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      Deep learning-based reduced order models in cardiac electrophysiology

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          Abstract

          Predicting the electrical behavior of the heart, from the cellular scale to the tissue level, relies on the numerical approximation of coupled nonlinear dynamical systems. These systems describe the cardiac action potential, that is the polarization/depolarization cycle occurring at every heart beat that models the time evolution of the electrical potential across the cell membrane, as well as a set of ionic variables. Multiple solutions of these systems, corresponding to different model inputs, are required to evaluate outputs of clinical interest, such as activation maps and action potential duration. More importantly, these models feature coherent structures that propagate over time, such as wavefronts. These systems can hardly be reduced to lower dimensional problems by conventional reduced order models (ROMs) such as, e.g., the reduced basis method. This is primarily due to the low regularity of the solution manifold (with respect to the problem parameters), as well as to the nonlinear nature of the input-output maps that we intend to reconstruct numerically. To overcome this difficulty, in this paper we propose a new, nonlinear approach relying on deep learning (DL) algorithms—such as deep feedforward neural networks and convolutional autoencoders—to obtain accurate and efficient ROMs, whose dimensionality matches the number of system parameters. We show that the proposed DL-ROM framework can efficiently provide solutions to parametrized electrophysiology problems, thus enabling multi-scenario analysis in pathological cases. We investigate four challenging test cases in cardiac electrophysiology, thus demonstrating that DL-ROM outperforms classical projection-based ROMs.

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          Most cited references28

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          Impulses and Physiological States in Theoretical Models of Nerve Membrane

          Van der Pol's equation for a relaxation oscillator is generalized by the addition of terms to produce a pair of non-linear differential equations with either a stable singular point or a limit cycle. The resulting "BVP model" has two variables of state, representing excitability and refractoriness, and qualitatively resembles Bonhoeffer's theoretical model for the iron wire model of nerve. This BVP model serves as a simple representative of a class of excitable-oscillatory systems including the Hodgkin-Huxley (HH) model of the squid giant axon. The BVP phase plane can be divided into regions corresponding to the physiological states of nerve fiber (resting, active, refractory, enhanced, depressed, etc.) to form a "physiological state diagram," with the help of which many physiological phenomena can be summarized. A properly chosen projection from the 4-dimensional HH phase space onto a plane produces a similar diagram which shows the underlying relationship between the two models. Impulse trains occur in the BVP and HH models for a range of constant applied currents which make the singular point representing the resting state unstable.
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            Whole-heart modeling: applications to cardiac electrophysiology and electromechanics.

            Recent developments in cardiac simulation have rendered the heart the most highly integrated example of a virtual organ. We are on the brink of a revolution in cardiac research, one in which computational modeling of proteins, cells, tissues, and the organ permit linking genomic and proteomic information to the integrated organ behavior, in the quest for a quantitative understanding of the functioning of the heart in health and disease. The goal of this review is to assess the existing state-of-the-art in whole-heart modeling and the plethora of its applications in cardiac research. General whole-heart modeling approaches are presented, and the applications of whole-heart models in cardiac electrophysiology and electromechanics research are reviewed. The article showcases the contributions that whole-heart modeling and simulation have made to our understanding of the functioning of the heart. A summary of the future developments envisioned for the field of cardiac simulation and modeling is also presented. Biophysically based computational modeling of the heart, applied to human heart physiology and the diagnosis and treatment of cardiac disease, has the potential to dramatically change 21st century cardiac research and the field of cardiology.
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              Non-intrusive reduced order modeling of nonlinear problems using neural networks

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                Author and article information

                Contributors
                Role: ConceptualizationRole: Formal analysisRole: InvestigationRole: MethodologyRole: SoftwareRole: ValidationRole: VisualizationRole: Writing – original draft
                Role: ConceptualizationRole: MethodologyRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: SupervisionRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                2020
                1 October 2020
                : 15
                : 10
                : e0239416
                Affiliations
                [1 ] MOX - Dipartimento di Matematica, Politecnico di Milano, Milano, Italy
                [2 ] Mathematics Institute, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
                Queensland University of Technology, AUSTRALIA
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0001-8599-6588
                Article
                PONE-D-20-17553
                10.1371/journal.pone.0239416
                7529269
                33002014
                dde69610-c06f-4831-8cf8-cdc758bdd49a
                © 2020 Fresca et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 9 June 2020
                : 6 September 2020
                Page count
                Figures: 18, Tables: 4, Pages: 32
                Funding
                Funded by: H2020-EU.1.1.
                Award ID: ERC2016AdG, project ID: 740132
                Award Recipient :
                - A. Q. - ERC Advanced Grant iHEART (ERC2016AdG, project ID: 740132) - H2020-EU.1.1. - cordis.europa.eu/project/id/740132 - The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Computer and Information Sciences
                Systems Science
                Dynamical Systems
                Physical Sciences
                Mathematics
                Systems Science
                Dynamical Systems
                Research and Analysis Methods
                Bioassays and Physiological Analysis
                Electrophysiological Techniques
                Cardiac Electrophysiology
                Computer and Information Sciences
                Systems Science
                Nonlinear Systems
                Physical Sciences
                Mathematics
                Systems Science
                Nonlinear Systems
                Computer and Information Sciences
                Systems Science
                Nonlinear Dynamics
                Physical Sciences
                Mathematics
                Systems Science
                Nonlinear Dynamics
                Biology and Life Sciences
                Physiology
                Electrophysiology
                Membrane Potential
                Action Potentials
                Biology and Life Sciences
                Physiology
                Electrophysiology
                Neurophysiology
                Action Potentials
                Biology and Life Sciences
                Neuroscience
                Neurophysiology
                Action Potentials
                Computer and Information Sciences
                Neural Networks
                Biology and Life Sciences
                Neuroscience
                Neural Networks
                Biology and Life Sciences
                Physiology
                Electrophysiology
                Membrane Potential
                Biology and Life Sciences
                Neuroscience
                Cognitive Science
                Cognitive Psychology
                Learning
                Biology and Life Sciences
                Psychology
                Cognitive Psychology
                Learning
                Social Sciences
                Psychology
                Cognitive Psychology
                Learning
                Biology and Life Sciences
                Neuroscience
                Learning and Memory
                Learning
                Custom metadata
                The code used in this work is publicly available on GitHub ( https://github.com/stefaniafresca/DL-ROM). The training and testing datasets are available on Zenodo ( doi.org/10.5281/zenodo.4022140).

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