Aligning Knowledge Concepts to Whole Slide Images for Precise Histopathology Image Analysis

Due to the large size and lack of fine-grained annotation, Whole Slide Images (WSIs) analysis is commonly approached as a Multiple Instance Learning (MIL) problem. However, previous studies only learn from training data, posing a stark contrast to how human clinicians teach each other and reason about histopathologic entities and factors. Here we present a novel knowledge concept-based MIL framework, named ConcepPath to fill this gap. Specifically, ConcepPath utilizes GPT-4 to induce reliable diseasespecific human expert concepts from medical literature, and incorporate them with a group of purely learnable concepts to extract complementary knowledge from training data. In ConcepPath, WSIs are aligned to these linguistic knowledge concepts by utilizing pathology vision-language model as the basic building component. In the application of lung cancer subtyping, breast cancer HER2 scoring, and gastric cancer immunotherapy-sensitive subtyping task, ConcepPath significantly outperformed previous SOTA methods which lack the guidance of human expert knowledge.

Free Lunch in Pathology Foundation Model: Task-specific Model Adaptation with Concept-Guided Feature Enhancement

Whole slide image (WSI) analysis is gaining prominence within the medical imaging field. Recent advances in pathology foundation models have shown the potential to extract powerful feature representations from WSIs for downstream tasks. However, these foundation models are usually designed for general-purpose pathology image analysis and may not be optimal for specific downstream tasks or cancer types. In this work, we present Concept Anchor-guided Task-specific Feature Enhancement (CATE), an adaptable paradigm that can boost the expressivity and discriminativeness of pathology foundation models for specific downstream tasks. Based on a set of task-specific concepts derived from the pathology vision-language model with expert-designed prompts, we introduce two interconnected modules to dynamically calibrate the generic image features extracted by foundation models for certain tasks or cancer types. Specifically, we design a Concept-guided Information Bottleneck module to enhance task-relevant characteristics by maximizing the mutual information between image features and concept anchors while suppressing superfluous information. Moreover, a Concept-Feature Interference module is proposed to utilize the similarity between calibrated features and concept anchors to further generate discriminative task-specific features. The extensive experiments on public WSI datasets demonstrate that CATE significantly enhances the performance and generalizability of MIL models. Additionally, heatmap and umap visualization results also reveal the effectiveness and interpretability of CATE. The source code is available at https://github.com/HKU-MedAI/CATE.

CTPD: Cross-Modal Temporal Pattern Discovery for Enhanced Multimodal Electronic Health Records Analysis

Integrating multimodal Electronic Health Records (EHR) data, such as numerical time series and free-text clinical reports, has great potential in predicting clinical outcomes. However, prior work has primarily focused on capturing temporal interactions within individual samples and fusing multimodal information, overlooking critical temporal patterns across patients. These patterns, such as trends in vital signs like abnormal heart rate or blood pressure, can indicate deteriorating health or an impending critical event. Similarly, clinical notes often contain textual descriptions that reflect these patterns. Identifying corresponding temporal patterns across different modalities is crucial for improving the accuracy of clinical outcome predictions, yet it remains a challenging task. To address this gap, we introduce a Cross-Modal Temporal Pattern Discovery (CTPD) framework, designed to efficiently extract meaningful cross-modal temporal patterns from multimodal EHR data. Our approach introduces shared initial temporal pattern representations which are refined using slot attention to generate temporal semantic embeddings. To ensure rich cross-modal temporal semantics in the learned patterns, we introduce a contrastive-based TPNCE loss for cross-modal alignment, along with two reconstruction losses to retain core information of each modality. Evaluations on two clinically critical tasks, 48-hour in-hospital mortality and 24-hour phenotype classification, using the MIMIC-III database demonstrate the superiority of our method over existing approaches.

ToolBridge: An Open-Source Dataset to Equip LLMs with External Tool Capabilities

Through the integration of external tools, large language models (LLMs) such as GPT-4o and Llama 3.1 significantly expand their functional capabilities, evolving from elementary conversational agents to general-purpose assistants. We argue that the primary drivers of these advancements are the quality and diversity of the training data. However, the existing LLMs with external tool integration provide only limited transparency regarding their datasets and data collection methods, which has led to the initiation of this research. Specifically, in this paper, our objective is to elucidate the detailed process involved in constructing datasets that empower LLMs to effectively learn how to utilize external tools and make this information available to the public through the introduction of ToolBridge. ToolBridge proposes to employ a collection of general open-access datasets as its raw dataset pool and applies a series of strategies to identify appropriate data entries from the pool for external tool API insertions. By supervised fine-tuning on these curated data entries, LLMs can invoke external tools in appropriate contexts to boost their predictive accuracy, particularly for basic functions including data processing, numerical computation, and factual retrieval. Our experiments rigorously isolates model architectures and training configurations, focusing exclusively on the role of data. The experimental results indicate that LLMs trained on ToolBridge demonstrate consistent performance improvements on both standard benchmarks and custom evaluation datasets. All the associated code and data will be open-source at https://github.com/CharlesPikachu/ToolBridge, promoting transparency and facilitating the broader community to explore approaches for equipping LLMs with external tools capabilities.

Multi-sensor Learning Enables Information Transfer across Different Sensory Data and Augments Multi-modality Imaging

Multi-modality imaging is widely used in clinical practice and biomedical research to gain a comprehensive understanding of an imaging subject. Currently, multi-modality imaging is accomplished by post hoc fusion of independently reconstructed images under the guidance of mutual information or spatially registered hardware, which limits the accuracy and utility of multi-modality imaging. Here, we investigate a data-driven multi-modality imaging (DMI) strategy for synergetic imaging of CT and MRI. We reveal two distinct types of features in multi-modality imaging, namely intra- and inter-modality features, and present a multi-sensor learning (MSL) framework to utilize the crossover inter-modality features for augmented multi-modality imaging. The MSL imaging approach breaks down the boundaries of traditional imaging modalities and allows for optimal hybridization of CT and MRI, which maximizes the use of sensory data. We showcase the effectiveness of our DMI strategy through synergetic CT-MRI brain imaging. The principle of DMI is quite general and holds enormous potential for various DMI applications across disciplines.

Multi-task Heterogeneous Graph Learning on Electronic Health Records

Learning electronic health records (EHRs) has received emerging attention because of its capability to facilitate accurate medical diagnosis. Since the EHRs contain enriched information specifying complex interactions between entities, modeling EHRs with graphs is shown to be effective in practice. The EHRs, however, present a great degree of heterogeneity, sparsity, and complexity, which hamper the performance of most of the models applied to them. Moreover, existing approaches modeling EHRs often focus on learning the representations for a single task, overlooking the multi-task nature of EHR analysis problems and resulting in limited generalizability across different tasks. In view of these limitations, we propose a novel framework for EHR modeling, namely MulT-EHR (Multi-Task EHR), which leverages a heterogeneous graph to mine the complex relations and model the heterogeneity in the EHRs. To mitigate the large degree of noise, we introduce a denoising module based on the causal inference framework to adjust for severe confounding effects and reduce noise in the EHR data. Additionally, since our model adopts a single graph neural network for simultaneous multi-task prediction, we design a multi-task learning module to leverage the inter-task knowledge to regularize the training process. Extensive empirical studies on MIMIC-III and MIMIC-IV datasets validate that the proposed method consistently outperforms the state-of-the-art designs in four popular EHR analysis tasks -- drug recommendation, and predictions of the length of stay, mortality, and readmission. Thorough ablation studies demonstrate the robustness of our method upon variations to key components and hyperparameters.

Personalizing Federated Instrument Segmentation with Visual Trait Priors in Robotic Surgery

Personalized federated learning (PFL) for surgical instrument segmentation (SIS) is a promising approach. It enables multiple clinical sites to collaboratively train a series of models in privacy, with each model tailored to the individual distribution of each site. Existing PFL methods rarely consider the personalization of multi-headed self-attention, and do not account for appearance diversity and instrument shape similarity, both inherent in surgical scenes. We thus propose PFedSIS, a novel PFL method with visual trait priors for SIS, incorporating global-personalized disentanglement (GPD), appearance-regulation personalized enhancement (APE), and shape-similarity global enhancement (SGE), to boost SIS performance in each site. GPD represents the first attempt at head-wise assignment for multi-headed self-attention personalization. To preserve the unique appearance representation of each site and gradually leverage the inter-site difference, APE introduces appearance regulation and provides customized layer-wise aggregation solutions via hypernetworks for each site's personalized parameters. The mutual shape information of instruments is maintained and shared via SGE, which enhances the cross-style shape consistency on the image level and computes the shape-similarity contribution of each site on the prediction level for updating the global parameters. PFedSIS outperforms state-of-the-art methods with +1.51% Dice, +2.11% IoU, -2.79 ASSD, -15.55 HD95 performance gains. The corresponding code and models will be released at https://github.com/wzjialang/PFedSIS.

HERGen: Elevating Radiology Report Generation with Longitudinal Data

Radiology reports provide detailed descriptions of medical imaging integrated with patients' medical histories, while report writing is traditionally labor-intensive, increasing radiologists' workload and the risk of diagnostic errors. Recent efforts in automating this process seek to mitigate these issues by enhancing accuracy and clinical efficiency. Emerging research in automating this process promises to alleviate these challenges by reducing errors and streamlining clinical workflows. However, existing automated approaches are based on a single timestamp and often neglect the critical temporal aspect of patients' imaging histories, which is essential for accurate longitudinal analysis. To address this gap, we propose a novel History Enhanced Radiology Report Generation (HERGen) framework that employs a employs a group causal transformer to efficiently integrate longitudinal data across patient visits. Our approach not only allows for comprehensive analysis of varied historical data but also improves the quality of generated reports through an auxiliary contrastive objective that aligns image sequences with their corresponding reports. More importantly, we introduce a curriculum learning-based strategy to adeptly handle the inherent complexity of longitudinal radiology data and thus stabilize the optimization of our framework. The extensive evaluations across three datasets demonstrate that our framework surpasses existing methods in generating accurate radiology reports and effectively predicting disease progression from medical images.

cDP-MIL: Robust Multiple Instance Learning via Cascaded Dirichlet Process

Multiple instance learning (MIL) has been extensively applied to whole slide histopathology image (WSI) analysis. The existing aggregation strategy in MIL, which primarily relies on the first-order distance (e.g., mean difference) between instances, fails to accurately approximate the true feature distribution of each instance, leading to biased slide-level representations. Moreover, the scarcity of WSI observations easily leads to model overfitting, resulting in unstable testing performance and limited generalizability. To tackle these challenges, we propose a new Bayesian nonparametric framework for multiple instance learning, which adopts a cascade of Dirichlet processes (cDP) to incorporate the instance-to-bag characteristic of the WSIs. We perform feature aggregation based on the latent clusters formed by the Dirichlet process, which incorporates the covariances of the patch features and forms more representative clusters. We then perform bag-level prediction with another Dirichlet process model on the bags, which imposes a natural regularization on learning to prevent overfitting and enhance generalizability. Moreover, as a Bayesian nonparametric method, the cDP model can accurately generate posterior uncertainty, which allows for the detection of outlier samples and tumor localization. Extensive experiments on five WSI benchmarks validate the superior performance of our method, as well as its generalizability and ability to estimate uncertainties. Codes are available at https://github.com/HKU-MedAI/cDPMIL.

Completed Feature Disentanglement Learning for Multimodal MRIs Analysis

Multimodal MRIs play a crucial role in clinical diagnosis and treatment. Feature disentanglement (FD)-based methods, aiming at learning superior feature representations for multimodal data analysis, have achieved significant success in multimodal learning (MML). Typically, existing FD-based methods separate multimodal data into modality-shared and modality-specific features, and employ concatenation or attention mechanisms to integrate these features. However, our preliminary experiments indicate that these methods could lead to a loss of shared information among subsets of modalities when the inputs contain more than two modalities, and such information is critical for prediction accuracy. Furthermore, these methods do not adequately interpret the relationships between the decoupled features at the fusion stage. To address these limitations, we propose a novel Complete Feature Disentanglement (CFD) strategy that recovers the lost information during feature decoupling. Specifically, the CFD strategy not only identifies modality-shared and modality-specific features, but also decouples shared features among subsets of multimodal inputs, termed as modality-partial-shared features. We further introduce a new Dynamic Mixture-of-Experts Fusion (DMF) module that dynamically integrates these decoupled features, by explicitly learning the local-global relationships among the features. The effectiveness of our approach is validated through classification tasks on three multimodal MRI datasets. Extensive experimental results demonstrate that our approach outperforms other state-of-the-art MML methods with obvious margins, showcasing its superior performance.