Multiple Instance Learning (MIL) has been widely used in weakly supervised whole slide image (WSI) classification. Typical MIL methods include a feature embedding part that embeds the instances into features via a pre-trained feature extractor and the MIL aggregator that combines instance embeddings into predictions. The current focus has been directed toward improving these parts by refining the feature embeddings through self-supervised pre-training and modeling the correlations between instances separately. In this paper, we proposed a sparsely coded MIL (SC-MIL) that addresses those two aspects at the same time by leveraging sparse dictionary learning. The sparse dictionary learning captures the similarities of instances by expressing them as a sparse linear combination of atoms in an over-complete dictionary. In addition, imposing sparsity help enhance the instance feature embeddings by suppressing irrelevant instances while retaining the most relevant ones. To make the conventional sparse coding algorithm compatible with deep learning, we unrolled it into an SC module by leveraging deep unrolling. The proposed SC module can be incorporated into any existing MIL framework in a plug-and-play manner with an acceptable computation cost. The experimental results on multiple datasets demonstrated that the proposed SC module could substantially boost the performance of state-of-the-art MIL methods. The codes are available at \href{https://github.com/sotiraslab/SCMIL.git}{https://github.com/sotiraslab/SCMIL.git}.

Multiple Instance learning (MIL) models have been extensively used in pathology to predict biomarkers and risk-stratify patients from gigapixel-sized images. Machine learning problems in medical imaging often deal with rare diseases, making it important for these models to work in a label-imbalanced setting. In pathology images, there is another level of imbalance, where given a positively labeled Whole Slide Image (WSI), only a fraction of pixels within it contribute to the positive label. This compounds the severity of imbalance and makes imbalanced classification in pathology challenging. Furthermore, these imbalances can occur in out-of-distribution (OOD) datasets when the models are deployed in the real-world. We leverage the idea that decoupling feature and classifier learning can lead to improved decision boundaries for label imbalanced datasets. To this end, we investigate the integration of supervised contrastive learning with multiple instance learning (SC-MIL). Specifically, we propose a joint-training MIL framework in the presence of label imbalance that progressively transitions from learning bag-level representations to optimal classifier learning. We perform experiments with different imbalance settings for two well-studied problems in cancer pathology: subtyping of non-small cell lung cancer and subtyping of renal cell carcinoma. SC-MIL provides large and consistent improvements over other techniques on both in-distribution (ID) and OOD held-out sets across multiple imbalanced settings.