on behalf of the PINNACLE consortium
Abstract:Leveraging big data for patient care is promising in many medical fields such as cardiovascular health. For example, hemodynamic biomarkers like wall shear stress could be assessed from patient-specific medical images via machine learning algorithms, bypassing the need for time-intensive computational fluid simulation. However, it is extremely challenging to amass large-enough datasets to effectively train such models. We could address this data scarcity by means of self-supervised pre-training and foundations models given large datasets of geometric artery models. In the context of coronary arteries, leveraging learned representations to improve hemodynamic biomarker assessment has not yet been well studied. In this work, we address this gap by investigating whether a large dataset (8449 shapes) consisting of geometric models of 3D blood vessels can benefit wall shear stress assessment in coronary artery models from a small-scale clinical trial (49 patients). We create a self-supervised target for the 3D blood vessels by computing the heat kernel signature, a quantity obtained via Laplacian eigenvectors, which captures the very essence of the shapes. We show how geometric representations learned from this datasets can boost segmentation of coronary arteries into regions of low, mid and high (time-averaged) wall shear stress even when trained on limited data.
Abstract: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.
Abstract:Digital twins offer a powerful framework for subject-specific simulation and clinical decision support, yet their development often hinges on accurate, individualized anatomical modeling. In this work, we present a rule-based approach for subpixel-accurate key-point extraction from MRI, adapted from prior CT-based methods. Our approach incorporates robust image alignment and vertebra-specific orientation estimation to generate anatomically meaningful landmarks that serve as boundary conditions and force application points, like muscle and ligament insertions in biomechanical models. These models enable the simulation of spinal mechanics considering the subject's individual anatomy, and thus support the development of tailored approaches in clinical diagnostics and treatment planning. By leveraging MR imaging, our method is radiation-free and well-suited for large-scale studies and use in underrepresented populations. This work contributes to the digital twin ecosystem by bridging the gap between precise medical image analysis with biomechanical simulation, and aligns with key themes in personalized modeling for healthcare.
Abstract:The explainability of deep learning models remains a significant challenge, particularly in the medical domain where interpretable outputs are critical for clinical trust and transparency. Path attribution methods such as Integrated Gradients rely on a baseline input representing the absence of relevant features ("missingness"). Commonly used baselines, such as all-zero inputs, are often semantically meaningless, especially in medical contexts where missingness can itself be informative. While alternative baseline choices have been explored, existing methods lack a principled approach to dynamically select baselines tailored to each input. In this work, we examine the notion of missingness in the medical setting, analyze its implications for baseline selection, and introduce a counterfactual-guided approach to address the limitations of conventional baselines. We argue that a clinically normal but input-close counterfactual represents a more accurate representation of a meaningful absence of features in medical data. To implement this, we use a Variational Autoencoder to generate counterfactual baselines, though our concept is generative-model-agnostic and can be applied with any suitable counterfactual method. We evaluate the approach on three distinct medical data sets and empirically demonstrate that counterfactual baselines yield more faithful and medically relevant attributions compared to standard baseline choices.
Abstract:Deep learning-based medical image segmentation techniques have shown promising results when evaluated based on conventional metrics such as the Dice score or Intersection-over-Union. However, these fully automatic methods often fail to meet clinically acceptable accuracy, especially when topological constraints should be observed, e.g., continuous boundaries or closed surfaces. In medical image segmentation, the correctness of a segmentation in terms of the required topological genus sometimes is even more important than the pixel-wise accuracy. Existing topology-aware approaches commonly estimate and constrain the topological structure via the concept of persistent homology (PH). However, these methods are difficult to implement for high dimensional data due to their polynomial computational complexity. To overcome this problem, we propose a novel and fast approach for topology-aware segmentation based on the Euler Characteristic ($\chi$). First, we propose a fast formulation for $\chi$ computation in both 2D and 3D. The scalar $\chi$ error between the prediction and ground-truth serves as the topological evaluation metric. Then we estimate the spatial topology correctness of any segmentation network via a so-called topological violation map, i.e., a detailed map that highlights regions with $\chi$ errors. Finally, the segmentation results from the arbitrary network are refined based on the topological violation maps by a topology-aware correction network. Our experiments are conducted on both 2D and 3D datasets and show that our method can significantly improve topological correctness while preserving pixel-wise segmentation accuracy.
Abstract:Reliable recognition and localization of surgical instruments in endoscopic video recordings are foundational for a wide range of applications in computer- and robot-assisted minimally invasive surgery (RAMIS), including surgical training, skill assessment, and autonomous assistance. However, robust performance under real-world conditions remains a significant challenge. Incorporating surgical context - such as the current procedural phase - has emerged as a promising strategy to improve robustness and interpretability. To address these challenges, we organized the Surgical Procedure Phase, Keypoint, and Instrument Recognition (PhaKIR) sub-challenge as part of the Endoscopic Vision (EndoVis) challenge at MICCAI 2024. We introduced a novel, multi-center dataset comprising thirteen full-length laparoscopic cholecystectomy videos collected from three distinct medical institutions, with unified annotations for three interrelated tasks: surgical phase recognition, instrument keypoint estimation, and instrument instance segmentation. Unlike existing datasets, ours enables joint investigation of instrument localization and procedural context within the same data while supporting the integration of temporal information across entire procedures. We report results and findings in accordance with the BIAS guidelines for biomedical image analysis challenges. The PhaKIR sub-challenge advances the field by providing a unique benchmark for developing temporally aware, context-driven methods in RAMIS and offers a high-quality resource to support future research in surgical scene understanding.
Abstract: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.
Abstract:Magnetic resonance imaging of fetal and neonatal brains reveals rapid neurodevelopment marked by substantial anatomical changes unfolding within days. Studying this critical stage of the developing human brain, therefore, requires accurate brain models-referred to as atlases-of high spatial and temporal resolution. To meet these demands, established traditional atlases and recently proposed deep learning-based methods rely on large and comprehensive datasets. This poses a major challenge for studying brains in the presence of pathologies for which data remains scarce. We address this limitation with CINeMA (Conditional Implicit Neural Multi-Modal Atlas), a novel framework for creating high-resolution, spatio-temporal, multimodal brain atlases, suitable for low-data settings. Unlike established methods, CINeMA operates in latent space, avoiding compute-intensive image registration and reducing atlas construction times from days to minutes. Furthermore, it enables flexible conditioning on anatomical features including GA, birth age, and pathologies like ventriculomegaly (VM) and agenesis of the corpus callosum (ACC). CINeMA supports downstream tasks such as tissue segmentation and age prediction whereas its generative properties enable synthetic data creation and anatomically informed data augmentation. Surpassing state-of-the-art methods in accuracy, efficiency, and versatility, CINeMA represents a powerful tool for advancing brain research. We release the code and atlases at https://github.com/m-dannecker/CINeMA.
Abstract:We propose a self-supervised feature learning assisted reconstruction (SSFL-Recon) framework for MRI reconstruction to address the limitation of existing supervised learning methods. Although recent deep learning-based methods have shown promising performance in MRI reconstruction, most require fully-sampled images for supervised learning, which is challenging in practice considering long acquisition times under respiratory or organ motion. Moreover, nearly all fully-sampled datasets are obtained from conventional reconstruction of mildly accelerated datasets, thus potentially biasing the achievable performance. The numerous undersampled datasets with different accelerations in clinical practice, hence, remain underutilized. To address these issues, we first train a self-supervised feature extractor on undersampled images to learn sampling-insensitive features. The pre-learned features are subsequently embedded in the self-supervised reconstruction network to assist in removing artifacts. Experiments were conducted retrospectively on an in-house 2D cardiac Cine dataset, including 91 cardiovascular patients and 38 healthy subjects. The results demonstrate that the proposed SSFL-Recon framework outperforms existing self-supervised MRI reconstruction methods and even exhibits comparable or better performance to supervised learning up to $16\times$ retrospective undersampling. The feature learning strategy can effectively extract global representations, which have proven beneficial in removing artifacts and increasing generalization ability during reconstruction.
Abstract:Improving performance on complex tasks and enabling interpretable decision making in large language models (LLMs), especially for clinical applications, requires effective reasoning. Yet this remains challenging without supervised fine-tuning (SFT) on costly chain-of-thought (CoT) data distilled from closed-source models (e.g., GPT-4o). In this work, we present AlphaMed, the first medical LLM to show that reasoning capability can emerge purely through reinforcement learning (RL), using minimalist rule-based rewards on public multiple-choice QA datasets, without relying on SFT or distilled CoT data. AlphaMed achieves state-of-the-art results on six medical QA benchmarks, outperforming models trained with conventional SFT+RL pipelines. On challenging benchmarks (e.g., MedXpert), AlphaMed even surpasses larger or closed-source models such as DeepSeek-V3-671B and Claude-3.5-Sonnet. To understand the factors behind this success, we conduct a comprehensive data-centric analysis guided by three questions: (i) Can minimalist rule-based RL incentivize reasoning without distilled CoT supervision? (ii) How do dataset quantity and diversity impact reasoning? (iii) How does question difficulty shape the emergence and generalization of reasoning? Our findings show that dataset informativeness is a key driver of reasoning performance, and that minimalist RL on informative, multiple-choice QA data is effective at inducing reasoning without CoT supervision. We also observe divergent trends across benchmarks, underscoring limitations in current evaluation and the need for more challenging, reasoning-oriented medical QA benchmarks.