IEEE Trans Med Imaging. 2021 Dec;40(12):3739-3747. doi: 10.1109/TMI.2021.3097319. Epub 2021 Nov 30.
Whole-Slide Histopathology Image (WSI) is generally considered the gold standard for cancer diagnosis and prognosis. Given the large inter-operator variation among pathologists, there is an imperative need to develop machine learning models based on WSIs for consistently predicting patient prognosis. The existing WSI-based prediction methods do not utilize the ordinal ranking loss to train the prognosis model, and thus cannot model the strong ordinal information among different patients in an efficient way. Another challenge is that a WSI is of large size (e.g., 100,000-by-100,000 pixels) with heterogeneous patterns but often only annotated with a single WSI-level label, which further complicates the training process. To address these challenges, we consider the ordinal characteristic of the survival process by adding a ranking-based regularization term on the Cox model and propose a weakly supervised deep ordinal Cox model (BDOCOX) for survival prediction from WSIs. Here, we generate amounts of bags from WSIs, and each bag is comprised of the image patches representing the heterogeneous patterns of WSIs, which is assumed to match the WSI-level labels for training the proposed model. The effectiveness of the proposed method is well validated by theoretical analysis as well as the prognosis and patient stratification results on three cancer datasets from The Cancer Genome Atlas (TCGA).
全切片组织病理学图像(WSI)通常被认为是癌症诊断和预后的金标准。鉴于病理学家之间存在较大的操作者间差异,因此迫切需要基于 WSI 开发机器学习模型,以持续预测患者的预后。现有的基于 WSI 的预测方法没有利用有序排名损失来训练预后模型,因此无法有效地对不同患者之间的强有序信息进行建模。另一个挑战是,WSI 尺寸较大(例如,100,000 像素×100,000 像素),且具有异质模式,但通常仅标注有单个 WSI 级别的标签,这进一步增加了训练过程的复杂性。为了解决这些挑战,我们通过在 Cox 模型上添加基于排序的正则化项来考虑生存过程的有序特征,并提出了一种基于弱监督的深度有序 Cox 模型(BDOCOX),用于从 WSI 进行生存预测。在这里,我们从 WSI 中生成大量的袋子,每个袋子都包含代表 WSI 异质模式的图像补丁,这些补丁被认为与 WSI 级别的标签匹配,用于训练所提出的模型。通过理论分析以及对来自癌症基因组图谱(TCGA)的三个癌症数据集的预后和患者分层结果,验证了该方法的有效性。
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