Yubo Ye

Ziqi Zhou, Yubo Ye, Sumeet Atul Vadhavka et al.

Building personalized cardiac electrophysiology (EP) digital twins requires identifying the appropriate model structure for each patient, not merely fitting parameters. Traditional methods rely on experts to manually prescribe hybrid physics-neural architectures, which requires deep domain expertise and does not transfer across patients. Recent works have applied large language models (LLMs) to generate or act as hybrid models. However, despite their promising generalization capacity, these LLM-based methods lack the structural priors needed for stable cardiac simulations. Hence, we propose LEADS, a framework that formulates cardiac EP domain knowledge as a structured action space and utilizes an LLM agent to discover hybrid models. The agent follows an iterative reasoning-and-action loop to select, combine, and refine hybrid models, whilst gradient descent handles parameter fitting. The proposed LEADS designs every candidate model towards physically grounded, interpretable, and numerically stable, while allowing open-ended architectural discovery. We validate LEADS on synthetic data with three ground-truth reaction models and on real cardiac EP data, demonstrating that it outperforms both human-designed hybrid models and other LLM-based hybrid modeling.

Casey Meisenzahl, Jon Heiselman, Michael Holtz et al.

Accurate intraoperative liver registration is challenging due to substantial soft-tissue deformation yet sparse intraoperative measurements. Biomechanical models regularize this ill-posedness with prior knowledge but exhibit persistent prediction bias due to simplifying assumptions, while data-driven learning solutions struggle with data efficiency, generalization, and physical plausibility. We propose a hybrid registration framework that adapts a biomechanical prior using sparse intraoperative correspondences. Rather than learning a full deformation field, we learn a residual deformation function that corrects linear biomechanical predictions, modeled as a graph neural diffusion function with geometry-aware attention over the 3D liver mesh. To enable long-range information transfer of sparse observations, we take a novel perspective of sparse intraoperative measurements as \textit{context} samples where input-output pairs of the residual deformation function are fully observed, casting the problem into learning-to-learn this residual function from intraoperative context samples with feedforward meta-learners. Experiments on a deformable liver phantom dataset demonstrate improved registration accuracy and generalization compared to rigid, biomechanical, and data-driven baselines, particularly for out-of-distribution geometries and deformations.

Sumeet Vadhavkar, Xiajun Jiang, Yubo Ye et al.

A digital twin (DT) of a patient-specific heart offers significant potential in personalized medicine. However, its rapid and dynamic adaptation to an individual's live data and its predictive capability after adaptation remains central challenges. We examine this challenge from its two building blocks: DT formulation where mechanistic and data-driven models show competing merits and limitations, and DT optimization strategies that are largely driven by a reconstruction objective leading to un-identifiable models. We address both bottlenecks via HAPI -- an AI framework for building hybrid, adaptive, and predictive DTs with three key enablers. First, HAPI constructs a physics-integrated gray-box model in which an interpretable mechanistic backbone is augmented by a neural component that models its residual to the observed data. Second, rather than attempting to pre-encode all possible variations in a static hybrid model, HAPI enables rapid on-the-fly adaptation of the hybrid model to few-shot live data, achieved by feedforward meta-learners realizing amortized inference of both mechanistic and neural parameters of the hybrid model trained with predictive objectives. Finally, we show that this adaptivity corresponds to the construction of a conditional generative model (i.e., the hybrid DT) that endows it with theoretical identifiability and thus strong performance in predictive scenarios. We demonstrate the proof-of-concept of HAPI in cardiac electrophysiology using a hybrid monodomain model with mechanistic reaction kinetics and neural graph diffusion. Across synthetic and real-data studies, we show that HAPI's mechanistic-neural hybridization and predictive adaptation are critical for obtaining identifiable DTs with strong predictive and out-of-distribution capabilities.

Xiajun Jiang, Sumeet Vadhavkar, Yubo Ye et al.

Personalized virtual heart models have demonstrated increasing potential for clinical use, although the estimation of their parameters given patient-specific data remain a challenge. Traditional physics-based modeling approaches are computationally costly and often neglect the inherent structural errors in these models due to model simplifications and assumptions. Modern deep learning approaches, on the other hand, rely heavily on data supervision and lacks interpretability. In this paper, we present a novel hybrid modeling framework to describe a personalized cardiac digital twin as a combination of a physics-based known expression augmented by neural network modeling of its unknown gap to reality. We then present a novel meta-learning framework to enable the separate identification of both the physics-based and neural components in the hybrid model. We demonstrate the feasibility and generality of this hybrid modeling framework with two examples of instantiations and their proof-of-concept in synthetic experiments.

Yubo Ye, Sumeet Vadhavkar, Xiajun Jiang et al.

Modern applications increasingly require unsupervised learning of latent dynamics from high-dimensional time-series. This presents a significant challenge of identifiability: many abstract latent representations may reconstruct observations, yet do they guarantee an adequate identification of the governing dynamics? This paper investigates this challenge from two angles: the use of physics inductive bias specific to the data being modeled, and a learn-to-identify strategy that separates forecasting objectives from the data used for the identification. We combine these two strategies in a novel framework for unsupervised meta-learning of hybrid latent dynamics (Meta-HyLaD) with: 1) a latent dynamic function that hybridize known mathematical expressions of prior physics with neural functions describing its unknown errors, and 2) a meta-learning formulation to learn to separately identify both components of the hybrid dynamics. Through extensive experiments on five physics and one biomedical systems, we provide strong evidence for the benefits of Meta-HyLaD to integrate rich prior knowledge while identifying their gap to observed data.