Flow-based conditional cardiac anatomy generation for virtual cohorts
Cardiac digital twin research is moving from subject-specific anatomical replicas toward virtual cohorts that represent clinically relevant population subgroups. Yet access to representative imaging-derived anatomy datasets remains limited by cohort size, subgroup sparsity, and data-sharing constraints. Conditional generative models could help address this gap, but virtual cohorts are useful only if they preserve realistic, metadata-dependent anatomical variability. Existing cardiac anatomy generators largely rely on conditional variational autoencoders (cVAEs), which couple representation learning and metadata conditioning through a shared regularized latent prior. We introduce CAN-FLOW, a two-step Conditional ANatomy generation framework based on normalizing FLOWs that first learns geometry-only latent representations of diffeomorphic cardiac shape momenta and then models their sex-, age-, and body-mass-index-dependent distribution with a conditional normalizing flow. We trained CAN-FLOW on 2,208 healthy UK Biobank subjects and compared it with cVAEs across regularization strengths. CAN-FLOW generated plausible stochastic biventricular anatomies that better reproduced clinical phenotype distributions, metadata-dependent trends, subgroup variability, point-cloud coverage, and high-dimensional shape variability. Together, these results establish CAN-FLOW as a shareable framework for generating realistic, stochastically varying, metadata-conditioned biventricular anatomies for virtual cohort construction and in silico clinical trial workflows.