基于nnU-Net的临床影像组学模型对胆囊癌预后的预测价值
Predictive value of clinical radiomics model based on nnU-Net for prognosis of gallbladder carcinoma
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摘要: 目的 探讨基于nnU?Net的临床影像组学模型对胆囊癌预后的预测价值。方法 采用回顾性队列研究方法。收集2012年1月至2020年12月西安交通大学第一附属医院收治的168例行胆囊癌意向性根治术患者的临床病理资料;男61例,女107例;年龄为(64±11)岁。168例患者通过随机数字表法按3∶1随机分为训练集126例和测试集42例。168例患者术前均行增强CT检查。对于门静脉期图像,2位影像学医师手动勾画感兴趣区。应用nnU?Net三维全分辨率模型自动分割图像,采用5折交叉验证及Dice相似系数评估模型泛化能力和预测效能。应用Python软件(3.7.10版本)及Pyradiomics工具库(3.0.1版本)提取影像组学特征,应用R软件(4.1.1版本)筛选影像组学特征,应用方差法、Pearson相关性分析、单因素COX分析及随机生存森林模型筛选重要的影像组学特征并计算影像组学评分(Radscore)。应用X?tile软件(3.6.1版本)确定Radscore最佳截断值,COX比例风险回归模型分析患者预后的独立影响因素。将训练集数据导入R软件(4.1.1版本)构建胆囊癌生存预测临床影像组学列线图模型。基于Radscore风险、影响患者预后的独立临床因素分别构建胆囊癌生存预测Radscore风险模型、临床模型。采用一致性指数(C?index)、校准曲线及决策曲线评估不同胆囊癌生存预测模型的预测效能。观察指标:(1)胆囊癌CT检查门静脉期图像分割结果。(2)影像组学特征筛选及Radscore计算。(3)影响胆囊癌意向性根治术后患者预后因素分析。(4)不同胆囊癌生存预测模型的构建及评价。正态分布的计量资料以x±s表示。计数资料以绝对数或百分比表示,组间比较采用χ2检验。单因素及多因素分析采用COX比例风险回归模型。采用寿命表法计算术后总生存率。结果 (1)胆囊癌CT检查门静脉期图像分割结果。基于手动分割和nnU?Net模型自动分割的感兴趣区在训练集Dice相似系数为0.92±0.08,在测试集为0.74±0.15。(2)影像组学特征筛选及Radscore计算。168例患者共提取1 502个影像组学特征,经方差法、Pearson相关性分析、单因素COX分析和随机森林生存模型筛选影像组学特征共13个(形状特征3个、高阶特征10个)。根据随机生存森林模型与X?tile软件分析结果显示:Radscore最佳截断值分别为6.68和25.01,训练集126例患者中Radscore低危(≤6.68)41例、中危(>6.68且<25.01)72例、高危(≥25.01)13例。(3)影响胆囊癌意向性根治术后患者预后因素分析。168例患者1、2、3年总生存率分别为75.8%、54.9%、45.7%。单因素分析结果显示:术前合并黄疸,血清CA19?9,Radscore风险(中危、高危),手术切除范围,病理学T分期,病理学N分期,肿瘤分化程度(中分化、低分化)是影响训练集患者预后的相关因素(风险比=3.28,3.00,3.78,6.34,4.48,6.43,3.35,7.44,15.11,95%可信区间为1.91~5.63,1.76~5.13,1.76~8.09,2.49~16.17,2.30~8.70,1.57~26.36,1.96~5.73,1.02~54.55,2.04~112.05,P<0.05)。多因素分析结果显示:术前合并黄疸,血清CA19?9,Radscore风险(高危),病理学N分期是训练集患者预后的独立影响因素(风险比=2.22,2.02,2.89,2.07,95%可信区间为1.20~4.11,1.11~3.68,1.04~8.01,1.15~3.73,P<0.05)。(4)不同胆囊癌生存预测模型的构建及评价。基于患者预后独立影响因素构建临床影像组学模型、Radscore风险模型、临床模型,其在训练集的C?index分别为0.775、0.651、0.747,在测试集的C?index分别为0.759、0.633、0.739。校准曲线显示:Radscore风险模型、临床模型及临床影像组学模型对患者生存的预测能力良好。决策曲线显示:临床影像组学模型对患者预后的预测能力优于Radscore风险模型及临床模型。结论 基于nnU?net的临床影像组学模型对胆囊癌预后具有良好的预测效能。
Abstract:Objective To investigate the predictive value of clinical radiomics model based on nnU-Net for the prognosis of gallbladder carcinoma (GBC). Methods The retrospective cohort study was conducted. The clinicopathological data of 168 patients who underwent curative-intent radical resection of GBC in the First Affiliated Hospital of Xi'an Jiaotong University from January 2012 to December 2020 were collected. There were 61 males and 107 females, aged (64±11)years. All the 168 patients who underwent preoperative enhanced computed tomography (CT) examina-tion were randomly divided into 126 cases in training set and 42 cases in test set according to the ratio of 3:1 based on random number table. For the portal venous phase images, 2 radiologists manually delineated the region of interest (ROI), and constructed a nnU-net model to automatically segment the images. The 5-fold cross-validation and Dice similarity coefficient were used to evaluate the generalization ability and predictive performance of the nnU-net model. The Python software (version 3.7.10) and Pyradiomics toolkit (version 3.0.1) were used to extract the radiomics features, the R software (version 4.1.1) was used to screen the radiomics features, and the variance method, Pearson correlation analysis, one-way COX analysis and random survival forest model were used to screen important radiomics features and calculate the Radiomics score (Radscore). X-tile software (version 3.6.1) was used to determine the best cut-off value of Radscore, and COX proportional hazard regression model was used to analyze the independent factors affecting the prognosis of patients. The training set data were imported into R software (version 4.1.1) to construct a clinical radiomics nomogram model of survival prediction for GBC. Based on the Radscore and the independent clinical factors affecting the prognosis of patients, the Radscore risk model and the clinical model for predicting the survival of GBC were constructed respectively. The C-index, calibration plot and decision curve analysis were used to evaluate the predictive ability of different survival prediction models for GBC. Observation indicators: (1) segmentation results of portal venous phase images in CT examination of GBC; (2) radiomic feature screening and Radscore calculation; (3) prognostic factors analysis of patients after curative-intent radical resection of GBC; (4) construction and evaluation of different survival prediction models for GBC. Measurement data with normal distribution were represented by Mean±SD. Count data were expressed as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test. Univariate and multivariate analyses were performed using the COX proportional hazard regression model. The postoperative overall survival rate was calculated by the life table method. Results (1) Segmentation results of portal venous phase images in CT examination of GBC: the Dice similarity coefficient of the ROI based on the manual segmentation and nnU-Net segmentation models was 0.92±0.08 in the training set and 0.74±0.15 in the test set, respectively. (2) Radiomic feature screening and Radscore calculation: 1 502 radiomics features were finally extracted from 168 patients. A total of 13 radiomic features (3 shape features and 10 high-order features) were screened by the variance method, Pearson correlation analysis, one-way COX analysis and random survival forest model. Results of random survival forest model analysis and X-tile software analysis showed that the best cut-off values of the Radscore were 6.68 and 25.01. A total of 126 patients in the training set were divided into 41 cases of low-risk (≤6.68), 72 cases of intermediate-risk (>6.68 and <25.01), and 13 cases of high-risk (≥25.01). (3) Prognostic factors analysis of patients after curative-intent radical resection of GBC: the 1-, 2-, and 3-year overall survival rates of 168 patients were 75.8%, 54.9% and 45.7%, respectively. The results of univariate analysis showed that preopera-tive jaundice, serum CA19-9 level, Radscore risk (medium risk and high risk), extent of surgical resection, pathological T staging, pathological N staging, tumor differentiation degree (moderate differentiation and low differentiation) were related factors affecting prognosis of patients in the training set (hazard ratio=3.28, 3.00, 3.78, 6.34, 4.48, 6.43, 3.35, 7.44, 15.11, 95% confidence interval as 1.91?5.63, 1.76?5.13, 1.76?8.09, 2.49?16.17, 2.30?8.70, 1.57?26.36, 1.96?5.73, 1.02?54.55, 2.04?112.05, P<0.05). Results of multivariate analysis showed that preoperative jaundice, serum CA19-9 level, Radscore risk as high risk and pathological N staging were independent influencing factors for prognosis of patients in the training set (hazard ratio=2.22, 2.02, 2.89, 2.07, 95% confidence interval as 1.20?4.11, 1.11?3.68, 1.04?8.01, 1.15?3.73, P<0.05). (4) Construction and evaluation of different survival prediction models for GBC. Clinical radiomics model, Radscore risk model and clinical model were established based on the independent influencing factors for prognosis, the C-index of which was 0.775, 0.651 and 0.747 in the training set, and 0.759, 0.633, 0.739 in the test set, respectively. The calibration plots showed that the Radscore risk model, clinical model and clinical radiomics model had good predictive ability for prognosis of patients. The decision curve analysis showed that the prognostic predictive ability of the clinical radiomics model was better than that of the Radscore risk and clinical models. Conclusion The clinical radiomics model based on the nnU-Net has a good predictive performance for prognosis of GBC.