Multiple Instance Learning (MIL) consists of two stages: feature encoding of instances and feature fusion of instances. This paper identifies two issues in the feature fusion stage of MIL when applied to pathological image classification, which creates performance bottlenecks. First, previous MIL methods lack positional encoding in the feature fusion stage. However, the number of positive instances is critical for pathological diagnosis. This makes it difficult for earlier MIL models to perceive positive instances, limiting their ability to capture the semantic correlation between the number of positive instances and the disease. Second, previous MIL methods base both inference and training on a single Whole Slide Image (WSI), failing to utilize cross-slide information effectively. To address these issues, this paper proposes a novel attention mechanism called CORE Attention (Contextual Position Encoding-based Retrievable Attention) during the instance fusion stage of MIL, and develops the COREMIL model based on it. CORE Attention consists of two modules: contextual position encoding and cross-slide retrieval-based attention fine-tuning. The contextual position encoding captures better contextual information, especially for counting tasks. Cross-slide retrieval-based attention fine-tuning allows the model to leverage previously learned historical information to guide the attention in the current feature fusion process. This paper validated COREMIL’s classification performance on several public datasets and a private dataset of pathological images. Extensive experiments demonstrate that COREMIL outperforms other current MIL models in terms of F1 Score and AUC on most datasets, with improvements of up to 14.414%. This CORE Attention-based approach offers an efficient solution for slide-level classification problems. Our code will be accessed shortly.

To deploy neural networks on clinical edge devices, quantization is the most commonly used method to compress the models, which requires a calibration set of hundreds of real images. However, due to privacy concerns, the scarcity of private histopathological images hinders the application of quantization. To address this issue, we develop HIQ, a novel one-shot quantization framework for histopathological image classification networks, which requires only one real image per class for calibration. To compensate for data scarcity, sample BNS alignment is introduced to generate synthetic images with similar distribution to the real ones. To improve the diversity of synthetic images, fine-grained diversity enhancement that provides fine-grained enhancement intensity for different classes and network layers is proposed, based on the observation of the class-wise and layer-wise fine-grained data. Finally, the asymptotic enhancement strategy is highlighted to achieve a trade-off between inter-class distance and intra-class diversity of synthetic images, based on the insight of the smaller inter-class distance of histopathological images than that of natural ones. Extensive experiments on the BRACS dataset show that our method achieves an extremely low accuracy loss even compared to the full precision model in low-bit cases and maintains robustness when missing classes of real images.

Histopathology analysis is the gold standard for medical diagnosis. Accurate classification of whole slide images (WSIs) and region-of-interests (ROIs) localization can assist pathologists in diagnosis. The gigapixel resolution of WSI and the absence of fine-grained annotations make direct classification and analysis challenging. In weakly supervised learning, multiple instance learning (MIL) presents a promising approach for WSI classification. The prevailing strategy is to use attention mechanisms to measure instance importance for classification. However, attention mechanisms fail to capture inter-instance information, and self-attention causes quadratic computational complexity. To address these challenges, we propose AMD-MIL, an agent aggregator with a mask denoise mechanism. The agent token acts as an intermediate variable between the query and key for computing instance importance. Mask and denoising matrices, mapped from agents-aggregated value, dynamically mask low-contribution representations and eliminate noise. AMD-MIL achieves better attention allocation by adjusting feature representations, capturing micro-metastases in cancer, and improving interpretability. Extensive experiments on CAMELYON-16, CAMELYON-17, TCGA-KIDNEY, and TCGA-LUNG show AMD-MIL's superiority over state-of-the-art methods.

Digitization of pathological slides has promoted the research of computer-aided diagnosis, in which artificial intelligence analysis of pathological images deserves attention. Appropriate deep learning techniques in natural images have been extended to computational pathology. Still, they seldom take into account prior knowledge in pathology, especially the analysis process of lesion morphology by pathologists. Inspired by the diagnosis decision of pathologists, we design a novel deep learning architecture based on tree-like strategies called DeepTree. It imitates pathological diagnosis methods, designed as a binary tree structure, to conditionally learn the correlation between tissue morphology, and optimizes branches to finetune the performance further. To validate and benchmark DeepTree, we build a dataset of frozen lung cancer tissues and design experiments on a public dataset of breast tumor subtypes and our dataset. Results show that the deep learning architecture based on tree-like strategies makes the pathological image classification more accurate, transparent, and convincing. Simultaneously, prior knowledge based on diagnostic strategies yields superior representation ability compared to alternative methods. Our proposed methodology helps improve the trust of pathologists in artificial intelligence analysis and promotes the practical clinical application of pathology-assisted diagnosis.