Flow-based conditional cardiac anatomy generation for virtual cohorts

In-silico trials of medical devices require the generation of virtual populations of anatomies. In cardiovascular applications, virtual anatomy is typically represented as a 3D+t mesh sampled from a generative model. However, most existing mesh generators focus on static anatomy, while sequence models often lack explicit periodicity. To this end, we propose 4D F-MeshLDM, a conditional generative framework comprising a convolutional mesh VAE to encode meshes, a structural latent space that parameterises motion using a truncated Fourier series, and a diffusion prior that learns the latent distribution over Fourier coefficient tokens. By conditioning the diffusion process on clinical covariates via affine modulation, we enable controllable synthesis. Sampling tokens and performing inverse Fourier synthesis yield cycle-consistent latent trajectories, which can be decoded into 3D+t cardiac mesh sequences. Experiments on 5,000 UK Biobank subjects demonstrate that 4D F-MeshLDM outperforms state-of-the-art baselines in anatomical fidelity and achieves near-zero cycle closure error. Furthermore, the generated cohorts accurately preserve clinical functional indices, highlighting the potential of our framework for reliable in-silico cardiac trials.

Computational models of the human heart are widely used to study electromechanical and fluid-dynamical cardiac function and to support applications such as in silico clinical trials. However, most studies remain limited to single or patient-specific anatomies, restricting the inclusion of population-level variability required for uncertainty quantification. A key challenge is translating medical-image segmentations, which may contain artifacts, mesh defects or disjoint domains, into topologically coherent geometries suitable for multiphysics simulations. In this work, we present a semi-automatic pipeline that converts CT-based segmentations into simulation-ready cardiac meshes within a few minutes while preserving anatomical and topological consistency. Building on modern deep learning segmentation methods, the framework incorporates a template-based registration stage to regularize artifacts and enforce mesh-quality constraints. A Chamfer-distance morphing strategy deforms a high-quality template toward each segmented heart, matching individual chambers while preserving topology. The resulting meshes are watertight, isotopological, and endowed with consistent point-to-point correspondence. The pipeline is validated on 58 healthy cardiac CT scans, including all cardiac chambers and proximal vessel segments. The resulting meshes can be represented in a unified shape space, enabling the construction of a statistical shape model of the heart and major vessels. Principal Component Analysis shows that a low-dimensional latent space efficiently captures population variability, while Gaussian Mixture Modeling enables synthetic anatomy generation. Overall, the proposed framework (released open-source) provides a pathway from raw segmentations to simulation-ready cardiac geometries, enabling anatomically consistent virtual cohorts for large-scale in silico studies.

Cine cardiac magnetic resonance is the gold standard for assessing cardiac function, but the scarcity of public datasets limits the development of advanced data-driven models. To address this limitation, we propose a generative method for synthesizing temporally coherent and anatomically consistent cardiac sequences. Our text-to-video framework decouples cardiac spatial structure from temporal motion. First, a fine-tuned diffusion model synthesizes an initial frame from a clinical text prompt, controlling anatomical features. Then, a latent flow model conditioned on a cardiac phase embedding generates the complete cardiac motion, ensuring spatial consistency and temporal control. Our model generates anatomically and pathologically diverse sequences with high temporal coherence and strong fidelity to input prompts, achieving a FID of 31.68 for image realism and a CLIP score of 31.04 for text-image alignment. These experimental results highlight its potential to produce high-fidelity, on-demand medical data, offering a scalable solution to data scarcity.