2026
Kelly Zhang Dimitris G Giovanis, Justin Tso
Probabilistic Cardiac Digital Twins for Robust Patient-Specific Modeling Journal Article Forthcoming
In: biorxiv, Forthcoming.
Abstract | Links | BibTeX | Tags: diffusion geometry, digital twins, Machine learning, uncertainty quantification
@article{nokey,
title = {Probabilistic Cardiac Digital Twins for Robust Patient-Specific Modeling},
author = {Dimitris G Giovanis, Kelly Zhang, Justin Tso, Mauro Maggioni, Ioannis G Kevrekidis, Natalia Trayanova},
url = {https://www.biorxiv.org/content/10.64898/2026.05.07.723610v1},
doi = {https://doi.org/10.64898/2026.05.07.723610},
year = {2026},
date = {2026-05-12},
journal = {biorxiv},
abstract = {Uncertainty quantification (UQ) in computational heart models is essential for reliable cardiac digital twins (DTs) in personalized medicine, yet remains challenging. Traditional Monte Carlo and stochastic Galerkin methods often become impractical in the high-dimensional, nonlinear state variable and parameter spaces of cardiac electrophysiology and mechanics. This article introduces a framework for learning a joint probability density over cardiac observables and model parameters, enabling the characterization of statistical dependencies across a large number of variables in patient-specific cardiac DTs. By sampling from this density and conditioning on available data, useful predictive distributions can be constructed, allowing uncertainty to be propagated through the model and quantified in terms of variability. Conditional regression can then be performed directly on this learned density, enabling systematic exploration of interdependencies among observables for both predictive inference and model design. The statistical methodology adopts a geometry-aware generative learning framework, recently introduced by the authors, that decouples the learning of data geometry from sampling. First it identifies a low-dimensional latent representation that captures the intrinsic structure of the data and its multiscale geometric features. A stochastic differential equation is then formulated directly in the low-dimensional latent space to generate samples efficiently; these are subsequently mapped back to the high-dimensional space of cardiac states and parameters through a smooth lifting operator. We demonstrate the approach on a ventricular arrhythmia prediction benchmark, where the learned joint probability density enables the construction of predictive distributions over key parameters (e.g., conductivities, fibrosis patterns) through sampling and conditioning. This enables uncertainty to be propagated and quantified through sampling and conditioning on the learned joint density, with substantially fewer model evaluations than conventional UQ methods.},
keywords = {diffusion geometry, digital twins, Machine learning, uncertainty quantification},
pubstate = {forthcoming},
tppubtype = {article}
}
Uncertainty quantification (UQ) in computational heart models is essential for reliable cardiac digital twins (DTs) in personalized medicine, yet remains challenging. Traditional Monte Carlo and stochastic Galerkin methods often become impractical in the high-dimensional, nonlinear state variable and parameter spaces of cardiac electrophysiology and mechanics. This article introduces a framework for learning a joint probability density over cardiac observables and model parameters, enabling the characterization of statistical dependencies across a large number of variables in patient-specific cardiac DTs. By sampling from this density and conditioning on available data, useful predictive distributions can be constructed, allowing uncertainty to be propagated through the model and quantified in terms of variability. Conditional regression can then be performed directly on this learned density, enabling systematic exploration of interdependencies among observables for both predictive inference and model design. The statistical methodology adopts a geometry-aware generative learning framework, recently introduced by the authors, that decouples the learning of data geometry from sampling. First it identifies a low-dimensional latent representation that captures the intrinsic structure of the data and its multiscale geometric features. A stochastic differential equation is then formulated directly in the low-dimensional latent space to generate samples efficiently; these are subsequently mapped back to the high-dimensional space of cardiac states and parameters through a smooth lifting operator. We demonstrate the approach on a ventricular arrhythmia prediction benchmark, where the learned joint probability density enables the construction of predictive distributions over key parameters (e.g., conductivities, fibrosis patterns) through sampling and conditioning. This enables uncertainty to be propagated and quantified through sampling and conditioning on the learned joint density, with substantially fewer model evaluations than conventional UQ methods.
- Lectures at Summer School at Peking University, July 2017.
- PCMI Lectures, Summer 2016: Lecture 1, Lecture 2, Problems/discussion points
- Google Scholar
- Papers on the ArXiv
- Papers on MathsciNet
- Tutorials on diffusion geometry and multiscale analysis on graphs at the MRA Internet Program at IPAM: Part I and Part II.
- Diffusion Geometries, Diffusion Wavelets and Harmonic Analysis of large data sets, IPAM, Multiscale Geometric Analysis Program, Fall 2004.
- Diffusion Geometries, global and multiscale, IPAM, 2005.