Multiple Instance Learning

Recent advances in multi-instance learning (MIL) have witnessed impressive performance in whole slide image (WSI) analysis. However, the inherent sparsity of tumors and their morphological diversity lead to obvious heterogeneity across regions, posing significant challenges in aggregating high-quality and discriminative representations. To address this, we introduce a novel concept of anchor instance (AI), a compact subset of instances that are representative within their regions (local) and discriminative at the bag (global) level. These AIs act as semantic references to guide interactions across regions, correcting non-discriminative patterns while preserving regional diversity. Specifically, we propose a dual-level anchor mining (DAM) module to select AIs from massive instances, where the most informative AI in each region is extracted by assessing its similarity to both local and global embeddings. Furthermore, to ensure completeness and diversity, we devise an anchor-guided region correction (ARC) module that explores the complementary information from all regions to correct each regional representation. Building upon DAM and ARC, we develop a concise yet effective framework, AINet, which employs a simple predictor and surpasses state-of-the-art methods with substantially fewer FLOPs and parameters. Moreover, both DAM and ARC are modular and can be seamlessly integrated into existing MIL frameworks, consistently improving their performance.

Vision language models (VLM) pre-trained on datasets of histopathological image-caption pairs enabled zero-shot slide-level classification. The ability of VLM image encoders to extract discriminative features also opens the door for supervised fine-tuning for whole-slide image (WSI) classification, ideally using few labeled samples. Slide-level prediction frameworks require the incorporation of multiple instance learning (MIL) due to the gigapixel size of the WSI. Following patch-level feature extraction and aggregation, MIL frameworks rely on linear classifiers trained on top of the slide-level aggregated features. Classifier weight initialization has a large influence on Linear Probing performance in efficient transfer learning (ETL) approaches based on few-shot learning. In this work, we propose Zero-Shot Multiple-Instance Learning (ZS-MIL) to address the limitations of random classifier initialization that underperform zero-shot prediction in MIL problems. ZS-MIL uses the class-level embeddings of the VLM text encoder as the classification layer's starting point to compute each sample's bag-level probabilities. Through multiple experiments, we demonstrate the robustness of ZS-MIL compared to well-known weight initialization techniques both in terms of performance and variability in an ETL few-shot scenario for subtyping prediction.

The study of histopathological subtypes is valuable for the personalisation of effective treatment strategies for ovarian cancer. However, increasing diagnostic workloads present a challenge for UK pathology departments, leading to the rise in AI approaches. While traditional approaches in this field have relied on pre-computed, frozen image features, recent advances have shifted towards end-to-end feature extraction, providing an improvement in accuracy but at the expense of significantly reduced scalability during training and time-consuming experimentation. In this paper, we propose a new approach for subtype classification and localisation in ovarian cancer histopathology images using contrastive and prototype learning with pre-computed, frozen features via feature-space augmentations. Compared to DSMIL, our method achieves an improvement of 70.4% and 15.3% in F1 score for instance- and slide-level classification, respectively, along with AUC gains of 16.9% for instance localisation and 2.3% for slide classification, while maintaining the use of frozen patch features.

Whole slide images (WSIs) are the gold standard for pathological diagnosis and sub-typing. Current main-stream two-step frameworks employ offline feature encoders trained without domain-specific knowledge. Among them, attention-based multiple instance learning (MIL) methods are outcome-oriented and offer limited interpretability. Clustering-based approaches can provide explainable decision-making process but suffer from high dimension features and semantically ambiguous centroids. To this end, we propose an end-to-end MIL framework that integrates Grassmann re-embedding and manifold adaptive clustering, where the manifold geometric structure facilitates robust clustering results. Furthermore, we design a prior knowledge guiding proxy instance labeling and aggregation strategy to approximate patch labels and focus on pathologically relevant tumor regions. Experiments on multicentre WSI datasets demonstrate that: 1) our cluster-incorporated model achieves superior performance in both grading accuracy and interpretability; 2) end-to-end learning refines better feature representations and it requires acceptable computation resources.

The tumor region plays a key role in pathological diagnosis. Tumor tissues are highly similar to precancerous lesions and non tumor instances often greatly exceed tumor instances in whole slide images (WSIs). These issues cause instance-semantic entanglement in multi-instance learning frameworks, degrading both model representation capability and interpretability. To address this, we propose an end-to-end prototype instance semantic disentanglement framework with low-rank regularized subspace clustering, PID-LRSC, in two aspects. First, we use secondary instance subspace learning to construct low-rank regularized subspace clustering (LRSC), addressing instance entanglement caused by an excessive proportion of non tumor instances. Second, we employ enhanced contrastive learning to design prototype instance semantic disentanglement (PID), resolving semantic entanglement caused by the high similarity between tumor and precancerous tissues. We conduct extensive experiments on multicentre pathology datasets, implying that PID-LRSC outperforms other SOTA methods. Overall, PID-LRSC provides clearer instance semantics during decision-making and significantly enhances the reliability of auxiliary diagnostic outcomes.

Multi-instance partial-label learning (MIPL) is a weakly supervised framework that extends the principles of multi-instance learning (MIL) and partial-label learning (PLL) to address the challenges of inexact supervision in both instance and label spaces. However, existing MIPL approaches often suffer from poor calibration, undermining classifier reliability. In this work, we propose a plug-and-play calibratable disambiguation loss (CDL) for classification and calibration, which modulates a disambiguation objective by a top-vs-competitor prediction margin. The competitor is instantiated either as the second strongest candidate label or as the strongest non-candidate label, yielding two variants that respectively emphasize candidate-level separation and candidate-vs-non-candidate suppression. Theoretically, we analyze CDL as a margin-modulated momentum-based disambiguation loss (MDL) objective, derive a lower-bound and a pseudo-label confidence-alignment bound for calibration, and show through gradient and momentum analyses how margin shaping affects weight updates. Experimental results on benchmark and real-world MIPL datasets, together with representative PLL adaptation, confirm that our CDL significantly improves both classification accuracy and expected calibration error.