College of Medicine and Biomedical Information Engineering, Northeastern University, Shenyang, Liaoning, 110819, China.
Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, School of Medicine and Engineering, Beihang University, Beijing, 100191, China.
Theranostics. 2020 Jun 5;10(16):7231-7244. doi: 10.7150/thno.46428. eCollection 2020.
Given the rapid spread of COVID-19, an updated risk-stratify prognostic tool could help clinicians identify the high-risk patients with worse prognoses. We aimed to develop a non-invasive and easy-to-use prognostic signature by chest CT to individually predict poor outcome (death, need for mechanical ventilation, or intensive care unit admission) in patients with COVID-19. From November 29, 2019 to February 19, 2020, a total of 492 patients with COVID-19 from four centers were retrospectively collected. Since different durations from symptom onsets to the first CT scanning might affect the prognostic model, we designated the 492 patients into two groups: 1) the early-phase group: CT scans were performed within one week after symptom onset (0-6 days, n = 317); and 2) the late-phase group: CT scans were performed one week later after symptom onset (≥7 days, n = 175). In each group, we divided patients into the primary cohort (n = 212 in the early-phase group, n = 139 in the late-phase group) and the external independent validation cohort (n = 105 in the early-phase group, n = 36 in the late-phase group) according to the centers. We built two separate radiomics models in the two patient groups. Firstly, we proposed an automatic segmentation method to extract lung volume for radiomics feature extraction. Secondly, we applied several image preprocessing procedures to increase the reproducibility of the radiomics features: 1) applied a low-pass Gaussian filter before voxel resampling to prevent aliasing; 2) conducted ComBat to harmonize radiomics features per scanner; 3) tested the stability of the features in the radiomics signature by several image transformations, such as rotating, translating, and growing/shrinking. Thirdly, we used least absolute shrinkage and selection operator (LASSO) to build the radiomics signature (RadScore). Afterward, we conducted a Fine-Gray competing risk regression to build the clinical model and the clinic-radiomics signature (CrrScore). Finally, performances of the three prognostic signatures (clinical model, RadScore, and CrrScore) were estimated from the two aspects: 1) cumulative poor outcome probability prediction; 2) 28-day poor outcome prediction. We also did stratified analyses to explore the potential association between the CrrScore and the poor outcomes regarding different age, type, and comorbidity subgroups. In the early-phase group, the CrrScore showed the best performance in estimating poor outcome (C-index = 0.850), and predicting the probability of 28-day poor outcome (AUC = 0.862). In the late-phase group, the RadScore alone achieved similar performance to the CrrScore in predicting poor outcome (C-index = 0.885), and 28-day poor outcome probability (AUC = 0.976). Moreover, the RadScore in both groups successfully stratified patients with COVID-19 into low- or high-RadScore groups with significantly different survival time in the training and validation cohorts (all < 0.05). The CrrScore in both groups can also significantly stratify patients with different prognoses regarding different age, type, and comorbidities subgroups in the combined cohorts (all < 0.05). This research proposed a non-invasive and quantitative prognostic tool for predicting poor outcome in patients with COVID-19 based on CT imaging. Taking the insufficient medical recourse into account, our study might suggest that the chest CT radiomics signature of COVID-19 is more effective and ideal to predict poor outcome in the late-phase COVID-19 patients. For the early-phase patients, integrating radiomics signature with clinical risk factors can achieve a more accurate prediction of individual poor prognostic outcome, which enables appropriate management and surveillance of COVID-19.
鉴于 COVID-19 的迅速传播,更新的风险分层预后工具可以帮助临床医生识别预后较差的高危患者。我们旨在通过胸部 CT 开发一种非侵入性和易于使用的预后标志物,以单独预测 COVID-19 患者的不良结局(死亡、需要机械通气或入住重症监护病房)。
从 2019 年 11 月 29 日至 2020 年 2 月 19 日,共回顾性收集了来自四个中心的 492 例 COVID-19 患者。由于从症状发作到首次 CT 扫描的不同时间可能会影响预后模型,我们将 492 例患者分为两组:1)早期组:症状发作后 1 周内进行 CT 扫描(0-6 天,n=317);2)晚期组:症状发作后 1 周后进行 CT 扫描(≥7 天,n=175)。在每组中,我们根据中心将患者分为主要队列(早期组 n=212,晚期组 n=139)和外部独立验证队列(早期组 n=105,晚期组 n=36)。我们在两组患者中分别建立了两个独立的放射组学模型。首先,我们提出了一种自动分割方法,用于提取肺体积进行放射组学特征提取。其次,我们应用了几种图像预处理程序来提高放射组学特征的可重复性:1)在体素重采样前应用低通高斯滤波器以防止混叠;2)通过 ComBat 对每个扫描仪的放射组学特征进行协调;3)通过对图像进行多次变换(如旋转、平移和放大/缩小)来测试放射组学特征的稳定性。第三,我们使用最小绝对值收缩和选择算子(LASSO)构建放射组学特征(RadScore)。然后,我们进行了 Fine-Gray 竞争风险回归来构建临床模型和临床放射组学特征(CrrScore)。最后,从两个方面评估了三个预后标志物(临床模型、RadScore 和 CrrScore)的性能:1)累积不良结局概率预测;2)28 天不良结局预测。我们还进行了分层分析,以探讨 CrrScore 与不同年龄、类型和合并症亚组的不良结局之间的潜在关联。
在早期组中,CrrScore 在估计不良结局(C 指数=0.850)和预测 28 天不良结局概率(AUC=0.862)方面表现最佳。在晚期组中,单独的 RadScore 在预测不良结局(C 指数=0.885)和 28 天不良结局概率(AUC=0.976)方面与 CrrScore 表现相似。此外,两组中的 RadScore 都成功地将 COVID-19 患者分为低或高 RadScore 组,两组的训练和验证队列的生存时间均有显著差异(均<0.05)。两组中的 CrrScore 也可以根据不同的年龄、类型和合并症亚组,在合并队列中显著分层具有不同预后的患者(均<0.05)。
这项研究提出了一种基于 CT 成像的非侵入性和定量预测 COVID-19 患者不良结局的预后工具。考虑到医疗资源不足,我们的研究可能表明,COVID-19 的胸部 CT 放射组学特征更有效和理想,可预测 COVID-19 晚期患者的不良结局。对于早期患者,将放射组学特征与临床危险因素相结合,可以更准确地预测个体不良预后,从而实现 COVID-19 的适当管理和监测。