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Section: Partnerships and Cooperations
National Initiatives
ANR HR-CEM
The project “High Resolution Cardiac Electrophysiology Models: HR-CEM” within the ANR call Modèles Numériques started in November 2013 and will last until November 2017.
It is an international project that involves three partners: Inria (coordinator), IHU LIRYC, and UMI-CRM in Montréal (Canada). The project has external collaborators in Univ. Bordeaux and Univ. Pau.
Based on these collaborations and new developments in structural and functional imaging of the heart available at LIRYC, we plan to reconsider the concepts behind the models in order to improve the accuracy and efficiency of simulations. Cardiac simulation software and high-resolution numerical models will be derived from experimental data from animal models. Validation will be performed by comparing of simulation output with experimentally recorded functional data. The validated numerical models will be made available to the community of researchers who take advantage of in-silico cardiac simulation and, hopefully, become references. In particular we shall provide the first exhaustive model of an animal heart including the four chambers coupled through the special conduction network, with highly detailed microstructure of both the atria and the ventricles. Such a model embedded in high-performance computational software will provide stronger medical foundations for in-silico experimentation, and elucidate mechanisms of cardiac arrhythmias.
ANR Labcom CardioXcomp
We are participant in the ANR Labcom project between Inria and the company Notocord (www.notocord.com). In this project, we propose a mathematical approach for the analysis of drug effects on the electrical activity of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) based on multi-electrode array (MEA) experiments. Our goal is to produce an in-silico tool able to simulate drug actions in MEA/hiPSC-CM assays. The mathematical model takes into account the geometry of the MEA and the electrode properties. The electrical activity of the stem cells at the ion-channel level is governed by a system of ordinary differential equations (ODEs). The ODEs are coupled to the bidomain equations, describing the propagation of the electrical wave in the stem cells preparation. The field potential (FP) measured by the MEA is modeled by the extra-cellular potential of the bidomain equations. First, we propose a strategy allowing us to generate a field potential in good agreement with the experimental data. We show that we are able to reproduce realistic field potentials by introducing different scenarios of heterogeneity in the action potential. This heterogeneity reflects the differentiation atria/ventricles and the age of the cells. Second, we introduce a drug/ion channels interaction based on a pore block model. We conduct different simulations for five drugs (mexiletine, dofetilide, bepridil, ivabradine and BayK). We compare the simulation results with the field potential collected from experimental measurements. Different biomarkers computed on the FP are considered, including depolarization amplitude, repolarization delay, repolarization amplitude and depolarization-repolarization segment. The simulation results show that the model reflect properly the main effects of these drugs on the FP.
REO
The CARMEN team is a partner with the REO team at Inria Paris Rocquencourt and the Notocord company in the CardioXcomp project.
MedicActiv
The CARMEN team cooperates in interaction with the MedicActiV project.
GENCI
GENCI (grand équipement national de calcul intensif) is the agency that grants access to all national high-performance resources for scientific purposes in France. GENCI projects have to be renewed yearly. Our project renewal Interaction between tissue structure and ion-channel function in cardiac arrhythmia, submitted in October 2015, has been granted 9.4 million core-hours on the three major systems Curie, Occigen, and Turing. This compute time, to be used in the calendar year 2016, is primarily destined for our research into the interaction between ionic and structural heart disease in atrial fibrillation, Brugada syndrome, and early repolarisation syndrome [51]. A renewal request has been submitted in October 2016 and was granted with 9.8 million core-hours.