Steven Niederer

Matteo Salvador, Marina Strocchi, Francesco Regazzoni et al.

Cardiac digital twins provide a physics and physiology informed framework to deliver predictive and personalized medicine. However, high-fidelity multi-scale cardiac models remain a barrier to adoption due to their extensive computational costs and the high number of model evaluations needed for patient-specific personalization. Artificial Intelligence-based methods can make the creation of fast and accurate whole-heart digital twins feasible. In this work, we use Latent Neural Ordinary Differential Equations (LNODEs) to learn the temporal pressure-volume dynamics of a heart failure patient. Our surrogate model based on LNODEs is trained from 400 3D-0D whole-heart closed-loop electromechanical simulations while accounting for 43 model parameters, describing single cell through to whole organ and cardiovascular hemodynamics. The trained LNODEs provides a compact and efficient representation of the 3D-0D model in a latent space by means of a feedforward fully-connected Artificial Neural Network that retains 3 hidden layers with 13 neurons per layer and allows for 300x real-time numerical simulations of the cardiac function on a single processor of a standard laptop. This surrogate model is employed to perform global sensitivity analysis and robust parameter estimation with uncertainty quantification in 3 hours of computations, still on a single processor. We match pressure and volume time traces unseen by the LNODEs during the training phase and we calibrate 4 to 11 model parameters while also providing their posterior distribution. This paper introduces the most advanced surrogate model of cardiac function available in the literature and opens new important venues for parameter calibration in cardiac digital twins.

Ezequiel de la Rosa, Ruisheng Su, Mauricio Reyes et al.

Accurate estimation of brain infarction (i.e., irreversibly damaged tissue) is critical for guiding treatment decisions in acute ischemic stroke. Reliable infarct prediction informs key clinical interventions, including the need for patient transfer to comprehensive stroke centers, the potential benefit of additional reperfusion attempts during mechanical thrombectomy, decisions regarding secondary neuroprotective treatments, and ultimately, prognosis of clinical outcomes. This work introduces the Ischemic Stroke Lesion Segmentation (ISLES) 2024 challenge, which focuses on the prediction of final infarct volumes from pre-interventional acute stroke imaging and clinical data. ISLES24 provides a comprehensive, multimodal setting where participants can leverage all clinically and practically available data, including full acute CT imaging, sub-acute follow-up MRI, and structured clinical information, across a train set of 150 cases. On the hidden test set of 98 cases, the top-performing model, a multimodal nnU-Net-based architecture, achieved a Dice score of 0.285 (+/- 0.213) and an absolute volume difference of 21.2 (+/- 37.2) mL, underlining the significant challenges posed by this task and the need for further advances in multimodal learning. This work makes two primary contributions: first, we establish a standardized, clinically realistic benchmark for post-treatment infarct prediction, enabling systematic evaluation of multimodal algorithmic strategies on a longitudinal stroke dataset; second, we analyze current methodological limitations and outline key research directions to guide the development of next-generation infarct prediction models.

Bei Zhou, Cesare Corrado, Shuang Qian et al.

Accurate maps of atrial electrical activation are essential for personalised treatment of arrhythmias, yet biophysically detailed simulations remain computationally intensive for real-time clinical use or population-scale analyses. Here we introduce a geometry-independent operator-learning framework that predicts local activation time (LAT) fields across diverse left atrial anatomies with near-instantaneous inference. We generated a dataset of 308,700 simulations using a GPU-accelerated electrophysiology solver, systematically varying multiple pacing sites and physiologically varied conduction properties across 147 patient-specific geometries derived from two independent clinical cohorts. All anatomical and functional data are expressed in a Universal Atrium Coordinate system, providing a consistent representation that decouples electrophysiological patterns from mesh topology. Within this coordinate space, we designed a neural operator with a vision-transformer backbone to learn the mapping from structural and electrophysiological inputs to LAT fields. With a mean prediction error of 5.1 ms over a 455 ms maximum simulation time, the model outperforms established operator-learning approaches and performs inference in 0.12 ms per sample. Our framework establishes a general strategy for learning domain-invariant biophysical mappings across variable anatomical domains and enables integration of computational electrophysiology into real-time and large-scale clinical workflows.

Devran Ugurlu, Shuang Qian, Elliot Fairweather et al.

A cardiac digital twin is a virtual replica of a patient's heart for screening, diagnosis, prognosis, risk assessment, and treatment planning of cardiovascular diseases. This requires an anatomically accurate patient-specific 3D structural representation of the heart, suitable for electro-mechanical simulations or study of disease mechanisms. However, generation of cardiac digital twins at scale is demanding and there are no public repositories of models across demographic groups. We describe an automatic open-source pipeline for creating patient-specific left and right ventricular meshes from cardiovascular magnetic resonance images, its application to a large cohort of ~55000 participants from UK Biobank, and the construction of the most comprehensive cohort of adult heart models to date, comprising 1423 representative meshes across sex (male, female), body mass index (range: 16 - 42 kg/m$^2$) and age (range: 49 - 80 years). Our code is available at https://github.com/cdttk/biv-volumetric-meshing/tree/plos2025 , and pre-trained networks, representative volumetric meshes with fibers and UVCs will be made available soon.

Kaiyuan Yang, Fabio Musio, Yihui Ma et al.

The Circle of Willis (CoW) is an important network of arteries connecting major circulations of the brain. Its vascular architecture is believed to affect the risk, severity, and clinical outcome of serious neurovascular diseases. However, characterizing the highly variable CoW anatomy is still a manual and time-consuming expert task. The CoW is usually imaged by two non-invasive angiographic imaging modalities, magnetic resonance angiography (MRA) and computed tomography angiography (CTA), but there exist limited datasets with annotations on CoW anatomy, especially for CTA. Therefore, we organized the TopCoW challenge with the release of an annotated CoW dataset. The TopCoW dataset is the first public dataset with voxel-level annotations for 13 CoW vessel components, enabled by virtual reality technology. It is also the first large dataset using 200 pairs of MRA and CTA from the same patients. As part of the benchmark, we invited submissions worldwide and attracted over 250 registered participants from six continents. The submissions were evaluated on both internal and external test datasets of 226 scans from over five centers. The top performing teams achieved over 90% Dice scores at segmenting the CoW components, over 80% F1 scores at detecting key CoW components, and over 70% balanced accuracy at classifying CoW variants for nearly all test sets. The best algorithms also showed clinical potential in classifying fetal-type posterior cerebral artery and locating aneurysms with CoW anatomy. TopCoW demonstrated the utility and versatility of CoW segmentation algorithms for a wide range of downstream clinical applications with explainability. The annotated datasets and best performing algorithms have been released as public Zenodo records to foster further methodological development and clinical tool building.

Weitong Zhang, Mengyun Qiao, Chengqi Zang et al.

Identifying associations between imaging phenotypes, disease risk factors, and clinical outcomes is essential for understanding disease mechanisms. However, traditional approaches rely on human-driven hypothesis testing and selection of association factors, often overlooking complex, non-linear dependencies among imaging phenotypes and other multi-modal data. To address this, we introduce Multi-agent Exploratory Synergy for the Heart (MESHAgents): a framework that leverages large language models as agents to dynamically elicit, surface, and decide confounders and phenotypes in association studies. Specifically, we orchestrate a multi-disciplinary team of AI agents, which spontaneously generate and converge on insights through iterative, self-organizing reasoning. The framework dynamically synthesizes statistical correlations with multi-expert consensus, providing an automated pipeline for phenome-wide association studies (PheWAS). We demonstrate the system's capabilities through a population-based study of imaging phenotypes of the heart and aorta. MESHAgents autonomously uncovered correlations between imaging phenotypes and a wide range of non-imaging factors, identifying additional confounder variables beyond standard demographic factors. Validation on diagnosis tasks reveals that MESHAgents-discovered phenotypes achieve performance comparable to expert-selected phenotypes, with mean AUC differences as small as $-0.004_{\pm0.010}$ on disease classification tasks. Notably, the recall score improves for 6 out of 9 disease types. Our framework provides clinically relevant imaging phenotypes with transparent reasoning, offering a scalable alternative to expert-driven methods.

Yu Deng, Yiyang Xu, Linglong Qian et al.

Cardiac Magnetic Resonance (CMR) imaging is widely used for heart modelling and digital twin computational analysis due to its ability to visualize soft tissues and capture dynamic functions. However, the anisotropic nature of CMR images, characterized by large inter-slice distances and misalignments from cardiac motion, poses significant challenges to accurate model reconstruction. These limitations result in data loss and measurement inaccuracies, hindering the capture of detailed anatomical structures. This study introduces MorphiNet, a novel network that enhances heart model reconstruction by leveraging high-resolution Computer Tomography (CT) images, unpaired with CMR images, to learn heart anatomy. MorphiNet encodes anatomical structures as gradient fields, transforming template meshes into patient-specific geometries. A multi-layer graph subdivision network refines these geometries while maintaining dense point correspondence. The proposed method achieves high anatomy fidelity, demonstrating approximately 40% higher Dice scores, half the Hausdorff distance, and around 3 mm average surface error compared to state-of-the-art methods. MorphiNet delivers superior results with greater inference efficiency. This approach represents a significant advancement in addressing the challenges of CMR-based heart model reconstruction, potentially improving digital twin computational analyses of cardiac structure and functions.