Jonas Weidner

Michal Balcerak, Tamaz Amiranashvili, Andreas Wagner et al.

Physical models in the form of partial differential equations serve as important priors for many under-constrained problems. One such application is tumor treatment planning, which relies on accurately estimating the spatial distribution of tumor cells within a patient's anatomy. While medical imaging can detect the bulk of a tumor, it cannot capture the full extent of its spread, as low-concentration tumor cells often remain undetectable, particularly in glioblastoma, the most common primary brain tumor. Machine learning approaches struggle to estimate the complete tumor cell distribution due to a lack of appropriate training data. Consequently, most existing methods rely on physics-based simulations to generate anatomically and physiologically plausible estimations. However, these approaches face challenges with complex and unknown initial conditions and are constrained by overly rigid physical models. In this work, we introduce a novel method that integrates data-driven and physics-based cost functions, akin to Physics-Informed Neural Networks (PINNs). However, our approach parametrizes the solution directly on a dynamic discrete mesh, allowing for the effective modeling of complex biomechanical behaviors. Specifically, we propose a unique discretization scheme that quantifies how well the learned spatiotemporal distributions of tumor and brain tissues adhere to their respective growth and elasticity equations. This quantification acts as a regularization term, offering greater flexibility and improved integration of patient data compared to existing models. We demonstrate enhanced coverage of tumor recurrence areas using real-world data from a patient cohort, highlighting the potential of our method to improve model-driven treatment planning for glioblastoma in clinical practice.

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

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

Jonas Weidner, Yeray Martin-Ruisanchez, Daniel Rückert et al.

Neural surrogate models for computational fluid dynamics (CFD) are typically trained as forward operators that map explicit problem specifications, such as geometry and boundary conditions, to solution fields. This ties the model to the conditioning variables seen during training and limits reuse under boundary-condition shifts or local geometry changes. We propose to reformulate steady CFD inference as an inpainting problem: instead of training on explicit boundary conditions, we learn a self-supervised prior over velocity fields and impose boundary constraints only during inference by fixing known regions such as inlet, outlet or unchanged regions from previous simulations. To scale this idea to large 3D meshes, we introduce a local neighbourhood tokeniser that represents high-resolution velocity fields as compact spatial latent tokens and train latent flow-matching and masked-autoencoder models on these tokens. On intracranial aneurysm hemodynamics, our method reconstructs full velocity fields from sparse boundary context, outperforms supervised neural surrogates under boundary-condition and dataset shift and enables local geometry editing by reusing unchanged simulation context. These results suggest that viewing CFD inference as context-conditioned inpainting can turn neural surrogates from task-specific predictors into reusable flow priors.

Jonas Weidner, Ivan Ezhov, Michal Balcerak et al.

Biophysical modeling, particularly involving partial differential equations (PDEs), offers significant potential for tailoring disease treatment protocols to individual patients. However, the inverse problem-solving aspect of these models presents a substantial challenge, either due to the high computational requirements of model-based approaches or the limited robustness of deep learning (DL) methods. We propose a novel framework that leverages the unique strengths of both approaches in a synergistic manner. Our method incorporates a DL ensemble for initial parameter estimation, facilitating efficient downstream evolutionary sampling initialized with this DL-based prior. We showcase the effectiveness of integrating a rapid deep-learning algorithm with a high-precision evolution strategy in estimating brain tumor cell concentrations from magnetic resonance images. The DL-Prior plays a pivotal role, significantly constraining the effective sampling-parameter space. This reduction results in a fivefold convergence acceleration and a Dice-score of 95%.

Laurin Lux, Alexander H. Berger, Maria Romeo Tricas et al.

Interpretability is crucial to enhance trust in machine learning models for medical diagnostics. However, most state-of-the-art image classifiers based on neural networks are not interpretable. As a result, clinicians often resort to known biomarkers for diagnosis, although biomarker-based classification typically performs worse than large neural networks. This work proposes a method that surpasses the performance of established machine learning models while simultaneously improving prediction interpretability for diabetic retinopathy staging from optical coherence tomography angiography (OCTA) images. Our method is based on a novel biology-informed heterogeneous graph representation that models retinal vessel segments, intercapillary areas, and the foveal avascular zone (FAZ) in a human-interpretable way. This graph representation allows us to frame diabetic retinopathy staging as a graph-level classification task, which we solve using an efficient graph neural network. We benchmark our method against well-established baselines, including classical biomarker-based classifiers, convolutional neural networks (CNNs), and vision transformers. Our model outperforms all baselines on two datasets. Crucially, we use our biology-informed graph to provide explanations of unprecedented detail. Our approach surpasses existing methods in precisely localizing and identifying critical vessels or intercapillary areas. In addition, we give informative and human-interpretable attributions to critical characteristics. Our work contributes to the development of clinical decision-support tools in ophthalmology.

Zeineb Haouari, Jonas Weidner, Yeray Martin-Ruisanchez et al.

Glioblastoma, a highly aggressive brain tumor, poses major challenges due to its poor prognosis and high morbidity rates. Partial differential equation-based models offer promising potential to enhance therapeutic outcomes by simulating patient-specific tumor behavior for improved radiotherapy planning. However, model calibration remains a bottleneck due to the high computational demands of optimization methods like Monte Carlo sampling and evolutionary algorithms. To address this, we recently introduced an approach leveraging a neural forward solver with gradient-based optimization to significantly reduce calibration time. This approach requires a highly accurate and fully differentiable forward model. We investigate multiple architectures, including (i) an enhanced TumorSurrogate, (ii) a modified nnU-Net, and (iii) a 3D Vision Transformer (ViT). The nnU-Net achieved the best overall results, excelling in both tumor outline matching and voxel-level prediction of tumor cell concentration. It yielded the lowest MSE in tumor cell concentration compared to ground truth numerical simulation and the highest Dice score across all tumor cell concentration thresholds. Our study demonstrates significant enhancement in forward solver performance and outlines important future research directions.

Jonas Weidner, Michal Balcerak, Ivan Ezhov et al.

Glioblastoma, the most aggressive primary brain tumor, poses a severe clinical challenge due to its diffuse microscopic infiltration, which remains largely undetected on standard MRI. As a result, current radiotherapy planning employs a uniform 15 mm margin around the resection cavity, failing to capture patient-specific tumor spread. Tumor growth modeling offers a promising approach to reveal this hidden infiltration. However, methods based on partial differential equations or physics-informed neural networks tend to be computationally intensive or overly constrained, limiting their clinical adaptability to individual patients. In this work, we propose a lightweight, rapid, and robust optimization framework that estimates the 3D tumor concentration by fitting it to MRI tumor segmentations while enforcing a smooth concentration landscape. This approach achieves superior tumor recurrence prediction on 192 brain tumor patients across two public datasets, outperforming state-of-the-art baselines while reducing runtime from 30 minutes to less than one minute. Furthermore, we demonstrate the framework's versatility and adaptability by showing its ability to seamlessly integrate additional imaging modalities or physical constraints.

Hongwei Bran Li, Fernando Navarro, Ivan Ezhov et al.

Uncertainty in medical image segmentation tasks, especially inter-rater variability, arising from differences in interpretations and annotations by various experts, presents a significant challenge in achieving consistent and reliable image segmentation. This variability not only reflects the inherent complexity and subjective nature of medical image interpretation but also directly impacts the development and evaluation of automated segmentation algorithms. Accurately modeling and quantifying this variability is essential for enhancing the robustness and clinical applicability of these algorithms. We report the set-up and summarize the benchmark results of the Quantification of Uncertainties in Biomedical Image Quantification Challenge (QUBIQ), which was organized in conjunction with International Conferences on Medical Image Computing and Computer-Assisted Intervention (MICCAI) 2020 and 2021. The challenge focuses on the uncertainty quantification of medical image segmentation which considers the omnipresence of inter-rater variability in imaging datasets. The large collection of images with multi-rater annotations features various modalities such as MRI and CT; various organs such as the brain, prostate, kidney, and pancreas; and different image dimensions 2D-vs-3D. A total of 24 teams submitted different solutions to the problem, combining various baseline models, Bayesian neural networks, and ensemble model techniques. The obtained results indicate the importance of the ensemble models, as well as the need for further research to develop efficient 3D methods for uncertainty quantification methods in 3D segmentation tasks.

Eric Müller, Sebastian Schmitt, Christian Mauch et al.

BrainScaleS-1 is a wafer-scale mixed-signal accelerated neuromorphic system targeted for research in the fields of computational neuroscience and beyond-von-Neumann computing. The BrainScaleS Operating System (BrainScaleS OS) is a software stack giving users the possibility to emulate networks described in the high-level network description language PyNN with minimal knowledge of the system. At the same time, expert usage is facilitated by allowing to hook into the system at any depth of the stack. We present operation and development methodologies implemented for the BrainScaleS-1 neuromorphic architecture and walk through the individual components of BrainScaleS OS constituting the software stack for BrainScaleS-1 platform operation.