Zhengxing Huang

Zhoujian Sun, Wenzhuo Zhang, Zhengxing Huang et al.

Non-communicable disease is the leading cause of death, emphasizing the need for accurate prediction of disease progression and informed clinical decision-making. Machine learning (ML) models have shown promise in this domain by capturing non-linear patterns within patient features. However, existing ML-based models cannot provide causal interpretable predictions and estimate treatment effects, limiting their decision-making perspective. In this study, we propose a novel model called causal trajectory prediction (CTP) to tackle the limitation. The CTP model combines trajectory prediction and causal discovery to enable accurate prediction of disease progression trajectories and uncover causal relationships between features. By incorporating a causal graph into the prediction process, CTP ensures that ancestor features are not influenced by the treatment of descendant features, thereby enhancing the interpretability of the model. By estimating the bounds of treatment effects, even in the presence of unmeasured confounders, the CTP provides valuable insights for clinical decision-making. We evaluate the performance of the CTP using simulated and real medical datasets. Experimental results demonstrate that our model achieves satisfactory performance, highlighting its potential to assist clinical decisions. Source code is in \href{https://github.com/DanielSun94/CFPA}{here}.

Haitao Li, Ziyu Li, Yiheng Mao et al.

Accurate segmentation of brain images typically requires the integration of complementary information from multiple image modalities. However, clinical data for all modalities may not be available for every patient, creating a significant challenge. To address this, previous studies encode multiple modalities into a shared latent space. While somewhat effective, it remains suboptimal, as each modality contains distinct and valuable information. In this study, we propose DC-Seg (Disentangled Contrastive Learning for Segmentation), a new method that explicitly disentangles images into modality-invariant anatomical representation and modality-specific representation, by using anatomical contrastive learning and modality contrastive learning respectively. This solution improves the separation of anatomical and modality-specific features by considering the modality gaps, leading to more robust representations. Furthermore, we introduce a segmentation-based regularizer that enhances the model's robustness to missing modalities. Extensive experiments on the BraTS 2020 and a private white matter hyperintensity(WMH) segmentation dataset demonstrate that DC-Seg outperforms state-of-the-art methods in handling incomplete multimodal brain tumor segmentation tasks with varying missing modalities, while also demonstrate strong generalizability in WMH segmentation. The code is available at https://github.com/CuCl-2/DC-Seg.

Haitao Li, Ziyu Li, Yiheng Mao et al.

The advent of multimodal large language models (MLLMs) has sparked interest in their application to electrocardiogram (ECG) analysis. However, existing ECG-focused MLLMs primarily focus on report generation tasks, often limited to single 12-lead, short-duration (10s) ECG inputs, thereby underutilizing the potential of MLLMs. To this end, we aim to develop a MLLM for ECG analysis that supports a broader range of tasks and more flexible ECG inputs. However, existing ECG-QA datasets are often monotonous. To address this gap, we first constructed the anyECG dataset, which encompasses a wide variety of tasks, including report generation, abnormal waveform localization, and open-ended question answering. In addition to standard hospital ECGs, we introduced long-duration reduced-lead ECGs for home environments and multiple ECG comparison scenarios commonly encountered in clinical practice. Furthermore, we propose the anyECG-chat model, which supports dynamic-length ECG inputs and multiple ECG inputs. We trained the model using a three-stage curriculum training recipe with the anyECG dataset. A comprehensive evaluation was conducted, demonstrating that anyECG-chat is capable of supporting various practical application scenarios, including not only common report generation tasks but also abnormal waveform localization for long-duration reduced-lead ECGs in home environments and comprehensive comparative analysis of multiple ECGs. Our code and data are available at: https://github.com/CuCl-2/anyECG-chat.

Haitao Li, Chunxiang Jin, Chenglin Li et al.

Zero-shot text-to-speech models can clone a speaker's timbre from a short reference audio, but they also strongly inherit the speaking style present in the reference. As a result, synthesizing speech with a desired style often requires carefully selecting reference audio, which is impractical when only limited or mismatched references are available. While recent controllable TTS methods attempt to address this issue, they typically rely on absolute style targets and discrete textual prompts, and therefore do not support continuous and reference-relative style control. We propose ReStyle-TTS, a framework that enables continuous and reference-relative style control in zero-shot TTS. Our key insight is that effective style control requires first reducing the model's implicit dependence on reference style before introducing explicit control mechanisms. To this end, we introduce Decoupled Classifier-Free Guidance (DCFG), which independently controls text and reference guidance, reducing reliance on reference style while preserving text fidelity. On top of this, we apply style-specific LoRAs together with Orthogonal LoRA Fusion to enable continuous and disentangled multi-attribute control, and introduce a Timbre Consistency Optimization module to mitigate timbre drift caused by weakened reference guidance. Experiments show that ReStyle-TTS enables user-friendly, continuous, and relative control over pitch, energy, and multiple emotions while maintaining intelligibility and speaker timbre, and performs robustly in challenging mismatched reference-target style scenarios.

Zhoujian Sun, Cheng Luo, Ziyi Liu et al.

The development of large language models (LLMs) has brought unprecedented possibilities for artificial intelligence (AI) based medical diagnosis. However, the application perspective of LLMs in real diagnostic scenarios is still unclear because they are not adept at collecting patient data proactively. This study presents a LLM-based diagnostic system that enhances planning capabilities by emulating doctors. Our system involves two external planners to handle planning tasks. The first planner employs a reinforcement learning approach to formulate disease screening questions and conduct initial diagnoses. The second planner uses LLMs to parse medical guidelines and conduct differential diagnoses. By utilizing real patient electronic medical record data, we constructed simulated dialogues between virtual patients and doctors and evaluated the diagnostic abilities of our system. We demonstrated that our system obtained impressive performance in both disease screening and differential diagnoses tasks. This research represents a step towards more seamlessly integrating AI into clinical settings, potentially enhancing the accuracy and accessibility of medical diagnostics.

Haitao Li, Che Liu, Zhengyao Ding et al.

Electrocardiograms (ECGs) are essential for diagnosing cardiovascular diseases. However, existing ECG-Report contrastive learning methods focus on whole-ECG and report alignment, missing the link between local ECG features and individual report tags. In this paper, we propose FG-CLEP (Fine-Grained Contrastive Language ECG Pre-training), which achieves fine-grained alignment between specific ECG segments and each tag in the report via tag-specific ECG representations. Furthermore, we found that nearly 55\% of ECG reports in the MIMIC-ECG training dataset lack detailed waveform features, which hinders fine-grained alignment. To address this, we introduce a coarse-to-fine training process that leverages large language models (LLMs) to recover these missing waveform features and validate the LLM outputs using a coarse model. Additionally, fine-grained alignment at the tag level, rather than at the report level, exacerbates the false negative problem, as different reports may share common tags. To mitigate this, we introduce a semantic similarity matrix to guide the model in identifying and correcting false negatives. Experiments on six datasets demonstrate that FG-CLEP significantly improves fine-grained alignment, outperforming state-of-the-art methods in both zero-shot prediction and linear probing. Meanwhile, the fine-grained reports we generate also enhance the performance of other methods.

Ziyu Li, Yujian Hu, Zhengyao Ding et al.

Cardiac Magnetic Resonance (CMR) imaging is a vital non-invasive tool for diagnosing heart diseases and evaluating cardiac health. However, the limited availability of large-scale, high-quality CMR datasets poses a major challenge to the effective application of artificial intelligence (AI) in this domain. Even the amount of unlabeled data and the health status it covers are difficult to meet the needs of model pretraining, which hinders the performance of AI models on downstream tasks. In this study, we present Cardiac Phenotype-Guided CMR Generation (CPGG), a novel approach for generating diverse CMR data that covers a wide spectrum of cardiac health status. The CPGG framework consists of two stages: in the first stage, a generative model is trained using cardiac phenotypes derived from CMR data; in the second stage, a masked autoregressive diffusion model, conditioned on these phenotypes, generates high-fidelity CMR cine sequences that capture both structural and functional features of the heart in a fine-grained manner. We synthesized a massive amount of CMR to expand the pretraining data. Experimental results show that CPGG generates high-quality synthetic CMR data, significantly improving performance on various downstream tasks, including diagnosis and cardiac phenotypes prediction. These gains are demonstrated across both public and private datasets, highlighting the effectiveness of our approach. Code is availabel at https://anonymous.4open.science/r/CPGG.

Zhoujian Sun, Ziyi Liu, Cheng Luo et al.

Recent advances in large language models (LLMs) have shown promising results in medical diagnosis, with some studies indicating superior performance compared to human physicians in specific scenarios. However, the diagnostic capabilities of LLMs are often overestimated, as their performance significantly deteriorates in interactive diagnostic settings that require active information gathering. This study investigates the underlying mechanisms behind the performance degradation phenomenon and proposes a solution. We identified that the primary deficiency of LLMs lies in the initial diagnosis phase, particularly in information-gathering efficiency and initial diagnosis formation, rather than in the subsequent differential diagnosis phase. To address this limitation, we developed a plug-and-play method enhanced (PPME) LLM agent, leveraging over 3.5 million electronic medical records from Chinese and American healthcare facilities. Our approach integrates specialized models for initial disease diagnosis and inquiry into the history of the present illness, trained through supervised and reinforcement learning techniques. The experimental results indicate that the PPME LLM achieved over 30% improvement compared to baselines. The final diagnostic accuracy of the PPME LLM in interactive diagnostic scenarios approached levels comparable to those achieved using complete clinical data. These findings suggest a promising potential for developing autonomous diagnostic systems, although further validation studies are needed.

Yicong Wu, Ting Chen, Irit Hochberg et al.

Therapy recommendation for chronic patients with multimorbidity is challenging due to risks of treatment conflicts. Existing decision support systems face scalability limitations. Inspired by the way in which general practitioners (GP) manage multimorbidity patients, occasionally convening multidisciplinary team (MDT) collaboration, this study investigated the feasibility and value of using a Large Language Model (LLM)-based multi-agent system (MAS) for safer therapy recommendations. We designed a single agent and a MAS framework simulating MDT decision-making by enabling discussion among LLM agents to resolve medical conflicts. The systems were evaluated on therapy planning tasks for multimorbidity patients using benchmark cases. We compared MAS performance with single-agent approaches and real-world benchmarks. An important contribution of our study is the definition of evaluation metrics that go beyond the technical precision and recall and allow the inspection of clinical goals met and medication burden of the proposed advices to a gold standard benchmark. Our results show that with current LLMs, a single agent GP performs as well as MDTs. The best-scoring models provide correct recommendations that address all clinical goals, yet the advices are incomplete. Some models also present unnecessary medications, resulting in unnecessary conflicts between medication and conditions or drug-drug interactions.

Haitao Li, Ziyu Li, Yiheng Mao et al.

Multimodal large language models (MLLMs) are increasingly being applied in the medical field, particularly in medical imaging. However, developing MLLMs for ECG signals, which are crucial in clinical settings, has been a significant challenge beyond medical imaging. Previous studies have attempted to address this by converting ECGs into several text tags using an external classifier in a training-free manner. However, this approach significantly compresses the information in ECGs and underutilizes the reasoning capabilities of LLMs. In this work, we directly feed the embeddings of ECGs into the LLM through a projection layer, retaining more information about ECGs and better leveraging the reasoning abilities of LLMs. Our method can also effectively handle a common situation in clinical practice where it is necessary to compare two ECGs taken at different times. Recent studies found that MLLMs may rely solely on text input to provide answers, ignoring inputs from other modalities. We analyzed this phenomenon from a causal perspective in the context of ECG MLLMs and discovered that the confounder, severity of illness, introduces a spurious correlation between the question and answer, leading the model to rely on this spurious correlation and ignore the ECG input. Such models do not comprehend the ECG input and perform poorly in adversarial tests where different expressions of the same question are used in the training and testing sets. We designed a de-biased pre-training method to eliminate the confounder's effect according to the theory of backdoor adjustment. Our model performed well on the ECG-QA task under adversarial testing and demonstrated zero-shot capabilities. An interesting random ECG test further validated that our model effectively understands and utilizes the input ECG signal.

Zhengyao Ding, Ziyu Li, Yujian Hu et al.

Cardiovascular diseases (CVDs) are the leading cause of global mortality, necessitating accessible and accurate diagnostic tools. While cardiac magnetic resonance imaging (CMR) provides gold-standard insights into cardiac structure and function, its clinical utility is limited by high cost and complexity. In contrast, electrocardiography (ECG) is inexpensive and widely available but lacks the granularity of CMR. We propose CardioNets, a deep learning framework that translates 12-lead ECG signals into CMR-level functional parameters and synthetic images, enabling scalable cardiac assessment. CardioNets integrates cross-modal contrastive learning and generative pretraining, aligning ECG with CMR-derived cardiac phenotypes and synthesizing high-resolution CMR images via a masked autoregressive model. Trained on 159,819 samples from five cohorts, including the UK Biobank (n=42,483) and MIMIC-IV-ECG (n=164,550), and externally validated on independent clinical datasets (n=3,767), CardioNets achieved strong performance across disease screening and phenotype estimation tasks. In the UK Biobank, it improved cardiac phenotype regression R2 by 24.8% and cardiomyopathy AUC by up to 39.3% over baseline models. In MIMIC, it increased AUC for pulmonary hypertension detection by 5.6%. Generated CMR images showed 36.6% higher SSIM and 8.7% higher PSNR than prior approaches. In a reader study, ECG-only CardioNets achieved 13.9% higher accuracy than human physicians using both ECG and real CMR. These results suggest that CardioNets offers a promising, low-cost alternative to CMR for large-scale CVD screening, particularly in resource-limited settings. Future efforts will focus on clinical deployment and regulatory validation of ECG-based synthetic imaging.

Yujian Hu, Yilang Xiang, Yan-Jie Zhou et al.

The accurate and timely diagnosis of acute aortic syndromes (AAS) in patients presenting with acute chest pain remains a clinical challenge. Aortic CT angiography (CTA) is the imaging protocol of choice in patients with suspected AAS. However, due to economic and workflow constraints in China, the majority of suspected patients initially undergo non-contrast CT as the initial imaging testing, and CTA is reserved for those at higher risk. In this work, we present an artificial intelligence-based warning system, iAorta, using non-contrast CT for AAS identification in China, which demonstrates remarkably high accuracy and provides clinicians with interpretable warnings. iAorta was evaluated through a comprehensive step-wise study. In the multi-center retrospective study (n = 20,750), iAorta achieved a mean area under the receiver operating curve (AUC) of 0.958 (95% CI 0.950-0.967). In the large-scale real-world study (n = 137,525), iAorta demonstrated consistently high performance across various non-contrast CT protocols, achieving a sensitivity of 0.913-0.942 and a specificity of 0.991-0.993. In the prospective comparative study (n = 13,846), iAorta demonstrated the capability to significantly shorten the time to correct diagnostic pathway. For the prospective pilot deployment that we conducted, iAorta correctly identified 21 out of 22 patients with AAS among 15,584 consecutive patients presenting with acute chest pain and under non-contrast CT protocol in the emergency department (ED) and enabled the average diagnostic time of these 21 AAS positive patients to be 102.1 (75-133) mins. Last, the iAorta can help avoid delayed or missed diagnosis of AAS in settings where non-contrast CT remains the unavoidable the initial or only imaging test in resource-constrained regions and in patients who cannot or did not receive intravenous contrast.

Zhoujian Sun, Chenyang Zhao, Zhengxing Huang et al.

Policy learning (PL) is a module of a task-oriented dialogue system that trains an agent to make actions in each dialogue turn. Imitating human action is a fundamental problem of PL. However, both supervised learning (SL) and reinforcement learning (RL) frameworks cannot imitate humans well. Training RL models require online interactions with user simulators, while simulating complex human policy is hard. Performances of SL-based models are restricted because of the covariate shift problem. Specifically, a dialogue is a sequential decision-making process where slight differences in current utterances and actions will cause significant differences in subsequent utterances. Therefore, the generalize ability of SL models is restricted because statistical characteristics of training and testing dialogue data gradually become different. This study proposed an offline imitation learning model that learns policy from real dialogue datasets and does not require user simulators. It also utilizes state transition information, which alleviates the influence of the covariate shift problem. We introduced a regularization trick to make our model can be effectively optimized. We investigated the performance of our model on four independent public dialogue datasets. The experimental result showed that our model performed better in the action prediction task.

Zhoujian Sun, Zhengxing Huang, Nai Ding

Dialogue state tracking (DST) is a component of the task-oriented dialogue system. It is responsible for extracting and managing slot values according to dialogue utterances, where each slot represents an essential part of the information to accomplish a task, and slot value is updated recurrently in each dialogue turn. However, many DST models cannot update slot values appropriately. These models may repeatedly inherit wrong slot values extracted in previous turns, resulting in the fail of the entire DST task. They cannot update indirectly mentioned slots well, either. This study designed a model with a mentioned slot pool (MSP) to tackle the update problem. The MSP is a slot-specific memory that records all mentioned slot values that may be inherited, and our model updates slot values according to the MSP and the dialogue context. Our model rejects inheriting the previous slot value when it predicates the value is wrong. Then, it re-extracts the slot value from the current dialogue context. As the contextual information accumulates with the dialogue progress, the new value is more likely to be correct. It also can track the indirectly mentioned slot by picking a value from the MSP. Experimental results showed our model reached state-of-the-art DST performance on MultiWOZ 2.1 and 2.2 datasets.

Zhoujian Sun, Wei Dong, Jinlong Shi et al.

Objective: To combine medical knowledge and medical data to interpretably predict the risk of disease. Methods: We formulated the disease prediction task as a random walk along a knowledge graph (KG). Specifically, we build a KG to record relationships between diseases and risk factors according to validated medical knowledge. Then, a mathematical object walks along the KG. It starts walking at a patient entity, which connects the KG based on the patient current diseases or risk factors and stops at a disease entity, which represents the predicted disease. The trajectory generated by the object represents an interpretable disease progression path of the given patient. The dynamics of the object are controlled by a policy-based reinforcement learning (RL) module, which is trained by electronic health records (EHRs). Experiments: We utilized two real-world EHR datasets to evaluate the performance of our model. In the disease prediction task, our model achieves 0.743 and 0.639 in terms of macro area under the curve (AUC) in predicting 53 circulation system diseases in the two datasets, respectively. This performance is comparable to the commonly used machine learning (ML) models in medical research. In qualitative analysis, our clinical collaborator reviewed the disease progression paths generated by our model and advocated their interpretability and reliability. Conclusion: Experimental results validate the proposed model in interpretably evaluating and optimizing disease prediction. Significance: Our work contributes to leveraging the potential of medical knowledge and medical data jointly for interpretable prediction tasks.