Paul Hager

Özgün Turgut, Philip Müller, Paul Hager et al.

Cardiovascular diseases (CVD) can be diagnosed using various diagnostic modalities. The electrocardiogram (ECG) is a cost-effective and widely available diagnostic aid that provides functional information of the heart. However, its ability to classify and spatially localise CVD is limited. In contrast, cardiac magnetic resonance (CMR) imaging provides detailed structural information of the heart and thus enables evidence-based diagnosis of CVD, but long scan times and high costs limit its use in clinical routine. In this work, we present a deep learning strategy for cost-effective and comprehensive cardiac screening solely from ECG. Our approach combines multimodal contrastive learning with masked data modelling to transfer domain-specific information from CMR imaging to ECG representations. In extensive experiments using data from 40,044 UK Biobank subjects, we demonstrate the utility and generalisability of our method for subject-specific risk prediction of CVD and the prediction of cardiac phenotypes using only ECG data. Specifically, our novel multimodal pre-training paradigm improves performance by up to 12.19 % for risk prediction and 27.59 % for phenotype prediction. In a qualitative analysis, we demonstrate that our learned ECG representations incorporate information from CMR image regions of interest. Our entire pipeline is publicly available at https://github.com/oetu/MMCL-ECG-CMR.

Paul Hager, Martin J. Menten, Daniel Rueckert

Medical datasets and especially biobanks, often contain extensive tabular data with rich clinical information in addition to images. In practice, clinicians typically have less data, both in terms of diversity and scale, but still wish to deploy deep learning solutions. Combined with increasing medical dataset sizes and expensive annotation costs, the necessity for unsupervised methods that can pretrain multimodally and predict unimodally has risen. To address these needs, we propose the first self-supervised contrastive learning framework that takes advantage of images and tabular data to train unimodal encoders. Our solution combines SimCLR and SCARF, two leading contrastive learning strategies, and is simple and effective. In our experiments, we demonstrate the strength of our framework by predicting risks of myocardial infarction and coronary artery disease (CAD) using cardiac MR images and 120 clinical features from 40,000 UK Biobank subjects. Furthermore, we show the generalizability of our approach to natural images using the DVM car advertisement dataset. We take advantage of the high interpretability of tabular data and through attribution and ablation experiments find that morphometric tabular features, describing size and shape, have outsized importance during the contrastive learning process and improve the quality of the learned embeddings. Finally, we introduce a novel form of supervised contrastive learning, label as a feature (LaaF), by appending the ground truth label as a tabular feature during multimodal pretraining, outperforming all supervised contrastive baselines.

Robbie Holland, Thomas R. P. Taylor, Christopher Holmes et al.

Clinicians spend a significant amount of time reviewing medical images and transcribing their findings regarding patient diagnosis, referral and treatment in text form. Vision-language models (VLMs), which automatically interpret images and summarize their findings as text, have enormous potential to alleviate clinical workloads and increase patient access to high-quality medical care. While foundational models have stirred considerable interest in the medical community, it is unclear whether their general capabilities translate to real-world clinical utility. In this work, we demonstrate that OpenAI's ChatGPT-4o model, in addition to two foundation VLMs designed for medical use, markedly underperform compared to practicing ophthalmologists on specialist tasks crucial to the care of patients with age-related macular degeneration (AMD). To address this, we initially identified the essential capabilities required for image-based clinical decision-making, and then developed a curriculum to selectively train VLMs in these skills. The resulting model, RetinaVLM, can be instructed to write reports that significantly outperform those written by leading foundation medical VLMs and ChatGPT-4o in disease staging (F1 score of 0.63 vs. 0.33) and patient referral (0.67 vs. 0.50), and approaches the diagnostic performance of junior ophthalmologists (who achieve 0.77 and 0.78 on the respective tasks). Furthermore, in a single-blind reader study two senior ophthalmologists with up to 32 years of experience found RetinaVLM's reports were found to be substantially more accurate than those by ChatGPT-4o (64.3% vs. 14.3%). These results reinforce that our curriculum-based approach provides a blueprint towards specializing foundation medical VLMs for real-world clinical tasks.

Leonhard F. Feiner, Martin J. Menten, Kerstin Hammernik et al.

Uncertainty estimation, which provides a means of building explainable neural networks for medical imaging applications, have mostly been studied for single deep learning models that focus on a specific task. In this paper, we propose a method to propagate uncertainty through cascades of deep learning models in medical imaging pipelines. This allows us to aggregate the uncertainty in later stages of the pipeline and to obtain a joint uncertainty measure for the predictions of later models. Additionally, we can separately report contributions of the aleatoric, data-based, uncertainty of every component in the pipeline. We demonstrate the utility of our method on a realistic imaging pipeline that reconstructs undersampled brain and knee magnetic resonance (MR) images and subsequently predicts quantitative information from the images, such as the brain volume, or knee side or patient's sex. We quantitatively show that the propagated uncertainty is correlated with input uncertainty and compare the proportions of contributions of pipeline stages to the joint uncertainty measure.

Jiazhen Pan, Bailiang Jian, Paul Hager et al.

Ensuring the safety and reliability of large language models (LLMs) in clinical practice is critical to prevent patient harm and promote trustworthy healthcare applications of AI. However, LLMs are advancing so rapidly that static safety benchmarks often become obsolete upon publication, yielding only an incomplete and sometimes misleading picture of model trustworthiness. We demonstrate that a Dynamic, Automatic, and Systematic (DAS) red-teaming framework that continuously stress-tests LLMs can reveal significant weaknesses of current LLMs across four safety-critical domains: robustness, privacy, bias/fairness, and hallucination. A suite of adversarial agents is applied to autonomously mutate test cases, identify/evolve unsafe-triggering strategies, and evaluate responses, uncovering vulnerabilities in real time without human intervention. Applying DAS to 15 proprietary and open-source LLMs revealed a stark contrast between static benchmark performance and vulnerability under adversarial pressure. Despite a median MedQA accuracy exceeding 80\%, 94\% of previously correct answers failed our dynamic robustness tests. We observed similarly high failure rates across other domains: privacy leaks were elicited in 86\% of scenarios, cognitive-bias priming altered clinical recommendations in 81\% of fairness tests, and we identified hallucination rates exceeding 66\% in widely used models. Such profound residual risks are incompatible with routine clinical practice. By converting red-teaming from a static checklist into a dynamic stress-test audit, DAS red-teaming offers the surveillance that hospitals/regulators/technology vendors require as LLMs become embedded in patient chatbots, decision-support dashboards, and broader healthcare workflows. Our framework delivers an evolvable, scalable, and reliable safeguard for the next generation of medical AI.

David Mildenberger, Paul Hager, Daniel Rueckert et al.

Supervised contrastive learning (SupCon) has proven to be a powerful alternative to the standard cross-entropy loss for classification of multi-class balanced datasets. However, it struggles to learn well-conditioned representations of datasets with long-tailed class distributions. This problem is potentially exacerbated for binary imbalanced distributions, which are commonly encountered during many real-world problems such as medical diagnosis. In experiments on seven binary datasets of natural and medical images, we show that the performance of SupCon decreases with increasing class imbalance. To substantiate these findings, we introduce two novel metrics that evaluate the quality of the learned representation space. By measuring the class distribution in local neighborhoods, we are able to uncover structural deficiencies of the representation space that classical metrics cannot detect. Informed by these insights, we propose two new supervised contrastive learning strategies tailored to binary imbalanced datasets that improve the structure of the representation space and increase downstream classification accuracy over standard SupCon by up to 35%. We make our code available.

Dmitrii Seletkov, Paul Hager, Rickmer Braren et al.

Survival analysis is crucial for many medical applications but remains challenging for modern machine learning due to limited data, censoring, and the heterogeneity of tabular covariates. While the prior-fitted paradigm, which relies on pretraining models on large collections of synthetic datasets, has recently facilitated tabular foundation models for classification and regression, its suitability for time-to-event modeling remains unclear. We propose a flexible survival data generation framework that defines a rich survival prior with explicit control over covariates and time-event distributions. Building on this prior, we introduce Survival In-Context (SIC), a prior-fitted in-context learning model for survival analysis that is pretrained exclusively on synthetic data. SIC produces individualized survival prediction in a single forward pass, requiring no task-specific training or hyperparameter tuning. Across a broad evaluation on real-world survival datasets, SIC achieves competitive or superior performance compared to classical and deep survival models, particularly in medium-sized data regimes, highlighting the promise of prior-fitted foundation models for survival analysis. The code will be made available upon publication.

Yundi Zhang, Paul Hager, Che Liu et al.

Cardiac magnetic resonance imaging is the gold standard for non-invasive cardiac assessment, offering rich spatio-temporal views of the cardiac anatomy and physiology. Patient-level health factors, such as demographics, metabolic, and lifestyle, are known to substantially influence cardiovascular health and disease risk, yet remain uncaptured by CMR alone. To holistically understand cardiac health and to enable the best possible interpretation of an individual's disease risk, CMR and patient-level factors must be jointly exploited within an integrated framework. Recent multi-modal approaches have begun to bridge this gap, yet they often rely on limited spatio-temporal data and focus on isolated clinical tasks, thereby hindering the development of a comprehensive representation for cardiac health evaluation. To overcome these limitations, we introduce ViTa, a step toward foundation models that delivers a comprehensive representation of the heart and a precise interpretation of individual disease risk. Leveraging data from 42,000 UK Biobank participants, ViTa integrates 3D+T cine stacks from short-axis and long-axis views, enabling a complete capture of the cardiac cycle. These imaging data are then fused with detailed tabular patient-level factors, enabling context-aware insights. This multi-modal paradigm supports a wide spectrum of downstream tasks, including cardiac phenotype and physiological feature prediction, segmentation, and classification of cardiac and metabolic diseases within a single unified framework. By learning a shared latent representation that bridges rich imaging features and patient context, ViTa moves beyond traditional, task-specific models toward a universal, patient-specific understanding of cardiac health, highlighting its potential to advance clinical utility and scalability in cardiac analysis.

Chengzhi Shen, Martin J. Menten, Hrvoje Bogunović et al.

Analyzing temporal developments is crucial for the accurate prognosis of many medical conditions. Temporal changes that occur over short time scales are key to assessing the health of physiological functions, such as the cardiac cycle. Moreover, tracking longer term developments that occur over months or years in evolving processes, such as age-related macular degeneration (AMD), is essential for accurate prognosis. Despite the importance of both short and long term analysis to clinical decision making, they remain understudied in medical deep learning. State of the art methods for spatiotemporal representation learning, developed for short natural videos, prioritize the detection of temporal constants rather than temporal developments. Moreover, they do not account for varying time intervals between acquisitions, which are essential for contextualizing observed changes. To address these issues, we propose two approaches. First, we combine clip-level contrastive learning with a novel temporal embedding to adapt to irregular time series. Second, we propose masking and predicting latent frame representations of the temporal sequence. Our two approaches outperform all prior methods on temporally-dependent tasks including cardiac output estimation and three prognostic AMD tasks. Overall, this enables the automated analysis of temporal patterns which are typically overlooked in applications of deep learning to medicine.

Linus Kreitner, Paul Hager, Jonathan Mengedoht et al.

To drive progress in science and engineering, large language models (LLMs) must be able to process large amounts of numerical data and solve long calculations efficiently. This is currently only possible through the use of external tools or extensive reasoning chains, either limiting the numerical intuition of LLMs or limiting the length of problems they can solve. We show that frontier LLMs require excessive amounts of reasoning tokens to solve even basic calculations, which is exacerbated by their tokenization strategies that split single numbers into multiple tokens. This motivates the need for efficient and effective single-token number encodings. We introduce a set of desiderata for such encodings and show that existing approaches fail to fulfill them. To address these shortcomings, we propose BitTokens, a novel tokenization strategy that embeds any number into a single token using its IEEE 754 binary floating-point representation. Through extensive experiments we show that our BitTokens allow even small language models to learn algorithms that solve basic arithmetic operations nearly perfectly. This newly gained efficiency could expand the length and complexity of problems language models can solve.

Simon Langer, Jessica Ritter, Rickmer Braren et al.

Modern deep learning-based clinical imaging workflows rely on accurate labels of the examined anatomical region. Knowing the anatomical region is required to select applicable downstream models and to effectively generate cohorts of high quality data for future medical and machine learning research efforts. However, this information may not be available in externally sourced data or generally contain data entry errors. To address this problem, we show the effectiveness of self-supervised methods such as SimCLR and BYOL as well as supervised contrastive deep learning methods in assigning one of 14 anatomical region classes in our in-house dataset of 48,434 skeletal radiographs. We achieve a strong linear evaluation accuracy of 96.6% with a single model and 97.7% using an ensemble approach. Furthermore, only a few labeled instances (1% of the training set) suffice to achieve an accuracy of 92.2%, enabling usage in low-label and thus low-resource scenarios. Our model can be used to correct data entry mistakes: a follow-up analysis of the test set errors of our best-performing single model by an expert radiologist identified 35% incorrect labels and 11% out-of-domain images. When accounted for, the radiograph anatomical region labelling performance increased -- without and with an ensemble, respectively -- to a theoretical accuracy of 98.0% and 98.8%.

Christian Bayer, Denis Belomestny, Paul Hager et al.

Least squares Monte Carlo methods are a popular numerical approximation method for solving stochastic control problems. Based on dynamic programming, their key feature is the approximation of the conditional expectation of future rewards by linear least squares regression. Hence, the choice of basis functions is crucial for the accuracy of the method. Earlier work by some of us [Belomestny, Schoenmakers, Spokoiny, Zharkynbay. Commun.~Math.~Sci., 18(1):109-121, 2020](arXiv:1808.02341) proposes to reinforce the basis functions in the case of optimal stopping problems by already computed value functions for later times, thereby considerably improving the accuracy with limited additional computational cost. We extend the reinforced regression method to a general class of stochastic control problems, while considerably improving the method's efficiency, as demonstrated by substantial numerical examples as well as theoretical analysis.