It is an essential task to accurately diagnose cancer subtypes in computational pathology for personalized cancer treatment. Recent studies have indicated that the combination of multimodal data, such as whole slide images (WSIs) and multi-omics data, could achieve more accurate diagnosis. However, robust cancer diagnosis remains challenging due to the heterogeneity among multimodal data, as well as the performance degradation caused by insufficient multimodal patient data. In this work, we propose a novel multimodal co-attention fusion network (MCFN) with online data augmentation (ODA) for cancer subtype classification. Specifically, a multimodal mutual-guided co-attention (MMC) module is proposed to effectively perform dense multimodal interactions. It enables multimodal data to mutually guide and calibrate each other during the integration process to alleviate inter- and intra-modal heterogeneities. Subsequently, a self-normalizing network (SNN)-Mixer is developed to allow information communication among different omics data and alleviate the high-dimensional small-sample size problem in multi-omics data. Most importantly, to compensate for insufficient multimodal samples for model training, we propose an ODA module in MCFN. The ODA module leverages the multimodal knowledge to guide the data augmentations of WSIs and maximize the data diversity during model training. Extensive experiments are conducted on the public TCGA dataset. The experimental results demonstrate that the proposed MCFN outperforms all the compared algorithms, suggesting its effectiveness.

Computer-aided diagnosis (CAD) can help pathologists improve diagnostic accuracy together with consistency and repeatability for cancers. However, the CAD models trained with the histopathological images only from a single center (hospital) generally suffer from the generalization problem due to the straining inconsistencies among different centers. In this work, we propose a pseudo-data based self-supervised federated learning (FL) framework, named SSL-FT-BT, to improve both the diagnostic accuracy and generalization of CAD models. Specifically, the pseudo histopathological images are generated from each center, which contain both inherent and specific properties corresponding to the real images in this center, but do not include the privacy information. These pseudo images are then shared in the central server for self-supervised learning (SSL) to pre-train the backbone of global mode. A multi-task SSL is then designed to effectively learn both the center-specific information and common inherent representation according to the data characteristics. Moreover, a novel Barlow Twins based FL (FL-BT) algorithm is proposed to improve the local training for the CAD models in each center by conducting model contrastive learning, which benefits the optimization of the global model in the FL procedure. The experimental results on four public histopathological image datasets indicate the effectiveness of the proposed SSL-FL-BT on both diagnostic accuracy and generalization.

The multi-scale information among the whole slide images (WSIs) is essential for cancer diagnosis. Although the existing multi-scale vision Transformer has shown its effectiveness for learning multi-scale image representation, it still cannot work well on the gigapixel WSIs due to their extremely large image sizes. To this end, we propose a novel Multi-scale Efficient Graph-Transformer (MEGT) framework for WSI classification. The key idea of MEGT is to adopt two independent efficient Graph-based Transformer (EGT) branches to process the low-resolution and high-resolution patch embeddings (i.e., tokens in a Transformer) of WSIs, respectively, and then fuse these tokens via a multi-scale feature fusion module (MFFM). Specifically, we design an EGT to efficiently learn the local-global information of patch tokens, which integrates the graph representation into Transformer to capture spatial-related information of WSIs. Meanwhile, we propose a novel MFFM to alleviate the semantic gap among different resolution patches during feature fusion, which creates a non-patch token for each branch as an agent to exchange information with another branch by cross-attention mechanism. In addition, to expedite network training, a new token pruning module is developed in EGT to reduce the redundant tokens. Extensive experiments on both TCGA-RCC and CAMELYON16 datasets demonstrate the effectiveness of the proposed MEGT.