Marcus Makowski

Tobias Czempiel, Coco Rogers, Matthias Keicher et al. · stanford

Quantifying COVID-19 infection over time is an important task to manage the hospitalization of patients during a global pandemic. Recently, deep learning-based approaches have been proposed to help radiologists automatically quantify COVID-19 pathologies on longitudinal CT scans. However, the learning process of deep learning methods demands extensive training data to learn the complex characteristics of infected regions over longitudinal scans. It is challenging to collect a large-scale dataset, especially for longitudinal training. In this study, we want to address this problem by proposing a new self-supervised learning method to effectively train longitudinal networks for the quantification of COVID-19 infections. For this purpose, longitudinal self-supervision schemes are explored on clinical longitudinal COVID-19 CT scans. Experimental results show that the proposed method is effective, helping the model better exploit the semantics of longitudinal data and improve two COVID-19 quantification tasks.

Christian Wachinger, Bernhard Renger, Christopher Späth et al.

Interpreting quantitative CT biomarkers, such as organ volume and tissue attenuation, requires large-scale healthy reference distributions. However, creating these is challenging because clinical datasets are often heavily enriched with pathology. Here, we develop an evidence-grounded, cross-verified large language model (LLM) ensemble to filter pathological findings from radiology reports, enabling the construction of pathology-reduced cohorts from over 350,000 CT examinations. Five LLMs, first, flag structure-level abnormality candidates grounded in verbatim report evidence and, second, resolve disagreements via cross-verification. Using distribution-aware generalized additive models for location, scale, and shape, we establish comprehensive whole-body reference charts for 106 anatomical structures (volumes and attenuation) across adulthood, accounting for age, sex, contrast enhancement, and acquisition parameters. Longitudinal analyses reveal structure- and contrast-dependent changes distinct from cross-sectional trends. These resources facilitate covariate-adjusted centile scoring from routine CT, supporting standardized quantitative phenotyping, multi-site imaging studies, and scalable opportunistic screening research.

Soroosh Tayebi Arasteh, Alexander Ziller, Christiane Kuhl et al.

Artificial intelligence (AI) models are increasingly used in the medical domain. However, as medical data is highly sensitive, special precautions to ensure its protection are required. The gold standard for privacy preservation is the introduction of differential privacy (DP) to model training. Prior work indicates that DP has negative implications on model accuracy and fairness, which are unacceptable in medicine and represent a main barrier to the widespread use of privacy-preserving techniques. In this work, we evaluated the effect of privacy-preserving training of AI models regarding accuracy and fairness compared to non-private training. For this, we used two datasets: (1) A large dataset (N=193,311) of high quality clinical chest radiographs, and (2) a dataset (N=1,625) of 3D abdominal computed tomography (CT) images, with the task of classifying the presence of pancreatic ductal adenocarcinoma (PDAC). Both were retrospectively collected and manually labeled by experienced radiologists. We then compared non-private deep convolutional neural networks (CNNs) and privacy-preserving (DP) models with respect to privacy-utility trade-offs measured as area under the receiver-operator-characteristic curve (AUROC), and privacy-fairness trade-offs, measured as Pearson's r or Statistical Parity Difference. We found that, while the privacy-preserving trainings yielded lower accuracy, they did largely not amplify discrimination against age, sex or co-morbidity. Our study shows that -- under the challenging realistic circumstances of a real-life clinical dataset -- the privacy-preserving training of diagnostic deep learning models is possible with excellent diagnostic accuracy and fairness.

Felix Busch, Tianyu Han, Marcus Makowski et al.

The study evaluates and compares GPT-4 and GPT-4Vision for radiological tasks, suggesting GPT-4Vision may recognize radiological features from images, thereby enhancing its diagnostic potential over text-based descriptions.

Martin Rath, Morteza Ghahremani, Yitong Li et al.

Computed tomography (CT) provides rich 3D anatomical details but is often constrained by high radiation exposure, substantial costs, and limited availability. While standard chest X-rays are cost-effective and widely accessible, they only provide 2D projections with limited pathological information. Reconstructing 3D CT volumes from 2D X-rays offers a transformative solution to increase diagnostic accessibility, yet existing methods predominantly rely on synthetic X-ray projections, limiting clinical generalization. In this work, we propose AXON, a multi-stage diffusion-based framework that reconstructs high-fidelity 3D CT volumes directly from real X-rays. AXON employs a coarse-to-fine strategy, with a Brownian Bridge diffusion model-based initial stage for global structural synthesis, followed by a ControlNet-based refinement stage for local intensity optimization. It also supports bi-planar X-ray input to mitigate depth ambiguities inherent in 2D-to-3D reconstruction. A super-resolution network is integrated to upscale the generated volumes to achieve diagnostic-grade resolution. Evaluations on both public and external datasets demonstrate that AXON significantly outperforms state-of-the-art baselines, achieving a 11.9% improvement in PSNR and a 11.0% increase in SSIM with robust generalizability across disparate clinical distributions. Our code is available at https://github.com/ai-med/AXON.

Sebastian Ziegelmayer, Alexander W. Marka, Nicolas Lenhart et al.

The remarkable generative capabilities of multimodal foundation models are currently being explored for a variety of applications. Generating radiological impressions is a challenging task that could significantly reduce the workload of radiologists. In our study we explored and analyzed the generative abilities of GPT-4 for Chest X-ray impression generation. To generate and evaluate impressions of chest X-rays based on different input modalities (image, text, text and image), a blinded radiological report was written for 25-cases of the publicly available NIH-dataset. GPT-4 was given image, finding section or both sequentially to generate an input dependent impression. In a blind randomized reading, 4-radiologists rated the impressions and were asked to classify the impression origin (Human, AI), providing justification for their decision. Lastly text model evaluation metrics and their correlation with the radiological score (summation of the 4 dimensions) was assessed. According to the radiological score, the human-written impression was rated highest, although not significantly different to text-based impressions. The automated evaluation metrics showed moderate to substantial correlations to the radiological score for the image impressions, however individual scores were highly divergent among inputs, indicating insufficient representation of radiological quality. Detection of AI-generated impressions varied by input and was 61% for text-based impressions. Impressions classified as AI-generated had significantly worse radiological scores even when written by a radiologist, indicating potential bias. Our study revealed significant discrepancies between a radiological assessment and common automatic evaluation metrics depending on the model input. The detection of AI-generated findings is subject to bias that highly rated impressions are perceived as human-written.

Johannes Moll, Jannik Lübberstedt, Christoph Nuernbergk et al.

Multiple myeloma is managed through sequential lines of therapy over years to decades, with each decision depending on cumulative disease history distributed across dozens to hundreds of heterogeneous clinical documents. Whether LLM-based systems can synthesise this evidence at a level approaching expert agreement has not been established. A retrospective evaluation was conducted on longitudinal clinical records of 811 myeloma patients treated at a tertiary centre (2001-2026), covering 44,962 documents and 1,334,677 laboratory values, with external validation on MIMIC-IV. An agentic reasoning system was compared against single-pass retrieval-augmented generation (RAG), iterative RAG, and full-context input on 469 patient-question pairs from 48 templates at three complexity levels. Reference labels came from double annotation by four oncologists with senior haematologist adjudication. Iterative RAG and full-context input converged on a shared ceiling (75.4% vs 75.8%, p = 1.00). The agentic system reached 79.6% concordance (95% CI 76.4-82.8), exceeding both baselines (+3.8 and +4.2 pp; p = 0.006 and 0.007). Gains rose with question complexity, reaching +9.4 pp on criteria-based synthesis (p = 0.032), and with record length, reaching +13.5 pp in the top decile (n = 10). The system error rate (12.2%) was comparable to expert disagreement (13.6%), but severity was inverted: 57.8% of system errors were clinically significant versus 18.8% of expert disagreements. Agentic reasoning was the only approach to exceed the shared ceiling, with gains concentrated on the most complex questions and longest records. The greater clinical consequence of residual system errors indicates that prospective evaluation in routine care is required before these findings translate into patient benefit.

Bastien Le Guellec, Kokou Adambounou, Lisa C Adams et al.

Rationale and Objectives: To develop and validate PARROT (Polyglottal Annotated Radiology Reports for Open Testing), a large, multicentric, open-access dataset of fictional radiology reports spanning multiple languages for testing natural language processing applications in radiology. Materials and Methods: From May to September 2024, radiologists were invited to contribute fictional radiology reports following their standard reporting practices. Contributors provided at least 20 reports with associated metadata including anatomical region, imaging modality, clinical context, and for non-English reports, English translations. All reports were assigned ICD-10 codes. A human vs. AI report differentiation study was conducted with 154 participants (radiologists, healthcare professionals, and non-healthcare professionals) assessing whether reports were human-authored or AI-generated. Results: The dataset comprises 2,658 radiology reports from 76 authors across 21 countries and 13 languages. Reports cover multiple imaging modalities (CT: 36.1%, MRI: 22.8%, radiography: 19.0%, ultrasound: 16.8%) and anatomical regions, with chest (19.9%), abdomen (18.6%), head (17.3%), and pelvis (14.1%) being most prevalent. In the differentiation study, participants achieved 53.9% accuracy (95% CI: 50.7%-57.1%) in distinguishing between human and AI-generated reports, with radiologists performing significantly better (56.9%, 95% CI: 53.3%-60.6%, p<0.05) than other groups. Conclusion: PARROT represents the largest open multilingual radiology report dataset, enabling development and validation of natural language processing applications across linguistic, geographic, and clinical boundaries without privacy constraints.

Alina F. Dima, Suprosanna Shit, Huaqi Qiu et al.

Vessels are complex structures in the body that have been studied extensively in multiple representations. While voxelization is the most common of them, meshes and parametric models are critical in various applications due to their desirable properties. However, these representations are typically extracted through segmentations and used disjointly from each other. We propose a framework that joins the three representations under differentiable transformations. By leveraging differentiable voxelization, we automatically extract a parametric shape model of the vessels through shape-to-segmentation fitting, where we learn shape parameters from segmentations without the explicit need for ground-truth shape parameters. The vessel is parametrized as centerlines and radii using cubic B-splines, ensuring smoothness and continuity by construction. Meshes are differentiably extracted from the learned shape parameters, resulting in high-fidelity meshes that can be manipulated post-fit. Our method can accurately capture the geometry of complex vessels, as demonstrated by the volumetric fits in experiments on aortas, aneurysms, and brain vessels.

Michelle Xiao-Lin Foo, Seong Tae Kim, Magdalini Paschali et al.

Consistent segmentation of COVID-19 patient's CT scans across multiple time points is essential to assess disease progression and response to therapy accurately. Existing automatic and interactive segmentation models for medical images only use data from a single time point (static). However, valuable segmentation information from previous time points is often not used to aid the segmentation of a patient's follow-up scans. Also, fully automatic segmentation techniques frequently produce results that would need further editing for clinical use. In this work, we propose a new single network model for interactive segmentation that fully utilizes all available past information to refine the segmentation of follow-up scans. In the first segmentation round, our model takes 3D volumes of medical images from two-time points (target and reference) as concatenated slices with the additional reference time point segmentation as a guide to segment the target scan. In subsequent segmentation refinement rounds, user feedback in the form of scribbles that correct the segmentation and the target's previous segmentation results are additionally fed into the model. This ensures that the segmentation information from previous refinement rounds is retained. Experimental results on our in-house multiclass longitudinal COVID-19 dataset show that the proposed model outperforms its static version and can assist in localizing COVID-19 infections in patient's follow-up scans.

Alexander Ziller, Dmitrii Usynin, Moritz Knolle et al.

In recent years, formal methods of privacy protection such as differential privacy (DP), capable of deployment to data-driven tasks such as machine learning (ML), have emerged. Reconciling large-scale ML with the closed-form reasoning required for the principled analysis of individual privacy loss requires the introduction of new tools for automatic sensitivity analysis and for tracking an individual's data and their features through the flow of computation. For this purpose, we introduce a novel \textit{hybrid} automatic differentiation (AD) system which combines the efficiency of reverse-mode AD with an ability to obtain a closed-form expression for any given quantity in the computational graph. This enables modelling the sensitivity of arbitrary differentiable function compositions, such as the training of neural networks on private data. We demonstrate our approach by analysing the individual DP guarantees of statistical database queries. Moreover, we investigate the application of our technique to the training of DP neural networks. Our approach can enable the principled reasoning about privacy loss in the setting of data processing, and further the development of automatic sensitivity analysis and privacy budgeting systems.

Alexander Ziller, Dmitrii Usynin, Nicolas Remerscheid et al.

Collaborative machine learning techniques such as federated learning (FL) enable the training of models on effectively larger datasets without data transfer. Recent initiatives have demonstrated that segmentation models trained with FL can achieve performance similar to locally trained models. However, FL is not a fully privacy-preserving technique and privacy-centred attacks can disclose confidential patient data. Thus, supplementing FL with privacy-enhancing technologies (PTs) such as differential privacy (DP) is a requirement for clinical applications in a multi-institutional setting. The application of PTs to FL in medical imaging and the trade-offs between privacy guarantees and model utility, the ramifications on training performance and the susceptibility of the final models to attacks have not yet been conclusively investigated. Here we demonstrate the first application of differentially private gradient descent-based FL on the task of semantic segmentation in computed tomography. We find that high segmentation performance is possible under strong privacy guarantees with an acceptable training time penalty. We furthermore demonstrate the first successful gradient-based model inversion attack on a semantic segmentation model and show that the application of DP prevents it from divulging sensitive image features.

Alexander Ziller, Jonathan Passerat-Palmbach, Théo Ryffel et al.

The utilisation of artificial intelligence in medicine and healthcare has led to successful clinical applications in several domains. The conflict between data usage and privacy protection requirements in such systems must be resolved for optimal results as well as ethical and legal compliance. This calls for innovative solutions such as privacy-preserving machine learning (PPML). We present PriMIA (Privacy-preserving Medical Image Analysis), a software framework designed for PPML in medical imaging. In a real-life case study we demonstrate significantly better classification performance of a securely aggregated federated learning model compared to human experts on unseen datasets. Furthermore, we show an inference-as-a-service scenario for end-to-end encrypted diagnosis, where neither the data nor the model are revealed. Lastly, we empirically evaluate the framework's security against a gradient-based model inversion attack and demonstrate that no usable information can be recovered from the model.

Moritz Knolle, Georgios Kaissis, Friederike Jungmann et al.

For artificial intelligence-based image analysis methods to reach clinical applicability, the development of high-performance algorithms is crucial. For example, existent segmentation algorithms based on natural images are neither efficient in their parameter use nor optimized for medical imaging. Here we present MoNet, a highly optimized neural-network-based pancreatic segmentation algorithm focused on achieving high performance by efficient multi-scale image feature utilization.