Gigapixel image analysis, particularly for whole slide images (WSIs), often relies on multiple instance learning (MIL). Under the paradigm of MIL, patch image representations are extracted and then fixed during the training of the MIL classifiers for efficiency consideration. However, the invariance of representations makes it difficult to perform data augmentation for WSI-level model training, which significantly limits the performance of the downstream WSI analysis. The current data augmentation methods for gigapixel images either introduce additional computational costs or result in a loss of semantic information, which is hard to meet the requirements for efficiency and stability needed for WSI model training. In this paper, we propose a Promptable Representation Distribution Learning framework (PRDL) for both patch-level representation learning and WSI-level data augmentation. Meanwhile, we explore the use of prompts to guide data augmentation in feature space, which achieves promptable data augmentation for training robust WSI-level models. The experimental results have demonstrated that the proposed method stably outperforms state-of-the-art methods.

In the domain of histopathology analysis, existing representation learning methods for biomarkers prediction from whole slide images (WSIs) face challenges due to the complexity of tissue subtypes and label noise problems. This paper proposed a novel partial-label contrastive representation learning approach to enhance the discrimination of histopathology image representations for fine-grained biomarkers prediction. We designed a partial-label contrastive clustering (PLCC) module for partial-label disambiguation and a dynamic clustering algorithm to sample the most representative features of each category to the clustering queue during the contrastive learning process. We conducted comprehensive experiments on three gene mutation prediction datasets, including USTC-EGFR, BRCA-HER2, and TCGA-EGFR. The results show that our method outperforms 9 existing methods in terms of Accuracy, AUC, and F1 Score. Specifically, our method achieved an AUC of 0.950 in EGFR mutation subtyping of TCGA-EGFR and an AUC of 0.853 in HER2 0/1+/2+/3+ grading of BRCA-HER2, which demonstrates its superiority in fine-grained biomarkers prediction from histopathology whole slide images.

The development of computational pathology lies in the consensus that pathological characteristics of tumors are significant guidance for cancer diagnostics. Most existing research focuses on the inner-contextual information within each WSI yet ignores the possible inter-correlations between slides. As the development of tumors is a continuous process involving a series of histological, morphological, and genetic changes that accumulate over time, the similarities and differences between WSIs across various stages, grades, locations and patients should potentially contribute to the representation of WSIs and deserve to be taken into account in WSI modeling. To verify the advancement of introducing the slide inter-correlations into the representation learning of WSIs, we proposed a generic WSI analysis pipeline SlideGCD that can be adapted to any existing Multiple Instance Learning (MIL) frameworks and improve their performance. With the new paradigm, the prior knowledge of cancer development can participate in the end-to-end workflow, which concurrently initializes and refines the slide representation, as a guide for message passing in the slide-based graph. Extensive comparisons and experiments are conducted to validate the effectiveness and robustness of the proposed pipeline across 4 different tasks, including cancer subtyping, cancer staging, survival prediction, and gene mutation prediction, with 8 representative SOTA WSI analysis frameworks as backbones. The code is available at https://github.com/HFUT-miaLab/SlideGCD.

Multiple instance learning (MIL) based whole slide image (WSI) classification is often carried out on the representations of patches extracted from WSI with a pre-trained patch encoder. The performance of classification relies on both patch-level representation learning and MIL classifier training. Most MIL methods utilize a frozen model pre-trained on ImageNet or a model trained with self-supervised learning on histopathology image dataset to extract patch image representations and then fix these representations in the training of the MIL classifiers for efficiency consideration. However, the invariance of representations cannot meet the diversity requirement for training a robust MIL classifier, which has significantly limited the performance of the WSI classification. In this paper, we propose a Self-Supervised Representation Distribution Learning framework (SSRDL) for patch-level representation learning with an online representation sampling strategy (ORS) for both patch feature extraction and WSI-level data augmentation. The proposed method was evaluated on three datasets under three MIL frameworks. The experimental results have demonstrated that the proposed method achieves the best performance in histopathology image representation learning and data augmentation and outperforms state-of-the-art methods under different WSI classification frameworks. The code is available at https://github.com/lazytkm/SSRDL.

Large-scale pre-training models have promoted the development of histopathology image analysis. However, existing self-supervised methods for histopathology images primarily focus on learning patch features, while there is a notable gap in the availability of pre-training models specifically designed for WSI-level feature learning. In this paper, we propose a novel self-supervised learning framework for pan-cancer WSI-level representation pre-training with the designed position-aware masked autoencoder (PAMA). Meanwhile, we propose the position-aware cross-attention (PACA) module with a kernel reorientation (KRO) strategy and an anchor dropout (AD) mechanism. The KRO strategy can capture the complete semantic structure and eliminate ambiguity in WSIs, and the AD contributes to enhancing the robustness and generalization of the model. We evaluated our method on 7 large-scale datasets from multiple organs for pan-cancer classification tasks. The results have demonstrated the effectiveness and generalization of PAMA in discriminative WSI representation learning and pan-cancer WSI pre-training. The proposed method was also compared with 8 WSI analysis methods. The experimental results have indicated that our proposed PAMA is superior to the state-of-the-art methods. The code and checkpoints are available at https://github.com/WkEEn/PAMA.

Traditional PCR/NGS-based multigene panel testing is time-consuming and costly. Predicting EGFR mutations directly from H&E stained whole slide images (WSIs) can alleviate these limitations. Furthermore, histopathological reports contain valuable textual information that correlates with tissue areas in WSIs. However, recent research mainly analyses EGFR mutation status only from a single modality, ignoring rich information contained in reports. In this paper, we propose a report-guided cross-modal representation learning method for predicting EGFR mutations by WSIs. Specifically, we reconstruct report-level embeddings through exploring intrinsic relationships between diagnostic words in histopathological reports and tissue areas in WSIs. Finally, reconstructed histopathological report embedding and aggregated WSI embedding are fused for final prediction. More importantly, molecular testing report is also introduced as prior supervision information at the training stage to guarantee semantic consistency of fused feature and molecular report embedding. We evaluate our method on the TCGA-EGFR public benchmark dataset and an in-house clinical dataset (USTC-EGFR). Experimental results demonstrate that our method outperforms existing approaches in EGFR mutation prediction, highlighting the benefits of cross-modal learning in enhancing feature representational ability. The code is available at https://github.com/HFUT-miaLab/RCRL.