OpenCMISS: A multi-physics & multi-scale computational infrastructure for the VPH/Physiome project
The VPH/Physiome Project is developing the model encoding standards CellML (cellml.org) and FieldML (fieldml.org) as well as web-accessible model repositories based on these standards (models.physiome.org). Freely available open source computational modelling software is also being developed to solve the partial differential equations described by the models and to visualise results. The OpenCMISS code (opencmiss.org), described here, has been developed by the authors over the last six years to replace the CMISS code that has supported a number of organ system Physiome projects. OpenCMISS is designed to encompass multiple sets of physical equations and to link subcellular and tissue-level b…
Sensitivity analysis of mesh warping and subsampling strategies for generating large scale electrophysiological simulation data
The analysis of large-scale simulation data from virtual populations can be effective to gain computational insight into disease mechanisms and treatment strategies, which can serve for generating hypotheses for and focusing subsequent clinical trials. This can be instrumental in shortening the critical path in medical product development and more cost-effective clinical trials. A previously published pipeline established point correspondence among volumetric meshes to enable meaningful statistics on cardiac electrophysiological simulations on the anatomical distribution of a large-scale virtual population. Thin Plate Splines (TPS), derived from surface deformations, were used to warp a tem…
Personalization of Fast Conduction Purkinje System in Eikonal-Based Electrophysiological Models with Optical Mapping Data
We present a pipeline for the personalization of model-based Purkinje fast conduction system using fast electrophysiological models and optical mapping data acquired from ex-vivo porcine hearts. The regional density of the Purkinje terminals as well as the latest endocardial activation time were the parameters personalized in an iterative procedure maximizing the similarity between the outcome of the electrophysiological simulations and measurements obtained from optical mapping data. We used a fast wave-front Eikonal-based electrophysiological model that generated the depolarization time maps that were subsequently compared with measurements at each iteration of the optimization stage. The…
An atlas- and data-driven approach to initializing reaction-diffusion systems in computer cardiac electrophysiology
The cardiac electrophysiology (EP) problem is governed by a nonlinear anisotropic reaction-diffusion system with a very rapidly varying reaction term associated with the transmembrane cell current. The nonlinearity associated with the cell models requires a stabilization process before any simulation is performed. More importantly, when used in a 3-dimensional (3D) anatomy, it is not sufficient to perform this stabilization on the basis of isolated cells only, since the coupling of the different cells through the tissue greatly modulates the dynamics of the system. Therefore, stabilization of the system must be performed on the entire 3D model. This work develops a novel procedure for the i…
Inter-Model Consistency and Complementarity: Learning from ex-vivo Imaging and Electrophysiological Data towards an Integrated Understanding of Cardiac Physiology
International audience; Computational models of the heart at various scales and levels of complexity have been independently developed, parameterised and validated using a wide range of experimental data for over four decades. However, despite remarkable progress, the lack of coordinated efforts to compare and combine these computational models has limited their impact on the numerous open questions in cardiac physiology. To address this issue, a comprehensive dataset has previously been made available to the community that contains the cardiac anatomy and fibre orientations from magnetic resonance imaging as well as epicardial transmembrane potentials from optical mapping measured on a per…
Effect of Scar Development on Fast Electrophysiological Models of the Human Heart: In-Silico Study on Atlas-Based Virtual Populations
The main goal of this work is to study the effect of scar development in the electrophysiological function of the human left ventricle by statistically analyzing large-scale simulation data including hypertrophic and dilated hearts. Electrophysiological simulations are obtained by solving the classical Eikonal equation in both the ventricular tissue and a customized Purkinje system. This Purkinje system is obtained assuming a geodesic rule to connect different Purkinje-myocardial junctions into a tree-like structure. Infarction shape and function is modeled with taking into account the occlusion in coronary arteries. Infarct, core and border zones of the scar are estimated by calculating bl…
Towards High Resolution Computational Models of the Cardiac Conduction System: A Pipeline for Characterization of Purkinje-Ventricular-Junctions
The cardiac conduction system (CCS) has been in the spot light of the clinical and modeling community in recent years because of its fundament role in physiology and pathophysiology of the heart. Experimental research has focused mainly on investigating the electrical properties of the Purkinje-ventricular-junctions (PVJs). The structure of the PVJs has only been described through schematic drawings but not thoroughly studied. In this work confocal microscopy was used with the aim of three-dimensional characterization of PVJs. Adult rabbit hearts were labeled with fluorescent dyes, imaged with confocal microscopy and Purkinje fibers differentiated from other cardiac tissue by their lack of …
Atlas construction and image analysis using statistical cardiac models
International audience; This paper presents a brief overview of current trends in the construction of population and multi-modal heart atlases in our group and their application to atlas-based cardiac image analysis. The technical challenges around the construction of these atlases are organized around two main axes: groupwise image registration of anatomical, motion and fiber images and construction of statistical shape models. Application-wise, this paper focuses on the extraction of atlas-based biomarkers for the detection of local shape or motion abnormalities, addressing several cardiac applications where the extracted information is used to study and grade different pathologies. The p…
Flexible modeling for anatomically-based cardiac conduction system construction.
We present a method to automatically deploy the peripheral section of the cardiac conduction system in ventricles. The method encodes anatomical information thorough rules that ensure that Purkinje network structures generated are realistic and comparable to those observed in ex-vivo studies. The core methodology is based in non-deterministic production rules that are parameterized by means of statistical functions. Input parameters allow the construction of a great diversity of Purkinje structures that could be incorporated in fine element ventricular models to perform electrophysiology simulations. Resulting Purkinje trees show good geometrical approximations of Purkinje core network and …
Influence of geometric variations on LV activation times: A study on an atlas-based virtual population
We present the fully automated pipeline we have developed to obtain electrophysiological simulations of the heart on a large atlas-based virtual population. This virtual population was generated from a statistical model of left ventricular geometry, represented by a surface model. Correspondence between tetrahedralized volumetric meshes was obtained using Thin Plate Spline warps. Simulations are based on the fast solving of Eikonal equations, and stimulation sites correspond to physiological activation. We report variations of total activation time introduced by geometry, as well as variations in the location of last activation. The obtained results suggest that the total activation time ha…