3D virtual human atria: A computational platform for studying clinical atrial fibrillation

Abstract

Despite a vast amount of experimental and clinical data on the underlying ionic, cellular and tissue substrates, the mechanisms of common atrial arrhythmias (such as atrial fibrillation, AF) arising from the functional interactions at the whole atria level remain unclear. Computational modelling provides a quantitative framework for integrating such multi-scale data and understanding the arrhythmogenic behaviour that emerges from the collective spatio-temporal dynamics in all parts of the heart. In this study, we have developed a multi-scale hierarchy of biophysically detailed computational models for the human atria--the 3D virtual human atria. Primarily, diffusion tensor MRI reconstruction of the tissue geometry and fibre orientation in the human sinoatrial node (SAN) and surrounding atrial muscle was integrated into the 3D model of the whole atria dissected from the Visible Human dataset. The anatomical models were combined with the heterogeneous atrial action potential (AP) models, and used to simulate the AP conduction in the human atria under various conditions: SAN pacemaking and atrial activation in the normal rhythm, break-down of regular AP wave-fronts during rapid atrial pacing, and the genesis of multiple re-entrant wavelets characteristic of AF. Contributions of different properties of the tissue to mechanisms of the normal rhythm and arrhythmogenesis were investigated. Primarily, the simulations showed that tissue heterogeneity caused the break-down of the normal AP wave-fronts at rapid pacing rates, which initiated a pair of re-entrant spiral waves; and tissue anisotropy resulted in a further break-down of the spiral waves into multiple meandering wavelets characteristic of AF. The 3D virtual atria model itself was incorporated into the torso model to simulate the body surface ECG patterns in the normal and arrhythmic conditions. Therefore, a state-of-the-art computational platform has been developed, which can be used for studying multi-scale electrical phenomena during atrial conduction and AF arrhythmogenesis. Results of such simulations can be directly compared with electrophysiological and endocardial mapping data, as well as clinical ECG recordings. The virtual human atria can provide in-depth insights into 3D excitation propagation processes within atrial walls of a whole heart in vivo, which is beyond the current technical capabilities of experimental or clinical set-ups.

A novel computational sheep atria model for the study of atrial fibrillation

“…It adds support to the conclusions of the studies of Aslanidi et al [20,21] in showing the important role of electrical heterogeneity and anisotropy in AF genesis. But the current study is distinct from those previous computational studies [20,21] as the present study focuses on the role of electrical heterogeneity and anisotropy in the initiation of AF in the PV region, rather than in the junction of the PM and CT [20]. In the study of Aslanidi et al [21], simulations were carried out in a model of human atria that implemented rule-based fibre orientation, not anatomically accurate structure determined from experimental reconstruction.…”

“…But the current study is distinct from those previous computational studies [20,21] as the present study focuses on the role of electrical heterogeneity and anisotropy in the initiation of AF in the PV region, rather than in the junction of the PM and CT [20]. In the study of Aslanidi et al [21], simulations were carried out in a model of human atria that implemented rule-based fibre orientation, not anatomically accurate structure determined from experimental reconstruction. The present study is, therefore, the first computational study that investigates the development of AF using an anatomically detailed model that includes heterogeneous electrophysiologically detailed cell models.…”

“…However, it is possible to validate the three-dimensional model based on experimental conduction velocity measurements. Simulated conduction velocities in the atria are between 0.8 and 1.5 m s 21 , with the fastest conduction being seen along BB. These results are consistent with experimental conduction velocity measurements from sheep atria [22,30,31].…”

Antenatal architecture and activity of the human heart

“…Detailed models of human cardiomyocytes have been constructed for pacemaking [5], atrial [6] and ventricular cells [4,7], and been embedded into tissue architecture and organ models based on post-mortem anatomy and architecture [8,9], or atlases of cardiac anatomy [10]. Patient-specific modelling is becoming technically possible.…”

Three-dimensional Multiscale Modelling and Simulation of Atria and Torso Electrophysiology

“…Detailed electrophysiology cell models have been developed to describe the voltage-and timedependent currents, in human atrial cells (Courtemanche et al 1998;Nygren et al 2001;Maleckar et al 2009) and in human SAN cells (Chandler et al 2011). Those models have been integrated into tissue models of the human atria based on partial descriptions from animal experiments and clinical data to reproduce specific AF patterns (Harrild & Henriquez 2000;Seemann et al 2006;Tobón et al 2008;Aslanidi et al 2011;Tobón et al 2013). To study the spatiotemporal organization of atrial arrhythmias, different techniques are being used, including the analysis of the electrogram morphology, dominant frequency and regularity or organization index (Tobón et al 2012).…”