Nuclei-level prior knowledge constrained multiple instance learning for breast histopathology whole slide image classification

New breast cancer cases have surpassed lung cancer, becoming the world's most prevalent cancer. Despite advancing medical image analysis, deep learning's lack of interpretability limits its adoption among pathologists. Hence, a nuclei-level prior knowledge constrained multiple instance learning (MIL) (NPKC-MIL) for breast whole slide image (WSI) classification is proposed. NPKC-MIL primarily involves the following steps: Initially, employing the transfer learning to extract patch-level features and aggregate them into slide-level features through attention pooling. Subsequently, abstract the extracted nuclei as nodes, establish nucleus topology using the K-NN (K-Nearest Neighbors, K-NN) algorithm, and create handcrafted features for nodes. Finally, combine patch-level deep learning features with nuclei-level handcrafted features to fine-tune classification results generated by slide-level deep learning features. The experimental results demonstrate that NPKC-MIL outperforms current comparable deep learning models. NPKC-MIL expands the analytical dimension of WSI classification tasks and integrates prior knowledge into deep learning models to improve interpretability.