论文标题

乳腺癌分子亚型在病理图像上的预测和歧视性斑块选择和多构度学习

Breast Cancer Molecular Subtypes Prediction on Pathological Images with Discriminative Patch Selecting and Multi-Instance Learning

论文作者

Liu, Hong, Xu, Wen-Dong, Shang, Zi-Hao, Wang, Xiang-Dong, Zhou, Hai-Yan, Ma, Ke-Wen, Zhou, Huan, Qi, Jia-Lin, Jiang, Jia-Rui, Tan, Li-Lan, Zeng, Hui-Min, Cai, Hui-Juan, Wang, Kuan-Song, Qian, Yue-Liang

论文摘要

乳腺癌的分子亚型是对个性化临床治疗的重要参考。为了节省成本和人工,通常只选择患者的石蜡块中的一个用于随后的免疫组织化学(IHC)以获得分子亚型。由于肿瘤的异质性,必然的采样误差是有风险的,并且可能导致治疗延迟。使用AI方法从常规H&E病理全幻灯片图像(WSI)提出的分子亚型预测是有用的且至关重要的,可帮助病理学家预屏幕前适当的Popaffin Block IHC。这是一项具有挑战性的任务,因为只能从IHC获得分子亚型的WSI水平标签。 GigaiPixel WSI被分为大量的补丁,可以在深度学习上进行计算。虽然使用粗幻灯片级标签,但基于斑块的方法可能会遭受丰富的噪声斑块,例如褶皱,斑点区域或非肿瘤组织。提出了一个基于判别性斑块选择和多构度学习的弱监督学习框架,用于H&E WSIS的乳腺癌分子亚型预测。首先,采用了共同教学策略来学习分子亚型表示并过滤噪声贴片。然后,使用平衡的采样策略来处理数据集中的子类型的不平衡。此外,提出了基于群集中心使用局部离群因子的噪声贴片过滤算法,以进一步选择歧视性斑块。最后,将损失函数与幻灯片约束信息整合在一起,以对获得的歧视性斑块进行验证MIL框架,并进一步改善分子亚型的性能。实验结果证实了该方法的有效性,我们的模型甚至超过了高级病理学家,潜力有助于病理学家在诊所的IHC前屏幕上的石蜡块。

Molecular subtypes of breast cancer are important references to personalized clinical treatment. For cost and labor savings, only one of the patient's paraffin blocks is usually selected for subsequent immunohistochemistry (IHC) to obtain molecular subtypes. Inevitable sampling error is risky due to tumor heterogeneity and could result in a delay in treatment. Molecular subtype prediction from conventional H&E pathological whole slide images (WSI) using AI method is useful and critical to assist pathologists pre-screen proper paraffin block for IHC. It's a challenging task since only WSI level labels of molecular subtypes can be obtained from IHC. Gigapixel WSIs are divided into a huge number of patches to be computationally feasible for deep learning. While with coarse slide-level labels, patch-based methods may suffer from abundant noise patches, such as folds, overstained regions, or non-tumor tissues. A weakly supervised learning framework based on discriminative patch selecting and multi-instance learning was proposed for breast cancer molecular subtype prediction from H&E WSIs. Firstly, co-teaching strategy was adopted to learn molecular subtype representations and filter out noise patches. Then, a balanced sampling strategy was used to handle the imbalance in subtypes in the dataset. In addition, a noise patch filtering algorithm that used local outlier factor based on cluster centers was proposed to further select discriminative patches. Finally, a loss function integrating patch with slide constraint information was used to finetune MIL framework on obtained discriminative patches and further improve the performance of molecular subtyping. The experimental results confirmed the effectiveness of the proposed method and our models outperformed even senior pathologists, with potential to assist pathologists to pre-screen paraffin blocks for IHC in clinic.

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