CACL: Cluster-Aware Adversarial Contrastive Learning for Pathological Image Analysis

Junjian Li, Hulin Kuang, Jin Liu, Hailin Yue, Jianxin Wang

Published: 2025, Last Modified: 27 Feb 2026IEEE J. Biomed. Health Informatics 2025EveryoneRevisionsBibTeXCC BY-SA 4.0
Abstract: Pathological diagnosis assists in saving human lives, but such models are annotation hungry and pathological images are notably expensive to annotate. Contrastive learning could be a promising solution that relies only on the unlabeled training data to generate informative representations. However, the majority of current methods in contrastive learning have the following two issues: (1) positive samples produced through random augmentation are less challenging, and (2) false negative pairs problem caused by negative sampling bias. To alleviate the above issues, we propose a novel contrastive learning method called Cluster-Aware Adversarial Contrastive Learning (CA2CL). Specifically, a mixed data augmentation technique is provided to learn more transferable representations by generating more discriminative sample pairs. Furthermore, to mitigate the effects of inherent false negative pairs, we adopt a cluster-aware loss to identify similarities between instances and incorporate them into the process of contrastive learning. Finally, we generate challenging contrastive data pairs by adversarial learning, and adversarially learn robust representations in the representation space without the labeled training data, which aims to maximize the similarity between the augmented sample and the related adversarial sample. Our proposed CA2CL is evaluated on two public datasets: NCT-CRC-HE and PCam for the fine-tuning and linear evaluation tasks and on two other public datasets: GlaS and CARG for the detection and segmentation tasks, respectively. Extensive experimental results demonstrate the superior performance improvement of our method over several Self-supervised learning (SSL) methods and ImageNet pretraining particularly in scenarios with limited data availability for all four tasks.
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