Philip Müller

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.

Tim Tanida, Philip Müller, Georgios Kaissis et al.

The automatic generation of radiology reports has the potential to assist radiologists in the time-consuming task of report writing. Existing methods generate the full report from image-level features, failing to explicitly focus on anatomical regions in the image. We propose a simple yet effective region-guided report generation model that detects anatomical regions and then describes individual, salient regions to form the final report. While previous methods generate reports without the possibility of human intervention and with limited explainability, our method opens up novel clinical use cases through additional interactive capabilities and introduces a high degree of transparency and explainability. Comprehensive experiments demonstrate our method's effectiveness in report generation, outperforming previous state-of-the-art models, and highlight its interactive capabilities. The code and checkpoints are available at https://github.com/ttanida/rgrg .

Felix Meissen, Philip Müller, Georgios Kaissis et al.

Detection of pathologies is a fundamental task in medical imaging and the evaluation of algorithms that can perform this task automatically is crucial. However, current object detection metrics for natural images do not reflect the specific clinical requirements in pathology detection sufficiently. To tackle this problem, we propose Robust Detection Outcome (RoDeO); a novel metric for evaluating algorithms for pathology detection in medical images, especially in chest X-rays. RoDeO evaluates different errors directly and individually, and reflects clinical needs better than current metrics. Extensive evaluation on the ChestX-ray8 dataset shows the superiority of our metrics compared to existing ones. We released the code at https://github.com/FeliMe/RoDeO and published RoDeO as pip package (rodeometric).

Philip Müller, Georgios Kaissis, Daniel Rueckert

Image-text contrastive learning has proven effective for pretraining medical image models. When targeting localized downstream tasks like semantic segmentation or object detection, additional local contrastive losses that align image regions with sentences have shown promising results. We study how local contrastive losses are related to global (per-sample) contrastive losses and which effects they have on localized medical downstream tasks. Based on a theoretical comparison, we propose to remove some components of local losses and replace others by a novel distribution prior which enforces uniformity of representations within each sample. We empirically study this approach on chest X-ray tasks and find it to be very effective, outperforming methods without local losses on 12 of 18 tasks.

Nikola Cenikj, Özgün Turgut, Alexander Müller et al.

Coronary artery stenosis is a common cardiovascular disease, with severe, untreated cases posing significant risks of heart attack. Although coronary (X-ray) angiograms remain the standard for stenosis diagnosis, they are invasive, time- and resource-intensive, and therefore only performed on patients with a high probability of disease based on symptoms and prior clinical tests. However, a subset of patients, especially those without symptoms, may remain undiagnosed. Detecting indications of stenosis from ECGs, which are fast, cheap, non-invasive, and thus routinely acquired even in asymptomatic patients, would support early diagnosis. However, as no reliable stenosis-specific signal has been identified in ECGs, they can not currently be used for stenosis risk stratification. To address this, we introduce StenCE, a pretraining framework, allowing stratification of patients based on features derived directly from ECGs. Evaluations across varying stenosis severity thresholds and additional ECG disease classification tasks demonstrate consistent performance improvements across different ECG encoders, outperforming previous work. The obtained models successfully detect signals for stenosis diagnosis in ECGs and are the first to achieve high performance in severe stenosis classification. The source code is available at https://github.com/NikolaCenic/ecg-stenosis-cls.

Mohammed Munzer Dwedari, William Consagra, Philip Müller et al.

The Orientation Distribution Function (ODF) characterizes key brain microstructural properties and plays an important role in understanding brain structural connectivity. Recent works introduced Implicit Neural Representation (INR) based approaches to form a spatially aware continuous estimate of the ODF field and demonstrated promising results in key tasks of interest when compared to conventional discrete approaches. However, traditional INR methods face difficulties when scaling to large-scale images, such as modern ultra-high-resolution MRI scans, posing challenges in learning fine structures as well as inefficiencies in training and inference speed. In this work, we propose HashEnc, a grid-hash-encoding-based estimation of the ODF field and demonstrate its effectiveness in retaining structural and textural features. We show that HashEnc achieves a 10% enhancement in image quality while requiring 3x less computational resources than current methods. Our code can be found at https://github.com/MunzerDw/NODF-HashEnc.

Nikola Cenikj, Özgün Turgut, Alexander Müller et al.

Coronary artery stenosis is a leading cause of cardiovascular disease, diagnosed by analyzing the coronary arteries from multiple angiography views. Although numerous deep-learning models have been proposed for stenosis detection from a single angiography view, their performance heavily relies on expensive view-level annotations, which are often not readily available in hospital systems. Moreover, these models fail to capture the temporal dynamics and dependencies among multiple views, which are crucial for clinical diagnosis. To address this, we propose SegmentMIL, a transformer-based multi-view multiple-instance learning framework for patient-level stenosis classification. Trained on a real-world clinical dataset, using patient-level supervision and without any view-level annotations, SegmentMIL jointly predicts the presence of stenosis and localizes the affected anatomical region, distinguishing between the right and left coronary arteries and their respective segments. SegmentMIL obtains high performance on internal and external evaluations and outperforms both view-level models and classical MIL baselines, underscoring its potential as a clinically viable and scalable solution for coronary stenosis diagnosis. Our code is available at https://github.com/NikolaCenic/mil-stenosis.

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.

Philip Müller, Felix Meissen, Johannes Brandt et al.

Pathology detection and delineation enables the automatic interpretation of medical scans such as chest X-rays while providing a high level of explainability to support radiologists in making informed decisions. However, annotating pathology bounding boxes is a time-consuming task such that large public datasets for this purpose are scarce. Current approaches thus use weakly supervised object detection to learn the (rough) localization of pathologies from image-level annotations, which is however limited in performance due to the lack of bounding box supervision. We therefore propose anatomy-driven pathology detection (ADPD), which uses easy-to-annotate bounding boxes of anatomical regions as proxies for pathologies. We study two training approaches: supervised training using anatomy-level pathology labels and multiple instance learning (MIL) with image-level pathology labels. Our results show that our anatomy-level training approach outperforms weakly supervised methods and fully supervised detection with limited training samples, and our MIL approach is competitive with both baseline approaches, therefore demonstrating the potential of our approach.

Alexander Ziller, Ayhan Can Erdur, Marwa Trigui et al.

Training Artificial Intelligence (AI) models on 3D images presents unique challenges compared to the 2D case: Firstly, the demand for computational resources is significantly higher, and secondly, the availability of large datasets for pre-training is often limited, impeding training success. This study proposes a simple approach of adapting 2D networks with an intermediate feature representation for processing 3D images. Our method employs attention pooling to learn to assign each slice an importance weight and, by that, obtain a weighted average of all 2D slices. These weights directly quantify the contribution of each slice to the contribution and thus make the model prediction inspectable. We show on all 3D MedMNIST datasets as benchmark and two real-world datasets consisting of several hundred high-resolution CT or MRI scans that our approach performs on par with existing methods. Furthermore, we compare the in-built interpretability of our approach to HiResCam, a state-of-the-art retrospective interpretability approach.

Philip Müller, Nicholas Popovič, Michael Färber et al.

Large Language Models (LLMs) are commonly used in Question Answering (QA) settings, increasingly in the natural sciences if not science at large. Reliable Uncertainty Quantification (UQ) is critical for the trustworthy uptake of generated answers. Existing UQ approaches remain weakly validated in scientific QA, a domain relying on fact-retrieval and reasoning capabilities. We introduce the first large-scale benchmark for evaluating UQ metrics in reasoning-demanding QA studying calibration of UQ methods, providing an extensible open-source framework to reproducibly assess calibration. Our study spans up to 20 large language models of base, instruction-tuned and reasoning variants. Our analysis covers seven scientific QA datasets, including both multiple-choice and arithmetic question answering tasks, using prompting to emulate an open question answering setting. We evaluate and compare methods representative of prominent approaches on a total of 685,000 long-form responses, spanning different reasoning complexities representative of domain-specific tasks. At the token level, we find that instruction tuning induces strong probability mass polarization, reducing the reliability of token-level confidences as estimates of uncertainty. Models further fine-tuned for reasoning are exposed to the same effect, but the reasoning process appears to mitigate it depending on the provider. At the sequence level, we show that verbalized approaches are systematically biased and poorly correlated with correctness, while answer frequency (consistency across samples) yields the most reliable calibration. In the wake of our analysis, we study and report the misleading effect of relying exclusively on ECE as a sole measure for judging performance of UQ methods on benchmark datasets. Our findings expose critical limitations of current UQ methods for LLMs and standard practices in benchmarking thereof.

Philip Müller, Georgios Kaissis, Daniel Rueckert

Report generation models offer fine-grained textual interpretations of medical images like chest X-rays, yet they often lack interactivity (i.e. the ability to steer the generation process through user queries) and localized interpretability (i.e. visually grounding their predictions), which we deem essential for future adoption in clinical practice. While there have been efforts to tackle these issues, they are either limited in their interactivity by not supporting textual queries or fail to also offer localized interpretability. Therefore, we propose a novel multitask architecture and training paradigm integrating textual prompts and bounding boxes for diverse aspects like anatomical regions and pathologies. We call this approach the Chest X-Ray Explainer (ChEX). Evaluations across a heterogeneous set of 9 chest X-ray tasks, including localized image interpretation and report generation, showcase its competitiveness with SOTA models while additional analysis demonstrates ChEX's interactive capabilities. Code: https://github.com/philip-mueller/chex

Philip Müller, Felix Meissen, Georgios Kaissis et al.

Weakly supervised object detection (WSup-OD) increases the usefulness and interpretability of image classification algorithms without requiring additional supervision. The successes of multiple instance learning in this task for natural images, however, do not translate well to medical images due to the very different characteristics of their objects (i.e. pathologies). In this work, we propose Weakly Supervised ROI Proposal Networks (WSRPN), a new method for generating bounding box proposals on the fly using a specialized region of interest-attention (ROI-attention) module. WSRPN integrates well with classic backbone-head classification algorithms and is end-to-end trainable with only image-label supervision. We experimentally demonstrate that our new method outperforms existing methods in the challenging task of disease localization in chest X-ray images. Code: https://github.com/philip-mueller/wsrpn

Jun Li, Su Hwan Kim, Philip Müller et al.

This research explores the integration of language models and unsupervised anomaly detection in medical imaging, addressing two key questions: (1) Can language models enhance the interpretability of anomaly detection maps? and (2) Can anomaly maps improve the generalizability of language models in open-set anomaly detection tasks? To investigate these questions, we introduce a new dataset for multi-image visual question-answering on brain magnetic resonance images encompassing multiple conditions. We propose KQ-Former (Knowledge Querying Transformer), which is designed to optimally align visual and textual information in limited-sample contexts. Our model achieves a 60.81% accuracy on closed questions, covering disease classification and severity across 15 different classes. For open questions, KQ-Former demonstrates a 70% improvement over the baseline with a BLEU-4 score of 0.41, and achieves the highest entailment ratios (up to 71.9%) and lowest contradiction ratios (down to 10.0%) among various natural language inference models. Furthermore, integrating anomaly maps results in an 18% accuracy increase in detecting open-set anomalies, thereby enhancing the language model's generalizability to previously unseen medical conditions. The code and dataset are available at https://github.com/compai-lab/miccai-2024-junli?tab=readme-ov-file

Johannes Brandt, Maulik Chevli, Rickmer Braren et al.

Lung cancer risk estimation is gaining increasing importance as more countries introduce population-wide screening programs using low-dose CT (LDCT). As imaging volumes grow, scalable methods that can process entire lung volumes efficiently are essential to tap into the full potential of these large screening datasets. Existing approaches either over-rely on pixel-level annotations, limiting scalability, or analyze the lung in fragments, weakening performance. We present LungEvaty, a fully transformer-based framework for predicting 1-6 year lung cancer risk from a single LDCT scan. The model operates on whole-lung inputs, learning directly from large-scale screening data to capture comprehensive anatomical and pathological cues relevant for malignancy risk. Using only imaging data and no region supervision, LungEvaty matches state-of-the-art performance, refinable by an optional Anatomically Informed Attention Guidance (AIAG) loss that encourages anatomically focused attention. In total, LungEvaty was trained on more than 90,000 CT scans, including over 28,000 for fine-tuning and 6,000 for evaluation. The framework offers a simple, data-efficient, and fully open-source solution that provides an extensible foundation for future research in longitudinal and multimodal lung cancer risk prediction.

Alexander Selivanov, Philip Müller, Özgün Turgut et al.

An electrocardiogram (ECG) is a widely used, cost-effective tool for detecting electrical abnormalities in the heart. However, it cannot directly measure functional parameters, such as ventricular volumes and ejection fraction, which are crucial for assessing cardiac function. Cardiac magnetic resonance (CMR) is the gold standard for these measurements, providing detailed structural and functional insights, but is expensive and less accessible. To bridge this gap, we propose PTACL (Patient and Temporal Alignment Contrastive Learning), a multimodal contrastive learning framework that enhances ECG representations by integrating spatio-temporal information from CMR. PTACL uses global patient-level contrastive loss and local temporal-level contrastive loss. The global loss aligns patient-level representations by pulling ECG and CMR embeddings from the same patient closer together, while pushing apart embeddings from different patients. Local loss enforces fine-grained temporal alignment within each patient by contrasting encoded ECG segments with corresponding encoded CMR frames. This approach enriches ECG representations with diagnostic information beyond electrical activity and transfers more insights between modalities than global alignment alone, all without introducing new learnable weights. We evaluate PTACL on paired ECG-CMR data from 27,951 subjects in the UK Biobank. Compared to baseline approaches, PTACL achieves better performance in two clinically relevant tasks: (1) retrieving patients with similar cardiac phenotypes and (2) predicting CMR-derived cardiac function parameters, such as ventricular volumes and ejection fraction. Our results highlight the potential of PTACL to enhance non-invasive cardiac diagnostics using ECG. The code is available at: https://github.com/alsalivan/ecgcmr

Andrea Posada, Daniel Rueckert, Felix Meissen et al.

Since the Transformer architecture emerged, language model development has grown, driven by their promising potential. Releasing these models into production requires properly understanding their behavior, particularly in sensitive domains like medicine. Despite this need, the medical literature still lacks practical assessment of pre-trained language models, which are especially valuable in settings where only consumer-grade computational resources are available. To address this gap, we have conducted a comprehensive survey of language models in the medical field and evaluated a subset of these for medical text classification and conditional text generation. The subset includes 53 models with 110 million to 13 billion parameters, spanning the Transformer-based model families and knowledge domains. Different approaches are employed for text classification, including zero-shot learning, enabling tuning without the need to train the model. These approaches are helpful in our target settings, where many users of language models find themselves. The results reveal remarkable performance across the tasks and datasets evaluated, underscoring the potential of certain models to contain medical knowledge, even without domain specialization. This study thus advocates for further exploration of model applications in medical contexts, particularly in computational resource-constrained settings, to benefit a wide range of users. The code is available on https://github.com/anpoc/Language-models-in-medicine.

Philip Müller, Vladimir Golkov, Valentina Tomassini et al.

Convolutional networks are successful, but they have recently been outperformed by new neural networks that are equivariant under rotations and translations. These new networks work better because they do not struggle with learning each possible orientation of each image feature separately. So far, they have been proposed for 2D and 3D data. Here we generalize them to 6D diffusion MRI data, ensuring joint equivariance under 3D roto-translations in image space and the matching 3D rotations in $q$-space, as dictated by the image formation. Such equivariant deep learning is appropriate for diffusion MRI, because microstructural and macrostructural features such as neural fibers can appear at many different orientations, and because even non-rotation-equivariant deep learning has so far been the best method for many diffusion MRI tasks. We validate our equivariant method on multiple-sclerosis lesion segmentation. Our proposed neural networks yield better results and require fewer scans for training compared to non-rotation-equivariant deep learning. They also inherit all the advantages of deep learning over classical diffusion MRI methods. Our implementation is available at https://github.com/philip-mueller/equivariant-deep-dmri and can be used off the shelf without understanding the mathematical background.

Michelle Espranita Liman, Daniel Rueckert, Florian J. Fintelmann et al.

Field-of-view (FOV) recovery of truncated chest CT scans is crucial for accurate body composition analysis, which involves quantifying skeletal muscle and subcutaneous adipose tissue (SAT) on CT slices. This, in turn, enables disease prognostication. Here, we present a method for recovering truncated CT slices using generative image outpainting. We train a diffusion model and apply it to truncated CT slices generated by simulating a small FOV. Our model reliably recovers the truncated anatomy and outperforms the previous state-of-the-art despite being trained on 87% less data.

Philip Müller, Georgios Kaissis, Congyu Zou et al.

Contrastive learning has proven effective for pre-training image models on unlabeled data with promising results for tasks such as medical image classification. Using paired text (like radiological reports) during pre-training improves the results even further. Still, most existing methods target image classification downstream tasks and may not be optimal for localized tasks like semantic segmentation or object detection. We therefore propose Localized representation learning from Vision and Text (LoVT), to our best knowledge, the first text-supervised pre-training method that targets localized medical imaging tasks. Our method combines instance-level image-report contrastive learning with local contrastive learning on image region and report sentence representations. We evaluate LoVT and commonly used pre-training methods on an evaluation framework of 18 localized tasks on chest X-rays from five public datasets. LoVT performs best on 10 of the 18 studied tasks making it the preferred method of choice for localized tasks.