PathCo-LatticE: Pathology-Constrained Lattice-Of Experts Framework for Fully-supervised Few-Shot Cardiac MRI Segmentation

Few-shot learning (FSL) mitigates data scarcity in cardiac MRI segmentation but typically relies on semi-supervised techniques sensitive to domain shifts and validation bias, restricting zero-shot generalizability. We propose PathCo-LatticE, a fully supervised FSL framework that replaces unlabeled data with pathology-guided synthetic supervision. First, our Virtual Patient Engine models continuous latent disease trajectories from sparse clinical anchors, using generative modeling to synthesize physiologically plausible, fully labeled 3D cohorts. Second, Self-Reinforcing Interleaved Validation (SIV) provides a leakage-free protocol that evaluates models online with progressively challenging synthetic samples, eliminating the need for real validation data. Finally, a dynamic Lattice-of-Experts (LoE) organizes specialized networks within a pathology-aware topology and activates the most relevant experts per input, enabling robust zero-shot generalization to unseen data without target-domain fine-tuning. We evaluated PathCo-LatticE in a strict out-of-distribution (OOD) setting, deriving all anchors and severity statistics from a single-source domain (ACDC) and performing zero-shot testing on the multi-center, multi-vendor M&Ms dataset. PathCo-LatticE outperforms four state-of-the-art FSL methods by 4.2-11% Dice starting from only 7 labeled anchors, and approaches fully supervised performance (within 1% Dice) with only 19 labeled anchors. The method shows superior harmonization across four vendors and generalization to unseen pathologies. [Code will be made publicly available].