Chaste: an open source C++ library for computational physiology and biology

Chaste - Cancer, Heart And Soft Tissue Environment - is an open source C++ library for the computational simulation of mathematical models developed for physiology and biology. Code development has been driven by two initial applications: cardiac electrophysiology and cancer development. A large number of cardiac electrophysiology studies have been enabled and performed, including high performance computational investigations of defibrillation on realistic human cardiac geometries. New models for the initiation and growth of tumours have been developed. In particular, cell-based simulations have provided novel insight into the role of stem cells in the colorectal crypt. Chaste is constantly evolving and is now being applied to a far wider range of problems. The code provides modules for handling common scientific computing components, such as meshes and solvers for ordinary and partial differential equations (ODEs/PDEs). Re-use of these components avoids the need for researchers to "re-invent the wheel" with each new project, accelerating the rate of progress in new applications. Chaste is developed using industrially-derived techniques, in particular test-driven development, to ensure code quality, re-use and reliability. In this article we provide examples that illustrate the types of problems Chaste can be used to solve, which can be run on a desktop computer. We highlight some scientific studies that have used or are using Chaste, and the insights they have provided. The source code, both for specific releases and the development version, is available to download under an open source Berkeley Software Distribution (BSD) licence at http://www.cs.ox.ac.uk/chaste, together with details of a mailing list and links to documentation and tutorials

3D finite element electrical model of larval zebrafish ECG signals

Assessment of heart function in zebrafish larvae using electrocardiography (ECG) is a potentially useful tool in developing cardiac treatments and the assessment of drug therapies. In order to better understand how a measured ECG waveform is related to the structure of the heart, its position within the larva and the position of the electrodes, a 3D model of a 3 days post fertilisation (dpf) larval zebrafish was developed to simulate cardiac electrical activity and investigate the voltage distribution throughout the body. The geometry consisted of two main components; the zebrafish body was modelled as a homogeneous volume, while the heart was split into five distinct regions (sinoatrial region, atrial wall, atrioventricular band, ventricular wall and heart chambers). Similarly, the electrical model consisted of two parts with the body described by Laplace’s equation and the heart using a bidomain ionic model based upon the Fitzhugh-Nagumo equations. Each region of the heart was differentiated by action potential (AP) parameters and activation wave conduction velocities, which were fitted and scaled based on previously published experimental results. ECG measurements in vivo at different electrode recording positions were then compared to the model results. The model was able to simulate action potentials, wave propagation and all the major features (P wave, R wave, T wave) of the ECG, as well as polarity of the peaks observed at each position. This model was based upon our current understanding of the structure of the normal zebrafish larval heart. Further development would enable us to incorporate features associated with the diseased heart and hence assist in the interpretation of larval zebrafish ECGs in these conditions

Effects of amiodarone on short QT syndrome variant 3 in human ventricles: a simulation study.

Background Short QT syndrome (SQTS) is a newly identified clinical disorder associated with atrial and/or ventricular arrhythmias and increased risk of sudden cardiac death (SCD). The SQTS variant 3 is linked to D172N mutation to the KCNJ2 gene that causes a gain-of-function to the inward rectifier potassium channel current (I K1), which shortens the ventricular action potential duration (APD) and effective refractory period (ERP). Pro-arrhythmogenic effects of SQTS have been characterized, but less is known about the possible pharmacological treatment of SQTS. Therefore, in this study, we used computational modeling to assess the effects of amiodarone, class III anti-arrhythmic agent, on human ventricular electrophysiology in SQT3. Methods The ten Tusscher et al. model for the human ventricular action potentials (APs) was modified to incorporate I K1 formulations based on experimental data of Kir2.1 channels (including WT, WT-D172N and D172N conditions). The modified cell model was then implemented to construct one-dimensional (1D) and 2D tissue models. The blocking effects of amiodarone on ionic currents were modeled using IC50 and Hill coefficient values from literatures. Effects of amiodarone on APD, ERP and pseudo-ECG traces were computed. Effects of the drug on the temporal and spatial vulnerability of ventricular tissue to genesis and maintenance of re-entry were measured, as well as on the dynamic behavior of re-entry. Results Amiodarone prolonged the ventricular cell APD and decreased the maximal voltage heterogeneity (δV) among three difference cells types across transmural ventricular wall, leading to a decreased transmural heterogeneity of APD along a 1D model of ventricular transmural strand. Amiodarone increased cellular ERP, prolonged QT interval and decreased the T-wave amplitude. It reduced tissue’s temporal susceptibility to the initiation of re-entry and increased the minimum substrate size necessary to sustain re-entry in the 2D tissue. Conclusions At the therapeutic-relevant concentration of amiodarone, the APD and ERP at the single cell level were increased significantly. The QT interval in pseudo-ECG was prolonged and the re-entry in tissue was prevented. This study provides further evidence that amiodarone may be a potential pharmacological agent for preventing arrhythmogenesis for SQT3 patients

Azimuthal decomposition study of a realistic laser profile for efficient modeling of Laser WakeField Acceleration

Abstract The advent of ultra short high intensity lasers has paved the way to new and promising, yet challenging, areas of research in the laser-plasma interaction physics. The success of constructing petawatt femtosecond lasers, for instance the Apollon laser in France, will help understanding and designing future particle accelerators and next generation of light sources. Achieving this goal intrinsically relies on the combination between experiments and massively parallel simulations. So far, Particle-In-Cell (PIC) codes have been the ultimate tool to accurately describe the laser-plasma interaction especially in the field of Laser WakeField Acceleration (LWFA). Nevertheless, the numerical modelling of laser plasma accelerators in 3D can be a very challenging task. This is due to the large dispersity between the scales involved in this process. In order to make such simulations feasible with a significant speed up, we need to use reduced numerical models which simplify the problem while retaining a high fidelity. Among these models, Fourier field decomposition in azimuthal modes for the cylindrical geometry [1] is a promising reduced model especially for physical problems that have close to cylindrical symmetry which is the case in LWFA. This geometry has been implemented in the open-source code SMILEI [2] in Finite Difference Time Domain (FDTD) discretization scheme for the Maxwell solver. In this paper we will study the case of a realistic laser measurement from Apollon facility, the ability of this method to describe it correctly and the determination of the necessary number of modes for this purpose. We will also show the importance of higher modes inclusion in the case of realistic laser profiles to insure fidelity in simulation.</jats:p

Efficient cylindrical envelope modeling for laser wakefield acceleration

Abstract The resolution of the system given by Maxwell’s equations and Vlasov equation in three dimensions can describe all the phenomena of interest for laser wakefield acceleration, with few exceptions (e.g. ionization). Such arduous task can be numerically completed using Particle in Cell (PIC) codes, where the plasma is sampled by an ensemble of macroparticles and the electromagnetic fields are defined on a computational grid. However, the resulting three dimensional PIC simulations require substantial resources and often yield a larger amount of information than the one necessary to study a particular aspect of a phenomenon. Reduced models, i.e. models of the Maxwell-Vlasov system taking into account approximations and symmetries, are thus of fundamental importance for preliminary studies and parametric scans. In this work, the implementation of one of these models in the code SMILEI, an envelope description of the laser-plasma interaction with cylindrical symmetry, is described.</jats:p