Classification of lung pathologies in neonates using dual-tree complex wavelet transform.

INTRODUCTION: Undiagnosed and untreated lung pathologies are among the leading causes of neonatal deaths in developing countries. Lung Ultrasound (LUS) has been widely accepted as a diagnostic tool for neonatal lung pathologies due to its affordability, portability, and safety. However, healthcare institutions in developing countries lack well-trained clinicians to interpret LUS images, which limits the use of LUS, especially in remote areas. An automated point-of-care tool that could screen and capture LUS morphologies associated with neonatal lung pathologies could aid in rapid and accurate diagnosis. METHODS: We propose a framework for classifying the six most common neonatal lung pathologies using spatially localized line and texture patterns extracted via 2D dual-tree complex wavelet transform (DTCWT). We acquired 1550 LUS images from 42 neonates with varying numbers of lung pathologies. Furthermore, we balanced our data set to avoid bias towards a pathology class. RESULTS: Using DTCWT and clinical features as inputs to a linear discriminant analysis (LDA), our approach achieved a per-image cross-validated classification accuracy of 74.39% for the imbalanced data set. Our classification accuracy improved to 92.78% after balancing our data set. Moreover, our proposed framework achieved a maximum per-subject cross-validated classification accuracy of 64.97% with an imbalanced data set while using a balanced data set improves its classification accuracy up to 81.53%. CONCLUSION: Our work could aid in automating the diagnosis of lung pathologies among neonates using LUS. Rapid and accurate diagnosis of lung pathologies could help to decrease neonatal deaths in healthcare institutions that lack well-trained clinicians, especially in developing countries.

Information theory to tachycardia therapy: electrogram entropy predicts diastolic microstructure of reentrant ventricular tachycardia.

There is no known strategy to differentiate which multicomponent electrograms in sinus rhythm maintain reentrant ventricular tachycardia (VT). Low entropy in the voltage breakdown of a multicomponent electrogram can localize conditions suitable for reentry but has not been validated against the classic VT activation mapping. We examined whether low entropy in a late and diversely activated ventricular scar region characterizes and differentiates the diastolic path of VT and represents protected tissue channels devoid of side branches. Intraoperative bipolar electrogram (BiEGM) activation and entropy maps were obtained during sinus rhythm in 17 patients with ischemic cardiomyopathy and compared with diastolic activation paths of VT (total of 39 VTs). Mathematical modeling of a zigzag main channel with side branches was also used to further validate structural representation of low entropy in the ventricular scar. A median of one region per patient (range: 1-2 regions) was identified in sinus rhythm, in which BiEGM with the latest mean activation time and adjacent minimum entropy were assembled together in a high-activation dispersion region. These regions accurately recognized diastolic paths of 34 VTs, often to multiple inducible VTs within a single individual arrhythmogenic region. In mathematical modeling, side branching from the main channel had a strong influence on the BiEGM composition along the main channel. The BiEGM obtained from a long unbranched channel had the lowest entropy compared with those with multiple side branches. In conclusion, among a population of multicomponent sinus electrograms, those that demonstrate low entropy and are delayed colocalize to critical long-protected channels of VT. This information is pertinent for planning VT ablation in sinus rhythm. NEW & NOTEWORTHY Entropy is a measure to quantify breakdown in information. Electrograms from a protected tissue channel can only possess a few states in their voltage and thus less information. In contrast, current-load interactions from side branches in unprotected channels introduce a number of dissimilar voltage deflections and thus high information. We compare here a mapping approach based on entropy against a rigorous reference standard of activation mapping during VT and entropy was assessed in sinus rhythm.

Omnipolarity applied to equi-spaced electrode array for ventricular tachycardia substrate mapping.

AIMS: Bipolar electrogram (BiEGM)-based substrate maps are heavily influenced by direction of a wavefront to the mapping bipole. In this study, we evaluate high-resolution, orientation-independent peak-to-peak voltage (Vpp) maps obtained with an equi-spaced electrode array and omnipolar EGMs (OTEGMs), measure its beat-to-beat consistency, and assess its ability to delineate diseased areas within the myocardium compared against traditional BiEGMs on two orientations: along (AL) and across (AC) array splines. METHODS AND RESULTS: The endocardium of the left ventricle of 10 pigs (three healthy and seven infarcted) were each mapped using an Advisor™ HD grid with a research EnSite Precision™ system. Cardiac magnetic resonance images with late gadolinium enhancement were registered with electroanatomical maps and were used for gross scar delineation. Over healthy areas, OTEGM Vpp values are larger than AL bipoles by 27% and AC bipoles by 26%, and over infarcted areas OTEGM Vpp values are 23% larger than AL bipoles and 27% larger than AC bipoles (P < 0.05). Omnipolar EGM voltage maps were 37% denser than BiEGM maps. In addition, OTEGM Vpp values are more consistent than bipolar Vpps showing less beat-by-beat variation than BiEGM by 39% and 47% over both infarcted and healthy areas, respectively (P < 0.01). Omnipolar EGM better delineate infarcted areas than traditional BiEGMs from both orientations. CONCLUSION: An equi-spaced electrode grid when combined with omnipolar methodology yielded the largest detectable bipolar-like voltage and is void of directional influences, providing reliable voltage assessment within infarcted and non-infarcted regions of the heart.

Pro-arrhythmic role of adrenergic spatial densities in the human atria: An in-silico study.

Chronic stress among young patients (≤ 45 years old) could result in autonomic dysfunction. Autonomic dysfunction could be exhibited via sympathetic hyperactivity, sympathetic nerve sprouting, and diffuse adrenergic stimulation in the atria. Adrenergic spatial densities could alter atrial electrophysiology and increase arrhythmic susceptibility. Therefore, we examined the role of adrenergic spatial densities in creating arrhythmogenic substrates in silico. We simulated three 25 cm2 atrial sheets with varying adrenergic spatial densities (ASD), activation rates, and external transmembrane currents. We measured their effects on spatial and temporal heterogeneity of action potential durations (APD) at 50% and 20%. Increasing ASD shortens overall APD, and maximum spatial heterogeneity (31%) is achieved at 15% ASD. The addition of a few (5% to 10%) adrenergic elements decreases the excitation threshold, below 18 µA/cm2, while ASDs greater than 10% increase their excitation threshold up to 22 µA/cm2. Increase in ASD during rapid activation increases APD50 and APD20 by 21% and 41%, respectively. Activation times of captured beats during rapid activation could change by as much as 120 ms from the baseline cycle length. Rapidly activated atrial sheets with high ASDs significantly increase temporal heterogeneity of APD50 and APD20. Rapidly activated atrial sheets with 10% ASD have a high likelihood (0.7 ± 0.06) of fragmenting otherwise uniform wavefronts due to the transient inexcitability of adrenergically stimulated elements, producing an effective functional block. The likelihood of wave fragmentation due to ASD highly correlates with the spatial variations of APD20 (ρ = 0.90, p = 0.04). Our simulations provide a novel insight into the contributions of ASD to spatial and temporal heterogeneities of APDs, changes in excitation thresholds, and a potential explanation for wave fragmentation in the human atria due to sympathetic hyperactivity. Our work may aid in elucidating an electrophysiological link to arrhythmia initiation due to chronic stress among young patients.

An In-Silico model for evaluating the directional shock vectors in terminating and modulating rotors.

Out-of-hospital cardiac arrest (OHCA) accounts for a majority of mortality worldwide. Survivability from an OHCA highly depends on timely and effective defibrillation. Most of the OHCA cases are due to ventricular fibrillation (VF), a lethal form of cardiac arrhythmia. During VF, previous studies have shown the presence of spatiotemporally organized electrical activities called rotors and that terminating these rotor-like activities could modulate or terminate VF in an in-hospital or research setting. However, such an approach is not feasible for OHCA scenarios. In the case of an OHCA, external defibrillation remains the main therapeutic option despite the low survival rates. In this study, we evaluated whether defibrillation effectiveness in an OHCA scenario could be improved if a shock vector directly targets rotor-like, spatiotemporal electrical activities on the myocardium. Specifically, we hypothesized that the position of defibrillator pads with respect to a rotor's core axis and shock current density could influence the likelihood of rotor termination and thereby result in successful defibrillation. We created a bidomain cardiac model based on porcine heart data using Aliev-Panfilov bidomain equations. We simulated localized rotors, which we attempted to terminate using different defibrillation pad orientations relative to the rotor axis (i.e., perpendicular, parallel, and oblique). In addition, we gradually increased current densities for each defibrillation pad orientation from 4 to 12 A/m2. We repeated the above defibrillation procedure for rotors originating from four different locations on the ventricles. The shock parameters and the outcomes were analyzed using a Generalized Linear Mixed Model (GLMM) with Logistic Regression to link rotor termination with the defibrillation pad orientation and current density. Our results suggest the highest average likelihood of terminating rotors during VF is when defibrillator pads are placed perpendicular to the rotor axis (0.99 ± 0.03), with an average current density of 7.2 A/m2, compared to any other orientation (parallel: 0.76 ± 0.26 and oblique: 0.08 ± 0.12). Our simulations suggest that optimal defibrillator pad orientation, combined with sufficient current density magnitude, could improve the likelihood of rotor termination during VF and thereby improving defibrillation success in OHCA patients.

On the Electrophysiology and Mapping of Intramural Arrhythmic Focus.

BACKGROUND: Conventional mapping of focal ventricular arrhythmias relies on unipolar electrogram characteristics and early local activation times. Deep intramural foci are common and associated with high recurrence rates following catheter-based radiofrequency ablation. We assessed the accuracy of unipolar morphological patterns and mapping surface indices to predict the site and depth of ventricular arrhythmogenic focal sources. METHODS: An experimental beating-heart model used Langendorff-perfused, healthy swine hearts. A custom 56-pole electrode array catheter was positioned on the left ventricle. A plunge needle was placed perpendicular in the center of the grid to simulate arrhythmic foci at variable depths. Unipolar electrograms and local activation times were generated. Simulation models from 2 human hearts were also included with grids positioned simultaneously on the endocardium-epicardium from multiple left ventricular, septal, and outflow tract sites. RESULTS: A unipolar Q or QS complex lacks specificity for superficial arrhythmic foci, as this morphology pattern occupies a large surface area and is the predominant pattern as intramural depth increases without developing a R component. There is progressive displacement from the arrhythmic focus to the surface exit as intramural focus depth increases. A shorter total activation time over the overlying electrode array, larger surface area within initial 20 ms activation, and a dual surface breakout pattern all indicate a deep focus. CONCLUSIONS: Displacement from the focal intramural origin to the exit site on the mapping surface could lead to erroneous lesion delivery strategies. Traditional unipolar electrogram features lack specificity to predict the intramural arrhythmic source; however, novel endocardial-epicardial mapping surface indices can be used to determine the depth of arrhythmic foci.

Maximizing detection and optimal characterization of local abnormal ventricular activity in nonischemic cardiomyopathy: LAVAMAX & LAVAFLOW.

BACKGROUND: Sites of local abnormal ventricular activation (LAVA) are ventricular tachycardia (VT) ablation targets. In nonischemic cardiomyopathy (NICM), minute and sparse LAVA potentials are mapped with difficulty with direction-sensitive bipolar electrograms (EGM). A method for its optimal characterization independent of electrode orientation has not been explored. OBJECTIVE: Maximize voltages and calculate overall activation direction at LAVA sites, independent of catheter and wave direction, using omnipolar technology (OT) in NICM. METHODS: Four diseased isolated human hearts from NICM patients were mapped epicardially using a high-density grid. Bipolar EGMs with at least 2 activation segments separated by at least 25 ms were identified. We used OT to maximize voltages (LAVAMAX) and measured overall wave direction (LAVAFLOW) for both segments. Clinically relevant voltage proportion (CRVP) was used to estimate the proportion of directionally corrected bipoles. Concordance and changes in direction vectors were measured via mean vector length and angular change. RESULTS: OT provides maximal LAVA voltages (OT: 0.83 ± 0.09 mV vs Bi: 0.61 ± 0.06 mV, P < .05) compared to bipolar EGMs. OT optimizes LAVA voltages, with 32% (CRVP) of LAVA bipoles directionally corrected by OT. OT direction vectors at LAVA sites demonstrate general concordance, with an average of 62% ± 5%. A total of 72% of direction vectors change by more than 35° at LAVA sites. CONCLUSION: The omnipolar mapping approach allows maximizing voltage and determining the overall direction of wavefront activity at LAVA sites in NICM.

Multi-Axes Lead With Tetrahedral Electrode Tip for Cardiac-Implantable Devices: Creative Concept for Pacing and Sensing Technology.

BACKGROUND: We developed a multi-axes lead (MaxLead) incorporating 4 electrodes arranged at the lead-tip, organized in an equidistant tetrahedron. Here, we studied MaxLead performance in sensing, pacing, and activation wavefront-direction analysis. METHODS: Sixteen explanted animal hearts (from 7 pigs, 7 sheep, and 2 rabbits) were used. Pacing threshold was tested from all axes of MaxLead from right-ventricular (RV) apex before and after simulated dislodgement. In addition, conduction-system pacing was performed in sheep heart preparations from all axes of MaxLead. Sensing via MaxLead positioned at RV apex was tested during sinus rhythm (SR), pacing from RV and left-ventricular (LV) free-wall, and ventricular fibrillation (VF). MaxLead-enabled voltage (MaxV), defined as the largest span of the sensed electric field loop, was compared with traditional lead-tip voltage detection. RESULTS: Pacing: MaxLead minimized change in pacing threshold owing to lead dislodgement (average voltage change 0.2 mV; 95% confidence interval [CI], -0.5 to 0.9), using multiple bipoles available for pacing. In animals with high conduction system-pacing thresholds (> 2 mV) in 1 or more bipoles (3 of 7), acceptable thresholds (< 1 mV) were demonstrated in an average of 2.5 remaining bipoles. Sensing: MaxV of SR and VF was consistently higher than the highest bipolar voltage (voltage difference averaged -0.18 mV, 95% CI, -0.28 to -0.07), P = 0.001). Electric field-loop geometry consistently differentiated ventricular activation in SR from that during pacing from RV and LV free walls. CONCLUSIONS: The multi-axes MaxLead electrode showed advantages in pacing, sensing, and mapping and has the potential to allow for improvements in lead-electrode technology for cardiac-implanted electronic devices.

Direct and indirect mapping of intramural space in ventricular tachycardia.

BACKGROUND: The ventricular tachycardia (VT) circuit is often assumed to be located in the endocardium or epicardium. The plateauing success rate of VT ablation warrants reevaluation of this mapping paradigm. OBJECTIVE: The purpose of this study was to resolve the intramural components of VT circuits by mapping in human hearts. METHODS: Panoramic simultaneous endocardial-epicardial mapping (SEEM) during intraoperative mapping (IOM) was performed in human subjects. In explanted hearts (EH), SEEM and intramural multielectrode plunge needle mapping (NM) of the left ventricle were performed. Overall, 37 VTs (26 ischemic cardiomyopathy [ICM], 11 nonischemic cardiomyopathy [NICM]) were studied in 32 patients. Intraoperative SEEM was performed in 16 patients (16 ICM). Additionally, 16 explanted myopathic human hearts (9 NICM, 7 ICM) were studied in a Langendorff setup. Predominant intramural location of the VT was imputed by the absence of significant endocardial-epicardial activation during IOM (using SEEM and no NM) or by the presence of intramural activation spanning the entire cycle length (including mid-diastole) in EH (SEEM and NM). RESULTS: By IOM (SEEM), predominant endocardial activation (entire tachycardia cycle length including mid-diastolic activation) was present in 10 of 18 VTs (55%). In 8 of 18 VTs (44%), the VT circuit was presumed to be intramural due to incomplete diastolic activation in endocardium and epicardium. In EH (SEEM and NM), VT location was predominantly intramural, endocardial, and epicardial in 8 of 19 (42%), 5 of 19 (26%), and 1 of 19 VTs (5%), respectively. CONCLUSION: In a significant proportion of both ischemic and nonischemic ventricular tachycardias, the predominant activation was located in the intramural space.

Reinserting Physiology into Cardiac Mapping Using Omnipolar Electrograms.

Omnipolar electrograms (EGMs) make use of biophysical electric fields that accompany activation along the surface of the myocardium. A grid-like electrode array provides bipolar signals in orthogonal directions to deliver catheter-orientation-independent assessments of cardiac electrophysiology. Studies with myocyte monolayers, isolated animal and human hearts, and anesthetized animals validated the tenets of omnipolar EGMs. The combination of information from omnipolar-based activation vectors and voltages may aid in localizing areas of scar, lesion gaps, wavefront disorganization, and fractionation or collision during arrhythmias. The goal of omnipolar EGMs is to better characterize myocardium through reintroducing electrogram direction related fundamentals of cardiac electrophysiology.

Human Embryonic Stem Cell-Derived Cardiomyocytes Regenerate the Infarcted Pig Heart but Induce Ventricular Tachyarrhythmias.

Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) show considerable promise for regenerating injured hearts, and we therefore tested their capacity to stably engraft in a translationally relevant preclinical model, the infarcted pig heart. Transplantation of immature hESC-CMs resulted in substantial myocardial implants within the infarct scar that matured over time, formed vascular networks with the host, and evoked minimal cellular rejection. While arrhythmias were rare in infarcted pigs receiving vehicle alone, hESC-CM recipients experienced frequent monomorphic ventricular tachycardia before reverting back to normal sinus rhythm by 4 weeks post transplantation. Electroanatomical mapping and pacing studies implicated focal mechanisms, rather than macro-reentry, for these graft-related tachyarrhythmias as evidenced by an abnormal centrifugal pattern with earliest electrical activation in histologically confirmed graft tissue. These findings demonstrate the suitability of the pig model for the preclinical development of a hESC-based cardiac therapy and provide new insights into the mechanistic basis of electrical instability following hESC-CM transplantation.

Quantifying the determinants of decremental response in critical ventricular tachycardia substrate.

BACKGROUND: Decremental response evoked with extrastimulation (DEEP) is a useful tool for determining diastolic return path of ventricular tachycardia (VT). Though a targeted VT ablation is feasible with this approach, determinants of DEEP response have not been studied OBJECTIVES: To elucidate the effects of clinically relevant factors, specifically, the proximity of the stimulation site to the arrhythmogenic scar, stimulation wave direction, number of channels open in the scar, size of the scar and number of extra stimuli on decrement and entropy of DEEP potentials. METHODS: In a 3-dimensional bi-domain simulation of human ventricular tissue (TNNP cell model), an irregular subendocardial myopathic region was generated. An irregular channel of healthy tissue with five potential entry branches was shaped into the myopathic region. A bipolar electrogram was derived from two electrodes positioned in the centre of the myopathic region. Evoked delays between far-field and local Electrogram (EGM) following an extrastimulus (S1-S2, 500-350 ms) were measured as the stimulation site, channel branches, and inexcitable tissue size were altered. RESULTS: Stimulation adjacent to the inexcitable tissue from the side opposite to the point-of-entry produces longest DEEP delay. The DEEP delay shortens when the stimulation point is farther away from the scar, and it decreases maximally when stimulation is done from a site beside a conduction barrier. Entropy increases with S2 when stimulation site is from farther away. An unprotected channel structure with multiple side-branch openings had shorter DEEP delay compared to a protected channel structure with a paucity of additional side-branch openings and a point-of-entry on the side opposite to the pacing source. Addition of a second shorter extrastimulus did not universally lead to higher DEEP delay CONCLUSIONS: Location and direction of the wavefront in relation to scar entry and size of scar determine the degree of evoked response while the number of extrastimuli has a small additional decremental effect.

Determinants of atrial bipolar voltage: Inter electrode distance and wavefront angle.

BACKGROUND: Local bipolar electrogram (EGM) peak-to-peak voltage (Vpp) is currently used to characterise mapped myocardial substrate. However, how interelectrode distance and angle of wavefront incidence affect bipolar, Vpp values, in the current era of multi-electrode mapping is unknown. OBJECTIVES: To elucidate the effects of tissue and electrode geometry on bipolar Vpp measurements, when mapping healthy versus diseased atrial regions. METHODS: A bidomain model of human atrial tissue was used to quantify the influence on Vpp values of various electrode configurations in healthy tissue, and tissue containing an unexcitable region. The orientation angle and interelectrode spacing of a surface bipole, and thickness and depth of the unexcitable core were serially varied. Results were validated with data obtained from isolated porcine hearts. RESULTS: In healthy tissue, bipolar Vpp values increased with increasing interelectrode spacing and plateaued beyond a spacing of approximately 4 mm. The bipolar Vpp values in healthy tissue were relatively less sensitive to wavefront orientation angle with large interelectrode spacing. In diseased tissue, on the contrary, with increasing interelectrode spacing, bipolar Vpp values increased linearly without a plateau and were more sensitive to orientation angle. The bipolar Vpp values decreased with increasing thickness of the scar, with larger relative decrease in small bipoles than larger ones. Bipolar Vpp values increased with a progressively intramural location of fixed-size scar and became less distinguishable from healthy tissue especially for smaller interelectrode spacings. CONCLUSIONS: The scalable relationship established for interelectrode distances favour an electric-field-based assessment as opposed to traditional Vpp values as a tool for physiologically relevant measurement for mapping catheters with interelectrode spacing up to 4 mm. This will allow for universal assessment of myocardial health across catheters with varied spacing.

Physiological Assessment of Ventricular Myocardial Voltage Using Omnipolar Electrograms.

BACKGROUND: Characterization of myocardial health by bipolar electrograms are critical for ventricular tachycardia therapy. Dependence of bipolar electrograms on electrode orientation may reduce reliability of voltage assessment along the plane of arrhythmic myocardial substrate. Hence, we sought to evaluate voltage assessment from orientation-independent omnipolar electrograms. METHODS AND RESULTS: We mapped the ventricular epicardium of 5 isolated hearts from each species-healthy rabbits, healthy pigs, and diseased humans-under paced conditions. We derived bipolar electrograms and voltage peak-to-peak (Vpps) along 2 bipolar electrode orientations (horizontal and vertical). We derived omnipolar electrograms and Vpps using omnipolar electrogram methodology. Voltage maps were created for both bipoles and omnipole. Electrode orientation affects the bipolar voltage map with an average absolute difference between horizontal and vertical of 0.25±0.18 mV in humans. Vpps provide larger absolute values than horizontal and vertical bipolar Vpps by 1.6 and 1.4 mV, respectively, in humans. Bipolar electrograms with the largest Vpps from either along horizontal or vertical orientation are highly correlated with omnipolar electrograms and with Vpps values (0.97±0.08 and 0.94±0.08, respectively). Vpps values are more consistent than bipoles, in both beat-by-beat (CoV, 0.28±0.19 versus 0.08±0.13 in human hearts) and rhythm changes (0.55±0.21 versus 0.40±0.20 in porcine hearts). CONCLUSIONS: Omnipoles provide physiologically relevant and consistent voltages that are along the maximal bipolar direction on the plane of the myocardium.

Resolving Bipolar Electrogram Voltages During Atrial Fibrillation Using Omnipolar Mapping.

BACKGROUND: Low-voltage-guided substrate modification is an emerging strategy in atrial fibrillation (AF) ablation. A major limitation to contemporary bipolar electrogram (EGM) analysis in AF is the resultant lower peak-to-peak voltage (Vpp) from variations in wavefront direction relative to electrode orientation and from fractionation and collision events. We aim to compare bipole Vpp with novel omnipolar peak-to-peak voltages (Vmax) in sinus rhythm (SR) and AF. METHODS AND RESULTS: A high-density fixed multielectrode plaque was placed on the epicardial surface of the left atrium in dogs. Horizontal and vertical orientation bipolar EGMs, followed by omnipolar EGMs, were obtained and compared in both SR and AF. Bipole orientation has significant impact on bipolar EGM voltages obtained during SR and AF. In SR, vertical values were on average 66±119% larger than horizontal (P=0.004). In AF, vertical values were on average 31±96% larger than horizontal (P=0.07). Omnipole Vmax values were 99.9±125% larger than both horizontal (99.9±125%; P<0.001) and vertical (41±78%; P<0.0001) in SR and larger than both horizontal (76±109%; P<0.001) and vertical (52±70%; P value <0.0001) in AF. Vector field analysis of AF wavefronts demonstrates that omnipolar EGMs can account for collision and fractionation and record EGM voltages unaffected by these events. CONCLUSIONS: Omnipolar EGMs can extract maximal voltages from AF signals which are not influenced by directional factors, collision or fractionation, compared with contemporary bipolar techniques.

Resolving Myocardial Activation With Novel Omnipolar Electrograms.

BACKGROUND: With its inherent limitations, determining local activation times has been the basis of cardiac mapping for over a century. Here, we introduce omnipolar electrograms that originate from the natural direction of a travelling wave and from which instantaneous conduction velocity amplitude and direction can be computed at any single location without first determining activation times. We sought to validate omnipole-derived conduction velocities and explore potential application for localization of sources of arrhythmias. METHODS AND RESULTS: Electrograms from omnipolar mapping were derived and validated using 4 separate models and 2 independent signal acquisition methodologies. We used both electric signals and optical signals collected from monolayer cell preparations, 3-dimensional constructs built with cardiomyocytes derived from human embryonic stem cells, simultaneous optical and electric mapping of rabbit hearts, and in vivo pig electrophysiology studies. Conduction velocities calculated from omnipolar electrograms were compared with wavefront propagation from optical and electric-mapping studies with a traditional local activation time-based method. Bland-Altman analysis revealed that omnipolar measurements on optical data were in agreement with local activation time methods for wavefront direction and velocity within 25 cm/s and 30°, respectively. Similar agreement was also found on electric data. Furthermore, mathematical operations, such as curl and divergence, were applied to omnipole-derived velocity vector fields to locate rotational and focal sources, respectively. CONCLUSIONS: Electrode orientation-independent cardiac wavefront trajectory and speed at a single location for each cardiac activation can be determined accurately with omnipolar electrograms. Omnipole-derived vector fields, when combined with mathematical transforms may aid in real-time detection of cardiac activation sources.

Feature-based MRI data fusion for cardiac arrhythmia studies.

Current practices in studying cardiac arrhythmias primarily use electrical or optical surface recordings of a heart, spatially limited transmural recordings, and mathematical models. However, given that such arrhythmias occur on a 3D myocardial tissue, information obtained from such practices lack in dimension, completeness, and are sometimes prone to oversimplification. The combination of complementary Magnetic-Resonance Imaging (MRI)-based techniques such as Current Density Imaging (CDI) and Diffusion Tensor Imaging (DTI) could provide more depth to current practices in assessing the cardiac arrhythmia dynamics in entire cross sections of myocardium. In this work, we present an approach utilizing feature-based data fusion methods to demonstrate that complimentary information obtained from electrical current distribution and structural properties within a heart could be quantified and enhanced. Twelve (12) pairs of CDI and DTI image data sets were gathered from porcine hearts perfused through a Langendorff setup. Images were fused together using feature-based data fusion techniques such as Joint Independent Component Analysis (jICA), Canonical Correlation Analysis (CCA), and their combination (CCA+jICA). The results suggest that the complimentary information of cardiac states from CDI and DTI are enhanced and are better classified with the use of data fusion methods. For each data set, an increase in mean correlations of fused images were observed with 38% increase from CCA+jICA compared to the original images while mean mutual information of the fused images from jICA and CCA+jICA increased by approximately three-fold. We conclude that MRI-based techniques present potential viable tools in furthering studies for cardiac arrhythmias especially Ventricular Fibrillation.

The need for and the challenges of measuring renal sympathetic nerve activity.

Renal denervation (RDN) was primarily developed to treat hypertension and is potentially a new method for treating arrhythmias. Because of the lack of a standardized protocol to measure renal sympathetic nerve activity, RDN is administered in a blind manner. This inability to assess efficacy at the time of treatment delivery may be a large contributor to the ambiguity of RDN outcomes reported in the hypertension literature. The advancement of RDN as a treatment of hypertension or arrhythmias will be hampered by the lack of delivery assessment, a deficiency that the cardiovascular electrophysiology community, with its expertise in recording and mapping, may have a role in addressing and overcoming. The development of endovascular recording of renal nerve action potentials may provide a useful accessory tool for RDN. Innovation in this area will be crucial as we as a community reconsider the therapeutic value of RDN.

Noise distribution and denoising of current density images.

Current density imaging (CDI) is a magnetic resonance (MR) imaging technique that could be used to study current pathways inside the tissue. The current distribution is measured indirectly as phase changes. The inherent noise in the MR imaging technique degrades the accuracy of phase measurements leading to imprecise current variations. The outcome can be affected significantly, especially at a low signal-to-noise ratio (SNR). We have shown the residual noise distribution of the phase to be Gaussian-like and the noise in CDI images approximated as a Gaussian. This finding matches experimental results. We further investigated this finding by performing comparative analysis with denoising techniques, using two CDI datasets with two different currents (20 and 45 mA). We found that the block-matching and three-dimensional (BM3D) technique outperforms other techniques when applied on current density ([Formula: see text]). The minimum gain in noise power by BM3D applied to [Formula: see text] compared with the next best technique in the analysis was found to be around 2 dB per pixel. We characterize the noise profile in CDI images and provide insights on the performance of different denoising techniques when applied at two different stages of current density reconstruction.