Cardiac digital twins (Cardiac Digital Twin (CDT)s) of human electrophysiology (Electrophysiology... more Cardiac digital twins (Cardiac Digital Twin (CDT)s) of human electrophysiology (Electrophysiology (EP)) are digital replicas of patient hearts derived from clinical data that match like-for-like all available clinical observations. Due to their inherent predictive potential, CDTs show high promise as a complementary modality aiding in clinical decision making and also in the cost-effective, saf e and ethical testing of novel EP device therapies. However, current workflows for both the anatomical and functional twinning phases within CDT generation, referring to the inference of model anatomy and parameters from clinical data, are not sufficiently efficient, robust and accurate for advanced clinical and industrial applications. Our study addresses three primary limitations impeding the routine generation of high-fidelity CDTs by introducing; a comprehensive parameter vector encapsulating all factors relating to the ventricular EP; an abstract reference frame within the model allowing the unattended manipulation of model parameter fields; a novel fast-forward electrocardiogram (Electrocardiogram (ECG)) model for efficient and biophysically-detailed simulation required for parameter inference. A novel workflow for the generation of CDTs is then introduced as an initial proof of concept. Anatomical twinning was performed within a reasonable time compatible with clinical workflows (< 4h) for 12 subjects from clinically-attained magnetic resonance images. After assessment of the underlying fast forward ECG model against a gold standard bidomain ECG model, functional twinning of optimal parameters according to a clinically-attained 12 lead ECG was then performed using a forward Saltelli sampling approach for a single subject. The achieved results in terms of efficiency and fidelity demonstrate that our workflow is well-suited and viable for generating biophysically-detailed CDTs at scale.
If citing, it is advised that you check and use the publisher's definitive version for pagination... more If citing, it is advised that you check and use the publisher's definitive version for pagination, volume/issue, and date of publication details. And where the final published version is provided on the Research Portal, if citing you are again advised to check the publisher's website for any subsequent corrections.
Biophysical models of the atrium provide a physically constrained framework for describing the cu... more Biophysical models of the atrium provide a physically constrained framework for describing the current state of an atrium and allow predictions of how that atrium will respond to therapy. We propose a work flow to simulate patient specific electrophysiological heterogeneity from clinical data and validate the resulting biophysical models. In 7 patients, we recorded the atrial anatomy with an electroanatomical mapping system (St Jude Velocity); we then applied an S1-S2 electrical stimulation protocol from the coronary sinus (CS) and the high right atrium (HRA) whilst recording the activation patterns using a PentaRay catheter with 10 bipolar electrodes at 12 ± 2 sites across the atrium. Using only the activation times measured with a PentaRay catheter and caused by a stimulus applied in the CS with a remote catheter we fitted the four parameters for a modified Mitchell-Schaeffer model and the tissue conductivity to the recorded local conduction velocity restitution curve and estimate...
Anatomically accurate and biophysically detailed bidomain models of the human heart have proven a... more Anatomically accurate and biophysically detailed bidomain models of the human heart have proven a powerful tool for gaining quantitative insight into the links between electrical sources in the myocardium and the concomitant current flow in the surrounding medium as they represent their relationship mechanistically based on first principles. Such models are increasingly considered as a clinical research tool with the perspective of being used, ultimately, as a complementary diagnostic modality. An important prerequisite in many clinical modeling applications is the ability of models to faithfully replicate potential maps and electrograms recorded from a given patient. However, while the personalization of electrophysiology models based on the gold standard bidomain formulation is in principle feasible, the associated computational expenses are significant, rendering their use incompatible with clinical time frames. In this study we report on the development of a novel computationall...
Models of blood flow in the left ventricle (LV) and aorta are an important tool for analysing the... more Models of blood flow in the left ventricle (LV) and aorta are an important tool for analysing the interplay between LV deformation and flow patterns. Typically, image-based kinematic models describing endocardial motion are used as an input to blood flow simulations. While such models are suitable for analysing the hemodynamic status quo, they are limited in predicting the response to interventions that alter afterload conditions. Mechano-fluidic models using biophysically detailed electromechanical (EM) models have the potential to overcome this limitation, but are more costly to build and compute. We report our recent advancements in developing an automated workflow for the creation of such CFD ready kinematic models to serve as drivers of blood flow simulations.
If citing, it is advised that you check and use the publisher's definitive version for pagination... more If citing, it is advised that you check and use the publisher's definitive version for pagination, volume/issue, and date of publication details. And where the final published version is provided on the Research Portal, if citing you are again advised to check the publisher's website for any subsequent corrections.
International journal for numerical methods in biomedical engineering, Jan 6, 2015
A computational study of an optimal control approach for cardiac defibrillation in a 3D geometry ... more A computational study of an optimal control approach for cardiac defibrillation in a 3D geometry is presented. The cardiac bioelectric activity at the tissue and bath volumes is modeled by the bidomain model equations. The model includes intramural fiber rotation, axially symmetric around the fiber direction, and anisotropic conductivity coefficients which are extracted from a histological image. The dynamics of the ionic currents are based on the regularized Mitchell-Schaeffer model. The controls enter in the form of electrodes which are placed at the boundary of the bath volume with the goal of dampening undesired arrhythmias. The numerical optimization is based on Newton techniques. We demonstrated the parallel architecture environment for the computation of potentials on multidomains and for the higher order optimization techniques. This article is protected by copyright. All rights reserved.
IEEE transactions on bio-medical engineering, Jan 9, 2015
Ectopic electrical activity which originates in the peri-infarct region can give rise to potentia... more Ectopic electrical activity which originates in the peri-infarct region can give rise to potentially lethal re-entrant arrhythmias. The spatial variation in electrotonic loading that results from structural remodelling in the infarct border zone may increase the probability that focal activity will trigger electrical capture, but this has not previously been investigated systematically. This study uses in-silico experiments to examine the structural modulation of effective refractory period on ectopic beat capture. Informed by 3D reconstructions of myocyte organization in the infarct border zone, a region of rapid tissue expansion is abstracted to an idealized representation. A novel metric is introduced that defines the local electrotonic loading as a function of passive tissue properties and boundary conditions. The effective refractory period correlates closely with local electrotonic loading, while the action potential duration, conduction and upstroke velocity reduce in regions...
Light scattering during optical imaging of electrical activation within the heart is known to sig... more Light scattering during optical imaging of electrical activation within the heart is known to significantly distort the optically-recorded action potential (AP) upstroke, as well as affecting the magnitude of the measured response of ventricular tissue to strong electric shocks. Modeling approaches based on the photon diffusion equation have recently been instrumental in quantifying and helping to understand the origin of the resulting distortion. However, they are unable to faithfully represent regions of non-scattering media, such as small cavities within the myocardium which are filled with perfusate during experiments. Stochastic Monte Carlo (MC) approaches allow simulation and tracking of individual photon "packets" as they propagate through tissue with differing scattering properties. Here, we present a novel application of the MC method of photon scattering simulation, applied for the first time to the simulation of cardiac optical mapping signals within unstructure...
Optimal control techniques are investigated with the goal of terminating reentry waves in cardiac... more Optimal control techniques are investigated with the goal of terminating reentry waves in cardiac tissue models. In this computational study the Luo-Rudy phase I ventricular action potential model is adopted which accounts for more biophysical details of cellular dynamics as compared to previously used phenomenological models. The parabolic and ordinary differential equations are solved as a coupled system and an AMG preconditioner is used to solve the discretized elliptic equation The numerical results demonstrate that defibrillation is possible by delivering a single strong shock. The optimal control approach also leads to successful defibrillation and demands less total current. The present study motivates us to further investigate optimal control techniques on realistic geometries by incorporating the structural heterogeneity in the cardiac tissue.
Proceedings of the 31st Annual International Conference of the IEEE Engineering in Medicine and Biology Society: Engineering the Future of Biomedicine, EMBC 2009, 2009
Simulations of cardiac bioelectric phenomena remain a significant challenge despite continual adv... more Simulations of cardiac bioelectric phenomena remain a significant challenge despite continual advancements in computational machinery. Spanning large temporal and spatial ranges demands millions of nodes to accurately depict geometry, and a comparable number of timesteps to capture dynamics. This study explores a new hardware computing paradigm, the graphics processing unit (GPU), to accelerate cardiac models, and analyzes results in the context of simulating a small mammalian heart in real time. The ODEs associated with membrane ionic flow were computed on traditional CPU and compared to GPU performance, for one to four parallel processing units. The scalability of solving the PDE responsible for tissue coupling was examined on a cluster using up to 128 cores. Results indicate that the GPU implementation was between 9 and 17 times faster than the CPU implementation and scaled similarly. Solving the PDE was still 160 times slower than real time.
Circulation: Arrhythmia and Electrophysiology, 2012
Background-The direct role of coronary vessels in defibrillation, although hypothesized to be imp... more Background-The direct role of coronary vessels in defibrillation, although hypothesized to be important, remains to be elucidated. We investigated how vessel-induced virtual electrode polarizations assist reentry termination. Methods and Results-A highly anatomically detailed rabbit ventricular slice bidomain computer model was constructed from 25-m magnetic resonance data, faithfully representing both structural and electric properties of blood vessels. For comparison, an equivalent simplified model with intramural cavities filled in was also built. Following fibrillation induction, 6 initial states were selected, and biphasic shocks (5-70 V) were applied using a realistic implanted cardioverter-defibrillator electrode configuration. A fundamental mechanism of biphasic defibrillation was uncovered in both models, involving successive break excitations (after each shock phase) emanating from opposing myocardial surfaces (in septum and left ventricle), which rapidly closed down excitable gaps. The presence of vessels accelerated this process, achieving more-rapid and successful defibrillation. Defibrillation failed in 5 cases (all because of initiation of new activity) compared with 8 with the simplified model (5/8 failures because of surviving activity). At stronger shocks, virtual electrodes formed around vessels, rapidly activating intramural tissue because of break excitations, assisting the main defibrillation mechanism, and eliminating all activity Ͻ15 ms of shock end in 60% of successful shocks (36% in simplified model). Subsequent analysis identified that only vessels Ͼ200 m in diameter participated through this mechanism. Consequently, wavefronts could survive intramurally in the simplified model, leading to reentry and shock failure. Conclusions-We provide new insight into defibrillation mechanisms by showing how intramural blood vessels facilitate more-effective elimination of existing wavefronts, rapid closing down of excitable gaps, and successful defibrillation and give guidance toward the required resolution of cardiac imaging and model generation endeavors for mechanistic defibrillation analysis.
The specific mechanisms by which fine-scale structures within the heart may interact with complex... more The specific mechanisms by which fine-scale structures within the heart may interact with complex excitation wavefronts during cardiac arrhythmias to increase their stability, and how this interaction may differ between species are currently incompletely understood. • Computational models provide an important basic science tool in mechanistic arrhythmia enquiry. Recent advances in cardiac imaging have allowed the generation of highly anatomically detailed computational ventricular models including fine-scale features such as blood vessels and endocardial structures. • Using such an anatomically detailed MR-derived rabbit ventricular model, in conjunction with a simplified equivalent model, we assessed the role played by fine-scale anatomy in the sustenance of different types of simulated arrhythmias. • Our simulation results suggest that, in the rabbit, anatomical structures such as the vasculature and endocardial structures play little role in the maintenance of cardiac arrhythmias, although their role becomes marginally more important with increasing arrhythmia complexity. • Consequently, in the rabbit, constructing computational models which represent the vasculature and endocardial structures may not be necessary for mechanistic investigation of arrhythmia maintenance.
• Defibrillation is known to be less efficient in infarcted than in healthy hearts. • In a rabbit... more • Defibrillation is known to be less efficient in infarcted than in healthy hearts. • In a rabbit model of myocardial infarction, altered 3D distribution of virtual electrodes and propagation delay in the peri-infarct zone caused increased vulnerability to electric shocks in infarcted hearts. • The infarct scar alone-without the presence of a peri-infarct zone-did not cause an increase in vulnerability. • The results help us to understand the mechanisms of increased vulnerability and decreased defibrillation efficacy in infarcted hearts.
Ventricular tachycardia, a life-threatening regular and repetitive fast heart rhythm, frequently ... more Ventricular tachycardia, a life-threatening regular and repetitive fast heart rhythm, frequently occurs in the setting of myocardial infarction. Recently, the peri-infarct zones surrounding the necrotic scar (termed gray zones) have been shown to correlate with ventricular tachycardia inducibility. However, it remains unknown how the latter is determined by gray zone distribution and size. The goal of this study is to examine how tachycardia circuits are maintained in the infarcted heart and to explore the relationship between the tachycardia organizing centers and the infarct gray zone size and degree of heterogeneity. To achieve the goals of the study, we employ a sophisticated high-resolution electrophysiological model of the infarcted canine ventricles reconstructed from imaging data, representing both scar and gray zone. The baseline canine ventricular model was also used to generate additional ventricular models with different gray zone sizes, as well as models in which the gray zone was represented as different heterogeneous combinations of viable tissue and necrotic scar. The results of the tachycardia induction simulations with a number of high-resolution canine ventricular models (22 altogether) demonstrated that the gray zone was the critical factor resulting in arrhythmia induction and maintenance. In all models with inducible arrhythmia, the scroll-wave filaments were contained entirely within the gray zone, regardless of its size or the level of heterogeneity of its composition. The gray zone was thus found to be the arrhythmogenic substrate that promoted wavebreak and reentry formation. We found that the scroll-wave filament locations were insensitive to the structural composition of the gray zone and were determined predominantly by the gray zone morphology and size. The findings of this study have important implications for the advancement of improved criteria for stratifying arrhythmia risk in post-infarction patients and for the development of new approaches for determining the ablation targets of infarct-related tachycardia.
Medical & Biological Engineering & Computing, 2012
Thin-walled cardiac tissue samples superfused with oxygenated solutions are widely used in experi... more Thin-walled cardiac tissue samples superfused with oxygenated solutions are widely used in experimental studies. However, due to decreased oxygen supply and insufficient wash out of waste products in the inner layers of such preparations, electrophysiological functions could be compromised. Although the cascade of events triggered by cutting off perfusion is well known, it remains unclear as to which degree electrophysiological function in viable surface layers is affected by pathological processes occurring in adjacent tissue. Using a 3D numerical bidomain model, we aim to quantify the impact of superfusioninduced heterogeneities occurring in the depth of the tissue on impulse propagation in superficial layers. Simulations demonstrated that both the pattern of activation as well as the distribution of extracellular potentials close to the surface remain essentially unchanged. This was true also for the electrophysiological properties of cells in the surface layer, where most relevant depolarization parameters varied by less than 5.5 %. The main observed effect on the surface was related to action potential duration that shortened noticeably by 53 % as hypoxia deteriorated. Despite the known limitations of such experimental methods, we conclude that superfusion is adequate for studying impulse propagation and depolarization whereas repolarization studies should consider the influence of pathological processes taking place at the core of tissue sample.
The bidomain equations with Neumann boundary stimulation and optimal control of these stimuli are... more The bidomain equations with Neumann boundary stimulation and optimal control of these stimuli are investigated. First an analytical framework for boundary control is provided. Then a parallel finite element based algorithm is devised and its efficiency is demonstrated not only for the direct problem but also for the optimal control problem. The computations realize a model configuration corresponding to optimal boundary defibrillation of a reentry phenomenon by applying current density stimuli.
This work proposes an optimal control approach for the termination of re-entry waves in cardiac e... more This work proposes an optimal control approach for the termination of re-entry waves in cardiac electrophysiology. The control enters as an extracellular current density into the bidomain equations which are well established model equations in the literature to describe the electrical behavior of the cardiac tissue. The optimal control formulation is inspired, in part, by the dynamical systems behavior of the underlying system of differential equations. Existence of optimal controls is established and the optimality system is derived formally. The numerical realization is described in detail and numerical experiments, which demonstrate the capability of influencing and terminating reentry phenomena, are presented.
Cardiac digital twins (Cardiac Digital Twin (CDT)s) of human electrophysiology (Electrophysiology... more Cardiac digital twins (Cardiac Digital Twin (CDT)s) of human electrophysiology (Electrophysiology (EP)) are digital replicas of patient hearts derived from clinical data that match like-for-like all available clinical observations. Due to their inherent predictive potential, CDTs show high promise as a complementary modality aiding in clinical decision making and also in the cost-effective, saf e and ethical testing of novel EP device therapies. However, current workflows for both the anatomical and functional twinning phases within CDT generation, referring to the inference of model anatomy and parameters from clinical data, are not sufficiently efficient, robust and accurate for advanced clinical and industrial applications. Our study addresses three primary limitations impeding the routine generation of high-fidelity CDTs by introducing; a comprehensive parameter vector encapsulating all factors relating to the ventricular EP; an abstract reference frame within the model allowing the unattended manipulation of model parameter fields; a novel fast-forward electrocardiogram (Electrocardiogram (ECG)) model for efficient and biophysically-detailed simulation required for parameter inference. A novel workflow for the generation of CDTs is then introduced as an initial proof of concept. Anatomical twinning was performed within a reasonable time compatible with clinical workflows (< 4h) for 12 subjects from clinically-attained magnetic resonance images. After assessment of the underlying fast forward ECG model against a gold standard bidomain ECG model, functional twinning of optimal parameters according to a clinically-attained 12 lead ECG was then performed using a forward Saltelli sampling approach for a single subject. The achieved results in terms of efficiency and fidelity demonstrate that our workflow is well-suited and viable for generating biophysically-detailed CDTs at scale.
If citing, it is advised that you check and use the publisher's definitive version for pagination... more If citing, it is advised that you check and use the publisher's definitive version for pagination, volume/issue, and date of publication details. And where the final published version is provided on the Research Portal, if citing you are again advised to check the publisher's website for any subsequent corrections.
Biophysical models of the atrium provide a physically constrained framework for describing the cu... more Biophysical models of the atrium provide a physically constrained framework for describing the current state of an atrium and allow predictions of how that atrium will respond to therapy. We propose a work flow to simulate patient specific electrophysiological heterogeneity from clinical data and validate the resulting biophysical models. In 7 patients, we recorded the atrial anatomy with an electroanatomical mapping system (St Jude Velocity); we then applied an S1-S2 electrical stimulation protocol from the coronary sinus (CS) and the high right atrium (HRA) whilst recording the activation patterns using a PentaRay catheter with 10 bipolar electrodes at 12 ± 2 sites across the atrium. Using only the activation times measured with a PentaRay catheter and caused by a stimulus applied in the CS with a remote catheter we fitted the four parameters for a modified Mitchell-Schaeffer model and the tissue conductivity to the recorded local conduction velocity restitution curve and estimate...
Anatomically accurate and biophysically detailed bidomain models of the human heart have proven a... more Anatomically accurate and biophysically detailed bidomain models of the human heart have proven a powerful tool for gaining quantitative insight into the links between electrical sources in the myocardium and the concomitant current flow in the surrounding medium as they represent their relationship mechanistically based on first principles. Such models are increasingly considered as a clinical research tool with the perspective of being used, ultimately, as a complementary diagnostic modality. An important prerequisite in many clinical modeling applications is the ability of models to faithfully replicate potential maps and electrograms recorded from a given patient. However, while the personalization of electrophysiology models based on the gold standard bidomain formulation is in principle feasible, the associated computational expenses are significant, rendering their use incompatible with clinical time frames. In this study we report on the development of a novel computationall...
Models of blood flow in the left ventricle (LV) and aorta are an important tool for analysing the... more Models of blood flow in the left ventricle (LV) and aorta are an important tool for analysing the interplay between LV deformation and flow patterns. Typically, image-based kinematic models describing endocardial motion are used as an input to blood flow simulations. While such models are suitable for analysing the hemodynamic status quo, they are limited in predicting the response to interventions that alter afterload conditions. Mechano-fluidic models using biophysically detailed electromechanical (EM) models have the potential to overcome this limitation, but are more costly to build and compute. We report our recent advancements in developing an automated workflow for the creation of such CFD ready kinematic models to serve as drivers of blood flow simulations.
If citing, it is advised that you check and use the publisher's definitive version for pagination... more If citing, it is advised that you check and use the publisher's definitive version for pagination, volume/issue, and date of publication details. And where the final published version is provided on the Research Portal, if citing you are again advised to check the publisher's website for any subsequent corrections.
International journal for numerical methods in biomedical engineering, Jan 6, 2015
A computational study of an optimal control approach for cardiac defibrillation in a 3D geometry ... more A computational study of an optimal control approach for cardiac defibrillation in a 3D geometry is presented. The cardiac bioelectric activity at the tissue and bath volumes is modeled by the bidomain model equations. The model includes intramural fiber rotation, axially symmetric around the fiber direction, and anisotropic conductivity coefficients which are extracted from a histological image. The dynamics of the ionic currents are based on the regularized Mitchell-Schaeffer model. The controls enter in the form of electrodes which are placed at the boundary of the bath volume with the goal of dampening undesired arrhythmias. The numerical optimization is based on Newton techniques. We demonstrated the parallel architecture environment for the computation of potentials on multidomains and for the higher order optimization techniques. This article is protected by copyright. All rights reserved.
IEEE transactions on bio-medical engineering, Jan 9, 2015
Ectopic electrical activity which originates in the peri-infarct region can give rise to potentia... more Ectopic electrical activity which originates in the peri-infarct region can give rise to potentially lethal re-entrant arrhythmias. The spatial variation in electrotonic loading that results from structural remodelling in the infarct border zone may increase the probability that focal activity will trigger electrical capture, but this has not previously been investigated systematically. This study uses in-silico experiments to examine the structural modulation of effective refractory period on ectopic beat capture. Informed by 3D reconstructions of myocyte organization in the infarct border zone, a region of rapid tissue expansion is abstracted to an idealized representation. A novel metric is introduced that defines the local electrotonic loading as a function of passive tissue properties and boundary conditions. The effective refractory period correlates closely with local electrotonic loading, while the action potential duration, conduction and upstroke velocity reduce in regions...
Light scattering during optical imaging of electrical activation within the heart is known to sig... more Light scattering during optical imaging of electrical activation within the heart is known to significantly distort the optically-recorded action potential (AP) upstroke, as well as affecting the magnitude of the measured response of ventricular tissue to strong electric shocks. Modeling approaches based on the photon diffusion equation have recently been instrumental in quantifying and helping to understand the origin of the resulting distortion. However, they are unable to faithfully represent regions of non-scattering media, such as small cavities within the myocardium which are filled with perfusate during experiments. Stochastic Monte Carlo (MC) approaches allow simulation and tracking of individual photon "packets" as they propagate through tissue with differing scattering properties. Here, we present a novel application of the MC method of photon scattering simulation, applied for the first time to the simulation of cardiac optical mapping signals within unstructure...
Optimal control techniques are investigated with the goal of terminating reentry waves in cardiac... more Optimal control techniques are investigated with the goal of terminating reentry waves in cardiac tissue models. In this computational study the Luo-Rudy phase I ventricular action potential model is adopted which accounts for more biophysical details of cellular dynamics as compared to previously used phenomenological models. The parabolic and ordinary differential equations are solved as a coupled system and an AMG preconditioner is used to solve the discretized elliptic equation The numerical results demonstrate that defibrillation is possible by delivering a single strong shock. The optimal control approach also leads to successful defibrillation and demands less total current. The present study motivates us to further investigate optimal control techniques on realistic geometries by incorporating the structural heterogeneity in the cardiac tissue.
Proceedings of the 31st Annual International Conference of the IEEE Engineering in Medicine and Biology Society: Engineering the Future of Biomedicine, EMBC 2009, 2009
Simulations of cardiac bioelectric phenomena remain a significant challenge despite continual adv... more Simulations of cardiac bioelectric phenomena remain a significant challenge despite continual advancements in computational machinery. Spanning large temporal and spatial ranges demands millions of nodes to accurately depict geometry, and a comparable number of timesteps to capture dynamics. This study explores a new hardware computing paradigm, the graphics processing unit (GPU), to accelerate cardiac models, and analyzes results in the context of simulating a small mammalian heart in real time. The ODEs associated with membrane ionic flow were computed on traditional CPU and compared to GPU performance, for one to four parallel processing units. The scalability of solving the PDE responsible for tissue coupling was examined on a cluster using up to 128 cores. Results indicate that the GPU implementation was between 9 and 17 times faster than the CPU implementation and scaled similarly. Solving the PDE was still 160 times slower than real time.
Circulation: Arrhythmia and Electrophysiology, 2012
Background-The direct role of coronary vessels in defibrillation, although hypothesized to be imp... more Background-The direct role of coronary vessels in defibrillation, although hypothesized to be important, remains to be elucidated. We investigated how vessel-induced virtual electrode polarizations assist reentry termination. Methods and Results-A highly anatomically detailed rabbit ventricular slice bidomain computer model was constructed from 25-m magnetic resonance data, faithfully representing both structural and electric properties of blood vessels. For comparison, an equivalent simplified model with intramural cavities filled in was also built. Following fibrillation induction, 6 initial states were selected, and biphasic shocks (5-70 V) were applied using a realistic implanted cardioverter-defibrillator electrode configuration. A fundamental mechanism of biphasic defibrillation was uncovered in both models, involving successive break excitations (after each shock phase) emanating from opposing myocardial surfaces (in septum and left ventricle), which rapidly closed down excitable gaps. The presence of vessels accelerated this process, achieving more-rapid and successful defibrillation. Defibrillation failed in 5 cases (all because of initiation of new activity) compared with 8 with the simplified model (5/8 failures because of surviving activity). At stronger shocks, virtual electrodes formed around vessels, rapidly activating intramural tissue because of break excitations, assisting the main defibrillation mechanism, and eliminating all activity Ͻ15 ms of shock end in 60% of successful shocks (36% in simplified model). Subsequent analysis identified that only vessels Ͼ200 m in diameter participated through this mechanism. Consequently, wavefronts could survive intramurally in the simplified model, leading to reentry and shock failure. Conclusions-We provide new insight into defibrillation mechanisms by showing how intramural blood vessels facilitate more-effective elimination of existing wavefronts, rapid closing down of excitable gaps, and successful defibrillation and give guidance toward the required resolution of cardiac imaging and model generation endeavors for mechanistic defibrillation analysis.
The specific mechanisms by which fine-scale structures within the heart may interact with complex... more The specific mechanisms by which fine-scale structures within the heart may interact with complex excitation wavefronts during cardiac arrhythmias to increase their stability, and how this interaction may differ between species are currently incompletely understood. • Computational models provide an important basic science tool in mechanistic arrhythmia enquiry. Recent advances in cardiac imaging have allowed the generation of highly anatomically detailed computational ventricular models including fine-scale features such as blood vessels and endocardial structures. • Using such an anatomically detailed MR-derived rabbit ventricular model, in conjunction with a simplified equivalent model, we assessed the role played by fine-scale anatomy in the sustenance of different types of simulated arrhythmias. • Our simulation results suggest that, in the rabbit, anatomical structures such as the vasculature and endocardial structures play little role in the maintenance of cardiac arrhythmias, although their role becomes marginally more important with increasing arrhythmia complexity. • Consequently, in the rabbit, constructing computational models which represent the vasculature and endocardial structures may not be necessary for mechanistic investigation of arrhythmia maintenance.
• Defibrillation is known to be less efficient in infarcted than in healthy hearts. • In a rabbit... more • Defibrillation is known to be less efficient in infarcted than in healthy hearts. • In a rabbit model of myocardial infarction, altered 3D distribution of virtual electrodes and propagation delay in the peri-infarct zone caused increased vulnerability to electric shocks in infarcted hearts. • The infarct scar alone-without the presence of a peri-infarct zone-did not cause an increase in vulnerability. • The results help us to understand the mechanisms of increased vulnerability and decreased defibrillation efficacy in infarcted hearts.
Ventricular tachycardia, a life-threatening regular and repetitive fast heart rhythm, frequently ... more Ventricular tachycardia, a life-threatening regular and repetitive fast heart rhythm, frequently occurs in the setting of myocardial infarction. Recently, the peri-infarct zones surrounding the necrotic scar (termed gray zones) have been shown to correlate with ventricular tachycardia inducibility. However, it remains unknown how the latter is determined by gray zone distribution and size. The goal of this study is to examine how tachycardia circuits are maintained in the infarcted heart and to explore the relationship between the tachycardia organizing centers and the infarct gray zone size and degree of heterogeneity. To achieve the goals of the study, we employ a sophisticated high-resolution electrophysiological model of the infarcted canine ventricles reconstructed from imaging data, representing both scar and gray zone. The baseline canine ventricular model was also used to generate additional ventricular models with different gray zone sizes, as well as models in which the gray zone was represented as different heterogeneous combinations of viable tissue and necrotic scar. The results of the tachycardia induction simulations with a number of high-resolution canine ventricular models (22 altogether) demonstrated that the gray zone was the critical factor resulting in arrhythmia induction and maintenance. In all models with inducible arrhythmia, the scroll-wave filaments were contained entirely within the gray zone, regardless of its size or the level of heterogeneity of its composition. The gray zone was thus found to be the arrhythmogenic substrate that promoted wavebreak and reentry formation. We found that the scroll-wave filament locations were insensitive to the structural composition of the gray zone and were determined predominantly by the gray zone morphology and size. The findings of this study have important implications for the advancement of improved criteria for stratifying arrhythmia risk in post-infarction patients and for the development of new approaches for determining the ablation targets of infarct-related tachycardia.
Medical & Biological Engineering & Computing, 2012
Thin-walled cardiac tissue samples superfused with oxygenated solutions are widely used in experi... more Thin-walled cardiac tissue samples superfused with oxygenated solutions are widely used in experimental studies. However, due to decreased oxygen supply and insufficient wash out of waste products in the inner layers of such preparations, electrophysiological functions could be compromised. Although the cascade of events triggered by cutting off perfusion is well known, it remains unclear as to which degree electrophysiological function in viable surface layers is affected by pathological processes occurring in adjacent tissue. Using a 3D numerical bidomain model, we aim to quantify the impact of superfusioninduced heterogeneities occurring in the depth of the tissue on impulse propagation in superficial layers. Simulations demonstrated that both the pattern of activation as well as the distribution of extracellular potentials close to the surface remain essentially unchanged. This was true also for the electrophysiological properties of cells in the surface layer, where most relevant depolarization parameters varied by less than 5.5 %. The main observed effect on the surface was related to action potential duration that shortened noticeably by 53 % as hypoxia deteriorated. Despite the known limitations of such experimental methods, we conclude that superfusion is adequate for studying impulse propagation and depolarization whereas repolarization studies should consider the influence of pathological processes taking place at the core of tissue sample.
The bidomain equations with Neumann boundary stimulation and optimal control of these stimuli are... more The bidomain equations with Neumann boundary stimulation and optimal control of these stimuli are investigated. First an analytical framework for boundary control is provided. Then a parallel finite element based algorithm is devised and its efficiency is demonstrated not only for the direct problem but also for the optimal control problem. The computations realize a model configuration corresponding to optimal boundary defibrillation of a reentry phenomenon by applying current density stimuli.
This work proposes an optimal control approach for the termination of re-entry waves in cardiac e... more This work proposes an optimal control approach for the termination of re-entry waves in cardiac electrophysiology. The control enters as an extracellular current density into the bidomain equations which are well established model equations in the literature to describe the electrical behavior of the cardiac tissue. The optimal control formulation is inspired, in part, by the dynamical systems behavior of the underlying system of differential equations. Existence of optimal controls is established and the optimality system is derived formally. The numerical realization is described in detail and numerical experiments, which demonstrate the capability of influencing and terminating reentry phenomena, are presented.
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Papers by Gernot Plank