ExperimentalMapping of cardiac electrical activation with electromechanical wave imaging: An in silico–in vivo reciprocity study
Introduction
Disturbances in the electrical activation of the heart constitute a major cause of death and disability, affecting millions of people worldwide. However, no imaging method is currently capable of mapping the three-dimensional (3D) electrical activation sequence in the heart for clinical use. Currently available clinical methods are all catheter based, and are thus limited to mapping the endocardial or epicardial activation sequence; they are also time consuming and costly. Newly developed electrocardiographic imaging methods based on high-density body surface potential maps hold high promise for reconstruction of the 3D activation sequence in the heart1, 2 and have demonstrated clinical relevance.3, 4 However, these methods rely on either ionizing exposure, i.e., 3D computed tomography, or magnetic resonance imaging (MRI), which can be contraindicated for patients with pacemakers or stents. Even in a laboratory setting, mapping the 3D electrical activation sequence of the heart can be a daunting task.5 Studies of transmural electrical activation usually require usage of a large number of plunge electrodes to attain sufficient resolution,6, 7, 8 or are applied to small regions of interest in vivo,9 or to small animals, e.g., the rabbit.2 Optical imaging methods can map the activation sequence of ex vivo tissue on the endocardial and epicardial surfaces10, 11, 12 and transmurally.13, 14, 15, 16
Recently, we have developed a novel imaging technique termed electromechanical wave imaging (EWI), which is an entirely noninvasive, nonionizing, ultrasound-based imaging method capable of mapping along various echocardiographic planes in vivo17 the electromechanical activation sequence, i.e., the sequence of first instants at which the muscle transitions from a relaxation to a contraction state following the electrical activation of the heart. Spatially, this electromechanical activation forms a wavefront, i.e., the electromechanical wave (EW), that follows a propagation pattern similar to the electrical activation sequence. EWI maps the EW with high accuracy by using a frame rate up to 7 times higher than that of standard echocardiography. In its essence, EWI uses cross-correlation of the radiofrequency (RF) signals to estimate the minute, electromechanically induced, interframe axial strains at an accuracy and spatial resolution never achieved before in a full view of the heart within a 2- to 3-millisecond-long time interval. Using these interframe axial strains, the timings at which a region in the heart transitions from a relaxing to a contracting state of the heart can be mapped.
EWI has previously been performed in mice,18 dogs,19 and humans.20 These reports have demonstrated correlation of the EW with the pacing protocol and the conduction velocity of the electrical wave,18 and have shown that EWI can be used to determine the location of the pacing site21 and map the presence of ischemic regions.17 Because the only required equipment to perform EWI is a clinical ultrasound scanner,20 the application of EWI as a surrogate for the 3D electrical activation in the ventricles can be flexible and broad, at the doctor's office or point of care, to identify patients at risk, inform caregivers, or plan, monitor, and assist with follow-up of therapeutic interventions such as cardiac resynchronization therapy and ablation. However, to exploit the full potential of EWI in the clinic, it is of paramount importance that the degree to which EWI adequately represents the pattern of 3D electrical activation in the ventricles is explicitly determined.
To perform such an evaluation, the propagation of the EW needs to be compared with the 3D electrical activation in the ventricles, preferably in a large animal heart, such as the canine one. However, currently available experimental methods do not allow for simultaneous mapping of both the EW and the 3D (and in particular, the transmural) electrical activation sequence. Indeed, the spatial resolution of plunge needle recordings is insufficient for the adequate comparison with the EW sequence; moreover, because the strains associated with the EW are minute,17 the insertion of needle electrodes is likely to significantly alter the normal EW.
Because of the limitations in current experimental techniques for mapping the 3D electrical activation sequence with high spatiotemporal resolution, an anatomically realistic modeling approach to cardiac function appears to be an attractive alternative in providing the 3D electrical activation sequence in the ventricles. We developed a high-resolution dynamic model of coupled cardiac electromechanics in the rabbit heart22 and used it to ascertain the mechanisms of spontaneously induced arrhythmias in acute regional ischemia.23 The model was recently extended to the canine heart, where the geometry and structure of the canine heart was reconstructed from MRI and diffusion tensor magnetic resonance (DTMR) imaging scans.24 In this study, we use this novel electromechanics model of the canine heart for the first time and apply it, after optimizing it, to fully assess the utility of EWI in mapping the electrical activation sequence in the canine ventricles.
To achieve this goal, we simulate the EW in the model of the normal canine ventricles and compare the results to the in vivo experimental EW in the canine. Once the match between simulated and experimental EWs is obtained and the predictive capabilities of the canine electromechanics model are established, the EW is compared with the electrical activation sequence obtained from the model, providing the desired relationship between the EW and the 3D electrical activation maps in the canine ventricles, thus assessing the utility of EWI in mapping the electrical activation.
Section snippets
Experimental protocol
In this study, approved by the Institutional Animal Care and Use Committee of Columbia University, 1 male mongrel dog of 28 kg in weight was anesthetized with an intravenous injection of thiopental (10 to 17 mg/kg). The animal was mechanically ventilated with a rate- and volume-regulated ventilator on a mixture of oxygen and titrated isoflurane (0.5% to 5.0%). Morphine (0.15 mg/kg, epidural) was administered before surgery, and lidocaine (50 micrograms/kg/h, intravenous) was used during the
Results
Figures 2A and 2B depict the experimental and simulated EW maps during pacing from the basal region of the lateral wall. Blue and red indicate local compression and expansion of the tissue, respectively, in the direction of the ultrasound beam (Figure 1A). In the view presented here, activation results in expansion (red) throughout the ventricles with the exception of the apical region, which undergoes local compression (blue).17 In both experiments and simulations, the EW emerged from the
Discussion
The EW is a direct, tissue-level result of the cardiac excitation-contraction coupling: the depolarization of a myocyte is followed by contraction after the electromechanical delay. EWI characterizes the electromechanical activation of myofibers by mapping the interframe axial strains. In this study, a realistic canine cardiac electromechanics model was used to reproduce the experimentally obtained EW from 3 different pacing sites to better understand the relationship between EW and the
Acknowledgements
The authors thank Wei-Ning Lee, Kana Fujikura, Edward Ciaccio, Eiichi Hyodo, Asawinee Danpinid, Aram Safarov, and Ihsaan Sebro for their help during experiments; and Heather S. Duffy, Peter Danilo, and Iryna N. Shlapakova for their advice on the experimental procedure. The authors also thank Jianwen Luo and Stanley J. Okrasinski for helpful discussions and Dr. Shunichi Homma for his guidance in the echocardiography scanning efforts.
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2017, Ultrasound in Medicine and BiologyCitation Excerpt :In fact, typical values for transseptal conduction times are in general larger than 40 ms in patients with left bundle branch block (Prinzen and Auricchio 2008). These findings confirm the angle independence of EWI for the assessment of electromechanical activation in vivo as previously established in silico (Provost et al. 2011c). There are several limitations to this study.
Computational modeling of cardiac optogenetics: Methodology overview & review of findings from simulations
2015, Computers in Biology and MedicineCitation Excerpt :The cardiac optogenetics simulation methodology described in the first part of this review is highly versatile and can be used in heart models of arbitrary complexity, simulating diseased stated and different species, and capturing the complex electromechanical response of the heart. Boyle et al. [44] simulated optogenetics-based pacing in a canine model of cardiac electromechanical contraction, within which myofilament shortening was coupled to electrical activation via the intracellular calcium signal at each point in the ventricles [86,87]. For the case shown here, 10 optical stimulation sites were chosen at endocardial locations corresponding to Purkinje system endpoints in the left and right ventricles; for each site, cells within a hemispherical tissue volume (3 mm in diameter) were modeled as light-sensitive and uniform endocardial illumination was applied.
Drs. Trayanova and Konofagou are the senior authors and contributed equally to this work.
This study was supported in part by the National Institutes of Health (R01EB006042, R21HL096094) and the Wallace H. Coulter Foundation. Jean Provost was funded in part by the Natural Sciences and Engineering Research Council of Canada (NSERC) and by Fonds Québécois de la Recherche sur la Nature et les Technologies (FQRNT).