用Logistic回归(LR)、支持向量机(SVM)、K-近邻算法(KNN)、随机森林(RandomForest)、极限梯度提升(XGBoost)、轻量级梯度提升机(LightGBM)、极端随机树(ExtraTrees)等7种机器学习算法构建影像组学模型和临床模型,结合影像组学模型和临床模型的预测结果,基于软投票法构建联合模型,采用Delong检验比较影像组学模型、临床模型和临床-影像联合模型的性能,并通过外部验证评估模型性能。 结果 共430例患者被纳入进行模型开发训练,171例患者作为外部验证,筛选出51个影像特征及5个临床特征用于构建模型。7种机器学习模型中,以XGBoost算法性能表现最佳,其构建的临床模型在训练集和外部验证集上的AUC值均最大,分别为0.977[95%置信区间(95% CI):0.964~0.990]和0.839(95% CI:0.776~0.901);其构建的影像组学模型AUC值均最大,分别为0.998(95% CI:0.997~1.000和0.874(95% CI:0.822~0.927);其构建的联合模型AUC值均最大,分别为1.000(95% CI:0.999~1.000)和0.931(95% CI:0.894~0.968)。DeLong检验结果表明,联合模型在训练集上的性能优于临床模型(Z = 2.154,P < 0.05),与影像组学模型差异无统计学意义(Z = 0.562,P > 0.05);在外部验证集上的性能优于临床模型和影像组学模型(Z = 3.338、3.331,P < 0.05)。校准曲线和决策分析(DCA)曲线表明,联合模型在训练集和外部验证集的校准性能最佳、净收益最高,在不同数据集上性能稳定,在外部验证中展现了良好的泛化能力和可靠性。 结论 基于影像组学以及临床数据开发的机器学习模型能够精准鉴别肝细粒棘球蚴病病灶的生物活性,联合模型具更高的诊断精度和临床应用潜力,可为HCE患者的治疗方案提供参考。
中图分类号:
汪占金, 陈志恒, 李富源, 蔡俊杰, 薛张佗, 周瀛, 曹云太, 王展. 基于影像组学及临床特征的机器学习模型鉴别肝细粒棘球蚴病病灶活性的研究[J]. 中国寄生虫学与寄生虫病杂志, 2024, 42(5): 582-593.
WANG Zhanjin, CHEN Zhiheng, LI Fuyuan, CAI Junjie, XUE Zhangtuo, ZHOU Ying, CAO Yuntai, WANG Zhan. Identification of lesion activities in haptic cystic echinococcosis using machine learning model based on radiomics and clinical features[J]. Chinese Journal of Parasitology and Parasitic Diseases, 2024, 42(5): 582-593.
表1
病灶有无活性与肝细粒棘球蚴病患者基本信息及临床特征的单因素和多因素Logistic回归分析
临床特征 Clinical features | 无活性 Inactive (n = 272) | 有活性 Active (n = 158) | 单因素Logistic回归 Univariatelogistic regression analysis | 多因素Logistic回归 Multivariate logistic regression analysis | |||||
---|---|---|---|---|---|---|---|---|---|
优势比(95% CI) OR(95% CI) | P | 优势比(95% CI)OR(95% CI) | P | ||||||
年龄/岁 Age/Year | 48.0 (40.0-57.0) | 41.5 (34.0-49.0) | 0.991(0.988~0.933) | < 0.05 | 0.992(0.990-0.995) | < 0.05 | |||
性别/例 Gender/case | 1.070(0.991~1.156) | > 0.05 | |||||||
男 Male | 123(45.2%)a | 83(52.5%)a | |||||||
女 Famale | 149(54.8%)a | 75(47.5%)a | |||||||
病灶位置/例 Lesion location/case | 0.989(0.946~1.034) | > 0.05 | |||||||
肝右叶 Right liver | 165(60.7%)a | 92(58.2%)a | |||||||
肝左叶 Left liver | 75(27.6%)a | 34(21.5%)a | |||||||
肝左右叶 Both liver | 32(11.8%)a | 32(20.3%)a | |||||||
病灶数量/例 No. lesion/case | 1.072(0.991~1.160) | > 0.05 | |||||||
单发 Single lesion | 171(62.9%) | 88(55.7%) | |||||||
多发 Multiple lesions | 101(37.1%) | 70(44.3%) | |||||||
病灶最大直径/cm Lesion max diameter/cm | 5.6(4.4-7.3) | 7.9(5.9-9.9) | 1.064(1.049~1.079) | < 0.05 | 1.049(1.036-1.062) | < 0.05 | |||
红细胞/ × 109L Red blood cells/ × 109L | 6.1(5.2-7.2) | 6.2(5.0-7.6) | 1.211(1.141~1.284) | < 0.05 | 1.297(1.219-1.379) | < 0.05 | |||
白细胞/ × 109L White blood cells/ × 109L | 4.6(4.2-5.0) | 5.0(4.5-5.4) | 1.018(1.000~1.037) | > 0.05 | |||||
血红蛋白/ × 109L Hemoglobin/ × 109L | 153.0(144.0-162.0) | 151.0(133.0-163.0) | 0.997(0.996~0.999) | < 0.05 | 0.995(0.993-0.997) | < 0.05 | |||
淋巴细胞/ × 109L Lymphocytes/ × 109L | 1.8(1.5-2.1) | 1.8(1.4-2.3) | 1.047(0.984~1.114) | > 0.05 | |||||
中性粒细胞/ × 109L Neutrophils/ × 109L | 3.3(2.7-4.0) | 3.5(2.7-4.7) | 0.911(0.807~1.029) | > 0.05 | |||||
单核细胞/ × 109L Monocytes/ × 109L | 0.4(0.3-0.5) | 0.4(0.3-0.4) | 1.007(0.996~1.160) | > 0.05 | |||||
血小板/ × 109L Platelets/ × 109L | 226.0(185.5-256.0) | 232.5(196.0-279.0) | 1.001(1.000~1.001) | < 0.05 | 1.000(0.999-1.000) | > 0.05 | |||
丙氨酸转氨酶/U·L-1 Alanine aminotransferase/U·L-1 | 34.0(21.0-54.0) | 27.0(18.0-44.0) | 1.000(0.999~1.000) | > 0.05 | |||||
总胆红素/U·L-1 Total bilirubin/μmol U·L-1 | 10.2(7.5-14.3) | 10.9(7.5-14.7) | 1.001(1.000~1.002) | < 0.05 | 1.001(1.000-1.002) | > 0.05 | |||
直接胆红素/U·L-1 Direct bilirubin/μmol U·L-1 | 3.4(2.6-4.6) | 4.0(2.9-5.5) | 1.001(1.000~1.003) | > 0.05 | |||||
间接胆红素/U·L-1 Indirect bilirubin/μmol U·L-1 | 6.6(4.2-10.2) | 6.2(4.2-8.9) | 0.996(0.999~1.000) | > 0.05 | |||||
总蛋白/g·L-1 Total protein/g·L-1 | 69.5(66.4-71.6) | 68.6(65.0-72.0) | 0.998(1.000~1.037) | > 0.05 | |||||
白蛋白/g·L-1 Albumin/g·L-1 | 40.1(37.7-43.5) | 39.6(37.1-42.1) | 0.985(0.977~0.993) | < 0.05 | 0.988(0.981-0.995) | < 0.05 | |||
碱性磷酸酶/U·L-1 Alkaline phosphatase/U·L-1 | 91.5(68.0-122.5) | 97.0(74.0-140.0) | 1.000(1.000~1.000) | > 0.05 | |||||
天冬氨酸转氨酶/U·L-1 Aspartate aminotransferase/U·L-1 | 25.0(18.0-38.5) | 24.0(20.0-35.0) | 1.000(0.999~1.001) | > 0.05 | |||||
凝血酶原时间/s Prothrombin time/s | 11.1(10.5-11.8) | 10.9(10.4-11.7) | 1.018(0.987~1.050) | > 0.05 | |||||
国际标准化比率 International normalized ratio | 0.9(0.9-1.0) | 0.9(0.9-1.0) | 1.414(0.978~1.114) | > 0.05 | |||||
D-二聚体/µg·L-1 D-Dimer/µg·L-1 | 0.7(0.5-0.9) | 0.6(0.4-0.9) | 1.010(0.985~1.035) | > 0.05 |
图1
训练集中肝细粒棘球蚴病患者的CT影像特征类型分布 A:扇形图 Sector plot;B:小提琴图 Violin plot。glcm:灰度共生矩阵 Gray level co-occurrence matrix;Shape features:形状特征;glrlm:灰度运行长度矩阵 Gray level run length matrix;glszm:灰度区域大小矩阵 Gray level size zone matrix;gldm:灰度依赖矩阵 Gray level dependence matrix;ngtdm:邻域灰度差矩阵 Neighbourhood gray-tone difference matrix;First-order statistical features:一阶统计特征。
表2
最终筛选的51个影像特征
类型 Type | 影像特征 Radiomics features |
---|---|
灰度共生矩阵(n = 9) Gray level co-occurrence matrix (n = 9) | gradient_glcm_InverseVariance、lbp_3D_m1_glcm_ClusterShade、lbp_3D_m2_glcm_ClusterShade、wavelet_HLH_glcm_Correlation、wavelet_HLL_glcm_Correlation、wavelet_LHL_glcm_Correlation、wavelet_LHL_glcm_Imc2、wavelet_LLH_glcm_Imc2、wavelet_LLL_glcm_MaximumProbability |
形状特征(n = 2) Shape features (n = 2) | original_shape_MinorAxisLength、original_shape_Sphericity |
灰度运行长度矩阵(n = 6) Gray level run length matrix(n = 6) | exponential_glrlm_GrayLevelNonUniformity、exponential_glrlm_RunVariance、lbp_3D_k_glrlm_RunVariance、lbp_3D_m1_glrlm_ShortRunLowGrayLevelEmphasis、lbp_3D_m2_glrlm_RunVariance、wavelet_HHH_glrlm_ShortRunLowGrayLevelEmphasis |
灰度区域大小矩阵(n = 16) Gray level size zone matrix (n = 16) | exponential_glszm_GrayLevelNonUniformity、exponential_glszm_GrayLevelNonUniformityNormalized、exponential_glszm_ZoneEntropy、lbp_3D_k_glszm_GrayLevelNonUniformityNormalized、lbp_3D_k_glszm_GrayLevelVariance、lbp_3D_k_glszm_SmallAreaEmphasis、lbp_3D_k_glszm_SmallAreaLowGrayLevelEmphasis、lbp_3D_k_glszm_ZoneEntropy、lbp_3D_m1_glszm_GrayLevelNonUniformityNormalized、lbp_3D_m1_glszm_SmallAreaEmphasis、lbp_3D_m2_glszm_GrayLevelVariance、lbp_3D_m2_glszm_SmallAreaLowGrayLevelEmphasis、 log_sigma_2_0_mm_3D_glszm_LargeAreaHighGrayLevelEmphasis、original_glszm_SmallAreaHighGrayLevelEmphasis、wavelet_HHL_glszm_SmallAreaLowGrayLevelEmphasis、wavelet_LLH_glszm_SmallAreaLowGrayLevelEmphasis |
灰度依赖矩阵(n = 6) Gray level dependence matrix (n = 6) | lbp_3D_k_gldm_DependenceEntropy、lbp_3D_k_gldm_DependenceVariance、lbp_3D_m1_gldm_SmallDependenceEmphasis、wavelet_HHL_gldm_LargeDependenceLowGrayLevelEmphasis、wavelet_LHH_gldm_LargeDependenceHighGrayLevelEmphasis、wavelet_LHL_gldm_LargeDependenceHighGrayLevelEmphasis |
邻域灰度差矩阵(n = 6)Neighborhood gray-tone difference matrix (n = 2) | lbp_3D_m2_ngtdm_Complexity、log_sigma_2_0_mm_3D_ngtdm_Busyness、wavelet_HHH_ngtdm_Busyness、wavelet_LHH_ngtdm_Busyness、wavelet_LLH_ngtdm_Complexity、wavelet_LLL_ngtdm_Complexity |
一阶统计特征(n = 6) First-order statistics features (n = 6) | lbp_3D_k_firstorder_Minimum、lbp_3D_m1_glszm_GrayLevelNonUniformityNormalized、lbp_3D_m2_glszm_GrayLevelVariance、wavelet_HLH_firstorder_Median、wavelet_LLH_firstorder_Skewness、wavelet_LLL_firstorder_10Percentile |
表3
7种模型的最终参数
模型 Model | 参数 Parameter |
---|---|
逻辑回归 LR | LogisticRegression (penalty = ‘l1’, solver = ‘saga’, max_iter = 1, random_state = 0) |
支持向量机 SVM | SVC (kernel = ‘linear’, C = 0.1, probability = True, random_state = 0) |
K-近邻 KNN | KNeighborsClassifier (algorithm = ‘kd_tree’, n_neighbors = 5) |
随机森林 RandomForest | RandomForestClassifier (n_estimators = 10, max_depth = 3, min_samples_split = 4, random_state = 0) |
极限梯度提升 XGBoost | XGBClassifier (n_estimators = 10, objective = ‘binary:logistic’, max_depth = 3, min_child_weight = 2, use_label_encoder = False, eval_metric = ‘error’) |
轻量梯度提升 LightGBM | LGBMClassifier (n_estimators = 10, max_depth = 3, min_child_weight = 0.5) |
极端随机树 ExtraTrees | ExtraTreesClassifier (n_estimators = 10, max_depth = 3, min_samples_split = 2, random_state = 0) |
表4
7种机器学习模型在训练集和外部验证集的性能表现
模型 Model | 队列 Cohort | 准确率 Accuracy | 曲线下面积AUC | 95%置信区间 95%CI | 灵敏度 Sensitivity | 特异度 Specificity | 阳性预测值 PPV | 阴性预测值 NPV | F1值 F1 | 阈值 Threshold |
---|---|---|---|---|---|---|---|---|---|---|
逻辑回归 LR | 训练集 Train set | 0.940 | 0.983 | 0.974~0.993 | 0.943 | 0.937 | 0.898 | 0.966 | 0.920 | 0.374 |
验证集 Validation set | 0.789 | 0.867 | 0.813~0.922 | 0.898 | 0.675 | 0.745 | 0.862 | 0.814 | 0.021 | |
支持向量机SVM | 训练集 Train set | 0.963 | 0.984 | 0.974~0.994 | 0.943 | 0.974 | 0.955 | 0.967 | 0.949 | 0.464 |
验证集 Validation set | 0.807 | 0.852 | 0.792~0.912 | 0.795 | 0.819 | 0.824 | 0.791 | 0.809 | 0.225 | |
K-近邻 KNN | 训练集 Train set | 0.921 | 0.975 | 0.965~0.986 | 0.835 | 0.971 | 0.943 | 0.910 | 0.886 | 0.500 |
验证集 Validation set | 0.789 | 0.864 | 0.810~0.917 | 0.739 | 0.843 | 0.833 | 0.753 | 0.783 | 0.250 | |
随机森林 RandomForest | 训练集 Train set | 0.926 | 0.971 | 0.956~0.986 | 0.956 | 0.908 | 0.858 | 0.972 | 0.904 | 0.418 |
验证集 Validation set | 0.795 | 0.816 | 0.751~0.882 | 0.693 | 0.904 | 0.884 | 0.735 | 0.777 | 0.460 | |
极限梯度提升 XGBoost | 训练集 Train set | 0.981 | 0.998 | 0.997~1.000 | 0.968 | 0.989 | 0.981 | 0.982 | 0.975 | 0.483 |
验证集 Validation set | 0.813 | 0.874 | 0.822~0.927 | 0.841 | 0.783 | 0.804 | 0.823 | 0.822 | 0.190 | |
轻量梯度提升LightGBM | 训练集 Train set | 0.921 | 0.984 | 0.976~0.992 | 0.956 | 0.901 | 0.848 | 0.972 | 0.899 | 0.346 |
验证集 Validation set | 0.813 | 0.868 | 0.815~0.922 | 0.863 | 0.759 | 0.792 | 0.840 | 0.812 | 0.282 | |
极端随机树 ExtraTrees | 训练集 Train set | 0.916 | 0.964 | 0.948~0.980 | 0.930 | 0.908 | 0.855 | 0.957 | 0.891 | 0.420 |
验证集 Validation set | 0.784 | 0.870 | 0.818~0.922 | 0.636 | 0.940 | 0.918 | 0.709 | 0.752 | 0.467 |
表5
7种算法的临床模型、影像模型及联合模型的曲线下面积及准确率
模型 Model | 队列 Cohort | 临床模型 Clinical Models | 影像模型 Radiomics Models | 联合模型 Combined Models | |||||
---|---|---|---|---|---|---|---|---|---|
曲线下面积 AUC | 准确率 Accuracy | 曲线下面积 AUC | 准确率 Accuracy | 曲线下面积 AUC | 准确率 Accuracy | ||||
逻辑回归 LR | 训练集 Train set | 0.905 | 0.896 | 0.983 | 0.940 | 0.993 | 0.986 | ||
验证集 Validation set | 0.812 | 0.813 | 0.867 | 0.789 | 0.886 | 0.836 | |||
支持向量机 SVM | 训练集 Train set | 0.923 | 0.904 | 0.963 | 0.984 | 0.987 | 0.991 | ||
验证集 Validation set | 0.814 | 0.819 | 0.807 | 0.852 | 0.826 | 0.863 | |||
K-近邻 KNN | 训练集 Train set | 0.861 | 0.854 | 0.975 | 0.921 | 0.979 | 0.977 | ||
验证集 Validation set | 0.764 | 0.783 | 0.864 | 0.789 | 0.889 | 0.816 | |||
随机森林 RandomForest | 训练集 Train set | 0.951 | 0.921 | 0.971 | 0.926 | 0.988 | 0.957 | ||
验证集 Validation set | 0.798 | 0.762 | 0.816 | 0.795 | 0.835 | 0.826 | |||
极度梯度提升 XGBoost | 训练集 Train set | 0.977 | 0.916 | 0.998 | 0.981 | 1.000 | 0.988 | ||
验证集 Validation set | 0.839 | 0.789 | 0.874 | 0.813 | 0.931 | 0.871 | |||
轻量梯度提升 LightGBM | 训练集 Train set | 0.895 | 0.862 | 0.984 | 0.921 | 0.992 | 0.975 | ||
验证集 Validation set | 0.789 | 0.819 | 0.868 | 0.813 | 0.921 | 0.854 | |||
极端梯度树 ExtraTrees | 训练集 Train set | 0.912 | 0.919 | 0.964 | 0.916 | 0.978 | 0.964 | ||
验证集 Validation set | 0.834 | 0.824 | 0.870 | 0.784 | 0.905 | 0.865 |
表6
临床模型、影像组学模型、联合模型在训练集和外部验证集上的表现
模型 Model | 队列 Cohort | 准确率 Accuracy | 曲线下面积AUC | 95%置信区间 95% CI | 灵敏度 Sensitivity | 特异度 Specificity | 阳性预测值 PPV | 阴性预测值 NPV | F1值 F1 | 阈值 Threshold |
---|---|---|---|---|---|---|---|---|---|---|
临床模型 Clinical model | 训练集 Train set | 0.916 | 0.977 | 0.964~0.990 | 0.943 | 0.901 | 0.847 | 0.965 | 0.892 | 0.384 |
影像模型 Radiomics model | 训练集 Train set | 0.981 | 0.998 | 0.997~1.000 | 0.968 | 0.989 | 0.981 | 0.982 | 0.975 | 0.483 |
联合模型 Combined model | 训练集 Train set | 0.988 | 1.000 | 0.999~1.000 | 0.987 | 0.989 | 0.981 | 0.993 | 0.984 | 0.323 |
临床模型 Clinical model | 验证集 Validation set | 0.789 | 0.839 | 0.776~0.901 | 0.955 | 0.614 | 0.724 | 0.927 | 0.824 | 0.164 |
影像模型 Radiomics model | 验证集 Validation set | 0.813 | 0.874 | 0.822~0.927 | 0.841 | 0.783 | 0.804 | 0.823 | 0.822 | 0.190 |
联合模型 Combined model | 验证集 Validation set | 0.871 | 0.931 | 0.894~0.968 | 0.920 | 0.819 | 0.844 | 0.907 | 0.880 | 0.409 |
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