Joseph J. Y. Sung

Conghao Xiong, Hao Chen, Joseph J. Y. Sung et al.

Multiple Instance Learning (MIL) and transformers are increasingly popular in histopathology Whole Slide Image (WSI) classification. However, unlike human pathologists who selectively observe specific regions of histopathology tissues under different magnifications, most methods do not incorporate multiple resolutions of the WSIs, hierarchically and attentively, thereby leading to a loss of focus on the WSIs and information from other resolutions. To resolve this issue, we propose a Hierarchical Attention-Guided Multiple Instance Learning framework to fully exploit the WSIs. This framework can dynamically and attentively discover the discriminative regions across multiple resolutions of the WSIs. Within this framework, an Integrated Attention Transformer is proposed to further enhance the performance of the transformer and obtain a more holistic WSI (bag) representation. This transformer consists of multiple Integrated Attention Modules, which is the combination of a transformer layer and an aggregation module that produces a bag representation based on every instance representation in that bag. The experimental results show that our method achieved state-of-the-art performances on multiple datasets, including Camelyon16, TCGA-RCC, TCGA-NSCLC, and an in-house IMGC dataset. The code is available at https://github.com/BearCleverProud/HAG-MIL.

Conghao Xiong, Yi Lin, Hao Chen et al.

Transferring knowledge from a source domain to a target domain can be crucial for whole slide image classification, since the number of samples in a dataset is often limited due to high annotation costs. However, domain shift and task discrepancy between datasets can hinder effective knowledge transfer. In this paper, we propose a Target-Aware Knowledge Transfer framework, employing a teacher-student paradigm. Our framework enables the teacher model to learn common knowledge from the source and target domains by actively incorporating unlabelled target images into the training of the teacher model. The teacher bag features are subsequently adapted to supervise the training of the student model on the target domain. Despite incorporating the target features during training, the teacher model tends to overlook them under the inherent domain shift and task discrepancy. To alleviate this, we introduce a target-aware feature alignment module to establish a transferable latent relationship between the source and target features by solving the optimal transport problem. Experimental results show that models employing knowledge transfer outperform those trained from scratch, and our method achieves state-of-the-art performance among other knowledge transfer methods on various datasets, including TCGA-RCC, TCGA-NSCLC, and Camelyon16.

Dianzhi Yu, Conghao Xiong, Yankai Chen et al.

Survival prediction of cancers is crucial for clinical practice, as it informs mortality risks and influences treatment plans. However, a static model trained on a single dataset fails to adapt to the dynamically evolving clinical environment and continuous data streams, limiting its practical utility. While continual learning (CL) offers a solution to learn dynamically from new datasets, existing CL methods primarily focus on unimodal inputs and suffer from severe catastrophic forgetting in survival prediction. In real-world scenarios, multimodal inputs often provide comprehensive and complementary information, such as whole slide images and genomics; and neglecting inter-modal correlations negatively impacts the performance. To address the two challenges of catastrophic forgetting and complex inter-modal interactions between gigapixel whole slide images and genomics, we propose ConSurv, the first multimodal continual learning (MMCL) method for survival analysis. ConSurv incorporates two key components: Multi-staged Mixture of Experts (MS-MoE) and Feature Constrained Replay (FCR). MS-MoE captures both task-shared and task-specific knowledge at different learning stages of the network, including two modality encoders and the modality fusion component, learning inter-modal relationships. FCR further enhances learned knowledge and mitigates forgetting by restricting feature deviation of previous data at different levels, including encoder-level features of two modalities and the fusion-level representations. Additionally, we introduce a new benchmark integrating four datasets, Multimodal Survival Analysis Incremental Learning (MSAIL), for comprehensive evaluation in the CL setting. Extensive experiments demonstrate that ConSurv outperforms competing methods across multiple metrics.

Conghao Xiong, Hao Chen, Joseph J. Y. Sung

Computational pathology, which involves analyzing whole slide images for automated cancer diagnosis, relies on multiple instance learning, where performance depends heavily on the feature extractor and aggregator. Recent Pathology Foundation Models (PFMs), pretrained on large-scale histopathology data, have significantly enhanced both the extractor and aggregator, but they lack a systematic analysis framework. In this survey, we present a hierarchical taxonomy organizing PFMs through a top-down philosophy applicable to foundation model analysis in any domain: model scope, model pretraining, and model design. Additionally, we systematically categorize PFM evaluation tasks into slide-level, patch-level, multimodal, and biological tasks, providing comprehensive benchmarking criteria. Our analysis identifies critical challenges in both PFM development (pathology-specific methodology, end-to-end pretraining, data-model scalability) and utilization (effective adaptation, model maintenance), paving the way for future directions in this promising field. Resources referenced in this survey are available at https://github.com/BearCleverProud/AwesomeWSI.

Conghao Xiong, Hao Chen, Hao Zheng et al.

Survival analysis, as a challenging task, requires integrating Whole Slide Images (WSIs) and genomic data for comprehensive decision-making. There are two main challenges in this task: significant heterogeneity and complex inter- and intra-modal interactions between the two modalities. Previous approaches utilize co-attention methods, which fuse features from both modalities only once after separate encoding. However, these approaches are insufficient for modeling the complex task due to the heterogeneous nature between the modalities. To address these issues, we propose a Biased Progressive Encoding (BPE) paradigm, performing encoding and fusion simultaneously. This paradigm uses one modality as a reference when encoding the other. It enables deep fusion of the modalities through multiple alternating iterations, progressively reducing the cross-modal disparities and facilitating complementary interactions. Besides modality heterogeneity, survival analysis involves various biomarkers from WSIs, genomics, and their combinations. The critical biomarkers may exist in different modalities under individual variations, necessitating flexible adaptation of the models to specific scenarios. Therefore, we further propose a Mixture of Multimodal Experts (MoME) layer to dynamically selects tailored experts in each stage of the BPE paradigm. Experts incorporate reference information from another modality to varying degrees, enabling a balanced or biased focus on different modalities during the encoding process. Extensive experimental results demonstrate the superior performance of our method on various datasets, including TCGA-BLCA, TCGA-UCEC and TCGA-LUAD. Codes are available at https://github.com/BearCleverProud/MoME.

Andrew J. Loza, Jun Yup Kim, Shangzheng Song et al.

Real-world processes often generate data that are a mix of categorical and numeric values that are recorded at irregular and informative intervals. Discrete token-based approaches are limited in numeric representation capacity while methods like neural ordinary differential equations are not well suited for categorical data or informative sampling and require augmentation to handle certain classes of trajectories. Here, we present multivariateGPT, a single architecture for modeling sequences of mixed categorical (including tokenized text) and numeric data. This is accomplished with an autoregressive sequence decomposition, embedding scheme, and loss function that extend the next token prediction task to likelihood estimation of the joint distribution of next token class and value. We demonstrate how this approach can efficiently learn to generalize patterns in simple physical systems and model complex time series including electrocardiograms and multivariate electronic health record data. This work extends the utility of transformer based models to additional classes of data.

Conghao Xiong, Zhengrui Guo, Zhe Xu et al.

Deep learning has advanced computational pathology but expert annotations remain scarce. Few-shot learning mitigates annotation burdens yet suffers from overfitting and discriminative feature mischaracterization. In addition, the current few-shot multiple instance learning (MIL) approaches leverage pretrained vision-language models to alleviate these issues, but at the cost of complex preprocessing and high computational cost. We propose a Squeeze-and-Recalibrate (SR) block, a drop-in replacement for linear layers in MIL models to address these challenges. The SR block comprises two core components: a pair of low-rank trainable matrices (squeeze pathway, SP) that reduces parameter count and imposes a bottleneck to prevent spurious feature learning, and a frozen random recalibration matrix that preserves geometric structure, diversifies feature directions, and redefines the optimization objective for the SP. We provide theoretical guarantees that the SR block can approximate any linear mapping to arbitrary precision, thereby ensuring that the performance of a standard MIL model serves as a lower bound for its SR-enhanced counterpart. Extensive experiments demonstrate that our SR-MIL models consistently outperform prior methods while requiring significantly fewer parameters and no architectural changes.