Activation Wavefront Research Articles

Simulation Methods and Validation Criteria for Modeling Cardiac Ventricular Electrophysiology.

We describe a sequence of methods to produce a partial differential equation model of the electrical activation of the ventricles. In our framework, we incorporate the anatomy and cardiac microstructure obtained from magnetic resonance imaging and diffusion tensor imaging of a New Zealand White rabbit, the Purkinje structure and the Purkinje-muscle junctions, and an electrophysiologically accurate model of the ventricular myocytes and tissue, which includes transmural and apex-to-base gradients of action potential characteristics. We solve the electrophysiology governing equations using the finite element method and compute both a 6-lead precordial electrocardiogram (ECG) and the activation wavefronts over time. We are particularly concerned with the validation of the various methods used in our model and, in this regard, propose a series of validation criteria that we consider essential. These include producing a physiologically accurate ECG, a correct ventricular activation sequence, and the inducibility of ventricular fibrillation. Among other components, we conclude that a Purkinje geometry with a high density of Purkinje muscle junctions covering the right and left ventricular endocardial surfaces as well as transmural and apex-to-base gradients in action potential characteristics are necessary to produce ECGs and time activation plots that agree with physiological observations.

Improving active space telescope wavefront control using predictive thermal modeling

Active control algorithms for space telescopes are less mature than those for large ground telescopes due to differences in the wavefront control problems. Active wavefront control for space telescopes at L2, such as the James Webb Space Telescope (JWST), requires weighing control costs against the benefits of correcting wavefront perturbations that are a predictable byproduct of the observing schedule, which is known and deter- mined in advance. To improve the control algorithms for these telescopes, we have developed a model that calculates the temperature and wavefront evolution during a hypothetical mission, assuming the dominant wave- front perturbations are due to changes in the spacecraft attitude with respect to the sun. Using this model, we show that the wavefront can be controlled passively by introducing scheduling constraints that limit the allowable attitudes for an observation based on the observation duration and the mean telescope temperature. We also describe the implementation of a predictive controller designed to prevent the wavefront error (WFE) from exceeding a desired threshold. This controller outperforms simpler algorithms even with substantial model error, achieving a lower WFE without requiring significantly more corrections. Consequently, predictive wave- front control based on known spacecraft attitude plans is a promising approach for JWST and other future active space observatories. © The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or repro- duction of this work in whole or in part requires full attribution of the original publication, including its DOI. (DOI: 10.1117/1.JATIS.1.1.014004)

Colonic migrating motor complexes, high amplitude propagating contractions, neural reflexes and the importance of neuronal and mucosal serotonin.

The colonic migrating motor complex (CMMC) is a critical neurally mediated rhythmic propulsive contraction observed in the large intestine of many mammals. It seems to be equivalent to the high amplitude propagating contractions (HAPCs) in humans. This review focuses on the probable neural mechanisms involved in producing the CMMC or HAPC, their likely dependence on mucosal and neuronal serotonin and pacemaker insterstitial cells of Cajal networks and how intrinsic neural reflexes affect them. Discussed is the possibility that myenteric 5-hydroxytryptamine (5-HT) neurons are not only involved in tonic inhibition of the colon, but are also involved in generating the CMMC and modulation of the entire enteric nervous system, including coupling motility to secretion and blood flow. Mucosal 5-HT appears to be important for the initiation and effective propagation of CMMCs, although this mechanism is a longstanding controversy since the 1950s, which we will address. We argue that the slow apparent propagation of the CMMC/HAPC down the colon is unlikely to result from a slowly conducting wave front of neural activity, but more likely because of an interaction between ascending excitatory and descending (serotonergic) inhibitory neural pathways interacting both within the myenteric plexus and at the level of the muscle. That is, CMMC/HAPC propagation appears to be similar to esophageal peristalsis. The suppression of inhibitory (neuronal nitric oxide synthase) motor neurons and mucosal 5-HT release by an upregulation of prostaglandins has important implications in a number of gastrointestinal disorders, especially slow transit constipation.

Body surface potential mapping for mapping and treatment of persistent atrial fibrillation.

Techniques facilitating individual mapping and ablation of arrhythmogenic substrates are desired to enhance our understanding of persistent atrial fibrillation (persAF) mechanisms as a prerequisite to increasing the success rates of single procedure persAF catheter ablation. The technique of body surface potential mapping (BSM) involves the use of multiple electrodes to collect the potentials over a large body surface area and, with the use of a computed tomography scan, it facilitates their correlation to a 3D model of the atrial structures. During AF,the visualization and localization of AF driver activity, both reentrant and focal wavefronts, is possible with this technique. The ECVUE system from CardioInsight was examined for this indication in clinical studies and showed a termination rate of persAF of 63 % in a large multicenter trial (AFACART) with a promising low recurrence rate during follow-up. From our initial experience, the system appears to be effective in persAF patients who have continuous AF for less than 1 year. However, the utility of the system for highly challenging cases like long-standing persistent AF and patients with very short AF cycle length remains to be explored. Further studies are needed to confirm these data and answer the multitude of open questions in this field.

Editor’s Perspective: The Isthmus of Uncertainty

Whether in the atrium or the ventricle, macro–reentrant tachyarrhythmias are among the most challenging arrhythmias to eliminate with ablation. Namdar et al,1 in this installment of Teaching Rounds in Cardiac Electrophysiology, present and explain insightful findings from a patient with a complex macro–reentrant circuit encountered after prior cardiac surgery. They take us through a step-by-step approach and their thought process in identifying the eventual curative ablation target. Article see p 171 In addition to the outstanding educational points specific to this case, several important principles for mapping and ablating macro–reentrant arrhythmia when multiple boundaries and isthmuses are possible can be gleaned from their report. Does identifying a site of early activation from an activation map of the arrhythmia facilitate ablation? Unlike focal tachycardias, reentrant arrhythmias have no true early or late sites of activation. Timing is based completely on the empirical choice of a reference electrogram and the setting of the mapping window.2 Although this principle is apparent and most experienced electrophysiologists will either map and define the entire circuit of tachycardia or use entrainment mapping to identify appropriate sites for ablation, several corollaries to this principle are equally important but not as readily recognized.3,4 ### P-Wave Morphology P-wave vector and morphology (or QRS morphology in the case of ventricular tachycardia) can be invaluable in estimating location of origin for a focal arrhythmia. With macro–reentry however, there is not necessarily a true onset for the P wave (or QRS). Thus, although patterns that have been identified as characteristic for cavotricuspid isthmus–dependent flutter are suggestive of the arrhythmia mechanism, general analysis of the flutter-wave morphology for other macro–reentrant arrhythmias and even common cavotricuspid isthmus–dependent arrhythmias in the presence of extensive atrial disease or prior surgery or ablation is often of little value. When an isoelectric segment is noted in …

Model of Bipolar Electrogram Fractionation and Conduction Block Associated With Activation Wavefront Direction at Infarct Border Zone Lateral Isthmus Boundaries

Improved understanding of the mechanisms underlying infarct border zone electrogram fractionation may be helpful to identify arrhythmogenic regions in the postinfarction heart. We describe the generation of electrogram fractionation from changes in activation wavefront curvature in experimental canine infarction. A model was developed to estimate the extracellular signal shape that would be generated by wavefront propagation parallel to versus perpendicular to the lateral boundary (LB) of the reentrant ventricular tachycardia (VT) isthmus or diastolic pathway. LBs are defined as locations where functional block forms during VT, and elsewhere they have been shown to coincide with sharp thin-to-thick transitions in infarct border zone thickness. To test the model, bipolar electrograms were acquired from infarct border zone sites in 10 canine heart experiments 3 to 5 days after experimental infarction. Activation maps were constructed during sinus rhythm and during VT. The characteristics of model-generated versus actual electrograms were compared. Quantitatively expressed VT fractionation (7.6±1.2 deflections; 16.3±8.9-ms intervals) was similar to model-generated values with wavefront propagation perpendicular to the LB (9.4±2.4 deflections; 14.4±5.2-ms intervals). Fractionation during sinus rhythm (5.9±1.8 deflections; 9.2±4.4-ms intervals) was similar to model-generated fractionation with wavefront propagation parallel to the LB (6.7±3.1 deflections; 7.1±3.8-ms intervals). VT and sinus rhythm fractionation sites were adjacent to LBs ≈80% of the time. The results suggest that in a subacute canine infarct model, the LBs are a source of activation wavefront discontinuity and electrogram fractionation, with the degree of fractionation being dependent on activation rate and wavefront orientation with respect to the LB.

The value of the 12-lead ECG for evaluation and optimization of cardiac resynchronization therapy in daily clinical practice

Based on existing literature and some new data we propose a simple three-step strategy using the standard 12-lead ECG for patient selection and optimal delivery of cardiac resynchronization therapy (CRT). (1) Complete LBBB with regard to the indication for CRT can probably best be identified by a QRS duration of ≥130ms for women and ≥120ms for men with the presence of mid-QRS notch-/slurring in ≥2 contiguous leads of V1, V2, V5, V6, I and aVL. (2) Left ventricular (LV) free wall pacing should result in a positive QRS complex in lead V1, with estimation of the exact LV lead position in the circumferential and apico-basal direction using lead aVF and the precordial leads, respectively. Wide and fractionated LV-paced QRS complexes may indicate pacing in scar tissue. (3) Atrioventricular and interventricular stimulation intervals may be optimized by adjusting them until precordial leads show fusion patterns between left and right ventricular activation wavefronts in the QRS complex.

Glycogen and the propensity for atrial fibrillation: intrinsic anatomic differences in glycogen in the left and right atria in the goat heart.

Background:Previous experimental studies have demonstrated electrophysiological and structural remodeling in pacing induced atrial fibrillation. The latter has been characterized by glycogen accumulation but no connection to atrial fibrillation induction and maintenance has as yet been proposed.Aims:We determined the presence of glycogen in the right and left atrial appendages in the goat heart, in order to find any intrinsic disparity in distribution and concentration between these sites.Materials and Methods:Atrial appendages from 5 goats were stained by the Periodic acid Schiffmethod to determine the presence of glycogen and the concentration of glycogen by morphometric analysis.Results:We are reporting for the first time that the right atrial appendage showed scattered glycogen granules throughout the atrial myocytes which delineated the intercalated discs; whereas glycogen in the left atrial appendage was more dense within cells and coalesced against the intercalated discs and side to side junctions between myocytes. Also, morphometric analysis determined that the stained regions of the right atrial appendages averaged, 0.8 ± 1.3 μm2 compared to the left atrial appendage sections, 2.6 ± 3 μm2, P = 0.02. We show that glycogen is heterogeneously distributed in both atria in the normal goat heart; however, the density of glycogen deposits concentrating against the intercalated discs and side to side connections in the left atrial appendage is a critically distinct difference. Impediment of cell to cell conduction could result in a non-uniform wavefront of activation, with areas of slowed conduction, predisposing the left atrium to reentrant based atrial fibrillation.Conclusion:These findings provide a basis for the well-known greater propensity for atrial fibrillation in the left versus the right atrium.

Cancellation of atmospheric turbulence effects in entangled two-photon beams

Turbulent airflow in the atmosphere and the resulting random fluctuations in its refractive index have long been known as a major cause of image deterioration in astronomical imaging and figures among the obstacles for reliable optical communication when information is encoded in the spatial profile of a laser beam. Here we show that using correlation imaging and a suitably prepared source of photon pairs, the most severe of the disturbances inflicted on the beam by turbulence can be cancelled out. Other than a two-photon light source, only linear passive optical elements are needed and, as opposed to adaptive optics techniques, our scheme does not rely on active wavefront correction.

Comparison of the “Real-life” Diagnostic Value of Two Recently Published Electrocardiogram Methods for the Differential Diagnosis of Wide QRS Complex Tachycardias

The diagnostic values of the aVR lead or "Vereckei algorithm," and the lead II R-wave peak time (RWPT) criterion, recently devised for the differential diagnosis of wide QRS complex tachycardias (WCTs), were compared. A total of 212 WCTs (142 ventricular tachycardias [VTs], 62 supraventricular tachycardias [SVT], and eight preexcitation SVTs) from 145 patients with proven electrophysiologic diagnoses were retrospectively analyzed by seven examiners blinded to the electrophysiologic diagnoses. The overall test accuracy of the Vereckei algorithm was superior to that of the RWPT criterion (84.3% vs. 79.6%; p = 0.0003). The sensitivity of the Vereckei algorithm for VT diagnosis was greater than that of RWPT criterion (92.4% vs. 79.1%; p < 0.0001). The negative predictive value (NPV) for the Vereckei algorithm was also greater (77.8%; 95% confidence interval [CI] = 73.6% to 82.1%) than that of the RWPT criterion (61.6%; 95% CI = 57.6% to 65.6%). The specificity of the Vereckei algorithm was lower than that of the RWPT criterion (64.7% vs. 80.9%; p < 0.0001). The positive predictive value (PPV) was also lower for the Vereckei algorithm (86.4%; 95% CI = 84.4% to 88.4%) than for the RWPT criterion (90.9%; 95% CI = 89.1% to 92.8%). Incorrect diagnoses made by the Vereckei algorithm were mainly due to misdiagnosis of SVT as VT (65.7% of cases), and those made by the RWPT criterion were due to the more dangerous misdiagnosis of VT as SVT (72.5% of cases). The Vereckei algorithm was superior in overall test accuracy, sensitivity, and NPV for VT diagnosis and inferior in specificity and PPV to the RWPT criterion. All of these parameters were lower in "real life" than those reported by the original authors for each of the particular electrocardiographic methods.

A Clinical Protocol for Intraoral Digital Impression of Screw-Retained CAD/CAM Framework on Multiple Implants Based on Wavefront Sampling Technology

To obtain an accurate CAD/CAM metal framework over 6 implants using a Chairside Intraoral Scanner based on the principle of active (optical) wavefront sampling. Six prototype cylindrical scan bodies screwed in the implants were used to obtain an intraoral digital impression. A conventional resin tooth try-in was fabricated and digitized with an extraoral scanner, and this dataset was merged to the digital data obtained from the intraoral impression to calculate the best framework design with advanced CAD software. The framework was fabricated with a 5-axis computer numerical control milling unit. Three clinical tests (saliva intrusion, Sheffield test, and screw resistance test) were performed to assess the fit of the framework. Under 3 clinical tests, an accurate fit was observed. The case presented in this report proposes a new clinical protocol for obtaining accurate digital impressions of multiple implants.

Adipocytokines modulate ionic currents – A key to lipotoxicity potentiated cardiac arrhythmia

Obesity with excessive fat was an important risk factor for the occurrence or progression of cardiac arrhythmia. As compared to abdominal fat, the amount of epicardial fat more correlates with the occurrences of atrial fibrillation, which suggests the distinctive arrhythmogenic effects of epicardial fat. Adipose tissue secrets numerous adipocytokines, thus epicardial fat may have more cardiac effects than other body fat [1]. Adipocytokines can enhance local inflammation and generate myocardial remodeling, which play a role in the pathophysiology of arrhythmia. Fatty infiltration or fatty metamorphosis can induce abnormal automaticity from degenerated myocardial cells. Adipose tissues also serve as obstacles for an activation wave front or by producing atrial fibrosis, which may interfere with atrial conduction and enhance the generation of reentry circuits. Lee et al. investigated the effects of adipocytokines from different body fats on delayed rectifier K outward currents (IKr) in cardiomyocytes [2]. In their study, H9c2 cells were treated with adipocytokine-free medium (the Adipo-free group), and with adipocytokines from rat epicardial (central fat group) or limb (peripheral fat group) fat tissues. They found that adipocytokines significantly decreased IKr in H9c2 cells, and IKr was more prominently decreased by adipocytokines from epicardial fat than from limb fat. Although the mechanisms were not fully elucidated, Lee et al. pointed out the direct electrophysiological effects of adipocytokines and also demonstrated stronger ionic effects of epicardial fat than other body fat. Decreased IKr can prolong action

Accuracy of a Digital Impression System Based on Active Wavefront Sampling Technology for Implants Considering Operator Experience, Implant Angulation, and Depth

There is a scarce knowledge on the accuracy of intraoral digital impression systems for dental implants. The purpose of this study is to evaluate the accuracy of a digital impression system considering clinical parameters. A master model with six implants (27, 25, 22, 12, 15, 17) was fitted with polyether ether ketone scan bodies. Implant no. 25 was placed with 30° mesial angulation in relation to the vertical plane (y axis), and implant no. 15 was positioned with 30° distal angulation. Implant no. 22 was placed 2 mm and no. 12, 4 mm below the gingiva. Experienced (n = 2) and inexperienced operators (n = 2) performed scanning (Lava Chairside Oral Scanner; 3 M ESPE, St Paul, MN, USA) at standard and high accuracy mode. Measurements involved five distances (27-25, 27-22, 27-12, 27-15, 27-17). Measurements with high accuracy three-dimensional coordinated measuring machine (CMM) of the master model acted as the true values. The data obtained were subtracted from those of the CMM values. Experience of the operator significantly influenced the results (p = .000). Angulation (p = .195) and depth of implant (p = .399) did not show significant deviation from the true values. The mean difference between standard and high accuracy mode was 90 μm. With the active wavefront sampling, technology-based digital impression system training seems to be compulsory. Impressions of angulated implants may diminish the accuracy of the impression, yet the results were not significant.

Rapid Pacing Induces Fractionation of the Activation Wavefront into Multiple Wavelets

Article Rapid Pacing Induces Fractionation of the Activation Wavefront into Multiple Wavelets was published on September 7, 2013 in the journal Biomedical Engineering / Biomedizinische Technik (volume 58, issue SI-1-Track-S).

Rapid, parallel path planning by propagating wavefronts of spiking neural activity

Efficient path planning and navigation is critical for animals, robotics, logistics and transportation. We study a model in which spatial navigation problems can rapidly be solved in the brain by parallel mental exploration of alternative routes using propagating waves of neural activity. A wave of spiking activity propagates through a hippocampus-like network, altering the synaptic connectivity. The resulting vector field of synaptic change then guides a simulated animal to the appropriate selected target locations. We demonstrate that the navigation problem can be solved using realistic, local synaptic plasticity rules during a single passage of a wavefront. Our model can find optimal solutions for competing possible targets or learn and navigate in multiple environments. The model provides a hypothesis on the possible computational mechanisms for optimal path planning in the brain, at the same time it is useful for neuromorphic implementations, where the parallelism of information processing proposed here can fully be harnessed in hardware.

Programmable quasi-direct space-to-time pulse shaper with active wavefront correction

We experimentally demonstrate an extremely compact and programmable pulse shaper composed of a single phase mask encoded into a spatial light modulator. Its principle of operation is similar to the previously theoretically introduced quasi-direct space-to-time pulse shaper [Opt. Express16, 16993 (2008)], which is based on diffractive optics. The proposed pulse shaper exhibits not only real-time temporal modulation, but also high-efficiency output pulses thanks to an active correction of the wavefront aberrations.

Abstract 19817: Influence of the Purkinje Conduction System on the Ekg: A Modeling Study

Introduction - Computational modeling of cardiac electrophysiology (EP) is important for exploring the mechanisms that underlie fatal arrhythmias. Methods are limited for anatomically mapping the Purkinje conduction system (PCS) in whole hearts, and incorrect definition of the PCS geometry and/or conduction velocity leads to incorrectly modeled activation wavefronts, fractioned QRS, and T-wave inversion. The objective of this study was to design a PCS that resulted in the best simulated six-lead electrocardiogram (ECG), while maintaining consistency with known anatomy. Methods - Diffusion tensor (DT) MRI was used to define gross anatomy and fiber orientations, combined with a cell model to build a finite element model of rabbit cardiac EP, from which the six-lead ECG was simulated. An in vivo six-lead rabbit ECG served as a reference for the computed ECG. The number and distribution of Purkinje-muscle junctions (PMJ) and the conduction velocity in RV, LV, and septal branches were varied. Whole-heart activation wavefronts and the resultant ECG were compared to the normal rabbit ECG. Parameters assessed included activation wavefront timing and QRS/T-wave morphology in a six-lead ECG. Results - Forty combinations of PCS geometry and conduction speed were implemented. Increasing the density (from 34 to 399), uniformly distributing the PMJs, and a PCS with branches for earlier septal activation (3.0m/s) and a faster Purkinje conduction speed in the LV (3.0m/s) compared to the RV (2.1m/s) was necessary to produce the correct activation sequence, eliminate QRS fractionations, and produce the best T-wave morphology. The figure shows the comparison of the ECG output from V3 for three different iterations. Conclusion - The reported Purkinje conduction speed is 0.8-2m/s, but a heterogeneous Purkinje conduction speed distribution combined with a high PMJ density is needed to produce computationally accurate ECGs.

Cardiac resynchronization therapy (CRT): Clinical trials, guidelines, and target populations

Over the last 10 years, several large, well-designed clinical trials have firmly established the role of cardiac resynchronization therapy (CRT) as a recommended treatment strategy for moderate-to-severe heart failure (HF). A review of the relevant results from the MUSTIC, MIRACLE, CONAK-CD, and MIRACLE ICD trials reveals that in patients with New York Heart Association (NYHA) class III-IV HF, CRT produces consistent improvements in quality of life, functional status, and exercise capacity while also providing strong evidence for reverse remodeling and diminished functional mitral regurgitation, resulting in reductions in both HF hospitalizations and all-cause morbidity and mortality. In patients with earlier NYHA class I-II HF, the benefit of CRT has been more controversial. The principal ongoing challenges addressed in this article include the substantial 30% of patients who receive a CRT device but fail to respond, the wide variations in how to define "response" vs "nonresponse," and how to identify patients who will benefit from CRT, especially narrow QRS (<120 ms), those with right bundle branch block, and those with mild-to-moderate (NYHA class I-II) HF. An important result of this uncertainty is the lack of a good sense of the optimal rate of CRT implantation, making consideration of the data reviewed in this article crucial for identifying important gaps of knowledge and mechanisms of action that need to be studied in the near future.

Robert H. Koch's Work on Lightweight Medium-Aperture Mirrors

After a visit by Peter Waddell from the University of Strathclyde, Glasgow, UK in 1991, Robert H. Koch launched a program at the University of Pennsylvania to build lightweight pneumatic membrane mirrors, initially for balloon flight observations where weight is at a premium. Mirror cells were fabricated from sizes 0.18 m to 1.77 m, and experiments conducted to characterize the mirror figure and stability. Most of the work stopped after Prof. Koch's retirement in 1996 until 2006 when the authors expressed an interest in building an array of medium-aperture portable telescopes. The program restarted in earnest at Gravic, Inc. in Malvern, PA in 2008 with Koch using his extensive observational astronomy experience to guide the fabrication of a fully operational 1.07 m membrane mirror telescope with an optical tube assembly weighing under 45 Kg. Residual wavefront aberrations remediation resulted in Koch and the authors investigating membrane tensioning techniques with different cell designs, active secondary wavefront correction, photometric algorithms for aberrated images, and the use of additional lightweight mirror substrates from the Alt-Az Initiative Group, such as foamed glass. The best result for the lightweight mirrors was a point spread function spot size of several arc seconds. A lightweight 1.6 m cast aluminum cell alt-az telescope was subsequently designed by Koch and the authors for prime focus use.

Complete measurement of fiber modal content by wavefront analysis

We propose and demonstrate the use of a wavefront analyzer based on lateral shearing interferometry to characterize the modal content of multimode fibers. This wavefront measurement technique is applied to large mode area fibers, and allows us to recover both the intensity and relative phase of each guided mode. This constitutes an innovative complete characterization of the beam, and might be used as a probe in deterministic active wavefront correction techniques.