Imperial College London

Dr Chris Cantwell

Faculty of EngineeringDepartment of Aeronautics

Senior Lecturer in Aeronautics
 
 
 
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Contact

 

+44 (0)20 7594 5050c.cantwell Website

 
 
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Location

 

Department of Aeronautics, Room 219City and Guilds BuildingSouth Kensington Campus

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Summary

 

Publications

Publication Type
Year
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57 results found

Kim M-Y, Sandler B, Sikkel MB, Cantwell CD, Leong KM, Luther V, Malcolme-Lawes L, Koa-Wing M, Ng FS, Qureshi N, Sohaib A, Whinnett ZI, Fudge M, Lim E, Todd M, Wright I, Peters NS, Lim PB, Linton NWF, Kanagaratnam Pet al., 2020, The ectopy-triggering ganglionated plexuses in atrial fibrillation, Autonomic Neuroscience, Vol: 228, ISSN: 1566-0702

BackgroundEpicardial ganglionated plexus (GP) have an important role in the pathogenesis of atrial fibrillation (AF). The relationship between anatomical, histological and functional effects of GP is not well known. We previously described atrioventricular (AV) dissociating GP (AVD-GP) locations. In this study, we hypothesised that “ET-GP” are upstream triggers of atrial ectopy/AF and have different anatomical distribution to AVD-GP.ObjectivesWe mapped and characterised ET-GP to understand their neural mechanism in AF and anatomical distribution in the left atrium (LA).Methods26 patients with paroxysmal AF were recruited. All were paced in the LA with an ablation catheter. HFS (80 ms) was synchronised to each paced stimulus (after 20 ms delay) for delivery within the local atrial refractory period. HFS responses were tagged onto CARTO™ 3D LA geometry. All geometries were transformed onto one reference LA shell. A probability distribution atlas of ET-GP was created. This identified high/low ET-GP probability regions.Results2302 sites were tested with HFS, identifying 579 (25%) ET-GP. 464 ET-GP were characterised, where 74 (16%) triggered ≥30s AF/AT. Median 97 (IQR 55) sites were tested, identifying 19 (20%) ET-GP per patient. >30% of ET-GP were in the roof, mid-anterior wall, around all PV ostia except in the right inferior PV (RIPV) in the posterior wall.ConclusionET-GP can be identified by endocardial stimulation and their anatomical distribution, in contrast to AVD-GP, would be more likely to be affected by wide antral circumferential ablation. This may contribute to AF ablation outcomes.

Journal article

Ali R, Qureshi N, Liverani S, Roney C, Kim S, Lim P, Tweedy J, Cantwell C, Peters Net al., Left atrial enhancement correlates with myocardial conduction velocity in patients with persistent atrial fibrillation, Frontiers in Physiology

Journal article

Brook J, Kim M-Y, Koutsoftidis S, Pitcher D, Agha-Jaffar D, Sufi A, Jenkins C, Tzortzis K, Ma S, Jabbour R, Houston C, Handa B, Li X, Chow J-J, Jothidasan A, Bristow P, Perkins J, Harding S, Bharath A, Ng FS, Peters N, Cantwell C, Chowdhury R, Brook J, Kim M-Y, Koutsoftidis S, Pitcher D, Agha-Jaffar D, Sufi A, Jenkins C, Tzortzis K, Ma S, Jabbour R, Houston C, Handa B, Li X, Chow J-J, Jothidasan A, Bristow P, Perkins J, Harding S, Bharath A, Ng FS, Peters N, Cantwell C, Chowdhury Ret al., 2020, Development of a pro-arrhythmic ex vivo intact human and porcine model: cardiac electrophysiological changes associated with cellular uncoupling, Pflügers Archiv European Journal of Physiology, Vol: 472, Pages: 1435-1446, ISSN: 0031-6768

We describe a human and large animal Langendorff experimental apparatus for live electrophysiological studies and measure the electrophysiological changes due to gap-junction uncoupling in human and porcine hearts. The resultant ex vivo intact human and porcine model can bridge the translational gap between smaller simple laboratory models and clinical research. In particular, electrophysiological models would benefit from the greater myocardial mass of a large heart due to its effects on far field signal, electrode contact issues and motion artefacts, consequently more closely mimicking the clinical setting Porcine (n=9) and human (n=4) donor hearts were perfused on a custom-designed Langendorff apparatus. Epicardial electrograms were collected at 16 sites across the left atrium and left ventricle. 1mM of carbenoxolone was administered at 5ml/min to induce cellular uncoupling, and then recordings were repeated at the same sites. Changes in electrogram characteristics were analysed.We demonstrate the viability of a controlled ex vivo model of intact porcine and human hearts for electrophysiology with pharmacological modulation. Carbenoxolone reduces cellular coupling and changes contact electrogram features. The time from stimulus artefact to (-dV/dt)max increased between baseline and carbenoxolone (47.9±4.1ms to 67.2±2.7ms) indicating conduction slowing. The features with the largest percentage change between baseline to Carbenoxolone were Fractionation +185.3%, Endpoint amplitude -106.9%, S-Endpoint Gradient +54.9%, S Point, -39.4%, RS Ratio +38.6% and (-dV/dt)max -20.9%.The physiological relevance of this methodological tool is that it provides a model to further investigate pharmacologically-induced proarrhythmic substrates.

Journal article

Kim M-Y, Sandler B, Sikkel MB, Cantwell CD, Leong KM, Luther V, Malcolme-Lawes L, Koa-Wing M, Ng FS, Qureshi N, Sohaib A, Whinnett ZI, Fudge M, Lim E, Todd M, Wright I, Peters NS, Lim PB, Linton NWF, Kanagaratnam Pet al., 2020, The anatomical distribution of the ectopy-triggering ganglionated plexus in patients with atrial fibrillation, Circulation: Arrhythmia and Electrophysiology, Vol: 13, Pages: 1045-1047, ISSN: 1941-3084

Journal article

Niederer SA, Aboelkassem Y, Cantwell CD, Corrado C, Coveney S, Cherry EM, Delhaas T, Fenton FH, Panfilov AV, Pathmanathan P, Plank G, Riabiz M, Roney CH, Dos Santos RW, Wang Let al., 2020, Creation and application of virtual patient cohorts of heart models., Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences, Vol: 378, Pages: 1-20, ISSN: 1364-503X

Patient-specific cardiac models are now being used to guide therapies. The increased use of patient-specific cardiac simulations in clinical care will give rise to the development of virtual cohorts of cardiac models. These cohorts will allow cardiac simulations to capture and quantify inter-patient variability. However, the development of virtual cohorts of cardiac models will require the transformation of cardiac modelling from small numbers of bespoke models to robust and rapid workflows that can create large numbers of models. In this review, we describe the state of the art in virtual cohorts of cardiac models, the process of creating virtual cohorts of cardiac models, and how to generate the individual cohort member models, followed by a discussion of the potential and future applications of virtual cohorts of cardiac models. This article is part of the theme issue 'Uncertainty quantification in cardiac and cardiovascular modelling and simulation'.

Journal article

Clayton RH, Aboelkassem Y, Cantwell CD, Corrado C, Delhaas T, Huberts W, Lei CL, Ni H, Panfilov AV, Roney C, Dos Santos RWet al., 2020, An audit of uncertainty in multi-scale cardiac electrophysiology models., Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences, Vol: 378, Pages: 1-21, ISSN: 1364-503X

Models of electrical activation and recovery in cardiac cells and tissue have become valuable research tools, and are beginning to be used in safety-critical applications including guidance for clinical procedures and for drug safety assessment. As a consequence, there is an urgent need for a more detailed and quantitative understanding of the ways that uncertainty and variability influence model predictions. In this paper, we review the sources of uncertainty in these models at different spatial scales, discuss how uncertainties are communicated across scales, and begin to assess their relative importance. We conclude by highlighting important challenges that continue to face the cardiac modelling community, identifying open questions, and making recommendations for future studies. This article is part of the theme issue 'Uncertainty quantification in cardiac and cardiovascular modelling and simulation'.

Journal article

Lei CL, Ghosh S, Whittaker DG, Aboelkassem Y, Beattie KA, Cantwell CD, Delhaas T, Houston C, Novaes GM, Panfilov AV, Pathmanathan P, Riabiz M, Dos Santos RW, Walmsley J, Worden K, Mirams GR, Wilkinson RDet al., 2020, Considering discrepancy when calibrating a mechanistic electrophysiology model., Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences, Vol: 378, Pages: 1-23, ISSN: 1364-503X

Uncertainty quantification (UQ) is a vital step in using mathematical models and simulations to take decisions. The field of cardiac simulation has begun to explore and adopt UQ methods to characterize uncertainty in model inputs and how that propagates through to outputs or predictions; examples of this can be seen in the papers of this issue. In this review and perspective piece, we draw attention to an important and under-addressed source of uncertainty in our predictions-that of uncertainty in the model structure or the equations themselves. The difference between imperfect models and reality is termed model discrepancy, and we are often uncertain as to the size and consequences of this discrepancy. Here, we provide two examples of the consequences of discrepancy when calibrating models at the ion channel and action potential scales. Furthermore, we attempt to account for this discrepancy when calibrating and validating an ion channel model using different methods, based on modelling the discrepancy using Gaussian processes and autoregressive-moving-average models, then highlight the advantages and shortcomings of each approach. Finally, suggestions and lines of enquiry for future work are provided. This article is part of the theme issue 'Uncertainty quantification in cardiac and cardiovascular modelling and simulation'.

Journal article

Houston C, Marchand B, Engelbert L, Cantwell CDet al., 2020, Reducing complexity and unidentifiability when modelling human atrial cells, Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences, Vol: 378, Pages: 1-17, ISSN: 1364-503X

Mathematical models of a cellular action potential in cardiac modelling have become increasingly complex, particularly in gating kinetics which control the opening and closing of individual ion channel currents. As cardiac models advance towards use in personalised medicine to inform clinical decision-making, it is critical to understand the uncertainty hidden in parameter estimates from their calibration to experimental data. This study applies approximate Bayesian computation to re-calibrate the gating kinetics of four ion channels in two existing human atrial cell models to their original datasets, providing a measure of uncertainty and indication of potential issues with selecting a single unique value given the available experimental data. Two approaches are investigated to reduce the uncertainty present: re-calibrating the models to a more complete dataset and using a less complex formulation with fewer parameters to constrain. The re-calibrated models are inserted back into the full cell model to study the overall effect on the action potential. The use of more complete datasets does not eliminate uncertainty present in parameter estimates. The less complex model, particularly for the fast sodium current, gave a better fit to experimental data alongside lower parameter uncertainty and improved computational speed.

Journal article

Fotiadis S, Pignatelli E, Valencia ML, Cantwell C, Storkey A, Bharath AAet al., 2020, Comparing recurrent and convolutional neural networks for predicting wave propagation, Publisher: arXiv

Dynamical systems can be modelled by partial differential equations andnumerical computations are used everywhere in science and engineering. In thiswork, we investigate the performance of recurrent and convolutional deep neuralnetwork architectures to predict the surface waves. The system is governed bythe Saint-Venant equations. We improve on the long-term prediction overprevious methods while keeping the inference time at a fraction of numericalsimulations. We also show that convolutional networks perform at least as wellas recurrent networks in this task. Finally, we assess the generalisationcapability of each network by extrapolating in longer time-frames and indifferent physical settings.

Working paper

Moxey D, Cantwell CD, Bao Y, Cassinelli A, Castiglioni G, Chun S, Juda E, Kazemi E, Lackhove K, Marcon J, Mengaldo G, Serson D, Turner M, Xu H, Peiró J, Kirby RM, Sherwin SJet al., 2020, Nektar++: Enhancing the capability and application of high-fidelity spectral/hp element methods, Computer Physics Communications, Vol: 249, ISSN: 0010-4655

Nektar++ is an open-source framework that provides a flexible, performant and scalable platform for the development of solvers for partial differential equations using the high-order spectral/hp element method. In particular, Nektar++ aims to overcome the complex implementation challenges that are often associated with high-order methods, thereby allowing them to be more readily used in a wide range of application areas. In this paper, we present the algorithmic, implementation and application developments associated with our Nektar++ version 5.0 release. We describe some of the key software and performance developments, including our strategies on parallel I/O, on in-situ processing, the use of collective operations for exploiting current andemerging hardware, and interfaces to enable multi-solver coupling. Furthermore, we provide details on a newly developed Python interface that enable more rapid on-boarding of new users unfamiliar with spectral/$hp$ element methods, C++ and/or Nektar++. This release also incorporates a number of numerical method developments - in particular: the method of moving frames, which provides an additional approach for the simulation of equations on embedded curvilinear manifolds and domains; a means of handling spatially variable polynomial order; and a novel technique for quasi-3D simulations to permit spatially-varying perturbations to the geometry in the homogeneous direction. Finally, we demonstrate the new application-level features provided in this release, namely: a facility for generating high-order curvilinear meshes called NekMesh; a novel new AcousticSolver for aeroacoustic problems; our development of a 'thick' strip model for the modelling of fluid-structure interaction problems in the context of vortex-induced vibrations. We conclude by commenting some directions for future code development and expansion.

Journal article

Sorteberg WE, Garasto S, Cantwell CC, Bharath AAet al., 2020, Approximating the Solution of Surface Wave Propagation Using Deep Neural Networks

Poster

Cohen J, Nowell J, Mortari F, Moxey D, Cantwell Cet al., 2019, london-escience/tempss: v0.5

london-escience/tempss: v0.5

Software

Vymazal M, Moxey D, Cantwell CD, Sherwin SJ, Kirby RMet al., 2019, On weak Dirichlet boundary conditions for elliptic problems in the continuous Galerkin method, Journal of Computational Physics, Vol: 394, Pages: 732-744, ISSN: 0021-9991

We combine continuous and discontinuous Galerkin methods in the setting of a model diffusion problem. Starting from a hybrid discontinuous formulation, we replace element interiors by more general subsets of the computational domain – groups of elements that support a piecewise-polynomial continuous expansion. This step allows us to identify a new weak formulation of Dirichlet boundary condition in the continuous framework. We show that the boundary condition leads to a stable discretization with a single parameter insensitive to mesh size and polynomial order of the expansion. The robustness of the approach is demonstrated on several numerical examples.

Journal article

Qureshi N, Kim S, Cantwell C, Afonso V, Bai WJ, Ali R, Shun-Shin M, Louisa M-L, Luther V, Leong K, Lim E, Wright I, Nagy S, Hayat S, Ng FS, Koa-Wing M, Linton N, Lefroy D, Whinnett Z, Davies DW, Kanagaratnam P, Peters N, Lim PBet al., 2019, Voltage during atrial fibrillation is superior to voltage during sinus rhythm in localizing areas of delayed enhancement on magnetic resonance imaging: An assessment of the posterior left atrium in patients with persistent atrial fibrillation, Heart Rhythm, Vol: 16, Pages: 1357-1367, ISSN: 1547-5271

BackgroundBipolar electrogram voltage during sinus rhythm (VSR) has been used as a surrogate for atrial fibrosis in guiding catheter ablation of persistent AF, but the fixed rate and wavefront characteristics present during sinus rhythm may not accurately reflect underlying functional vulnerabilities responsible for AF maintenance.ObjectivesWe hypothesized that given adequate temporal sampling, the spatial distribution of mean AF voltage (VmAF) should better correlate with delayed-enhancement MRI (MRI-DE) detected atrial fibrosis than VSR.MethodsAF was mapped (8s) during index ablation for persistent AF (20 patients) using a 20-pole catheter (660±28 points/map). Following cardioversion, VSR was mapped (557±326 points/map). Electroanatomic and MRI-DE maps were co-registered in 14 patients.Results(i) The time course of VmAF was assessed from 1-40 AF-cycles (∼8s) at 1113 locations. VmAF stabilized with sampling >4s (mean voltage error=0.05mV). (ii) Paired point analysis of VmAF from segments acquired 30s apart (3,667-sites, 15-patients), showed strong correlation (r=0.95, p<0.001). (iii) Delayed-enhancement (DE) was assessed across the posterior left atrial (LA) wall, occupying 33±13%. VmAF distributions (median[IQR]) were 0.21[0.14-0.35]mV in DE vs. 0.52[0.34-0.77]mV in Non-DE regions. VSR distributions were 1.34[0.65-2.48]mV in DE vs. 2.37[1.27-3.97]mV in Non-DE. A VmAF threshold of 0.35mV yielded sensitivity/specificity 75%/79% in detecting MRI-DE, compared with 63%/67% for VSR (1.8mV threshold).ConclusionThe correlation between low-voltage and posterior LA MRI-DE is significantly improved when acquired during AF vs. sinus rhythm. With adequate sampling, mean AF voltage is a reproducible marker reflecting the functional response to the underlying persistent AF substrate.

Journal article

Cantwell C, Mohamied Y, Tzortzis K, Garasto S, Houston C, Chowdhury R, Ng F, Bharath A, Peters N, Cantwell CD, Mohamied Y, Tzortzis KN, Garasto S, Houston C, Chowdhury RA, Ng FS, Bharath AA, Peters NSet al., 2019, Rethinking multiscale cardiac electrophysiology with machine learning and predictive modelling, Computers in Biology and Medicine, Vol: 104, Pages: 339-351, ISSN: 0010-4825

We review some of the latest approaches to analysing cardiac electrophysiology data using machine learning and predictive modelling. Cardiac arrhythmias, particularly atrial fibrillation, are a major global healthcare challenge. Treatment is often through catheter ablation, which involves the targeted localised destruction of regions of the myocardium responsible for initiating or perpetuating the arrhythmia. Ablation targets are either anatomically defined, or identified based on their functional properties as determined through the analysis of contact intracardiac electrograms acquired with increasing spatial density by modern electroanatomic mapping systems. While numerous quantitative approaches have been investigated over the past decades for identifying these critical curative sites, few have provided a reliable and reproducible advance in success rates. Machine learning techniques, including recent deep-learning approaches, offer a potential route to gaining new insight from this wealth of highly complex spatio-temporal information that existing methods struggle to analyse. Coupled with predictive modelling, these techniques offer exciting opportunities to advance the field and produce more accurate diagnoses and robust personalised treatment. We outline some of these methods and illustrate their use in making predictions from the contact electrogram and augmenting predictive modelling tools, both by more rapidly predicting future states of the system and by inferring the parameters of these models from experimental observations.

Journal article

Sorteberg W, Garasto S, Cantwell C, Bharath Aet al., 2019, Approximating the solution of Surface Wave Propagation Using Deep Neural Networks, INNS Big Data and Deep Learning 2019, Publisher: Springer, ISSN: 2661-8141

Partial differential equations formalise the understanding of the behaviour of the physical world that humans acquire through experience and observation. Through their numerical solution, such equations are used to model and predict the evolution of dynamical systems. However, such techniques require extensive computational resources and assume the physics are prescribed \textit{a priori}. Here, we propose a neural network capable of predicting the evolution of a specific physical phenomenon: propagation of surface waves enclosed in a tank, which, mathematically, can be described by the Saint-Venant equations. The existence of reflections and interference makes this problem non-trivial. Forecasting of future states (i.e. spatial patterns of rendered wave amplitude) is achieved from a relatively small set of initial observations. Using a network to make approximate but rapid predictions would enable the active, real-time control of physical systems, often required for engineering design. We used a deep neural network comprising of three main blocks: an encoder, a propagator with three parallel Long Short-Term Memory layers, and a decoder. Results on a novel, custom dataset of simulated sequences produced by a numerical solver show reasonable predictions for as long as 80 time steps into the future on a hold-out dataset. Furthermore, we show that the network is capable of generalising to two other initial conditions that are qualitatively different from those seen at training time.

Conference paper

Cantwell C, Nielsen A, 2019, A minimally intrusive low-memory approach to resilience for existing transient solvers, Journal of Scientific Computing, Vol: 78, Pages: 565-581, ISSN: 0885-7474

We propose a novel, minimally intrusive approach to adding fault tolerance to existing complex scientific simulation codes, used for addressing a broad range of time-dependent problems on the next generation of supercomputers. Exascale systems have the potential to allow much larger, more accurate and scale-resolving simulations of transient processes than can be performed on current petascale systems. However, with a much larger number of components, exascale computers are expected to suffer a node failure every few minutes. Many existing parallel simulation codes are not tolerant of these failures and existing resilience methodologies would necessitate major modifications or redesign of the application. Our approach combines the proposed user-level failure mitigation extensions to the Message-Passing Interface (MPI), with the concepts of message-logging and remote in-memory checkpointing, to demonstrate how to add scalable resilience to transient solvers. Logging MPI communication reduces the storage requirement of static data, such as finite element operators, and allows a spare MPI process to rebuild these data structures independently of other ranks. Remote in-memory checkpointing avoids disk I/O contention on large parallel filesystems. A prototype implementation is applied to Nektar++, a scalable, production-ready transient simulation framework. Forward-path and recovery-path performance of the resilience algorithm is analysed through experiments using the solver for the incompressible Navier-Stokes equations, and strong scaling of the approach is observed.

Journal article

Kim M-Y, Sikkel MB, Hunter RJ, Haywood GA, Tomlinson DR, Tayebjee MH, Ali R, Cantwell CD, Gonna H, Sandler B, Limb E, Furniss G, Mrcp DP, Begg G, Dhillon G, Hill NJ, O'Neill J, Francis DP, Lim PB, Peters NS, Linton NWF, Kanagaratnam Pet al., 2018, A novel approach to mapping the atrial ganglionated plexus network by generating a distribution probability atlas, Journal of Cardiovascular Electrophysiology, Vol: 29, Pages: 1624-1634, ISSN: 1045-3873

INTRODUCTION: The ganglionated plexuses (GPs) of the intrinsic cardiac autonomic system are implicated in arrhythmogenesis. GP localization by stimulation of the epicardial fat pads to produce atrioventricular dissociating (AVD) effects is well described. We determined the anatomical distribution of the left atrial GPs that influence AV dissociation. METHODS AND RESULTS: High frequency stimulation was delivered through a Smart-Touch™ catheter in the left atrium of patients undergoing atrial fibrillation (AF) ablation. 3D locations of points tested throughout the entire chamber were recorded on the CARTO™ system. Impact on the AV conduction was categorized as ventricular asystole, bradycardia or no effect. CARTO™ maps were exported, registered and transformed onto a reference left atrial geometry using a custom software, enabling data from multiple patients to be overlaid. In 28 patients, 2108 locations were tested and 283 sites (13%) demonstrated atrioventricular dissociation effects (AVD-GP). There were 10 AVD-GPs (IQR 11.5) per patient. 80% (226) produced asystole and 20% (57) showed bradycardia. The distribution of the two groups were very similar. Highest probability of AVD-GPs (>20%) were identified in: infero-septal portion (41%) and right inferior pulmonary vein base (30%) of the posterior wall, right superior pulmonary vein antrum (31%). CONCLUSION: It is feasible to map the entire left atrium for AVD-GPs prior to AF ablation. Aggregated data from multiple patients, producing a distribution probability atlas of AVD-GPs, identified three regions with a higher likelihood for finding AVD-GPs and these matched the histological descriptions. This approach could be used to better characterise the autonomic network. This article is protected by copyright. All rights reserved.

Journal article

Handa BS, Roney CH, Houston C, Qureshi N, Li X, Pitcher DS, Chowdhury RA, Lim PB, Dupont E, Niederer S, Cantwell C, Peters NS, Ng FSet al., 2018, Analytical approaches for myocardial fibrillation signals, Computers in Biology and Medicine, Vol: 102, Pages: 315-326, ISSN: 0010-4825

Atrial and ventricular fibrillation are complex arrhythmias, and their underlying mechanisms remain widely debated and incompletely understood. This is partly because the electrical signals recorded during myocardial fibrillation are themselves complex and difficult to interpret with simple analytical tools. There are currently a number of analytical approaches to handle fibrillation data. Some of these techniques focus on mapping putative drivers of myocardial fibrillation, such as dominant frequency, organizational index, Shannon entropy and phase mapping. Other techniques focus on mapping the underlying myocardial substrate sustaining fibrillation, such as voltage mapping and complex fractionated electrogram mapping. In this review, we discuss these techniques, their application and their limitations, with reference to our experimental and clinical data. We also describe novel tools including a new algorithm to map microreentrant circuits sustaining fibrillation.

Journal article

Roney C, Ng FS, Debney M, Eichhorn C, Nachiappan A, Chowdhury R, Qureshi N, Cantwell C, Tweedy J, Niederer S, Peters N, Vigmond Eet al., 2018, Determinants of new wavefront locations in cholinergic atrial fibrillation, EP-Europace, Vol: 20, Pages: iii3-iii15, ISSN: 1099-5129

AimsAtrial fibrillation (AF) wavefront dynamics are complex and difficult to interpret, contributing to uncertainty about the mechanisms that maintain AF. We aimed to investigate the interplay between rotors, wavelets, and focal sources during fibrillation.Methods and resultsArrhythmia wavefront dynamics were analysed for four optically mapped canine cholinergic AF preparations. A bilayer computer model was tuned to experimental preparations, and varied to have (i) fibrosis in both layers or the epicardium only, (ii) different spatial acetylcholine distributions, (iii) different intrinsic action potential duration between layers, and (iv) varied interlayer connectivity. Phase singularities (PSs) were identified and tracked over time to identify rotational drivers. New focal wavefronts were identified using phase contours. Phase singularity density and new wavefront locations were calculated during AF. There was a single dominant mechanism for sustaining AF in each of the preparations, either a rotational driver or repetitive new focal wavefronts. High-density PS sites existed preferentially around the pulmonary vein junctions. Three of the four preparations exhibited stable preferential sites of new wavefronts. Computational simulations predict that only a small number of connections are functionally important in sustaining AF, with new wavefront locations determined by the interplay between fibrosis distribution, acetylcholine concentration, and heterogeneity in repolarization within layers.ConclusionWe were able to identify preferential sites of new wavefront initiation and rotational activity, in order to determine the mechanisms sustaining AF. Electrical measurements should be interpreted differently according to whether they are endocardial or epicardial recordings.

Journal article

Houston CPJ, Tzortzis KN, Roney C, Saglietto A, Pitcher DS, Cantwell C, Chowdhury RA, Ng FS, Peters NS, Dupont Eet al., 2018, Characterisation of re-entrant circuit (or rotational activity) in vitro using the HL1-6 myocyte cell line, Journal of Molecular and Cellular Cardiology, Vol: 119, Pages: 155-164, ISSN: 0022-2828

Fibrillation is the most common arrhythmia observed in clinical practice. Understanding of the mechanisms underlying its initiation and maintenance remains incomplete. Functional re-entries are potential drivers of the arrhythmia. Two main concepts are still debated, the “leading circle” and the “spiral wave or rotor” theories. The homogeneous subclone of the HL1 atrial-derived cardiomyocyte cell line, HL1-6, spontaneously exhibits re-entry on a microscopic scale due to its slow conduction velocity and the presence of triggers, making it possible to examine re-entry at the cellular level.We therefore investigated the re-entry cores in cell monolayers through the use of fluorescence optical mapping at high spatiotemporal resolution in order to obtain insights into the mechanisms of re-entry.Re-entries in HL1-6 myocytes required at least two triggers and a minimum colony area to initiate (3.5 to 6.4 mm2). After electrical activity was completely stopped and re-started by varying the extracellular K+ concentration, re-entries never returned to the same location while 35% of triggers re-appeared at the same position. A conduction delay algorithm also allows visualisation of the core of the re-entries. This work has revealed that the core of re-entries is conduction blocks constituted by lines and/or groups of cells rather than the round area assumed by the other concepts of functional re-entry. This highlights the importance of experimentation at the microscopic level in the study of re-entry mechanisms.

Journal article

Chowdhury RA, Tzortzis KN, Dupont E, Selvadurai S, Perbellini F, Cantwell C, Ng FS, Simon A, Terracciano C, Peters NSet al., 2018, Concurrent micro- to macro-cardiac electrophysiology in myocyte cultures and human heart slices, Scientific Reports, Vol: 8, ISSN: 2045-2322

The contact cardiac electrogram is derived from the extracellular manifestation of cellular action potentials and cell-to-cell communication. It is used to guide catheter based clinical procedures. Theoretically, the contact electrogram and the cellular action potential are directly related, and should change in conjunction with each other during arrhythmogenesis, however there is currently no methodology by which to concurrently record both electrograms and action potentials in the same preparation for direct validation of their relationships and their direct mechanistic links. We report a novel dual modality apparatus for concurrent electrogram and cellular action potential recording at a single cell level within multicellular preparations. We further demonstrate the capabilities of this system to validate the direct link between these two modalities of voltage recordings.

Journal article

Cohen J, Marcon J, Turner M, Cantwell C, Sherwin SJ, Peiro J, Moxey Det al., 2019, Simplifying high-order mesh generation for computational scientists, 10th International Workshop on Science Gateways, Publisher: CEUR Workshop Proceedings, ISSN: 1613-0073

Computational modelling is now tightly integrated into many fields of research in science and industry. Computational fluid dynamics software, for example, gives engineers the ability to model fluid flow around complex geometries defined in Computer-Aided Design (CAD) packages, without the expense of constructing large wind tunnel experiments. However, such modelling requires translation from an initial CAD geometry to a mesh of many small elements that modelling software uses to represent the approximate solution in the numerical method. Generating sufficiently high-quality meshes for simulation is a time-consuming, iterative and error-prone process that is often complicated by the need to interact with multiple command-line tools to generate and visualise the mesh data. In this paper we describe our approach to overcoming this complexity through the addition of a meshing console to Nekkloud, a science gateway for simplifying access to the functionality of the Nektar++ spectral/hp element framework. The meshing console makes use of the NekMesh tool in Nektar++ to help reduce the complexity of the mesh generation process. It offers a web-based interface for specifying parameters, undertaking meshing and visualising results. The meshing console enables Nekkloud to offer support for a full, end-to-end simulation pipeline from initial CAD geometry to simulation results.

Conference paper

Xu H, Cantwell C, Monteserin C, Eskilsson C, Engsig-Karup AP, Sherwin SJet al., 2018, Spectral/hp element methods: Recent developments, applications, and perspectives, Journal of Hydrodynamics, Vol: 30, Pages: 1-22, ISSN: 1001-6058

The spectral/hp element method combines the geometric flexibility of the classical h-type finite element technique with the desirable numerical properties of spectral methods, employing high-degree piecewise polynomial basis functions on coarse finite element-type meshes. The spatial approximation is based upon orthogonal polynomials, such as Legendre or Chebychev polynomials, modified to accommodate a C0 - continuous expansion. Computationally and theoretically, by increasing the polynomial order p, high-precision solutions and fast convergence can be obtained and, in particular, under certain regularity assumptions an exponential reduction in approximation error between numerical and exact solutions can be achieved. This method has now been applied in many simulation studies of both fundamental and practical engineering flows. This paper briefly describes the formulation of the spectral/hp element method and provides an overview of its application to computational fluid dynamics. In particular, it focuses on the use of the spectral/hp element method in transitional flows and ocean engineering. Finally, some of the major challenges to be overcome in order to use the spectral/hp element method in more complex science and engineering applications are discussed.

Journal article

Leong KMW, Ng FS, Roney C, Cantwell C, Shun-Shin M, Linton N, Whinnett Z, Lefroy D, Davies DW, Harding S, Lim PB, Francis D, Peters N, Varnava A, Kanagaratnam P, Leong KM, Ng FS, Roney C, Cantwell C, Shun-Shin MJ, Linton NW, Whinnett ZI, Lefroy DC, Davies DW, Harding SE, Lim PB, Francis D, Peters NS, Varnava AM, Kanagaratnam Pet al., 2017, Repolarization abnormalities unmasked with exercise in sudden cardiac death survivors with structurally normal hearts, Journal of Cardiovascular Electrophysiology, Vol: 29, Pages: 115-126, ISSN: 1045-3873

BACKGROUND: Models of cardiac arrhythmogenesis predict that non-uniformity in repolarization and/or depolarization promotes ventricular fibrillation and is modulated by autonomic tone, but this is difficult to evaluate in patients. We hypothesize that such spatial heterogeneities would be detected by non-invasive ECG imaging (ECGi) in sudden cardiac death (SCD) survivors with structurally normal hearts under physiological stress. METHODS: ECGi was applied to 11 SCD survivors, 10 low-risk Brugada Syndrome patients (BrS) and 10 controls undergoing exercise treadmill testing. ECGi provides whole heart activation maps and > 1200 unipolar electrograms over the ventricular surface from which global dispersion of activation recovery interval (ARI) and regional delay in conduction were determined. These were used as surrogates for spatial heterogeneities in repolarization and depolarization. Surface ECG markers of dispersion (QT and Tpeak-end intervals) were also calculated for all patients for comparison. RESULTS: Following exertion, the SCD group demonstrated the largest increase in ARI dispersion compared to BrS and control groups (13±8 ms vs 4±7 ms vs 4±5 ms; p = 0.009), with baseline dispersion being similar in all groups. In comparison, surface ECG markers of dispersion of repolarisation were unable to discriminate between the groups at baseline or following exertion. Spatial heterogeneities in conduction were also present following exercise but were not significantly different between SCD survivors and the other groups. CONCLUSION: Increased dispersion of repolarization is apparent during physiological stress in SCD survivors and is detectable with ECGi but not with standard ECG parameters. The electrophysiological substrate revealed by ECGi could be the basis of alternative risk-stratification techniques. This article is protected by copyright. All rights reserved.

Journal article

Roney CH, Cantwell CD, Bayer JD, Qureshi NA, Lim PB, Tweedy JH, Kanagaratnam P, Peters NS, Vigmond EJ, Ng Fet al., 2017, Spatial resolution requirements for accurate identification of drivers of atrial fibrillation, Circulation-Arrhythmia and Electrophysiology, Vol: 10, ISSN: 1941-3084

Background—Recent studies have demonstrated conflicting mechanisms underlying atrial fibrillation (AF), with the spatial resolution of data often cited as a potential reason for the disagreement. The purpose of this study was to investigate whether the variation in spatial resolution of mapping may lead to misinterpretation of the underlying mechanism in persistent AF.Methods and Results—Simulations of rotors and focal sources were performed to estimate the minimum number of recording points required to correctly identify the underlying AF mechanism. The effects of different data types (action potentials and unipolar or bipolar electrograms) and rotor stability on resolution requirements were investigated. We also determined the ability of clinically used endocardial catheters to identify AF mechanisms using clinically recorded and simulated data. The spatial resolution required for correct identification of rotors and focal sources is a linear function of spatial wavelength (the distance between wavefronts) of the arrhythmia. Rotor localization errors are larger for electrogram data than for action potential data. Stationary rotors are more reliably identified compared with meandering trajectories, for any given spatial resolution. All clinical high-resolution multipolar catheters are of sufficient resolution to accurately detect and track rotors when placed over the rotor core although the low-resolution basket catheter is prone to false detections and may incorrectly identify rotors that are not present.Conclusions—The spatial resolution of AF data can significantly affect the interpretation of the underlying AF mechanism. Therefore, the interpretation of human AF data must be taken in the context of the spatial resolution of the recordings.

Journal article

Cantwell C, Sherwin S, 2017, Nektar++

Nektar++ is a tensor product based finite element package designed to allow one to construct efficient classical low polynomial order h-type solvers (where h is the size of the finite element) as well as higher p-order piecewise polynomial order solvers.

Software

Moxey D, Cantwell CD, Mengaldo G, Serson D, Ekelschot D, Peiró J, Sherwin SJ, Kirby RMet al., 2017, Towards p-adaptive spectral/hp element methods for modelling industrial flows, ICOSAHOM-2016 - International Conference on Spectral and High-order Methods, Publisher: Springer International Publishing AG, Pages: 63-79, ISSN: 1439-7358

There is an increasing requirement from both academia and industry for high-fidelity flow simulations that are able to accurately capture complicated and transient flow dynamics in complex geometries. Coupled with the growing availability of high-performance, highly parallel computing resources, there is therefore a demand for scalable numerical methods and corresponding software frameworks which can deliver the next-generation of complex and detailed fluid simulations to scientists and engineers in an efficient way. In this article we discuss recent and upcoming advances in the use of the spectral/hp element method for addressing these modelling challenges. To use these methods efficiently for such applications, is critical that computational resolution is placed in the regions of the flow where it is needed most, which is often not known a priori. We propose the use of spatially and temporally varying polynomial order, coupled with appropriate error estimators, as key requirements in permitting these methods to achieve computationally efficient high-fidelity solutions to complex flow problems in the fluid dynamics community.

Conference paper

Roney CH, Cantwell CD, Qureshi NA, Chowdhury RA, Dupont E, Lim PB, Vigmond EJ, Tweedy JH, Ng FS, Peters NSet al., 2016, Rotor tracking using phase of electrograms recorded during atrial fibrillation, Annals of Biomedical Engineering, Vol: 45, Pages: 910-923, ISSN: 1573-9686

Extracellular electrograms recorded during atrial fibrillation (AF) are challenging to interpret due to the inherent beat-to-beat variability in amplitude and duration. Phase mapping represents these voltage signals in terms of relative position within the cycle, and has been widely applied to action potential and unipolar electrogram data of myocardial fibrillation. To date, however, it has not been applied to bipolar recordings, which are commonly acquired clinically. The purpose of this study is to present a novel algorithm for calculating phase from both unipolar and bipolar electrograms recorded during AF. A sequence of signal filters and processing steps are used to calculate phase from simulated, experimental, and clinical, unipolar and bipolar electrograms. The algorithm is validated against action potential phase using simulated data (trajectory centre error <0.8 mm); between experimental multi-electrode array unipolar and bipolar phase; and for wavefront identification in clinical atrial tachycardia. For clinical AF, similar rotational content (R (2) = 0.79) and propagation maps (median correlation 0.73) were measured using either unipolar or bipolar recordings. The algorithm is robust, uses standard signal processing techniques, and accurately quantifies AF wavefronts and sources. Identifying critical sources, such as rotors, in AF, may allow for more accurate targeting of ablation therapy and improved patient outcomes.

Journal article

Moxey D, Cantwell C, Kirby RM, Sherwin Set al., 2016, Optimizing the performance of the spectral/hp element method with collective linear algebra operations, Computer Methods in Applied Mechanics and Engineering, Vol: 310, Pages: 628-645, ISSN: 0045-7825

As computing hardware evolves, increasing core counts mean that memory bandwidth is becomingthe deciding factor in attaining peak performance of numerical methods. High-orderfinite element methods, such as those implemented in the spectral/hp framework Nektar++,are particularly well-suited to this environment. Unlike low-order methods that typicallyutilize sparse storage, matrices representing high-order operators have greater density andricher structure. In this paper, we show how these qualities can be exploited to increaseruntime performance on nodes that comprise a typical high-performance computing system,by amalgamating the action of key operators on multiple elements into a single, memorye!cientblock. We investigate di↵erent strategies for achieving optimal performance acrossa range of polynomial orders and element types. As these strategies all depend on externalfactors such as BLAS implementation and the geometry of interest, we present a techniquefor automatically selecting the most e!cient strategy at runtime.

Journal article

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