Zhaoye Zhou

Noninvasive cardiac activation imaging of ventricular arrhythmias during drug-induced QT prolongation in the rabbit heart

BACKGROUND Imaging myocardial activation from noninvasive body surface potentials promises to aid in both cardiovascular research and clinical medicine. OBJECTIVE To investigate the ability of a noninvasive 3-dimensional cardiac electrical imaging technique for characterizing the activation patterns of dynamically changing ventricular arrhythmias during drug-induced QT prolongation in rabbits. METHODS Simultaneous body surface potential mapping and 3-dimensional intracardiac mapping were performed in a closed-chest condition in 8 rabbits. Data analysis was performed on premature ventricular complexes, couplets, and torsades de pointes (TdP) induced during intravenous administration of clofilium and phenylephrine with combinations of various infusion rates. RESULTS The drug infusion led to a significant increase in the QT interval (from 175 ± 7 to 274 ± 31 ms) and rate-corrected QT interval (from 183 ± 5 to 262 ± 21 ms) during the first dose cycle. All the ectopic beats initiated by a focal activation pattern. The initial beat of TdPs arose at the focal site, whereas the subsequent beats were due to focal activity from different sites or 2 competing focal sites. The imaged results captured the dynamic shift of activation patterns and were in good correlation with the simultaneous measurements, with a correlation coefficient of 0.65 ± 0.02 averaged over 111 ectopic beats. Sites of initial activation were localized to be ~5 mm from the directly measured initiation sites. CONCLUSIONS The 3-dimensional cardiac electrical imaging technique could localize the origin of activation and image activation sequence of TdP during QT prolongation induced by clofilium and phenylephrine in rabbits. It offers the potential to noninvasively investigate the proarrhythmic effects of drug infusion and assess the mechanisms of arrhythmias on a beat-to-beat basis.

Temporal Sparse Promoting Three Dimensional Imaging of Cardiac Activation

A new Cardiac Electrical Sparse Imaging (CESI) technique is proposed to image cardiac activation throughout the three-dimensional myocardium from body surface electrocardiogram (ECG) with the aid of individualized heart-torso geometry. The sparse property of cardiac electrical activity in the time domain is utilized in the temporal sparse promoting inverse solution, one formulated to achieve higher spatial-temporal resolution, stronger robustness and thus enhanced capability in imaging cardiac electrical activity. Computer simulations were carried out to evaluate the performance of this imaging method under various circumstances. A total of 12 single site pacing and 7 dual sites pacing simulations with artificial and the hospital recorded sensor noise were used to evaluate the accuracy and stability of the proposed method. Simulations with modeling error on heart-torso geometry and electrode-torso registration were also performed to evaluate the robustness of the technique. In addition to the computer simulations, the CESI algorithm was further evaluated using experimental data in an animal model where the noninvasively imaged activation sequences were compared with those measured with simultaneous intracardiac mapping. All of the CESI results were compared with conventional weighted minimum norm solutions. The present results show that CESI can image with better accuracy, stability and stronger robustness in both simulated and experimental circumstances. In sum, we have proposed a novel method for cardiac activation imaging, and our results suggest that the CESI has enhanced performance, and offers the potential to image the cardiac activation and to assist in the clinical management of ventricular arrhythmias.

Noninvasive Imaging of 3-Dimensional Myocardial Infarction From the Inverse Solution of Equivalent Current Density in Pathological Hearts

We propose a new approach to noninvasively image the 3-D myocardial infarction (MI) substrates based on equivalent current density (ECD) distribution that is estimated from the body surface potential maps (BSPMs) during S-T segment. The MI substrates were identified using a predefined threshold of ECD. Computer simulations were performed to assess the performance with respect to: 1) MI locations; 2) MI sizes; 3) measurement noise; 4) numbers of BSPM electrodes; and 5) volume conductor modeling errors. A total of 114 sites of transmural infarctions, 91 sites of epicardial infarctions, and 36 sites of endocardial infarctions were simulated. The simulation results show that: 1) Under 205 electrodes and 10-μV noise, the averaged accuracies of imaging transmural MI are 83.4% for sensitivity, 82.2% for specificity, 65.0% for Dices coefficient, and 6.5 mm for distances between the centers of gravity (DCG). 2) For epicardial infarction, the averaged imaging accuracies are 81.6% for sensitivity, 75.8% for specificity, 45.3% for Dices coefficient, and 7.5 mm for DCG; while for endocardial infarction, the imaging accuracies are 80.0% for sensitivity, 77.0% for specificity, 39.2% for Dices coefficient, and 10.4 mm for DCG. 3) A reasonably good imaging performance was obtained under higher noise levels, fewer BSPM electrodes, and mild volume conductor modeling errors. The present results suggest that this method has the potential to aid in the clinical identification of the MI substrates.

Imaging cardiac activation sequence during ventricular tachycardia in a canine model of nonischemic heart failure

Noninvasive cardiac activation imaging of ventricular tachycardia (VT) is important in the clinical diagnosis and treatment of arrhythmias in heart failure (HF) patients. This study investigated the ability of the three-dimensional cardiac electrical imaging (3DCEI) technique for characterizing the activation patterns of spontaneously occurring and norepinephrine (NE)-induced VTs in a newly developed arrhythmogenic canine model of nonischemic HF. HF was induced by aortic insufficiency followed by aortic constriction in three canines. Up to 128 body-surface ECGs were measured simultaneously with bipolar recordings from up to 232 intramural sites in a closed-chest condition. Data analysis was performed on the spontaneously occurring VTs (n=4) and the NE-induced nonsustained VTs (n=8) in HF canines. Both spontaneously occurring and NE-induced nonsustained VTs initiated by a focal mechanism primarily from the subendocardium, but occasionally from the subepicardium of left ventricle. Most focal initiation sites were located at apex, right ventricular outflow tract, and left lateral wall. The NE-induced VTs were longer, more rapid, and had more focal sites than the spontaneously occurring VTs. Good correlation was obtained between imaged activation sequence and direct measurements (averaged correlation coefficient of ∼0.70 over 135 VT beats). The reconstructed initiation sites were ∼10 mm from measured initiation sites, suggesting good localization in such a large animal model with cardiac size similar to a human. Both spontaneously occurring and NE-induced nonsustained VTs had focal initiation in this canine model of nonischemic HF. 3DCEI is feasible to image the activation sequence and help define arrhythmia mechanism of nonischemic HF-associated VTs.

Noninvasive Imaging of High Frequency Drivers and Reconstruction of Global Dominant Frequency Maps in Patients with Paroxysmal and Persistent Atrial Fibrillation.

Objective: Highest dominant-frequency (DF) drivers maintaining atrial fibrillation (AF) activities are effective ablation targets for restoring sinus rhythms in patients. This study aims to investigate whether AF drivers with highest activation rate can be noninvasively localized by means of a frequency-based cardiac electrical imaging (CEI) technique, which may aid in the planning of ablation strategy and the investigation of the underlying mechanisms of AF. Method: A total of seven out of 13 patients were recorded with spontaneous paroxysmal or persistent AF and analyzed. The biatrial DF maps were reconstructed by coupling 5-s BSPM with CT-determined patient geometry. The CEI results were compared with ablation sites and DFs found from BSPMs. Results: CEI imaged left-to-right maximal frequency gradient (7.42 ± 0.66 Hz versus 5.85 ± 1.2 Hz, LA versus RA, p <; 0.05) in paroxysmal AF patients. Patients with persistent AF were imaged with a loss of the intrachamber frequency gradient and a dispersion of the fast sources in both chambers. CEI was able to capture the AF behaviors, which were characterized by short-term stability, dynamic transition, and spatial repetition of the highest DF sites. The imaged highest DF sites were consistent with ablation sites in patients studied. Conclusions: The frequency-based CEI allows localization of AF drivers with highest DF and characterization of the spatiotemporal frequency behaviors, suggesting the possibility for individualizing treatment strategy and advancing understanding of the underlying AF mechanisms. Significance : The establishment of noninvasive imaging techniques localizing AF drivers would facilitate management of this significant cardiac arrhythmia.

Three-Dimensional Noninvasive Imaging of Ventricular Arrhythmias in Patients With Premature Ventricular Contractions

Objective: Noninvasive imaging of cardiac electrical activity promises to provide important information regarding the underlying arrhythmic substrates for successful ablation intervention and further understanding of the mechanism of such lethal disease. The aim of this study is to evaluate the performance of a novel 3-D cardiac activation imaging technique to noninvasively localize and image origins of focal ventricular arrhythmias in patients undergoing radio frequency ablation. Methods: Preprocedural ECG gated contrast enhanced cardiac CT images and body surface potential maps were collected from 13 patients within a week prior to the ablation. The electrical activation images were estimated over the 3-D myocardium using a cardiac electric sparse imaging technique, and compared with CARTO activation maps and the ablation sites in the same patients. Results : Noninvasively-imaged activation sequences were consistent with the CARTO mapping results with an average correlation coefficient of 0.79, average relative error of 0.19, and average relative resolution error of 0.017. The imaged initiation sites of premature ventricular contractions (PVCs) were, on average, within 8 mm of the last successful ablation site and within 3 mm of the nearest ablation site. Conclusion: The present results demonstrate the excellent performance of the 3-D cardiac activation imaging technique in imaging the activation sequence associated with PVC, and localizing the initial sites of focal ventricular arrhythmias in patients. These promising results suggest that the 3-D cardiac activation imaging technique may become a useful tool for aiding clinical diagnosis and management of ventricular arrhythmias.

Noninvasive Imaging of Human Atrial Activation during Atrial Flutter and Normal Rhythm from Body Surface Potential Maps.

Background Knowledge of atrial electrophysiological properties is crucial for clinical intervention of atrial arrhythmias and the investigation of the underlying mechanism. This study aims to evaluate the feasibility of a novel noninvasive cardiac electrical imaging technique in imaging bi-atrial activation sequences from body surface potential maps (BSPMs). Methods The study includes 7 subjects, with 3 atrial flutter patients, and 4 healthy subjects with normal atrial activations. The subject-specific heart-torso geometries were obtained from MRI/CT images. The equivalent current densities were reconstructed from 208-channel BSPMs by solving the inverse problem using individual heart-torso geometry models. The activation times were estimated from the time instant corresponding to the highest peak in the time course of the equivalent current densities. To evaluate the performance, a total of 32 cycles of atrial flutter were analyzed. The imaged activation maps obtained from single beats were compared with the average maps and the activation maps measured from CARTO, by using correlation coefficient (CC) and relative error (RE). Results The cardiac electrical imaging technique is capable of imaging both focal and reentrant activations. The imaged activation maps for normal atrial activations are consistent with findings from isolated human hearts. Activation maps for isthmus-dependent counterclockwise reentry were reconstructed on three patients with typical atrial flutter. The method was capable of imaging macro counterclockwise reentrant loop in the right atrium and showed inter-atria electrical conduction through coronary sinus. The imaged activation sequences obtained from single beats showed good correlation with both the average activation maps (CC = 0.91±0.03, RE = 0.29±0.05) and the clinical endocardial findings using CARTO (CC = 0.70±0.04, RE = 0.42±0.05). Conclusions The noninvasive cardiac electrical imaging technique is able to reconstruct complex atrial reentrant activations and focal activation patterns in good consistency with clinical electrophysiological mapping. It offers the potential to assist in radio-frequency ablation of atrial arrhythmia and help defining the underlying arrhythmic mechanism.

Estimation of activation sequence from time course of equivalent current density in pathological hearts — A simulation study

The equivalent current density (ECD) model has been previously used in the cardiac electrical imaging technique for non-invasively reconstructing the global activation sequence (AS) in the normal heart. However, its performance in estimating AS in the heart with structural defects remains uncertain. This study aims to evaluate its feasibility in two common cardiac structure diseases-ischemia and infarction, by performing forward simulation using a cellular automaton heart model. The AS was derived from ECD and quantitatively compared to the true AS simulated with the heart model by calculating correlation coefficient (CC) and relative error (RE). In ischemia condition, the ECD model returns a CC (0.97) and RE (0.13), comparable with those of normal heart. In infarction condition, it is also able to identify area of infarction and reconstruct global AS at the excitable myocardium with CC of 0.97 and RE of 0.12. The present pilot simulation results suggest the feasibility of applying ECD model in the pathological heart, which would help the investigation of pathology mechanism and clinical management of cardiac diseases.