National Institute of Health Data Science, Peking University, Beijing, China, Department of Emergency Medicine, Peking University First Hospital, Beijing, China
Abstract:Granger Causal Discovery (GCD) is fundamental for analyzing temporal dependencies in complex systems. However, existing neural GCD methods predominantly rely on a "one-size-fits-all" paradigm, struggling to capture distribution shifts and dynamic regime changes inherent in real-world time series. This often leads to entangled representations and spurious causal graphs. In this paper, we propose CausalMoE, a billion-scale multimodal Granger causal foundation model that explicitly models patch-level heterogeneity. CausalMoE introduces a Pattern-Routed Mixture of Heterogeneous Experts, which dynamically identifies latent temporal patterns and routes patches to specialized domain experts, effectively decoupling regime-specific mechanisms from shared dynamics. To ensure interpretable graph recovery, we design a Causality-Aware Self-Attention mechanism operating across variables, yielding sparse Granger causal graphs via proximal optimization. Furthermore, CausalMoE is the first to integrate LLMs and VLMs to align numerical signals with textual and visual priors, regularizing causal estimation in complex scenarios. Extensive experiments demonstrate that CausalMoE establishes a new state-of-the-art on fully supervised benchmarks, while effectively generalizing to few-shot settings where traditional methods fail.
Abstract:Structural heart disease (SHD) is a primary driver of heart failure and cardiovascular mortality, yet early detection remains constrained by the limited accessibility of echocardiography. While single-lead electrocardiogram (ECG) is ubiquitous through wearables, existing AI screening models often depend on 12-lead inputs, generalize poorly across institutions, or require massive, condition-specific labeled datasets. Recent work has demonstrated the feasibility of contrastive pre-training between single-lead ECGs and echocardiography reports within a single health system. Here, we present AnyECG-Echo, a framework that advance this paradigm toward clinical translation through three key developments: (1) evaluation in a geographically independent external cohort (n = 16,621); (2) diagnostic coverage of 13 fine-grained SHD subtypes spanning myocardial, chamber, valvular, and great-vessel pathologies; and (3) dual-axis mechanistic interpretability combining electrophysiology-grounded Shapley attribution with emergent correlations to quantitative measurements. Across validation cohorts totaling n = 25,222, the model demonstrated high AUROC for high-impact subtypes, including reduced left ventricular systolic function (AUROC 0.866-0.924), global heart enlargement (0.877-0.931), and mitral stenosis (0.836-0.906). Furthermore, we successfully validated the alignment of model outputs with established medical physiological traits, thereby enhancing interpretability. Notably, we discovered that AnyECG-Echo's outputs function as physiologically grounded digital biomarkers that accurately track objective metrics such as LVEF and myocardial wall thickness. These findings prove that wearable single-lead ECGs can effectively detect fine-grained structural heart disease, offering a practical solution for population-scale screening.
Abstract:Medical time-series data captures the dynamic progression of patient conditions, playing a vital role in modern clinical decision support systems. However, real-world clinical data is highly heterogeneous and inconsistently formatted. Furthermore, existing machine learning tools often have steep learning curves and fragmented workflows. Consequently, a significant gap remains between cutting-edge AI technologies and clinical application. To address this, we introduce mtslearn, an end-to-end integrated toolkit specifically designed for medical time-series data. First, the framework provides a unified data interface that automates the parsing and alignment of wide, long, and flat data formats. This design significantly reduces data cleaning overhead. Building on this, mtslearn provides a complete pipeline from data reading and feature engineering to model training and result visualization. Furthermore, it offers flexible interfaces for custom algorithms. Through a modular design, mtslearn simplifies complex data engineering tasks into a few lines of code. This significantly lowers the barrier to entry for clinicians with limited programming experience, empowering them to focus more on exploring medical hypotheses and accelerating the translation of advanced algorithms into real-world clinical practice. mtslearn is publicly available at https://github.com/PKUDigitalHealth/mtslearn.
Abstract:Sleep disturbances are tightly linked to cardiovascular risk, yet polysomnography (PSG)-the clinical reference standard-remains resource-intensive and poorly suited for multi-night, home-based, and large-scale screening. Single-lead electrocardiography (ECG), already ubiquitous in Holter and patch-based devices, enables comfortable long-term acquisition and encodes sleep-relevant physiology through autonomic modulation and cardiorespiratory coupling. Here, we present a proof-of-concept Holter-to-Sleep framework that, using single-lead ECG as the sole input, jointly supports overnight sleep phenotyping and Holter-grade cardiac phenotyping within the same recording, and further provides an explicit analytic pathway for scalable cardio-sleep association studies. The framework is developed and validated on a pooled multi-center PSG sample of 10,439 studies spanning four public cohorts, with independent external evaluation to assess cross-cohort generalizability, and additional real-world feasibility assessment using overnight patch-ECG recordings via objective-subjective consistency analysis. This integrated design enables robust extraction of clinically meaningful overnight sleep phenotypes under heterogeneous populations and acquisition conditions, and facilitates systematic linkage between ECG-derived sleep metrics and arrhythmia-related Holter phenotypes. Collectively, the Holter-to-Sleep paradigm offers a practical foundation for low-burden, home-deployable, and scalable cardio-sleep monitoring and research beyond traditional PSG-centric workflows.
Abstract:Hyperkalemia is a life-threatening electrolyte disorder that is common in patients with chronic kidney disease and heart failure, yet frequent monitoring remains difficult outside hospital settings. We developed and validated Pocket-K, a single-lead AI-ECG system initialized from the ECGFounder foundation model for non-invasive hyperkalemia screening and handheld deployment. In this multicentre observational study using routinely collected clinical ECG and laboratory data, 34,439 patients contributed 62,290 ECG--potassium pairs. Lead I data were used to fine-tune the model. Data from Peking University People's Hospital were divided into development and temporal validation sets, and data from The Second Hospital of Tianjin Medical University served as an independent external validation set. Hyperkalemia was defined as venous serum potassium > 5.5 mmol/L. Pocket-K achieved AUROCs of 0.936 in internal testing, 0.858 in temporal validation, and 0.808 in external validation. For KDIGO-defined moderate-to-severe hyperkalemia (serum potassium >= 6.0 mmol/L), AUROCs increased to 0.940 and 0.861 in the temporal and external sets, respectively. External negative predictive value exceeded 99.3%. Model-predicted high risk below the hyperkalemia threshold was more common in patients with chronic kidney disease and heart failure. A handheld prototype enabled near-real-time inference, supporting future prospective evaluation in native handheld and wearable settings.
Abstract:The scarcity of high-quality data remains a primary bottleneck in adapting multimodal generative models for medical image editing. Existing medical image editing datasets often suffer from limited diversity, neglect of medical image understanding and inability to balance quality with scalability. To address these gaps, we propose MieDB-100k, a large-scale, high-quality and diverse dataset for text-guided medical image editing. It categorizes editing tasks into perspectives of Perception, Modification and Transformation, considering both understanding and generation abilities. We construct MieDB-100k via a data curation pipeline leveraging both modality-specific expert models and rule-based data synthetic methods, followed by rigorous manual inspection to ensure clinical fidelity. Extensive experiments demonstrate that model trained with MieDB-100k consistently outperform both open-source and proprietary models while exhibiting strong generalization ability. We anticipate that this dataset will serve as a cornerstone for future advancements in specialized medical image editing.
Abstract:Traditional diagnosis of aortic valve disease relies on echocardiography, but its cost and required expertise limit its use in large-scale early screening. Photoplethysmography (PPG) has emerged as a promising screening modality due to its widespread availability in wearable devices and its ability to reflect underlying hemodynamic dynamics. However, the extreme scarcity of gold-standard labeled PPG data severely constrains the effectiveness of data-driven approaches. To address this challenge, we propose and validate a new paradigm, Physiology-Guided Self-Supervised Learning (PG-SSL), aimed at unlocking the value of large-scale unlabeled PPG data for efficient screening of Aortic Stenosis (AS) and Aortic Regurgitation (AR). Using over 170,000 unlabeled PPG samples from the UK Biobank, we formalize clinical knowledge into a set of PPG morphological phenotypes and construct a pulse pattern recognition proxy task for self-supervised pre-training. A dual-branch, gated-fusion architecture is then employed for efficient fine-tuning on a small labeled subset. The proposed PG-SSL framework achieves AUCs of 0.765 and 0.776 for AS and AR screening, respectively, significantly outperforming supervised baselines trained on limited labeled data. Multivariable analysis further validates the model output as an independent digital biomarker with sustained prognostic value after adjustment for standard clinical risk factors. This study demonstrates that PG-SSL provides an effective, domain knowledge-driven solution to label scarcity in medical artificial intelligence and shows strong potential for enabling low-cost, large-scale early screening of aortic valve disease.
Abstract:Electrocardiography (ECG) serves as an indispensable diagnostic tool in clinical practice, yet existing multimodal large language models (MLLMs) remain unreliable for ECG interpretation, often producing plausible but clinically incorrect analyses. To address this, we propose ECG-R1, the first reasoning MLLM designed for reliable ECG interpretation via three innovations. First, we construct the interpretation corpus using \textit{Protocol-Guided Instruction Data Generation}, grounding interpretation in measurable ECG features and monograph-defined quantitative thresholds and diagnostic logic. Second, we present a modality-decoupled architecture with \textit{Interleaved Modality Dropout} to improve robustness and cross-modal consistency when either the ECG signal or ECG image is missing. Third, we present \textit{Reinforcement Learning with ECG Diagnostic Evidence Rewards} to strengthen evidence-grounded ECG interpretation. Additionally, we systematically evaluate the ECG interpretation capabilities of proprietary, open-source, and medical MLLMs, and provide the first quantitative evidence that severe hallucinations are widespread, suggesting that the public should not directly trust these outputs without independent verification. Code and data are publicly available at \href{https://github.com/PKUDigitalHealth/ECG-R1}{here}, and an online platform can be accessed at \href{http://ai.heartvoice.com.cn/ECG-R1/}{here}.
Abstract:Cardiac Magnetic Resonance (CMR) imaging provides a comprehensive assessment of cardiac structure and function but remains constrained by high acquisition costs and reliance on expert annotations, limiting the availability of large-scale labeled datasets. In contrast, electrocardiograms (ECGs) are inexpensive, widely accessible, and offer a promising modality for conditioning the generative synthesis of cine CMR. To this end, we propose ECGFlowCMR, a novel ECG-to-CMR generative framework that integrates a Phase-Aware Masked Autoencoder (PA-MAE) and an Anatomy-Motion Disentangled Flow (AMDF) to address two fundamental challenges: (1) the cross-modal temporal mismatch between multi-beat ECG recordings and single-cycle CMR sequences, and (2) the anatomical observability gap due to the limited structural information inherent in ECGs. Extensive experiments on the UK Biobank and a proprietary clinical dataset demonstrate that ECGFlowCMR can generate realistic cine CMR sequences from ECG inputs, enabling scalable pretraining and improving performance on downstream cardiac disease classification and phenotype prediction tasks.
Abstract:Background: Conventional electrocardiogram (ECG) analysis faces a persistent dichotomy: expert-driven features ensure interpretability but lack sensitivity to latent patterns, while deep learning offers high accuracy but functions as a black box with high data dependency. We introduce ECGomics, a systematic paradigm and open-source platform for the multidimensional deconstruction of cardiac signals into digital biomarker. Methods: Inspired by the taxonomic rigor of genomics, ECGomics deconstructs cardiac activity across four dimensions: Structural, Intensity, Functional, and Comparative. This taxonomy synergizes expert-defined morphological rules with data-driven latent representations, effectively bridging the gap between handcrafted features and deep learning embeddings. Results: We operationalized this framework into a scalable ecosystem consisting of a web-based research platform and a mobile-integrated solution (https://github.com/PKUDigitalHealth/ECGomics). The web platform facilitates high-throughput analysis via precision parameter configuration, high-fidelity data ingestion, and 12-lead visualization, allowing for the systematic extraction of biomarkers across the four ECGomics dimensions. Complementarily, the mobile interface, integrated with portable sensors and a cloud-based engine, enables real-time signal acquisition and near-instantaneous delivery of structured diagnostic reports. This dual-interface architecture successfully transitions ECGomics from theoretical discovery to decentralized, real-world health management, ensuring professional-grade monitoring in diverse clinical and home-based settings. Conclusion: ECGomics harmonizes diagnostic precision, interpretability, and data efficiency. By providing a deployable software ecosystem, this paradigm establishes a robust foundation for digital biomarker discovery and personalized cardiovascular medicine.