Domain Generalization of Pathological Image Segmentation by Patch-Level and WSI-Level Contrastive Learning

In this paper, we address domain shifts in pathological images by focusing on shifts within whole slide images~(WSIs), such as patient characteristics and tissue thickness, rather than shifts between hospitals. Traditional approaches rely on multi-hospital data, but data collection challenges often make this impractical. Therefore, the proposed domain generalization method captures and leverages intra-hospital domain shifts by clustering WSI-level features from non-tumor regions and treating these clusters as domains. To mitigate domain shift, we apply contrastive learning to reduce feature gaps between WSI pairs from different clusters. The proposed method introduces a two-stage contrastive learning approach WSI-level and patch-level contrastive learning to minimize these gaps effectively.

Comprehensive Pathological Image Segmentation via Teacher Aggregation for Tumor Microenvironment Analysis

The tumor microenvironment (TME) plays a crucial role in cancer progression and treatment response, yet current methods for its comprehensive analysis in H&E-stained tissue slides face significant limitations in the diversity of tissue cell types and accuracy. Here, we present PAGET (Pathological image segmentation via AGgrEgated Teachers), a new knowledge distillation approach that integrates multiple segmentation models while considering the hierarchical nature of cell types in the TME. By leveraging a unique dataset created through immunohistochemical restaining techniques and existing segmentation models, PAGET enables simultaneous identification and classification of 14 key TME components. We demonstrate PAGET's ability to perform rapid, comprehensive TME segmentation across various tissue types and medical institutions, advancing the quantitative analysis of tumor microenvironments. This method represents a significant step forward in enhancing our understanding of cancer biology and supporting precise clinical decision-making from large-scale histopathology images.

Cluster Entropy: Active Domain Adaptation in Pathological Image Segmentation

The domain shift in pathological segmentation is an important problem, where a network trained by a source domain (collected at a specific hospital) does not work well in the target domain (from different hospitals) due to the different image features. Due to the problems of class imbalance and different class prior of pathology, typical unsupervised domain adaptation methods do not work well by aligning the distribution of source domain and target domain. In this paper, we propose a cluster entropy for selecting an effective whole slide image (WSI) that is used for semi-supervised domain adaptation. This approach can measure how the image features of the WSI cover the entire distribution of the target domain by calculating the entropy of each cluster and can significantly improve the performance of domain adaptation. Our approach achieved competitive results against the prior arts on datasets collected from two hospitals.

Domain Adaptive Multiple Instance Learning for Instance-level Prediction of Pathological Images

Pathological image analysis is an important process for detecting abnormalities such as cancer from cell images. However, since the image size is generally very large, the cost of providing detailed annotations is high, which makes it difficult to apply machine learning techniques. One way to improve the performance of identifying abnormalities while keeping the annotation cost low is to use only labels for each slide, or to use information from another dataset that has already been labeled. However, such weak supervisory information often does not provide sufficient performance. In this paper, we proposed a new task setting to improve the classification performance of the target dataset without increasing annotation costs. And to solve this problem, we propose a pipeline that uses multiple instance learning (MIL) and domain adaptation (DA) methods. Furthermore, in order to combine the supervisory information of both methods effectively, we propose a method to create pseudo-labels with high confidence. We conducted experiments on the pathological image dataset we created for this study and showed that the proposed method significantly improves the classification performance compared to existing methods.

Cluster-Guided Semi-Supervised Domain Adaptation for Imbalanced Medical Image Classification

Semi-supervised domain adaptation is a technique to build a classifier for a target domain by modifying a classifier in another (source) domain using many unlabeled samples and a small number of labeled samples from the target domain. In this paper, we develop a semi-supervised domain adaptation method, which has robustness to class-imbalanced situations, which are common in medical image classification tasks. For robustness, we propose a weakly-supervised clustering pipeline to obtain high-purity clusters and utilize the clusters in representation learning for domain adaptation. The proposed method showed state-of-the-art performance in the experiment using severely class-imbalanced pathological image patches.