ECG imaging of ventricular tachycardia: evaluation against simultaneous non-contact mapping and CMR-derived grey zone.

ECG imaging is an emerging technology for the reconstruction of cardiac electric activity from non-invasively measured body surface potential maps. In this case report, we present the first evaluation of transmurally imaged activation times against endocardially reconstructed isochrones for a case of sustained monomorphic ventricular tachycardia (VT). Computer models of the thorax and whole heart were produced from MR images. A recently published approach was applied to facilitate electrode localization in the catheter laboratory, which allows for the acquisition of body surface potential maps while performing non-contact mapping for the reconstruction of local activation times. ECG imaging was then realized using Tikhonov regularization with spatio-temporal smoothing as proposed by Huiskamp and Greensite and further with the spline-based approach by Erem et al. Activation times were computed from transmurally reconstructed transmembrane voltages. The results showed good qualitative agreement between the non-invasively and invasively reconstructed activation times. Also, low amplitudes in the imaged transmembrane voltages were found to correlate with volumes of scar and grey zone in delayed gadolinium enhancement cardiac MR. The study underlines the ability of ECG imaging to produce activation times of ventricular electric activity-and to represent effects of scar tissue in the imaged transmembrane voltages.

Influence of the earliest right atrial activation site and its proximity to interatrial connections on P-wave morphology.

AIMS: P-wave morphology correlates with the risk for atrial fibrillation (AF). Left atrial (LA) enlargement could explain both the higher risk for AF and higher P-wave terminal force (PTF) in lead V1. However, PTF-V1 has been shown to correlate poorly with LA size. We hypothesize that PTF-V1 is also affected by the earliest activated site (EAS) in the right atrium and its proximity to inter-atrial connections (IAC), which both show tremendous variability. METHODS AND RESULTS: Atrial excitation was triggered from seven different EAS in a cohort of eight anatomically personalized computational models. The posterior IACs were non-conductive in a second set of simulations. Body surface ECGs were computed and separated by left and right atrial contributions. Mid-septal EAS yielded the highest PTF-V1. More anterior/superior and more inferior EAS yielded lower absolute PTF-V1 values deviating by a factor of up to 2.0 for adjacent EAS. Earliest right-to-left activation was conducted via Bachmann's Bundle (BB) for anterior/superior EAS and shifted towards posterior IACs for more inferior EAS. Non-conducting posterior IACs increased PTF-V1 by up to 150% compared to intact posterior IACs for inferior EAS. LA contribution to the P-wave integral was 24% on average. CONCLUSION: The electrical contributor's site of earliest activation and intactness of posterior IACs affect PTF-V1 significantly by changing LA breakthrough sites independent from LA size. This should be considered for interpretation of electrocardiographical signs of LA abnormality and LA enlargement.

Patient-specific modeling of atrial fibrosis increases the accuracy of sinus rhythm simulations and may explain maintenance of atrial fibrillation.

Left atrial fibrosis is thought to contribute to the manifestation of atrial fibrillation (AF). Late Gadolinium enhancement (LGE) MRI has the potential to image regions of low perfusion, which can be related to fibrosis. We show that a simulation with a patient-specific model including left atrial regional fibrosis derived from LGE-MRI reproduces local activation in the left atrium more precisely than the regular simulation without fibrosis. AF simulations showed a spontaneous termination of the arrhythmia in the absence of fibrosis and a stable rotor center in the presence of fibrosis. The methodology may provide a tool for a deeper understanding of the mechanisms maintaining AF and eventually also for the planning of substrate-guided ablation procedures in the future.

In-silico modeling of atrial repolarization in normal and atrial fibrillation remodeled state.

Atrial fibrillation (AF) is the most common cardiac arrhythmia, and the total number of AF patients is constantly increasing. The mechanisms leading to and sustaining AF are not completely understood yet. Heterogeneities in atrial electrophysiology seem to play an important role in this context. Although some heterogeneities have been used in in-silico human atrial modeling studies, they have not been thoroughly investigated. In this study, the original electrophysiological (EP) models of Courtemanche et al., Nygren et al. and Maleckar et al. were adjusted to reproduce action potentials in 13 atrial regions. The parameter sets were validated against experimental action potential duration data and ECG data from patients with AV block. The use of the heterogeneous EP model led to a more synchronized repolarization sequence in a variety of 3D atrial anatomical models. Combination of the heterogeneous EP model with a model of persistent AF-remodeled electrophysiology led to a drastic change in cell electrophysiology. Simulated Ta-waves were significantly shorter under the remodeling. The heterogeneities in cell electrophysiology explain the previously observed Ta-wave effects. The results mark an important step toward the reliable simulation of the atrial repolarization sequence, give a deeper understanding of the mechanism of atrial repolarization and enable further clinical investigations.

Personalization of atrial anatomy and electrophysiology as a basis for clinical modeling of radio-frequency ablation of atrial fibrillation.

Multiscale cardiac modeling has made great advances over the last decade. Highly detailed atrial models were created and used for the investigation of initiation and perpetuation of atrial fibrillation. The next challenge is the use of personalized atrial models in clinical practice. In this study, a framework of simple and robust tools is presented, which enables the generation and validation of patient-specific anatomical and electrophysiological atrial models. Introduction of rule-based atrial fiber orientation produced a realistic excitation sequence and a better correlation to the measured electrocardiograms. Personalization of the global conduction velocity lead to a precise match of the measured P-wave duration. The use of a virtual cohort of nine patient and volunteer models averaged out possible model-specific errors. Intra-atrial excitation conduction was personalized manually from left atrial local activation time maps. Inclusion of LE-MRI data into the simulations revealed possible gaps in ablation lesions. A fast marching level set approach to compute atrial depolarization was extended to incorporate anisotropy and conduction velocity heterogeneities and reproduced the monodomain solution. The presented chain of tools is an important step towards the use of atrial models for the patient-specific AF diagnosis and ablation therapy planing.

Towards personalized clinical in-silico modeling of atrial anatomy and electrophysiology.

Computational atrial models aid the understanding of pathological mechanisms and therapeutic measures in basic research. The use of biophysical models in a clinical environment requires methods to personalize the anatomy and electrophysiology (EP). Strategies for the automation of model generation and for evaluation are needed. In this manuscript, the current efforts of clinical atrial modeling in the euHeart project are summarized within the context of recent publications in this field. Model-based segmentation methods allow for the automatic generation of ready-to-simulate patient-specific anatomical models. EP models can be adapted to patient groups based on a-priori knowledge and to the individual without significant further data acquisition. ECG and intracardiac data build the basis for excitation personalization. Information from late enhancement (LE) MRI can be used to evaluate the success of radio-frequency ablation (RFA) procedures and interactive virtual atria pave the way for RFA planning. Atrial modeling is currently in a transition from the sole use in basic research to future clinical applications. The proposed methods build the framework for model-based diagnosis and therapy evaluation and planning. Complex models allow to understand biophysical mechanisms and enable the development of simplified models for clinical applications.

Computational modeling of the human atrial anatomy and electrophysiology.

This review article gives a comprehensive survey of the progress made in computational modeling of the human atria during the last 10 years. Modeling the anatomy has emerged from simple "peanut"-like structures to very detailed models including atrial wall and fiber direction. Electrophysiological models started with just two cellular models in 1998. Today, five models exist considering e.g. details of intracellular compartments and atrial heterogeneity. On the pathological side, modeling atrial remodeling and fibrotic tissue are the other important aspects. The bridge to data that are measured in the catheter laboratory and on the body surface (ECG) is under construction. Every measurement can be used either for model personalization or for validation. Potential clinical applications are briefly outlined and future research perspectives are suggested.

Comparing measured and simulated wave directions in the left atrium - a workflow for model personalization and validation.

Atrial arrhythmias are frequently treated using catheter ablation during electrophysiological (EP) studies. However, success rates are only moderate and could be improved with the help of personalized simulation models of the atria. In this work, we present a workflow to generate and validate personalized EP simulation models based on routine clinical computed tomography (CT) scans and intracardiac electrograms. From four patient data sets, we created anatomical models from angiographic CT data with an automatic segmentation algorithm. From clinical intracardiac catheter recordings, individual conduction velocities were calculated. In these subject-specific EP models, we simulated different pacing maneuvers and measurements with circular mapping catheters that were applied in the respective patients. This way, normal sinus rhythm and pacing from a coronary sinus catheter were simulated. Wave directions and conduction velocities were quantitatively analyzed in both clinical measurements and simulated data and were compared. On average, the overall difference of wave directions was 15° (8%), and the difference of conduction velocities was 16 cm/s (17%). The method is based on routine clinical measurements and is thus easy to integrate into clinical practice. In the long run, such personalized simulations could therefore assist treatment planning and increase success rates for atrial arrhythmias.

Automatic multi-model-based segmentation of the left atrium in cardiac MRI scans.

Model-based segmentation approaches have been proven to produce very accurate segmentation results while simultaneously providing an anatomic labeling for the segmented structures. However, variations of the anatomy, as they are often encountered e.g. on the drainage pattern of the pulmonary veins to the left atrium, cannot be represented by a single model. Automatic model selection extends the model-based segmentation approach to handling significant variational anatomies without user interaction. Using models for the three most common anatomical variations of the left atrium, we propose a method that uses an estimation of the local fit of different models to select the best fitting model automatically. Our approach employs the support vector machine for the automatic model selection. The method was evaluated on 42 very accurate segmentations of MRI scans using three different models. The correct model was chosen in 88.1% of the cases. In a second experiment, reflecting average segmentation results, the model corresponding to the clinical classification was automatically found in 78.0% of the cases.

Myofiber orientation and electrical activation in human and sheep atrial models.

Anatomically realistic computational models provide a powerful platform for investigating mechanisms that underlie atrial rhythm disturbances. In recent years, novel techniques have been developed to construct structurally-detailed, image-based models of 3D atrial anatomy. However, computational models still do not contain full descriptions of the atrial intramural myofiber architecture throughout the entire atria. To address this, a semi-automatic rule-based method was developed for generating multi-layer myofiber orientations in the human atria. The rules for fiber generation are based on the careful anatomic studies of Ho, Anderson and co-workers using dissection, macrophotography and visual tracing of fiber tracts. Separately, a series of high color contrast images were obtained from sheep atria with a novel confocal surface microscopy method. Myofiber orientations in the normal sheep atria were estimated by eigen-analyis of the 3D image structure tensor. These data have been incorporated into an anatomical model that provides the quantitative representation of myofiber architecture in the atrial chambers. In this study, we attempted to compare the two myofiber generation approaches. We observed similar myo-bundle structure in the human and sheep atria, for example in Bachmann's bundle, atrial septum, pectinate muscles, superior vena cava and septo-pulmonary bundle. Our computational simulations also confirmed that the preferential propagation pathways of the activation sequence in both atrial models is qualitatively similar, largely due to the domination of the major muscle bundles.

Conduction velocity restitution of the human atrium--an efficient measurement protocol for clinical electrophysiological studies.

Conduction velocity (CV) and CV restitution are important substrate parameters for understanding atrial arrhythmias. The aim of this work is to (i) present a simple but feasible method to measure CV restitution in-vivo using standard circular catheters, and (ii) validate its feasibility with data measured during incremental pacing. From five patients undergoing catheter ablation, we analyzed eight datasets from sinus rhythm and incremental pacing sequences. Every wavefront was measured with a circular catheter and the electrograms were analyzed with a cosine-fit method that calculated the local CV. For each pacing cycle length, the mean local CV was determined. Furthermore, changes in global CV were estimated from the time delay between pacing stimulus and wavefront arrival. Comparing local and global CV between pacing at 500 and 300 ms, we found significant changes in seven of eight pacing sequences. On average, local CV decreased by 20 ± 15% and global CV by 17 ± 13%. The method allows for in-vivo measurements of absolute CV and CV restitution during standard clinical procedures. Such data may provide valuable insights into mechanisms of atrial arrhythmias. This is important both for improving cardiac models and also for clinical applications, such as characterizing arrhythmogenic substrates during sinus rhythm.

euHeart: personalized and integrated cardiac care using patient-specific cardiovascular modelling.

The loss of cardiac pump function accounts for a significant increase in both mortality and morbidity in Western society, where there is currently a one in four lifetime risk, and costs associated with acute and long-term hospital treatments are accelerating. The significance of cardiac disease has motivated the application of state-of-the-art clinical imaging techniques and functional signal analysis to aid diagnosis and clinical planning. Measurements of cardiac function currently provide high-resolution datasets for characterizing cardiac patients. However, the clinical practice of using population-based metrics derived from separate image or signal-based datasets often indicates contradictory treatments plans owing to inter-individual variability in pathophysiology. To address this issue, the goal of our work, demonstrated in this study through four specific clinical applications, is to integrate multiple types of functional data into a consistent framework using multi-scale computational modelling.

A framework for personalization of computational models of the human atria.

A framework for step-by-step personalization of a computational model of human atria is presented. Beginning with anatomical modeling based on CT or MRI data, next fiber structure is superimposed using a rule-based method. If available, late-enhancement-MRI images can be considered in order to mark fibrotic tissue. A first estimate of individual electrophysiology is gained from BSPM data solving the inverse problem of ECG. A final adjustment of electrophysiology is realized using intracardiac measurements. The framework is applied using several patient data. First clinical application will be computer assisted planning of RF-ablation for treatment of atrial flutter and atrial fibrillation.

Model-based assessment of tissue perfusion and temperature in deep hypothermic patients.

Deep hypothermic circulatory arrest is necessary for some types of cardiac and aortic surgery. Perfusion of the brain can be maintained using a heart-lung machine and unilateral antegrade cerebral perfusion. Cooling rates during extracorporeal circulation depend on local perfusion. A core temperature of 24 degrees C-25 degrees C is aimed at to extend ischemic tolerance of tissues. Information on cerebral perfusion and temperature is important for the safety of patients, but hardly accessible to measurement. A combined simulation model of hemodynamics and temperature is presented in this paper. The hemodynamics model employs the transmission-line approach and integrates the Circle of Willis (CoW). This allows for parameterization of individual aberrations. Simulation results of cerebral perfusion are shown for two configurations of the CoW. The temperature model provides spatial information on temperature fields. It considers heat transfer in the various tissues retrieving data of local tissue perfusion from the hemodynamics model. The combined model is evaluated by retrospective simulation of two aortic operations.