Automatic estimation of Purkinje-Myocardial junction hot-spots from noisy endocardial samples: A simulation study
The reconstruction of the ventricular cardiac conduction system (CCS) from patient-specific data is a challenging problem. High-resolution imaging techniques have allowed only the segmentation of proximal sections of the CCS from images acquired ex vivo. In this paper, we present an algorithm to estimate the location of a set of Purkinje-myocardial junctions (PMJs) from electro-anatomical maps, as those acquired during radio-frequency ablation procedures. The method requires a mesh representing the myocardium with local activation time measurements on a subset of nodes. We calculate the backwards propagation of the electrical signal from the measurement points to all the points in the mesh …
Fuzzy temporal random sets with an application to cell biology
Total Internal Reflection Fluorescence Microscopy (TIRFM) greatly facilitates to imaging the first steps of endocytosis, a process whereby cells traffic cargo from the cell surface to endosomes. Using TIRFM, fluorescent-tagged endocytic proteins are observed as overlapped areas forming random clumps of different sizes, shapes and durations. A common procedure to segment these objects consists of thresholding the original gray-level images to produce binary sequences in which a pixel is covered or not by a given fluorescent-tagged protein. This binary logic is not appropriate because it leaves a free tuning parameter to be set by the user which can influence on the conclusions of the statist…
Integration of different cardiac electrophysiological models into a single simulation pipeline
Clinical translation of computational models of the heart has been hampered by the absence of complete and rigorous technical and clinical validation, as well as benchmarking of the developed tools. To address this issue, a dataset containing the cardiac anatomy and fibre orientations from magnetic resonance images (MRI), as well as epicardial transmembrane potentials from optical mapping acquired on ex-vivo porcine hearts, have previously been made available to the community. Image processing techniques were developed to integrate MRI images with electrical information. Different models were tested and compared with the integrated data1, including: i) a new methodology to customize and reg…
Three-dimensional cardiac computational modelling: methods, features and applications
[EN] The combination of computational models and biophysical simulations can help to interpret an array of experimental data and contribute to the understanding, diagnosis and treatment of complex diseases such as cardiac arrhythmias. For this reason, three-dimensional (3D) cardiac computational modelling is currently a rising field of research. The advance of medical imaging technology over the last decades has allowed the evolution from generic to patient-specific 3D cardiac models that faithfully represent the anatomy and different cardiac features of a given alive subject. Here we analyse sixty representative 3D cardiac computational models developed and published during the last fifty …
Automatic Location of Sources of Electrical Activation from Electroanatomical Maps
Electro-anatomical mapping is a widely used technique used by electrophysiologists to understand patient's activation pattern. The system measures activation time at different locations but does not provide information on underlying electrical pathways or triggering points, such as Purkinje-myocardial junctions or ectopic foci. We present a method to estimate the locations of Purkinje-myocardial junctions from a discrete set of endocardial samples. Using less than 1000 endocardial samples it can recover locations and activation times of the most influencing Purkinje myocardial junctions from Purkinje trees of up to 500 junctions. A simulation study revealed that using the estimated Purkinje…
Clinically-Driven Virtual Patient Cohorts Generation: An Application to Aorta
The combination of machine learning methods together with computational modeling and simulation of the cardiovascular system brings the possibility of obtaining very valuable information about new therapies or clinical devices through in-silico experiments. However, the application of machine learning methods demands access to large cohorts of patients. As an alternative to medical data acquisition and processing, which often requires some degree of manual intervention, the generation of virtual cohorts made of synthetic patients can be automated. However, the generation of a synthetic sample can still be computationally demanding to guarantee that it is clinically meaningful and that it re…
Loss of endocytic clathrin-coated pits upon acute depletion of phosphatidylinositol 4,5-bisphosphate.
Phosphatidylinositol 4,5-bisphosphate [PI(4,5) P 2 ], a phosphoinositide concentrated predominantly in the plasma membrane, binds endocytic clathrin adaptors, many of their accessory factors, and a variety of actin-regulatory proteins. Here we have used fluorescent fusion proteins and total internal reflection fluorescence microscopy to investigate the effect of acute PI(4,5) P 2 breakdown on the dynamics of endocytic clathrin-coated pit components and of the actin regulatory complex, Arp2/3. PI(4,5) P 2 breakdown was achieved by the inducible recruitment to the plasma membrane of an inositol 5-phosphatase module through the rapamycin/FRB/FKBP system or by treatment with ionomycin. PI(4,5)…
Intra-cardiac Signatures of Atrial Arrhythmias Identified by Machine Learning and Traditional Features
Intracardiac devices separate atrial arrhythmias (AA) from sinus rhythm (SR) using electrogram (EGM) features such as rate, that are imperfect. We hypothesized that machine learning could improve this classification.
Personalized Cardiac Computational Models: From Clinical Data to Simulation of Infarct-Related Ventricular Tachycardia.
In the chronic stage of myocardial infarction, a significant number of patients develop life-threatening ventricular tachycardias (VT) due to the arrhythmogenic nature of the remodeled myocardium. Radiofrequency ablation (RFA) is a common procedure to isolate reentry pathways across the infarct scar that are responsible for VT. Unfortunately, this strategy show relatively low success rates; up to 50% of patients experience recurrent VT after the procedure. In the last decade, intensive research in the field of computational cardiac electrophysiology (EP) has demonstrated the ability of three-dimensional (3D) cardiac computational models to perform in-silico EP studies. However, the personal…
Analysis of in-silico body surface P-wave integral maps show important differences depending on the connections between coronary sinus and left atrium
The electrical connections between the atrial coronary sinus (CS) and the left atrial (LA) myocardium have an effect on the overall atrial activation pattern and the P-wave morphology. In this study, we use our validated multi-scale 3D human atrial-torso model to elucidate which electro-anatomical configuration of connections between CS and LA more accurately reproduces a set of body surface P-wave integral maps (BSPiM) acquired in the clinic. We performed atrial biophysical simulations by pacing in distal and proximal LA sites. The corresponding in-silico BSPiM were then computed and compared with published clinical patterns obtained from patients. Important differences in BSPiM were obser…
OpenCMISS: A multi-physics & multi-scale computational infrastructure for the VPH/Physiome project
The VPH/Physiome Project is developing the model encoding standards CellML (cellml.org) and FieldML (fieldml.org) as well as web-accessible model repositories based on these standards (models.physiome.org). Freely available open source computational modelling software is also being developed to solve the partial differential equations described by the models and to visualise results. The OpenCMISS code (opencmiss.org), described here, has been developed by the authors over the last six years to replace the CMISS code that has supported a number of organ system Physiome projects. OpenCMISS is designed to encompass multiple sets of physical equations and to link subcellular and tissue-level b…
Analysis of Microstructure of the Cardiac Conduction System Based on Three-Dimensional Confocal Microscopy
The specialised conducting tissues present in the ventricles are responsible for the fast distribution of the electrical impulse from the atrio-ventricular node to regions in the subendocardial myocardium. Characterisation of anatomical features of the specialised conducting tissues in the ventricles is highly challenging, in particular its most distal section, which is connected to the working myocardium via Purkinje-myocardial junctions. The goal of this work is to characterise the architecture of the distal section of the Purkinje network by differentiating Purkinje cells from surrounding tissue, performing a segmentation of Purkinje fibres at cellular scale, and mathematically describin…
Modelización computacional cardiaca
[EN] Cardiovascular diseases currently have a major social and economic impact, constituting one of the leading causes of mortality and morbidity. Personalized computational models of the heart are demonstrating their usefulness both to help understand the mechanisms underlying cardiac disease, and to optimize their treatment and predict the patient's response. Within this framework, the Spanish Research Network for Cardiac Computational Modelling (VHeart-SN) has been launched. The general objective of the VHeart-SN network is the development of an integrated, modular and multiscale multiphysical computational model of the heart. This general objective is addressed through the following spe…
Estimation of Electrical Pathways Finding Minimal Cost Paths from Electro-Anatomical Mapping of the Left Ventricle
The electrical activation of the heart is a complex physiological process that is essential for the understanding of several cardiac dysfunctions, such as ventricular tachycardia VT. Nowadays, electro-anatomical mappings of patient-specific activation times on the left ventricle surface can be estimated, providing crucial information to the clinicians for guiding cardiac treatment. However, some electrical pathways of particular interest such as Purkinje or still viable conduction channels are difficult to interpret in these maps. We present here a novel method to find some of these electrical pathways using minimal cost paths computations on surface maps. Experiments to validate the propos…
In silico pace-mapping: prediction of left vs. right outflow tract origin in idiopathic ventricular arrhythmias with patient-specific electrophysiological simulations
Abstract Aims A pre-operative non-invasive identification of the site of origin (SOO) of outflow tract ventricular arrhythmias (OTVAs) is important to properly plan radiofrequency ablation procedures. Although some algorithms based on electrocardiograms (ECGs) have been developed to predict left vs. right ventricular origins, their accuracy is still limited, especially in complex anatomies. The aim of this work is to use patient-specific electrophysiological simulations of the heart to predict the SOO in OTVA patients. Methods and results An in silico pace-mapping procedure was designed and used on 11 heart geometries, generating for each case simulated ECGs from 12 clinically plausible SOO…
Modeling Drug Effects on Personalized 3D Models of the Heart: A Simulation Study
[EN] The use of anti-arrhythmic drugs is common to treat heart rhythm disorders. Computational modeling and simulation are powerful tools that can be used to investigate the effects of specific drugs on cardiac electrophysiology. In this work a patient-specific anatomical heart model is built to study the effects of dofetilide, a drug that affects IKr current in cardiac cells. We study the multi-scale effects of the drug, from cellular to organ level, by simulating electrical propagation on tissue coupled cellular ion kinetics for several heart beats. Different cell populations configurations namely endocardial, midmyocardial and epicardial are used to test the effect of tissue heterogeneit…
Measuring Spatiotemporal Dependencies in Bivariate Temporal Random Sets with Applications to Cell Biology
Analyzing spatiotemporal dependencies between different types of events is highly relevant to many biological phenomena (e.g., signaling and trafficking), especially as advances in probes and microscopy have facilitated the imaging of dynamic processes in living cells. For many types of events, the segmented areas can overlap spatially and temporally, forming random clumps. In this paper, we model the binary image sequences of two different event types as a realization of a bivariate temporal random set and propose a nonparametric approach to quantify spatial and spatiotemporal interrelations using the pair correlation, cross-covariance, and the Ripley K functions. Based on these summary st…
Sensitivity analysis of mesh warping and subsampling strategies for generating large scale electrophysiological simulation data
The analysis of large-scale simulation data from virtual populations can be effective to gain computational insight into disease mechanisms and treatment strategies, which can serve for generating hypotheses for and focusing subsequent clinical trials. This can be instrumental in shortening the critical path in medical product development and more cost-effective clinical trials. A previously published pipeline established point correspondence among volumetric meshes to enable meaningful statistics on cardiac electrophysiological simulations on the anatomical distribution of a large-scale virtual population. Thin Plate Splines (TPS), derived from surface deformations, were used to warp a tem…
Ventricular Tachycardia and Early Fibrillation in Patients With Brugada Syndrome and Ischemic Cardiomyopathy Show Predictable Frequency-Phase Properties on the Precordial ECG Consistent With the Respective Arrhythmogenic Substrate
[EN] Background¿ Ventricular fibrillation (VF) has been proposed to be maintained by localized high-frequency sources. We tested whether spectral-phase analysis of the precordial ECG enabled identification of periodic activation patterns generated by such sources. Methods and Results¿Precordial ECGs were recorded from 15 ischemic cardiomyopathy and 15 Brugada syndrome (type 1 ECG) patients during induced VF and analyzed in the frequency-phase domain. Despite temporal variability, induced VF episodes lasting 19.6±7.9 s displayed distinctly high power at a common frequency (shared frequency, 5.7±1.1 Hz) in all leads about half of the time. In patients with Brugada syndrome, phase analysis of …
Personalization of Fast Conduction Purkinje System in Eikonal-Based Electrophysiological Models with Optical Mapping Data
We present a pipeline for the personalization of model-based Purkinje fast conduction system using fast electrophysiological models and optical mapping data acquired from ex-vivo porcine hearts. The regional density of the Purkinje terminals as well as the latest endocardial activation time were the parameters personalized in an iterative procedure maximizing the similarity between the outcome of the electrophysiological simulations and measurements obtained from optical mapping data. We used a fast wave-front Eikonal-based electrophysiological model that generated the depolarization time maps that were subsequently compared with measurements at each iteration of the optimization stage. The…
Prediction of CRT Activation Sequence by Personalization of Biventricular Models from Electroanatomical Maps
[EN] Optimization of lead placement and interventricular delay settings in patients under cardiac resynchronization therapy is a complex task that might benefit from prior information based on models. Biophysical models can be used to predict the sequence of electrical heart activation in a patient given a set of parameters which should be personalized to the patient. In this paper, we use electroanatomical maps to personalize the endocardial activation of the right ventricle, and the different tissue conductivities in a pig model with left bundle branch block, to reproduce personalized biventricular activations. Following, we tested the personalized heart model by virtually simulating card…
Studying endocytosis in space and time by means of temporal Boolean models
Endocytosis is a process by which cells carry traffic from the extracellular space into various intracellular compartments. Visualization of fluorescently tagged clathrin proteins (mediators of endocytosis) allows us to image endocytosis in real time. When imaging the plasma membrane, areas of fluorescence generated by different endocytic processes overlap spatially and temporally, forming random clumps. Here, a sequence of segmented clathrin spots is considered a realization of a non-isotropic 3D Boolean model. Estimates of the intensity, the mean perimeter and the density function of the durations of endocytic events are obtained.
An atlas- and data-driven approach to initializing reaction-diffusion systems in computer cardiac electrophysiology
The cardiac electrophysiology (EP) problem is governed by a nonlinear anisotropic reaction-diffusion system with a very rapidly varying reaction term associated with the transmembrane cell current. The nonlinearity associated with the cell models requires a stabilization process before any simulation is performed. More importantly, when used in a 3-dimensional (3D) anatomy, it is not sufficient to perform this stabilization on the basis of isolated cells only, since the coupling of the different cells through the tissue greatly modulates the dynamics of the system. Therefore, stabilization of the system must be performed on the entire 3D model. This work develops a novel procedure for the i…
Inter-Model Consistency and Complementarity: Learning from ex-vivo Imaging and Electrophysiological Data towards an Integrated Understanding of Cardiac Physiology
International audience; Computational models of the heart at various scales and levels of complexity have been independently developed, parameterised and validated using a wide range of experimental data for over four decades. However, despite remarkable progress, the lack of coordinated efforts to compare and combine these computational models has limited their impact on the numerous open questions in cardiac physiology. To address this issue, a comprehensive dataset has previously been made available to the community that contains the cardiac anatomy and fibre orientations from magnetic resonance imaging as well as epicardial transmembrane potentials from optical mapping measured on a per…
Analysis of Spatially and Temporally Overlapping Events with Application to Image Sequences
Counting spatially and temporally overlapping events in image sequences and estimating their shape-size and duration features are important issues in some applications. We propose a stochastic model, a particular case of the nonisotropic 3D Boolean model, for performing this analysis: the temporal Boolean model. Some probabilistic properties are derived and a methodology for parameter estimation from time-lapse image sequences is proposed using an explicit treatment of the temporal dimension. We estimate the mean number of germs per unit area and time, the mean grain size and the duration distribution. A wide simulation study in order to assess the proposed estimators showed promising resul…
Quasi-Conformal Technique for Integrating and Validating Myocardial Tissue Characterization in MRI with Ex-Vivo Human Histological Data
Ventricular tachycardia caused by a circuit of re-entry is one of the most critical arrhythmias. It is usually related with heterogeneous scar regions where slow velocity of conduction tissue is mixed with non-conductive tissue, creating pathways (CC) responsible for the tachycardia. Pre-operative DE-MRI can provide information on myocardial tissue viability and then improve therapy planning. However, the current DE-MRI resolution is not sufficient for identifying small CCs and therefore they have to be identified during the intervention, which requires considerable operator experience. In this work, we studied the relationship of histological data (with 10 \(\mu \)m resolution), with in-vi…
Effect of Scar Development on Fast Electrophysiological Models of the Human Heart: In-Silico Study on Atlas-Based Virtual Populations
The main goal of this work is to study the effect of scar development in the electrophysiological function of the human left ventricle by statistically analyzing large-scale simulation data including hypertrophic and dilated hearts. Electrophysiological simulations are obtained by solving the classical Eikonal equation in both the ventricular tissue and a customized Purkinje system. This Purkinje system is obtained assuming a geodesic rule to connect different Purkinje-myocardial junctions into a tree-like structure. Infarction shape and function is modeled with taking into account the occlusion in coronary arteries. Infarct, core and border zones of the scar are estimated by calculating bl…
Spatio-Temporal Analysis of Constitutive Exocytosis in Epithelial Cells
Exocytosis is an essential cellular trafficking process integral to the proper distribution and function of a plethora of molecules, including transporters, receptors, and enzymes. Moreover, incorrect protein targeting can lead to pathological conditions. Recently, the application of evanescent wave microscopy has allowed us to image the final steps of exocytosis. However, spatio-temporal analysis of fusion of constitutive vesicular traffic with the plasma membrane has not been systematically performed. Also, the spatial sites and times of vesicle fusion have not yet been analyzed together. In addition, more formal tests are required in testing biological hypotheses, rather than visual insp…
An Automata-Based Cardiac Electrophysiology Simulator to Assess Arrhythmia Inducibility
Personalized cardiac electrophysiology simulations have demonstrated great potential to study cardiac arrhythmias and help in therapy planning of radio-frequency ablation. Its application to analyze vulnerability to ventricular tachycardia and sudden cardiac death in infarcted patients has been recently explored. However, the detailed multi-scale biophysical simulations used in these studies are very demanding in terms of memory and computational resources, which prevents their clinical translation. In this work, we present a fast phenomenological system based on cellular automata (CA) to simulate personalized cardiac electrophysiology. The system is trained on biophysical simulations to re…
A rule‐based method to model myocardial fiber orientation in cardiac biventricular geometries with outflow tracts
Rule-based methods are often used for assigning fiber orientation to cardiac anatomical models. However, existing methods have been developed using data mostly from the left ventricle. As a consequence, fiber information obtained from rule-based methods often does not match histological data in other areas of the heart such as the right ventricle, having a negative impact in cardiac simulations beyond the left ventricle. In this work, we present a rule-based method where fiber orientation is separately modeled in each ventricle following observations from histology. This allows to create detailed fiber orientation in specific regions such as the endocardium of the right ventricle, the inter…
Towards High Resolution Computational Models of the Cardiac Conduction System: A Pipeline for Characterization of Purkinje-Ventricular-Junctions
The cardiac conduction system (CCS) has been in the spot light of the clinical and modeling community in recent years because of its fundament role in physiology and pathophysiology of the heart. Experimental research has focused mainly on investigating the electrical properties of the Purkinje-ventricular-junctions (PVJs). The structure of the PVJs has only been described through schematic drawings but not thoroughly studied. In this work confocal microscopy was used with the aim of three-dimensional characterization of PVJs. Adult rabbit hearts were labeled with fluorescent dyes, imaged with confocal microscopy and Purkinje fibers differentiated from other cardiac tissue by their lack of …
87Non-invasive virtual prediction of site of origin in outflow tract ventricular arrhythmias with a patient-specific computational model
A Rule-Based Method to Model Myocardial Fiber Orientation for Simulating Ventricular Outflow Tract Arrhythmias
Comunicació presentada a: FIMH 2017 9th International Conference, celebrada a Toronto, Canadà, de l'11 al 13 de juny de 2017. Myocardial fiber orientation determines the propagation of electrical waves in the heart and the contraction of cardiac tissue. One common approach for assigning fiber orientation to cardiac anatomi- cal models are Rule-Based Methods (RBM). However, RBM have been developed to assimilate data mostly from the Left Ventricle. In conse- quence, fiber information from RBM does not match with histological data in other areas of the heart, having a negative impact in cardiac simulations beyond the LV. In this work, we present a RBM where fiber orientation is separately mode…
Meshless Electrophysiological Modeling of Cardiac Resynchronization Therapy—Benchmark Analysis with Finite-Element Methods in Experimental Data
Computational models of cardiac electrophysiology are promising tools for reducing the rates of non-response patients suitable for cardiac resynchronization therapy (CRT) by optimizing electrode placement. The majority of computational models in the literature are mesh-based, primarily using the finite element method (FEM). The generation of patient-specific cardiac meshes has traditionally been a tedious task requiring manual intervention and hindering the modeling of a large number of cases. Meshless models can be a valid alternative due to their mesh quality independence. The organization of challenges such as the CRT-EPiggy19, providing unique experimental data as open access, enables b…
Training machine learning models with synthetic data improves the prediction of ventricular origin in outflow tract ventricular arrhythmias
In order to determine the site of origin (SOO) in outflow tract ventricular arrhythmias (OTVAs) before an ablation procedure, several algorithms based on manual identification of electrocardiogram (ECG) features, have been developed. However, the reported accuracy decreases when tested with different datasets. Machine learning algorithms can automatize the process and improve generalization, but their performance is hampered by the lack of large enough OTVA databases. We propose the use of detailed electrophysiological simulations of OTVAs to train a machine learning classification model to predict the ventricular origin of the SOO of ectopic beats. We generated a synthetic database of 12-l…
Non-invasive localization of atrial ectopic beats by using simulated body surface P-wave integral maps
Non-invasive localization of continuous atrial ectopic beats remains a cornerstone for the treatment of atrial arrhythmias. The lack of accurate tools to guide electrophysiologists leads to an increase in the recurrence rate of ablation procedures. Existing approaches are based on the analysis of the P-waves main characteristics and the forward body surface potential maps (BSPMs) or on the inverse estimation of the electric activity of the heart from those BSPMs. These methods have not provided an efficient and systematic tool to localize ectopic triggers. In this work, we propose the use of machine learning techniques to spatially cluster and classify ectopic atrial foci into clearly diffe…
A quantitative structural and morphometric analysis of the Purkinje network and the Purkinje-myocardial junctions in pig hearts
The morpho-functional properties of the distal section of the cardiac Purkinje network (PN) and the Purkinje-myocardial junctions (PMJs) are fundamental to understanding the sequence of electrical activation in the heart. The overall structure of the system has already been described, and several computational models have been developed to gain insight into its involvement in cardiac arrhythmias or its interaction with implantable devices, such as pacemakers. However, anatomical descriptions of the PN in the literature have not enabled enough improvements in the accuracy of anatomical-based electrophysiological simulations of the PN in 3D hearts models. In this work, we study the global dis…
Atlas construction and image analysis using statistical cardiac models
International audience; This paper presents a brief overview of current trends in the construction of population and multi-modal heart atlases in our group and their application to atlas-based cardiac image analysis. The technical challenges around the construction of these atlases are organized around two main axes: groupwise image registration of anatomical, motion and fiber images and construction of statistical shape models. Application-wise, this paper focuses on the extraction of atlas-based biomarkers for the detection of local shape or motion abnormalities, addressing several cardiac applications where the extracted information is used to study and grade different pathologies. The p…
Changes in the spatial distribution of the Purkinje network after acute myocardial infarction in the pig
Purkinje cells (PCs) are more resistant to ischemia than myocardial cells, and are suspected to participate in ventricular arrhythmias following myocardial infarction (MI). Histological studies afford little evidence on the behavior and adaptation of PCs in the different stages of MI, especially in the chronic stage, and no quantitative data have been reported to date beyond subjective qualitative depictions. The present study uses a porcine model to present the first quantitative analysis of the distal cardiac conduction system and the first reported change in the spatial distribution of PCs in three representative stages of MI: an acute model both with and without reperfusion; a subacute …
Introducción de metodologías de aprendizaje basado en problemas mediante tecnologías multimedia
La propuesta de trabajar por competencias en lugar de hacerlo como se hacía tradicionalmente, por objetivos, ha hecho proliferar las propuestas y alternativas metodológicas para favorecer un cambio en la Educación Superior. Una de estas metodologías es el aprendizaje basado en problemas (ABP). El ABP es una metodología de aprendizaje en la cual el punto de partida es un problema construido por el profesor que permite al estudiante identificar necesidades para comprender mejor ese problema, identificar principios que sustentan el conocimiento y cumplir objetivos de aprendizaje relacionados con cada porción del contenido de la materia. En el caso de las tecnologías de la información y las com…
Estimation of Location and Activation Time of Purkinje Myocardial Junctions from Sparse and Noisy Endocardial Electrical Samples
The activation of the myocardial muscle is triggered by Purkinje-myocardial junctions (PMJs), which are the terminal sites of the specialised cardiac conduction system (CCS). Obtaining the location of the PMJs and other sources of endocardial ectopic activity would be desirable for building computer models of cardiac electrophysiology and planning ablation interventions. We present a method to estimate the location and activation times of endocardial electrical sources in a 3D model of the ventricles. The algorithm requires a set of discrete electrical samples on the endocardium, which can include errors in location and activation time. The estimated sources are properly placed with a locat…
Factors affecting basket catheter detection of real and phantom rotors in the atria: A computational study
[EN] Anatomically based procedures to ablate atrial fibrillation (AF) are often successful in terminating paroxysmal AF. However, the ability to terminate persistent AF remains disappointing. New mechanistic approaches use multiple-electrode basket catheter mapping to localize and target AF drivers in the form of rotors but significant concerns remain about their accuracy. We aimed to evaluate how electrode-endocardium distance, far-field sources and inter-electrode distance affect the accuracy of localizing rotors. Sustained rotor activation of the atria was simulated numerically and mapped using a virtual basket catheter with varying electrode densities placed at different positions withi…
Estimation of Personalized Minimal Purkinje Systems From Human Electro-Anatomical Maps
The Purkinje system is a heart structure responsible for transmitting electrical impulses through the ventricles in a fast and coordinated way to trigger mechanical contraction. Estimating a patient-specific compatible Purkinje Network from an electro-anatomical map is a challenging task, that could help to improve models for electrophysiology simulations or provide aid in therapy planning, such as radiofrequency ablation. In this study, we present a methodology to inversely estimate a Purkinje network from a patient's electro-anatomical map. First, we carry out a simulation study to assess the accuracy of the method for different synthetic Purkinje network morphologies and myocardial junct…
Flexible modeling for anatomically-based cardiac conduction system construction.
We present a method to automatically deploy the peripheral section of the cardiac conduction system in ventricles. The method encodes anatomical information thorough rules that ensure that Purkinje network structures generated are realistic and comparable to those observed in ex-vivo studies. The core methodology is based in non-deterministic production rules that are parameterized by means of statistical functions. Input parameters allow the construction of a great diversity of Purkinje structures that could be incorporated in fine element ventricular models to perform electrophysiology simulations. Resulting Purkinje trees show good geometrical approximations of Purkinje core network and …
Morphometry and comparative histology of sinus and atrioventricular nodes in humans and pigs and their relevance in the prevention of nodal arrhythmias
The cardiac conduction system is a network structure that allows the initiation and fast propagation of electrical impulses that trigger the electrical depolarization of the myocardial tissue. The purpose of this work is to study the histological and morphometric characteristics of the different components of the sinus and atrioventricular nodes in humans and pigs and their relationship with supraventricular arrhythmias. In this study, we describe the morphometry of the sinus and atrioventricular nodes of 10 adult humans and 10 pig hearts. A computerized morphometric study has been carried out, where we determined the number of cells that compose the nodes as well as different parameters re…
Inverse estimation of terminal connections in the cardiac conduction system
Modeling the cardiac conduction system is a challenging problem in the context of computational cardiac electrophysiology. Its ventricular section, the Purkinje system, is responsible for triggering tissue electrical activation at discrete terminal locations, which subsequently spreads throughout the ventricles. In this paper, we present an algorithm that is capable of estimating the location of the Purkinje system triggering points from a set of random measurements on tissue. We present the properties and the performance of the algorithm under controlled synthetic scenarios. Results show that the method is capable of locating most of the triggering points in scenarios with a fair ratio bet…
Atrial Fibrosis Hampers Non-invasive Localization of Atrial Ectopic Foci From Multi-Electrode Signals: A 3D Simulation Study
[EN] Introduction: Focal atrial tachycardia is commonly treated by radio frequency ablation with an acceptable long-term success. Although the location of ectopic foci tends to appear in specific hot-spots, they can be located virtually in any atrial region. Multi-electrode surface ECG systems allow acquiring dense body surface potential maps (BSPM) for non-invasive therapy planning of cardiac arrhythmia. However, the activation of the atria could be affected by fibrosis and therefore biomarkers based on BSPM need to take these effects into account. We aim to analyze the effect of fibrosis on a BSPM derived index, and its potential application to predict the location of ectopic foci in the …
Combining Biophysical Modeling and Machine Learning to Predict Location of Atrial Ectopic Triggers
The search for focal ectopic activity in the atria triggered from non-standard regions can be time consuming. The use of body surface potential maps to plan the intervention can be helpful, but require an advance processing of the data, that usually involves to solve an ill-posed inverse problem. In addition, changes in maps due to pathological substrate such as fibrosis might affect the expected electrical patterns. In this work, we use a machine learning approach to relate ectopic focus activity in different atrial regions with body surface potential maps, and consider the effects of fibrosis in various densities and distributions. Results show that as fibrosis increases over 15% the syst…
Optimization of Lead Placement in the Right Ventricle During Cardiac Resynchronization Therapy. A Simulation Study
[EN] Patients suffering from heart failure and left bundle branch block show electrical ventricular dyssynchrony causing an abnormal blood pumping. Cardiac resynchronization therapy (CRT) is recommended for these patients. Patients with positive therapy response normally present QRS shortening and an increased left ventricle (LV) ejection fraction. However, around one third do not respond favorably. Therefore, optimal location of pacing leads, timing delays between leads and/or choosing related biomarkers is crucial to achieve the best possible degree of ventricular synchrony during CRT application. In this study, computational modeling is used to predict the optimal location and delay of p…
Simplified Electrophysiology Modeling Framework to Assess Ventricular Arrhythmia Risk in Infarcted Patients
Patients that have suffered a myocardial infarction are at lifetime high risk for sudden cardiac death (SCD). Personalized 3D computational modeling and simulation can help to find non-invasively arrhythmogenic features of patients’ infarcts, and to provide additional information for stratification and planning of radiofrequency ablation (RFA). Currently, multiscale biophysical models require high computational resources and long simulations times, which make them impractical for clinical environments. In this paper, we develop a phenomenological solver based on cellular automata to simulate cardiac electrophysiology, with results comparable to those of biophysical models. The solver can ru…
Modelización computacional cardiaca
Resumen Las enfermedades cardiovasculares tienen en la actualidad un gran impacto social y economico y constituyen una de las principales causas de mortalidad y morbilidad. Los modelos computacionales personalizados del corazon estan demostrando ser utiles tanto para ayudar a comprender los mecanismos subyacentes a las patologias cardiacas como para optimizar su tratamiento prediciendo la respuesta del paciente. En este contexto, se ha puesto en marcha la Red Espanola de Investigacion en Modelizacion Computacional Cardiaca (V-Heart SN). El objetivo general de V-Heart SN es el desarrollo de un modelo computacional multifisico y multiescala integrado del corazon. Este objetivo general se abor…
Estimation of Purkinje trees from electro-anatomical mapping of the left ventricle using minimal cost geodesics
The electrical activation of the heart is a complex physiological process that is essential for the understanding of several cardiac dysfunctions, such as ventricular tachycardia (VT). Nowadays, patient-specific activation times on ventricular chambers can be estimated from electro-anatomical maps, providing crucial information to clinicians for guiding cardiac radio-frequency ablation treatment. However, some relevant electrical pathways such as those of the Purkinje system are very difficult to interpret from these maps due to sparsity of data and the limited spatial resolution of the system. We present here a novel method to estimate these fast electrical pathways from the local activati…
Uncoupling of dynamin polymerization and GTPase activity revealed by the conformation-specific nanobody dynab
Dynamin is a large GTPase that forms a helical collar at the neck of endocytic pits, and catalyzes membrane fission (Schmid and Frolov, 2011; Ferguson and De Camilli, 2012). Dynamin fission reaction is strictly dependent on GTP hydrolysis, but how fission is mediated is still debated (Antonny et al., 2016): GTP energy could be spent in membrane constriction required for fission, or in disassembly of the dynamin polymer to trigger fission. To follow dynamin GTP hydrolysis at endocytic pits, we generated a conformation-specific nanobody called dynab, that binds preferentially to the GTP hydrolytic state of dynamin-1. Dynab allowed us to follow the GTPase activity of dynamin-1 in real-time. We…
Using Inverse Reinforcement Learning with Real Trajectories to Get More Trustworthy Pedestrian Simulations
Reinforcement learning is one of the most promising machine learning techniques to get intelligent behaviors for embodied agents in simulations. The output of the classic Temporal Difference family of Reinforcement Learning algorithms adopts the form of a value function expressed as a numeric table or a function approximator. The learned behavior is then derived using a greedy policy with respect to this value function. Nevertheless, sometimes the learned policy does not meet expectations, and the task of authoring is difficult and unsafe because the modification of one value or parameter in the learned value function has unpredictable consequences in the space of the policies it represents…
Granulometric analysis of corneal endothelium specular images by using a germ–grain model
Specular microscopy is widely used to study the human corneal endothelium status in vivo. In this paper, the corneal endothelium is represented as a binary image composed of the cell inscribed circles. The granulometric distribution function of the complement of this image is used as a functional descriptor, which provides information about the shape, size and spatial arrangement of cells. Experimental evaluation using bootstrap techniques shows its ability to discriminate between controls and pathological cases. It represents a reliable and graphical alternative to the classical indices (cell density, hexagonality and coefficient of variation of cell areas), which behave poorly when detect…
Influence of geometric variations on LV activation times: A study on an atlas-based virtual population
We present the fully automated pipeline we have developed to obtain electrophysiological simulations of the heart on a large atlas-based virtual population. This virtual population was generated from a statistical model of left ventricular geometry, represented by a surface model. Correspondence between tetrahedralized volumetric meshes was obtained using Thin Plate Spline warps. Simulations are based on the fast solving of Eikonal equations, and stimulation sites correspond to physiological activation. We report variations of total activation time introduced by geometry, as well as variations in the location of last activation. The obtained results suggest that the total activation time ha…