Remotely detuned receiver coil for high-resolution interventional cardiac magnetic resonance imaging.

Introduction: Interventional cardiac MRI in the context of the treatment of cardiac arrhythmia requires submillimeter image resolution to precisely characterize the cardiac substrate and guide the catheter-based ablation procedure in real-time. Conventional MRI receiver coils positioned on the thorax provide insufficient signal-to-noise ratio (SNR) and spatial selectivity to satisfy these constraints. Methods: A small circular MRI receiver coil was developed and evaluated under different experimental conditions, including high-resolution MRI anatomical and thermometric imaging at 1.5 T. From the perspective of developing a therapeutic MR-compatible catheter equipped with a receiver coil, we also propose alternative remote active detuning techniques of the receiver coil using one or two cables. Theoretical details are presented, as well as simulations and experimental validation. Results: Anatomical images of the left ventricle at 170 µm in-plane resolution are provided on ex vivo beating heart from swine using a 2 cm circular receiver coil. Taking advantage of the increase of SNR at its vicinity (up to 35 fold compared to conventional receiver coils), real-time MR-temperature imaging can reach an uncertainty below 0.1°C at the submillimetric spatial resolution. Remote active detuning using two cables has similar decoupling efficiency to conventional on-site decoupling, at the cost of an acceptable decrease in the resulting SNR. Discussion: This study shows the potential of small dimension surface coils for minimally invasive therapy of cardiac arrhythmia intraoperatively guided by MRI. The proposed remote decoupling approaches may simplify the construction process and reduce the cost of such single-use devices.

Investigation into the importance of using natural PVCs and pathological models for potential-based ECGI validation.

Introduction: Premature ventricular contractions (PVCs) are one of the most commonly targeted pathologies for ECGI validation, often through ventricular stimulation to mimic the ectopic beat. However, it remains unclear if such stimulated beats faithfully reproduce spontaneously occurring PVCs, particularly in the case of the R-on-T phenomenon. The objective of this study was to determine the differences in ECGI accuracy when reconstructing spontaneous PVCs as compared to ventricular-stimulated beats and to explore the impact of pathophysiological perturbation on this reconstruction accuracy. Methods: Langendorff-perfused pig hearts (n = 3) were suspended in a human torso-shaped tank, and local hyperkalemia was induced through perfusion of a high-K+ solution (8 mM) into the LAD. Recordings were taken simultaneously from the heart and tank surfaces during ventricular pacing and during spontaneous PVCs (including R-on-T), both at baseline and high K+. Epicardial potentials were reconstructed from torso potentials using ECGI. Results: Spontaneously occurring PVCs were better reconstructed than stimulated beats at baseline in terms of electrogram morphology [correlation coefficient (CC) = 0.74 ± 0.05 vs. CC = 0.60 ± 0.10], potential maps (CC = 0.61 ± 0.06 vs. CC = 0.51 ± 0.12), and activation time maps (CC = 0.86 ± 0.07 vs. 0.76 ± 0.10), though there was no difference in the localization error (LE) of epicardial origin (LE = 14 ± 6 vs. 15 ± 11 mm). High K+ perfusion reduced the accuracy of ECGI reconstructions in terms of electrogram morphology (CC = 0.68 ± 0.10) and AT maps (CC = 0.70 ± 0.12 and 0.59 ± 0.23) for isolated PVCs and paced beats, respectively. LE trended worse, but the change was not significant (LE = 17 ± 9 and 20 ± 12 mm). Spontaneous PVCs were less well when the R-on-T phenomenon occurred and the activation wavefronts encountered a line of block. Conclusion: This study demonstrates the differences in ECGI accuracy between spontaneous PVCs and ventricular-paced beats. We also observed a reduction in this accuracy near regions of electrically inactive tissue. These results highlight the need for more physiologically realistic experimental models when evaluating the accuracy of ECGI methods. In particular, reconstruction accuracy needs to be further evaluated in the presence of R-on-T or isolated PVCs, particularly when encountering obstacles (functional or anatomical) which cause line of block and re-entry.

Assessment of Cardiac Toxicity of Manganese Chloride for Cardiovascular Magnetic Resonance.

MRI is widely used in cardiology to characterize the structure and function of the heart. Currently, gadolinium-based contrast agents are widely used to improve sensitivity and specificity of diagnostic images. Recently, Manganese, a calcium analogue, has emerged as a complementary contrast agent with the potential to reveal remaining viable cells within altered tissue. Imaging applications may be limited by substantial toxicity of manganese. Indeed, cardiac safety of manganese is not yet comprehensively assessed. In this study we investigated the effect of MnCl2 (1-100 µM) on cardiac function. Hemodynamic function was determined ex vivo using an isolated working rat heart preparation. HL-1 cardiac myocytes were used to investigate cell viability (calcein AM) and calcium cycling (Cal-520 a.m.). Rat ventricular cardiomyocytes were dissociated by enzymatic digestion. Action potentials and calcium currents were recorded using the patch clamp technique. MRI experiments were performed at 1.5T on formalin-fixed rat hearts, previously perfused with MnCl2. MnCl2 perfusion from 1 up to 100 µM in isolated working hearts did not alter left ventricular hemodynamic parameters. Contractility and relaxation index were not altered up to 50 µM MnCl2. In HL-1 cardiac myocytes, incubation with increasing concentrations of MnCl2 did not impact cell viability. The amplitude of the calcium transients were significantly reduced at 50 and 100 µM MnCl2. In freshly isolated ventricular myocytes, action potential duration at 20, 50 and 90% of repolarization were not modified up to 10 µM of MnCl2. L-type calcium current amplitude was significantly decreased by 50 and 100 µM of MnCl2. MRI on heart perfused with 25 and 100 µM of MnCl2 showed a dose dependent decrease in the T1 relaxation time. In conclusion, our results show that low concentrations of MnCl2 (up to 25 µM) can be used as a contrast agent in MRI, without significant impact on cardiac hemodynamic or electrophysiology parameters.

Spectral Analysis of Tissue Displacement for Cardiac Activation Mapping: Ex Vivo Working Heart and In Vivo Study.

Characterizing myocardial activation is of major interest for understanding the underlying mechanism of cardiac arrhythmias. Electromechanical wave imaging (EWI) is an ultrafast ultrasound-based method used to map the propagation of the local contraction triggered by electrical activation of the heart. This study introduces a novel way to characterize cardiac activation based on the time evolution of the instantaneous frequency content of the cardiac tissue displacement curves. The first validation of this method was performed on an ex vivo dataset of 36 acquisitions acquired from two working heart models in paced rhythms. It was shown that the activation mapping described by spectral analysis of interframe displacement is similar to the standard EWI method based on zero-crossing of interframe strain. An average median error of 3.3 ms was found in the ex vivo dataset between the activation maps obtained with the two methods. The feasibility of mapping cardiac activation by EWI was then investigated on two open-chest pigs during sinus and paced rhythms in a pilot trial of cardiac mapping with an intracardiac probe. Seventy-five acquisitions were performed with reasonable stability and analyzed with the novel algorithm to map cardiac contraction propagation in the left ventricle (LV). Sixty-one qualitatively continuous isochrones were successfully computed based on this method. The region of contraction onset was coherently described while pacing in the imaging plane. These findings highlight the potential of implementing EWI acquisition on intracardiac probes and emphasize the benefit of performing short time-frequency analysis of displacement data to characterize cardiac activation in vivo.

Noninvasive detection of spatiotemporal activation-repolarization interactions that prime idiopathic ventricular fibrillation.

A comprehensive understanding of the interaction between triggers and electrical substrates leading to ventricular fibrillation (VF) and sudden cardiac arrest is lacking, and electrical substrates are difficult to detect and localize with current clinical tools. Here, we created repolarization time (RT) dispersion by regional drug infusion in perfused explanted human (n = 1) and porcine (n = 6) hearts and in a computational model of the human ventricle. Arrhythmia induction was tested with a single ventricular extrastimulus applied at the early or late RT region. Arrhythmias could only be induced from early RT regions. Vulnerability to VF increased with RT gradient steepness and with larger areas of early RT, but not with markers on the body-surface electrocardiogram. Noninvasive electrocardiographic imaging was performed in survivors of idiopathic VF (n = 11), patients with frequent premature ventricular complexes (PVCs) but no history of sudden cardiac arrest (n = 7), and controls (n = 10). In survivors of idiopathic VF, RT gradients were steeper than in controls, without differences in the clinical electrocardiogram, consistent with the ex vivo results. Patients with idiopathic VF also showed local myocardial regions with distinctly early-versus-late RT that were more balanced in size than in controls. Premature beats originated more often from the early RT regions in idiopathic VF survivors than in patients with frequent PVCs only. Thus, idiopathic VF emerges from the spatiotemporal interaction of a premature beat from an early-repolarization region with critical repolarization dispersion in that region. Electrocardiographic imaging can uncover the co-occurrence of these abnormalities.

Localized Pulmonary Vein Scar Promotes Atrial Fibrillation in High Left Atrial Pressure.

BACKGROUND: Pulmonary vein (PV) ablation is unsuccessful in atrial fibrillation (AF) patients with high left atrial (LA) pressure. Increased atrial stretch by increased pressure is proarrhythmic for AF, and myocardial scar alters wall deformation. We hypothesized that localized PV scar is proarrhythmic for AF in high LA pressure. METHODS: Radiofrequency energy was delivered locally in the right PV of healthy sheep. The sheep recovered for 4 months. Explanted hearts (n = 9 PV scar, n = 9 controls) were perfused with 1:4 blood:Tyrode's solution in a four-chamber working heart setup. Programmed PV stimulation was performed during low (∼12 mmHg) and high (∼25 mmHg) LA pressure. An AF inducibility index was calculated based on the number of induction attempts and the number of attempts causing AF (run of ≥ 20 premature atrial complexes). RESULTS: In high LA pressure, the presence of PV scar increased the AF inducibility index compared with control hearts (0.83 ± 0.20 vs. 0.38 ± 0.40 arb. unit, respectively, p = 0.014). The diastolic stimulation threshold in high LA pressure was higher (108 ± 23 vs. 77 ± 16 mA, respectively, p = 0.006), and its heterogeneity was increased in hearts with PV scar compared with controls. In high LA pressure, the refractory period was shorter in PV scar than in control hearts (178 ± 39 vs. 235 ± 48 ms, p = 0.011). CONCLUSION: Localized PV scar only in combination with increased LA pressure facilitated the inducibility of AF. This was associated with changes in tissue excitability remote from the PV scar. Localized PV ablation is potentially proarrhythmic in patients with increased LA pressure.

3-Dimensional ventricular electrical activation pattern assessed from a novel high-frequency electrocardiographic imaging technique: principles and clinical importance.

The study introduces and validates a novel high-frequency (100-400 Hz bandwidth, 2 kHz sampling frequency) electrocardiographic imaging (HFECGI) technique that measures intramural ventricular electrical activation. Ex-vivo experiments and clinical measurements were employed. Ex-vivo, two pig hearts were suspended in a human-torso shaped tank using surface tank electrodes, epicardial electrode sock, and plunge electrodes. We compared conventional epicardial electrocardiographic imaging (ECGI) with intramural activation by HFECGI and verified with sock and plunge electrodes. Clinical importance of HFECGI measurements was performed on 14 patients with variable conduction abnormalities. From 3 × 4 needle and 108 sock electrodes, 256 torso or 184 body surface electrodes records, transmural activation times, sock epicardial activation times, ECGI-derived activation times, and high-frequency activation times were computed. The ex-vivo transmural measurements showed that HFECGI measures intramural electrical activation, and ECGI-HFECGI activation times differences indicate endo-to-epi or epi-to-endo conduction direction. HFECGI-derived volumetric dyssynchrony was significantly lower than epicardial ECGI dyssynchrony. HFECGI dyssynchrony was able to distinguish between intraventricular conduction disturbance and bundle branch block patients.

Single-Particle Tracking Method in Fluorescence Microscopy to Monitor Bioenergetic Responses of Individual Mitochondria.

The spectroscopic methods commonly used to study mitochondria bioenergetics do not show the diversity of responses within a population of mitochondria (isolated or in a cell), and/or cannot measure individual dynamics. New methodological developments are necessary in order to improve quantitative and kinetic resolutions and eventually gain further insights on individual mitochondrial responses, such as studying activities of the mitochondrial permeability transition pore (mPTP ). The work reported herein is devoted to study responses of single mitochondria within a large population after isolation from cardiomyocytes. Mitochondria were preloaded with a commonly used membrane potential sensitive dye (TMRM), they are then deposited on a plasma-treated glass coverslip and subsequently energized or inhibited by additions of usual bioenergetics effectors. Responses were analyzed by fluorescence microscopy over few thousands of mitochondria simultaneously with a single organelle resolution. We report an automatic method to analyze each image of time-lapse stacks based on the TrackMate-ImageJ plug-in and specially made Python scripts. Images are processed to eliminate defects of illumination inhomogeneity, improving by at least two orders of magnitude the signal/noise ratio. This method enables us to follow the track of each mitochondrion within the observed field and monitor its fluorescence changes, with a time resolution of 400 ms, uninterrupted over the course of the experiment. Such methodological improvement is a prerequisite to further study the role of mPTP in single mitochondria during calcium transient loading.

A novel method to correct repolarization time estimation from unipolar electrograms distorted by standard filtering.

Reliable patient-specific ventricular repolarization times (RTs) can identify regions of functional block or afterdepolarizations, indicating arrhythmogenic cardiac tissue and the risk of sudden cardiac death. Unipolar electrograms (UEs) record electric potentials, and the Wyatt method has been shown to be accurate for estimating RT from a UE. High-pass filtering is an important step in processing UEs, however, it is known to distort the T-wave phase of the UE, which may compromise the accuracy of the Wyatt method. The aim of this study was to examine the effects of high-pass filtering, and improve RT estimates derived from filtered UEs. We first generated a comprehensive set of UEs, corresponding to early and late activation and repolarization, that were then high-pass filtered with settings that mimicked the CARTO filter. We trained a deep neural network (DNN) to output a probabilistic estimation of RT and a measure of confidence, using the filtered synthetic UEs and their true RTs. Unfiltered ex-vivo human UEs were also filtered and the trained DNN used to estimate RT. Even a modest 2 Hz high-pass filter imposes a significant error on RT estimation using the Wyatt method. The DNN outperformed the Wyatt method in 62.75% of cases, and produced a significantly lower absolute error (p=8.99E-13), with a median of 16.91 ms, on 102 ex-vivo UEs. We also applied the DNN to patient UEs from CARTO, from which an RT map was computed. In conclusion, DNNs trained on synthetic UEs improve the RT estimation from filtered UEs, which leads to more reliable repolarization maps that help to identify patient-specific repolarization abnormalities.

Electrocardiographic Imaging of Repolarization Abnormalities.

Background Dispersion and gradients in repolarization have been associated with life-threatening arrhythmias, but are difficult to quantify precisely from surface electrocardiography. The objective of this study was to evaluate electrocardiographic imaging (ECGI) to noninvasively detect repolarization-based abnormalities. Methods and Results Ex vivo data were obtained from Langendorff-perfused pig hearts (n=8) and a human donor heart. Unipolar electrograms were recorded simultaneously during sinus rhythm from an epicardial sock and the torso-shaped tank within which the heart was suspended. Regional repolarization heterogeneities were introduced through perfusion of dofetilide and pinacidil into separate perfusion beds. In vivo data included torso and epicardial potentials recorded simultaneously in anesthetized, closed-chest pigs (n=5), during sinus rhythm, and ventricular pacing. For both data sets, ECGI accurately reconstructed T-wave electrogram morphologies when compared with those recorded by the sock (ex vivo: correlation coefficient, 0.85 [0.52-0.96], in vivo: correlation coefficient, 0.86 [0.52-0.96]) and repolarization time maps (ex-vivo: correlation coefficient, 0.73 [0.63-0.83], in vivo: correlation coefficient, 0.76 [0.67-0.82]). ECGI-reconstructed repolarization time distributions were strongly correlated to those measured by the sock (both data sets, R2 ≥0.92). Although the position of the gradient was slightly shifted by 8.3 (0-13.9) mm, the mean, max, and SD between ECGI and recorded gradient values were highly correlated (R2=0.87, 0.75, and 0.86 respectively). There was no significant difference in ECGI accuracy between ex vivo and in vivo data. Conclusions ECGI reliably and accurately maps potentially critical repolarization abnormalities. This noninvasive approach allows imaging and quantifying individual parameters of abnormal repolarization-based substrates in patients with arrhythmogenesis, to improve diagnosis and risk stratification.

Critical repolarization gradients determine the induction of reentry-based torsades de pointes arrhythmia in models of long QT syndrome.

BACKGROUND: Torsades de pointes arrhythmia is a potentially lethal polymorphic ventricular tachyarrhythmia (pVT) in the setting of long QT syndrome. Arrhythmia susceptibility is influenced by risk factors modifying repolarization. OBJECTIVE: The purpose of this article was to characterize repolarization duration and heterogeneity in relation to pVT inducibility and maintenance. METHODS: Sotalol was infused regionally or globally in isolated Langendorff blood-perfused pig hearts (N = 7) to create repolarization time (RT) heterogeneities. Programmed stimulation and epicardial activation and repolarization mapping were performed. The role of RT (heterogeneities) was studied in more detail using a computer model of the human heart. RESULTS: pVTs (n = 11) were inducible at a critical combination of RT and RT heterogeneities. The pVT cycle lengths were similar in the short and long RT regions. Short-lasting pVTs were maintained by focal activity while longer-lasting pVTs by reentry wandering along the interface between the 2 regions. Local restitution curves from the long and short RT regions crossed. This was associated with T-wave inversion at coupling intervals at either side of the crossing point. These experimental observations were confirmed by the computer simulations. CONCLUSION: pVTs are inducible within a critical range of RT and RT heterogeneities and are maintained by reentry wandering along the repolarization gradient. Double potentials localize at the core of the reentrant circuit and reflect phase singularities. RT gradient and T waves invert with short-coupled premature beats in the long RT region as a result of the crossing of the restitution curves allowing reentry initiation.

Body Surface Mapping of Ventricular Repolarization Heterogeneity: An Ex-vivo Multiparameter Study.

BACKGROUND: Increased heterogeneity of ventricular repolarization is associated with life-threatening arrhythmia and sudden cardiac death (SCD). T-wave analysis through body surface potential mapping (BSPM) is a promising tool for risk stratification, but the clinical effectiveness of current electrocardiographic indices is still unclear, with limited experimental validation. This study aims to investigate performance of non-invasive state-of-the-art and novel T-wave markers for repolarization dispersion in an ex vivo model. METHODS: Langendorff-perfused pig hearts (N = 7) were suspended in a human-shaped 256-electrode torso tank. Tank potentials were recorded during sinus rhythm before and after introducing repolarization inhomogeneities through local perfusion with dofetilide and/or pinacidil. Drug-induced repolarization gradients were investigated from BSPMs at different experiment phases. Dispersion of electrical recovery was quantified by duration parameters, i.e., the time interval between the peak and the offset of T-wave (TPEAK-TEND) and QT interval, and variability over time and electrodes was also assessed. The degree of T-wave symmetry to the peak was quantified by the ratio between the terminal and initial portions of T-wave area (Asy). Morphological variability between left and right BSPM electrodes was measured by dynamic time warping (DTW). Finally, T-wave organization was assessed by the complexity of repolarization index (CR), i.e., the amount of energy non-preserved by the dominant eigenvector computed by principal component analysis (PCA), and the error between each multilead T-wave and its 3D PCA approximation (NMSE). Body surface indices were compared with global measures of epicardial dispersion of repolarization, and with local gradients between adjacent ventricular sites. RESULTS: After drug intervention, both regional and global repolarization heterogeneity were significantly enhanced. On the body surface, TPEAK-TEND was significantly prolonged and less stable in time in all experiments, while QT interval showed higher variability across the interventions in terms of duration and spatial dispersion. The rising slope of the repolarization profile was steeper, and T-waves were more asymmetric than at baseline. Interventricular shape dissimilarity was enhanced by repolarization gradients according to DTW. Organized T-wave patterns were associated with abnormal repolarization, and they were properly described by the first principal components. CONCLUSION: Repolarization heterogeneity significantly affects T-wave properties, and can be non-invasively captured by BSPM-based metrics.

High Frame Rate Ultrasound for Electromechanical Wave Imaging to Differentiate Endocardial From Epicardial Myocardial Activation.

Differentiation between epicardial and endocardial ventricular activation remains a challenge despite the latest technologies available. The aim of the present study was to develop a new tool method, based on electromechanical wave imaging (EWI), to improve arrhythmogenic substrate activation analysis. Experiments were conducted on left ventricles (LVs) of four isolated working mode swine hearts. The protocol aimed at demonstrating that different patterns of mechanical activation could be observed whether the ventricle was in sinus rhythm, paced from the epicardium or from the endocardium. A total of 72 EWI acquisitions were recorded on the anterior, lateral and posterior segments of the LV. A total of 54 loop records were blindly assigned to two readers. EWI sequences interpretations were correct in 89% of cases. The overall agreement rate between the two readers was 83%. When in a paced ventricle, the origin of the wave front was focal and originated from the endocardium or the epicardium. In sinus rhythm, wave front was global and activated within the entire endocardium toward the epicardium at a speed of 1.7 ± 0.28 m·s-1. Wave front speeds were respectively measured when the endocardium or the epicardium were paced at a speed of 1.1 ± 0.35 m·s-1 versus 1.3 ± 0.34 m·s-1 (p = NS). EWI activation mapping allows activation localization within the LV wall and calculation of the wave front propagation speed through the muscle. In the future, this technology could help localize activation within the LV thickness during complex ablation procedures.

Advantages and pitfalls of noninvasive electrocardiographic imaging.

BACKGROUND: With increasing clinical use of Electrocardiographic Imaging (ECGI), it is imperative to understand the limits of this technique. The objective of this study is to evaluate a potential-based ECGI approach for activation and repolarization mapping in sinus rhythm. METHOD: Langendorff-perfused pig hearts were suspended in a human-shaped torso tank. Electrograms were recorded with a 108-electrode sock and ECGs with 256 electrodes embedded in the tank surface. Left bundle branch block (LBBB) was developed in 4 hearts through ablation, and repolarization abnormalities in another 4 hearts through regional perfusion of dofetilide and pinacidil. Electrograms were noninvasively reconstructed and reconstructed activation and repolarization features were compared to those recorded. RESULTS: Visual consistency between ECGI and recorded activation and repolarization maps was high. While reconstructed repolarization times showed significantly more error than activation times quantitatively, patterns were reconstructed with a similar level of accuracy. The number of epicardial breakthrough sites was underestimated by ECGI and these were misplaced (>20 mm) in location. Likewise, ECGI reconstructed activation maps demonstrated artificial lines of block resulting from a W-shaped QRS waveform that were not present in recorded maps. Nevertheless, ECGI allowed identification of regions of abnormal repolarization reasonably accurately in terms of size, location and timing. CONCLUSIONS: This study validates a potential-based ECGI approach to noninvasively image activation and recovery in sinus rhythm. Despite inaccuracies in epicardial breakthroughs and lines of conduction block, other important clinical features such as regions of abnormal repolarization can be accurately derived making ECGI a valuable clinical tool.

Optical Imaging of Ventricular Action Potentials in a Torso Tank: A New Platform for Non-Invasive Electrocardiographic Imaging Validation.

Background: Non-invasive electrocardiographic imaging (ECGI) is a promising tool to provide high-resolution panoramic imaging of cardiac electrical activity noninvasively from body surface potential measurements. Current experimental methods for ECGI validation are limited to comparison with unipolar electrograms and the relatively low spatial resolution of cardiac mapping arrays. We aim to develop a novel experimental set up combining a human shaped torso tank with high-resolution optical mapping allowing the validation of ECGI reconstructions. Methods: Langendorff-perfused pig hearts (n = 3) were suspended in a human torso-shaped tank, with the left anterior descending artery (LAD) cannulated on a separate perfusion. Electrical signals were recorded from an 108-electrode epicardial sock and 128 electrodes embedded in the tank surface. Simultaneously, optical mapping of the heart was performed through the anterior surface of the tank. Recordings were made in sinus rhythm and ventricular pacing (n = 55), with activation and repolarization heterogeneities induced by perfusion of hot and cold solutions as well as Sotalol through the LAD. Fluoroscopy provided 3D cardiac and electrode geometries in the tank that were transformed to the 2D optical mapping window using an optimization algorithm. Epicardial unipolar electrograms were reconstructed from torso potentials using ECGI and validated using optical activation and repolarization maps. Results: The transformation and alignment of the 3D geometries onto the 2D optical mapping window was good with an average correlation of 0.87 ± 0.10 and error of 7.7 ± 3.1 ms with activation derived from the sock. The difference in repolarization times were more substantial (error = 17.4 ± 3.7 ms) although the sock and optical repolarization patterns themselves were very similar (correlation = 0.83 ± 0.13). Validation of ECGI reconstructions revealed ECGI accurately captures the pattern of activation (correlation = 0.79 ± 0.11) and identified regions of late and/or early repolarization during different perfusions through LAD. ECGI also correctly demonstrated gradients in both activation and repolarization, although in some cases these were under or over-estimated or shifted slightly in space. Conclusion: A novel experimental setup has been developed, combining a human-shaped torso tank with optical mapping, which can be effectively used in the validation of ECGI techniques; including the reconstruction of activation and repolarization patterns and gradients.

Myocardial Thermal Ablation with a Transesophageal High-Intensity Focused Ultrasound Probe: Experiments on Beating Heart Models.

Described here is a study of transesophageal thermal ablation of isolated and perfused beating hearts and non-human primates. An endoscope integrating a transesophageal echocardiography probe and a high-intensity focused ultrasound transducer was built and tested on five Langendorff-isolated hearts and three 30-kg baboons. B-Mode ultrasound, passive elastography and magnetic resonance imaging were performed to monitor thermal lesions. In isolated hearts, continuous and gated sonication parameters were evaluated with acoustic intensities of 9-12 W/cm2. Sonication parameters of gated exposures with 12 W/cm2 acoustic intensity for 5 min consistently produced visible lesions in the ventricles of isolated hearts. In animals, left atria and ventricles were exposed to repeated continuous sonications (4-15 times for 16 s) at an acoustic intensity at the surface of the transducer of 9 W/cm2. Clinical states of the baboons during and after the treatment were good. One suspected lesion in the left ventricle could be evidenced by elastography, but was not confirmed by magnetic resonance imaging. The transesophageal procedure therefore has the potential to create thermal lesions in beating hearts and its safety in clinical practice seems promising. However, further technical exploration of the energy deposition in the target would be necessary before the next pre-clinical experiments.

Chronic hypoxia aggravates monocrotaline-induced pulmonary arterial hypertension: a rodent relevant model to the human severe form of the disease.

Pulmonary arterial hypertension (PAH) is a severe form of pulmonary hypertension that combines multiple alterations of pulmonary arteries, including, in particular, thrombotic and plexiform lesions. Multiple-pathological-insult animal models, developed to more closely mimic this human severe PAH form, often require complex and/or long experimental procedures while not displaying the entire panel of characteristic lesions observed in the human disease. In this study, we further characterized a rat model of severe PAH generated by combining a single injection of monocrotaline with 4 weeks exposure to chronic hypoxia. This model displays increased pulmonary arterial pressure, right heart altered function and remodeling, pulmonary arterial inflammation, hyperresponsiveness and remodeling. In particular, severe pulmonary arteriopathy was observed, with thrombotic, neointimal and plexiform-like lesions similar to those observed in human severe PAH. This model, based on the combination of two conventional procedures, may therefore be valuable to further understand the pathophysiology of severe PAH and identify new potential therapeutic targets in this disease.