Niklas Bubeck

Valentin Biller, Niklas Bubeck, Lucas Zimmer et al.

Glioblastoma exhibits diverse, infiltrative, and patient-specific growth patterns that are only partially visible on routine MRI, making it difficult to reliably assess true tumor extent and personalize treatment planning and follow-up. We present a biophysically-conditioned generative framework that synthesizes biologically realistic 3D brain MRI volumes from estimated, spatially continuous tumor-concentration fields. Our approach combines a generative model with tumor-infiltration maps that can be propagated through time using a biophysical growth model, enabling fine-grained control over tumor shape and growth while preserving patient anatomy. This enables us to synthesize consistent tumor growth trajectories directly in the space of real patients, providing interpretable, controllable estimation of tumor infiltration and progression beyond what is explicitly observed in imaging. We evaluate the framework on longitudinal glioblastoma cases and demonstrate that it can generate temporally coherent sequences with realistic changes in tumor appearance and surrounding tissue response. These results suggest that integrating mechanistic tumor growth priors with modern generative modeling can provide a practical tool for patient-specific progression visualization and for generating controlled synthetic data to support downstream neuro-oncology workflows. In longitudinal extrapolation, we achieve a consistent 75% Dice overlap with the biophysical model while maintaining a constant PSNR of 25 in the surrounding tissue. Our code is available at: https://github.com/valentin-biller/lgm.git

Matteo Wohlrapp, Niklas Bubeck, Daniel Rueckert et al.

AI-based image reconstruction models are increasingly deployed in clinical workflows to improve image quality from noisy data, such as low-dose X-rays or accelerated MRI scans. However, these models are typically evaluated using pixel-level metrics like PSNR, leaving their impact on downstream diagnostic performance and fairness unclear. We introduce a scalable evaluation framework that applies reconstruction and diagnostic AI models in tandem, which we apply to two tasks (classification, segmentation), three reconstruction approaches (U-Net, GAN, diffusion), and two data types (X-ray, MRI) to assess the potential downstream implications of reconstruction. We find that conventional reconstruction metrics poorly track task performance, where diagnostic accuracy remains largely stable even as reconstruction PSNR declines with increasing image noise. Fairness metrics exhibit greater variability, with reconstruction sometimes amplifying demographic biases, particularly regarding patient sex. However, the overall magnitude of this additional bias is modest compared to the inherent biases already present in diagnostic models. To explore potential bias mitigation, we adapt two strategies from classification literature to the reconstruction setting, but observe limited efficacy. Overall, our findings emphasize the importance of holistic performance and fairness assessments throughout the entire medical imaging workflow, especially as generative reconstruction models are increasingly deployed.

Yundi Zhang, Sevgi Gokce Kafali, Niklas Bubeck et al.

Conventional clinical CMR pipelines rely on a sequential "reconstruct-then-analyze" paradigm, forcing an ill-posed intermediate step that introduces avoidable artifacts and information bottlenecks. This creates a fundamental mathematical paradox: it attempts to recover high-dimensional pixel arrays (i.e., images) from undersampled k-space, rather than directly extracting the low-dimensional physiological labels actually required for diagnosis. To unlock the direct diagnostic potential of k-space, we propose k-MTR (k-space Multi-Task Representation), a k-space representation learning framework that aligns undersampled k-space data and fully-sampled images into a shared semantic manifold. Leveraging a large-scale controlled simulation of 42,000 subjects, k-MTR forces the k-space encoder to restore anatomical information lost to undersampling directly within the latent space, bypassing the explicit inverse problem for downstream analysis. We demonstrate that this latent alignment enables the dense latent space embedded with high-level physiological semantics directly from undersampled frequencies. Across continuous phenotype regression, disease classification, and anatomical segmentation, k-MTR achieves highly competitive performance against state-of-the-art image-domain baselines. By showcasing that precise spatial geometries and multi-task features can be successfully recovered directly from the k-space representations, k-MTR provides a robust architectural blueprint for task-aware cardiac MRI workflows.

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.

Valentin Biller, Lucas Zimmer, Can Erdur et al.

Magnetic resonance imaging (MRI) inpainting supports numerous clinical and research applications. We introduce the first generative model that conditions on voxel-level, continuous tumor concentrations to synthesize high-fidelity brain tumor MRIs. For the BraTS 2025 Inpainting Challenge, we adapt this architecture to the complementary task of healthy tissue restoration by setting the tumor concentrations to zero. Our latent diffusion model conditioned on both tissue segmentations and the tumor concentrations generates 3D spatially coherent and anatomically consistent images for both tumor synthesis and healthy tissue inpainting. For healthy inpainting, we achieve a PSNR of 18.5, and for tumor inpainting, we achieve 17.4. Our code is available at: https://github.com/valentin-biller/ldm.git

Niklas Bubeck, Suprosanna Shit, Chen Chen et al.

Cardiac Magnetic Resonance (CMR) imaging is a critical tool for diagnosing and managing cardiovascular disease, yet its utility is often limited by the sparse acquisition of 2D short-axis slices, resulting in incomplete volumetric information. Accurate 3D reconstruction from these sparse slices is essential for comprehensive cardiac assessment, but existing methods face challenges, including reliance on predefined interpolation schemes (e.g., linear or spherical), computational inefficiency, and dependence on additional semantic inputs such as segmentation labels or motion data. To address these limitations, we propose a novel Cardiac Latent Interpolation Diffusion (CaLID) framework that introduces three key innovations. First, we present a data-driven interpolation scheme based on diffusion models, which can capture complex, non-linear relationships between sparse slices and improves reconstruction accuracy. Second, we design a computationally efficient method that operates in the latent space and speeds up 3D whole-heart upsampling time by a factor of 24, reducing computational overhead compared to previous methods. Third, with only sparse 2D CMR images as input, our method achieves SOTA performance against baseline methods, eliminating the need for auxiliary input such as morphological guidance, thus simplifying workflows. We further extend our method to 2D+T data, enabling the effective modeling of spatiotemporal dynamics and ensuring temporal coherence. Extensive volumetric evaluations and downstream segmentation tasks demonstrate that CaLID achieves superior reconstruction quality and efficiency. By addressing the fundamental limitations of existing approaches, our framework advances the state of the art for spatio and spatiotemporal whole-heart reconstruction, offering a robust and clinically practical solution for cardiovascular imaging.

Niklas Bubeck, Yundi Zhang, Suprosanna Shit et al.

In medical imaging, generative models are increasingly relied upon for two distinct but equally critical tasks: reconstruction, where the goal is to restore medical imaging (usually inverse problems like inpainting or superresolution), and generation, where synthetic data is created to augment datasets or carry out counterfactual analysis. Despite shared architecture and learning frameworks, they prioritize different goals: generation seeks high perceptual quality and diversity, while reconstruction focuses on data fidelity and faithfulness. In this work, we introduce a "generative model zoo" and systematically analyze how modern latent diffusion models and autoregressive models navigate the reconstruction-generation spectrum. We benchmark a suite of generative models across representative cardiac medical imaging tasks, focusing on image inpainting with varying masking ratios and sampling strategies, as well as unconditional image generation. Our findings show that diffusion models offer superior perceptual quality for unconditional generation but tend to hallucinate as masking ratios increase, whereas autoregressive models maintain stable perceptual performance across masking levels, albeit with generally lower fidelity.