HyPer-EP: Meta-Learning Hybrid Personalized Models for Cardiac Electrophysiology

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.

Interpretable Modeling and Reduction of Unknown Errors in Mechanistic Operators

Prior knowledge about the imaging physics provides a mechanistic forward operator that plays an important role in image reconstruction, although myriad sources of possible errors in the operator could negatively impact the reconstruction solutions. In this work, we propose to embed the traditional mechanistic forward operator inside a neural function, and focus on modeling and correcting its unknown errors in an interpretable manner. This is achieved by a conditional generative model that transforms a given mechanistic operator with unknown errors, arising from a latent space of self-organizing clusters of potential sources of error generation. Once learned, the generative model can be used in place of a fixed forward operator in any traditional optimization-based reconstruction process where, together with the inverse solution, the error in prior mechanistic forward operator can be minimized and the potential source of error uncovered. We apply the presented method to the reconstruction of heart electrical potential from body surface potential. In controlled simulation experiments and in-vivo real data experiments, we demonstrate that the presented method allowed reduction of errors in the physics-based forward operator and thereby delivered inverse reconstruction of heart-surface potential with increased accuracy.

Neural State-Space Modeling with Latent Causal-Effect Disentanglement

Despite substantial progress in deep learning approaches to time-series reconstruction, no existing methods are designed to uncover local activities with minute signal strength due to their negligible contribution to the optimization loss. Such local activities however can signify important abnormal events in physiological systems, such as an extra foci triggering an abnormal propagation of electrical waves in the heart. We discuss a novel technique for reconstructing such local activity that, while small in signal strength, is the cause of subsequent global activities that have larger signal strength. Our central innovation is to approach this by explicitly modeling and disentangling how the latent state of a system is influenced by potential hidden internal interventions. In a novel neural formulation of state-space models (SSMs), we first introduce causal-effect modeling of the latent dynamics via a system of interacting neural ODEs that separately describes 1) the continuous-time dynamics of the internal intervention, and 2) its effect on the trajectory of the system's native state. Because the intervention can not be directly observed but have to be disentangled from the observed subsequent effect, we integrate knowledge of the native intervention-free dynamics of a system, and infer the hidden intervention by assuming it to be responsible for differences observed between the actual and hypothetical intervention-free dynamics. We demonstrated a proof-of-concept of the presented framework on reconstructing ectopic foci disrupting the course of normal cardiac electrical propagation from remote observations.