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胶质母细胞瘤的预后影像生物标志物:基于多区域和磁共振图像定量分析的开发与独立验证

Prognostic Imaging Biomarkers in Glioblastoma: Development and Independent Validation on the Basis of Multiregion and Quantitative Analysis of MR Images.

作者信息

Cui Yi, Tha Khin Khin, Terasaka Shunsuke, Yamaguchi Shigeru, Wang Jeff, Kudo Kohsuke, Xing Lei, Shirato Hiroki, Li Ruijiang

机构信息

From the Global Station for Quantum Medical Science and Engineering, Global Institution for Collaborative Research and Education (Y.C., K.K.T., J.W., K.K., L.X., H.S., R.L.), and Graduate School of Medicine, Departments of Radiation Medicine (K.K.T., J.W., H.S.) and Neurosurgery (S.T., S.Y.), Hokkaido University, Sapporo, Japan; Department of Diagnostic and Interventional Radiology, Hokkaido University Hospital, Sapporo, Japan (K.K.); and Department of Radiation Oncology, Stanford University, 1070 Arastradero Rd, Palo Alto, CA 94304 (L.X., R.L.).

出版信息

Radiology. 2016 Feb;278(2):546-53. doi: 10.1148/radiol.2015150358. Epub 2015 Sep 4.

Abstract

PURPOSE

To develop and independently validate prognostic imaging biomarkers for predicting survival in patients with glioblastoma on the basis of multiregion quantitative image analysis.

MATERIALS AND METHODS

This retrospective study was approved by the local institutional review board, and informed consent was waived. A total of 79 patients from two independent cohorts were included. The discovery and validation cohorts consisted of 46 and 33 patients with glioblastoma from the Cancer Imaging Archive (TCIA) and the local institution, respectively. Preoperative T1-weighted contrast material-enhanced and T2-weighted fluid-attenuation inversion recovery magnetic resonance (MR) images were analyzed. For each patient, we semiautomatically delineated the tumor and performed automated intratumor segmentation, dividing the tumor into spatially distinct subregions that demonstrate coherent intensity patterns across multiparametric MR imaging. Within each subregion and for the entire tumor, we extracted quantitative imaging features, including those that fully capture the differential contrast of multimodality MR imaging. A multivariate sparse Cox regression model was trained by using TCIA data and tested on the validation cohort.

RESULTS

The optimal prognostic model identified five imaging biomarkers that quantified tumor surface area and intensity distributions of the tumor and its subregions. In the validation cohort, our prognostic model achieved a concordance index of 0.67 and significant stratification of overall survival by using the log-rank test (P = .018), which outperformed conventional prognostic factors, such as age (concordance index, 0.57; P = .389) and tumor volume (concordance index, 0.59; P = .409).

CONCLUSION

The multiregion analysis presented here establishes a general strategy to effectively characterize intratumor heterogeneity manifested at multimodality imaging and has the potential to reveal useful prognostic imaging biomarkers in glioblastoma.

摘要

目的

基于多区域定量图像分析,开发并独立验证用于预测胶质母细胞瘤患者生存情况的预后影像生物标志物。

材料与方法

本回顾性研究经当地机构审查委员会批准,且无需知情同意。共纳入来自两个独立队列的79例患者。发现队列和验证队列分别由来自癌症影像存档库(TCIA)和当地机构的46例和33例胶质母细胞瘤患者组成。对术前T1加权对比剂增强和T2加权液体衰减反转恢复磁共振(MR)图像进行分析。对于每位患者,我们半自动勾勒肿瘤轮廓并进行肿瘤内自动分割,将肿瘤划分为在多参数MR成像中显示连贯强度模式的空间上不同的子区域。在每个子区域内以及整个肿瘤中,我们提取了定量影像特征,包括那些能充分捕捉多模态MR成像差异对比的特征。使用TCIA数据训练多元稀疏Cox回归模型,并在验证队列上进行测试。

结果

最佳预后模型识别出五个影像生物标志物,这些标志物量化了肿瘤及其子区域 的表面积和强度分布。在验证队列中,我们的预后模型一致性指数达到0.67,通过对数秩检验实现了总生存的显著分层(P = 0.018),优于传统预后因素,如年龄(一致性指数,0.57;P = 0.389)和肿瘤体积(一致性指数,0.59;P = 0.409)。

结论

本文提出的多区域分析建立了一种有效表征多模态成像中表现出的肿瘤内异质性的通用策略,并且有潜力在胶质母细胞瘤中揭示有用的预后影像生物标志物。

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