IEEE Trans Med Imaging. 2023 May;42(5):1337-1348. doi: 10.1109/TMI.2022.3227066. Epub 2023 May 2.
Multi-instance learning (MIL) is widely adop- ted for automatic whole slide image (WSI) analysis and it usually consists of two stages, i.e., instance feature extraction and feature aggregation. However, due to the "weak supervision" of slide-level labels, the feature aggregation stage would suffer from severe over-fitting in training an effective MIL model. In this case, mining more information from limited slide-level data is pivotal to WSI analysis. Different from previous works on improving instance feature extraction, this paper investigates how to exploit the latent relationship of different instances (patches) to combat overfitting in MIL for more generalizable WSI classification. In particular, we propose a novel Multi-instance Rein- forcement Contrastive Learning framework (MuRCL) to deeply mine the inherent semantic relationships of different patches to advance WSI classification. Specifically, the proposed framework is first trained in a self-supervised manner and then finetuned with WSI slide-level labels. We formulate the first stage as a contrastive learning (CL) process, where positive/negative discriminative feature sets are constructed from the same patch-level feature bags of WSIs. To facilitate the CL training, we design a novel reinforcement learning-based agent to progressively update the selection of discriminative feature sets according to an online reward for slide-level feature aggregation. Then, we further update the model with labeled WSI data to regularize the learned features for the final WSI classification. Experimental results on three public WSI classification datasets (Camelyon16, TCGA-Lung and TCGA-Kidney) demonstrate that the proposed MuRCL outperforms state-of-the-art MIL models. In addition, MuRCL can achieve comparable performance to other state-of-the-art MIL models on TCGA-Esca dataset.
多实例学习 (MIL) 被广泛应用于自动全切片图像 (WSI) 分析,它通常由两个阶段组成,即实例特征提取和特征聚合。然而,由于幻灯片级标签的“弱监督”,在训练有效的 MIL 模型时,特征聚合阶段会受到严重的过拟合。在这种情况下,从有限的幻灯片级数据中挖掘更多信息对于 WSI 分析至关重要。与之前改进实例特征提取的工作不同,本文研究了如何利用不同实例(补丁)之间的潜在关系来对抗 MIL 中的过拟合,以实现更具泛化能力的 WSI 分类。具体来说,我们提出了一种新的多实例强化对比学习框架 (MuRCL),以深入挖掘不同补丁之间的固有语义关系,从而提高 WSI 分类性能。具体来说,所提出的框架首先以自监督的方式进行训练,然后使用 WSI 幻灯片级标签进行微调。我们将第一阶段表示为对比学习 (CL) 过程,其中正/负判别特征集是从同一补丁级 WSI 特征袋中构建的。为了便于 CL 训练,我们设计了一种新颖的基于强化学习的代理,根据在线奖励来逐步更新判别特征集的选择,以进行幻灯片级特征聚合。然后,我们使用带有标记的 WSI 数据进一步更新模型,以对学习到的特征进行正则化,从而进行最终的 WSI 分类。在三个公共的 WSI 分类数据集(Camelyon16、TCGA-Lung 和 TCGA-Kidney)上的实验结果表明,所提出的 MuRCL 优于最先进的 MIL 模型。此外,在 TCGA-Esca 数据集上,MuRCL 可以与其他最先进的 MIL 模型取得可比的性能。