Laurin Lux

Alexander Weers, Alexander H. Berger, Laurin Lux et al.

The histopathological analysis of whole-slide images (WSIs) is fundamental to cancer diagnosis but is a time-consuming and expert-driven process. While deep learning methods show promising results, dominant patch-based methods artificially fragment tissue, ignore biological boundaries, and produce black-box predictions. We overcome these limitations with a novel framework that transforms gigapixel WSIs into biologically-informed graph representations and is interpretable by design. Our approach builds graph nodes from tissue regions that respect natural structures, not arbitrary grids. We introduce an adaptive graph coarsening technique, guided by learned embeddings, to efficiently merge homogeneous regions while preserving diagnostically critical details in heterogeneous areas. Each node is enriched with a compact, interpretable feature set capturing clinically-motivated priors. A graph attention network then performs diagnosis on this compact representation. We demonstrate strong performance on challenging cancer staging and survival prediction tasks. Crucially, our resource-efficient model ($>$13x fewer parameters and $>$300x less data) achieves results competitive with a massive foundation model, while offering full interpretability through feature attribution. Our code is publicly available at https://github.com/HistoGraph31/pix2pathology.

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%.

Alexander H. Berger, Nico Stucki, Laurin Lux et al.

Topological accuracy in medical image segmentation is a highly important property for downstream applications such as network analysis and flow modeling in vessels or cell counting. Recently, significant methodological advancements have brought well-founded concepts from algebraic topology to binary segmentation. However, these approaches have been underexplored in multi-class segmentation scenarios, where topological errors are common. We propose a general loss function for topologically faithful multi-class segmentation extending the recent Betti matching concept, which is based on induced matchings of persistence barcodes. We project the N-class segmentation problem to N single-class segmentation tasks, which allows us to use 1-parameter persistent homology, making training of neural networks computationally feasible. We validate our method on a comprehensive set of four medical datasets with highly variant topological characteristics. Our loss formulation significantly enhances topological correctness in cardiac, cell, artery-vein, and Circle of Willis segmentation.

Laurin Lux, Alexander H. Berger, Alexander Weers et al.

Topological correctness plays a critical role in many image segmentation tasks, yet most networks are trained using pixel-wise loss functions, such as Dice, neglecting topological accuracy. Existing topology-aware methods often lack robust topological guarantees, are limited to specific use cases, or impose high computational costs. In this work, we propose a novel, graph-based framework for topologically accurate image segmentation that is both computationally efficient and generally applicable. Our method constructs a component graph that fully encodes the topological information of both the prediction and ground truth, allowing us to efficiently identify topologically critical regions and aggregate a loss based on local neighborhood information. Furthermore, we introduce a strict topological metric capturing the homotopy equivalence between the union and intersection of prediction-label pairs. We formally prove the topological guarantees of our approach and empirically validate its effectiveness on binary and multi-class datasets. Our loss demonstrates state-of-the-art performance with up to fivefold faster loss computation compared to persistent homology methods.

Alexander H. Berger, Laurin Lux, Alexander Weers et al.

Topological correctness, i.e., the preservation of structural integrity and specific characteristics of shape, is a fundamental requirement for medical imaging tasks, such as neuron or vessel segmentation. Despite the recent surge in topology-aware methods addressing this challenge, their real-world applicability is hindered by flawed benchmarking practices. In this paper, we identify critical pitfalls in model evaluation that include inadequate connectivity choices, overlooked topological artifacts in ground truth annotations, and inappropriate use of evaluation metrics. Through detailed empirical analysis, we uncover these issues' profound impact on the evaluation and ranking of segmentation methods. Drawing from our findings, we propose a set of actionable recommendations to establish fair and robust evaluation standards for topology-aware medical image segmentation methods.

Chenjun Li, Laurin Lux, Alexander H. Berger et al.

Accurate staging of Diabetic Retinopathy (DR) is essential for guiding timely interventions and preventing vision loss. However, current staging models are hardly interpretable, and most public datasets contain no clinical reasoning or interpretation beyond image-level labels. In this paper, we present a novel method that integrates graph representation learning with vision-language models (VLMs) to deliver explainable DR diagnosis. Our approach leverages optical coherence tomography angiography (OCTA) images by constructing biologically informed graphs that encode key retinal vascular features such as vessel morphology and spatial connectivity. A graph neural network (GNN) then performs DR staging while integrated gradients highlight critical nodes and edges and their individual features that drive the classification decisions. We collect this graph-based knowledge which attributes the model's prediction to physiological structures and their characteristics. We then transform it into textual descriptions for VLMs. We perform instruction-tuning with these textual descriptions and the corresponding image to train a student VLM. This final agent can classify the disease and explain its decision in a human interpretable way solely based on a single image input. Experimental evaluations on both proprietary and public datasets demonstrate that our method not only improves classification accuracy but also offers more clinically interpretable results. An expert study further demonstrates that our method provides more accurate diagnostic explanations and paves the way for precise localization of pathologies in OCTA images.

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.

Chenjun Li, Cheng Wan, Laurin Lux et al.

Vision-Language Models (VLMs) offer a promising path toward interpretable medical diagnosis by allowing users to ask about clinical explanations alongside predictions and across different modalities. However, training VLMs for detailed reasoning requires large-scale image-text datasets. In many specialized domains, for example in reading Optical Coherence Tomography Angiography (OCTA) images, such precise text with grounded description of pathologies is scarce or even non-existent. To overcome this bottleneck, we introduce Synthetic Vasculature Reasoning (SVR), a framework that controllably synthesizes images and corresponding text, specifically: realistic retinal vasculature with Diabetic Retinopathy (DR) features: capillary dropout, microaneurysms, neovascularization, and tortuosity, while automatically generating granular reasoning texts. Based on this we curate OCTA-100K-SVR, an OCTA image-reasoning dataset with 100,000 pairs. Our experiments show that a general-purpose VLM (Qwen3-VL-8b) trained on the dataset achieves a zero-shot balanced classification accuracy of 89.67% on real OCTA images, outperforming supervised baselines. Through human expert evaluation we also demonstrate that it significantly enhances explanation quality and pathology localization on clinical data.

Tim Mach, Daniel Rueckert, Alex Berger et al.

This work presents a novel deep learning framework for segmenting cerebral vasculature in hyperspectral brain images. We address the critical challenge of severe label scarcity, which impedes conventional supervised training. Our approach utilizes a novel unsupervised domain adaptation methodology, using a small, expert-annotated ground truth alongside unlabeled data. Quantitative and qualitative evaluations confirm that our method significantly outperforms existing state-of-the-art approaches, demonstrating the efficacy of domain adaptation for label-scarce biomedical imaging tasks.

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.

Alexander H. Berger, Laurin Lux, Suprosanna Shit et al.

Direct image-to-graph transformation is a challenging task that involves solving object detection and relationship prediction in a single model. Due to this task's complexity, large training datasets are rare in many domains, making the training of deep-learning methods challenging. This data sparsity necessitates transfer learning strategies akin to the state-of-the-art in general computer vision. In this work, we introduce a set of methods enabling cross-domain and cross-dimension learning for image-to-graph transformers. We propose (1) a regularized edge sampling loss to effectively learn object relations in multiple domains with different numbers of edges, (2) a domain adaptation framework for image-to-graph transformers aligning image- and graph-level features from different domains, and (3) a projection function that allows using 2D data for training 3D transformers. We demonstrate our method's utility in cross-domain and cross-dimension experiments, where we utilize labeled data from 2D road networks for simultaneous learning in vastly different target domains. Our method consistently outperforms standard transfer learning and self-supervised pretraining on challenging benchmarks, such as retinal or whole-brain vessel graph extraction.