Design and clinical validation of novel imaging strategies for analysis of arrhythmogenic substrate

_CURRENT CHALLENGES IN ELECTROPHYSIOLOGY_ Technical advances in cardiovascular electrophysiology have resulted in an increasing number of catheter ablation procedures reaching 200 000 in Europe for the year 2013. These advanced interventions are often complex and time consuming and may cause significant radiation exposure. Furthermore, a substantial number of ablation procedures remain associated with poor (initial) outcomes and frequently require ≥1 redo procedures. Innovations in modalities for substrate imaging could facilitate our understanding of the arrhythmogenic substrate, improve the design of patient-specific ablation strategies and improve the results of ablation procedures. _NOVEL SUBSTRATE IMAGING MODALITIES_ __Cardiac magnetic resonance__ Cardiac magnetic resonance imaging (CMR) can be considered the most comprehensive and suitable modality for the complete electrophysiology and catheter ablation workup (including patient selection, procedural guidance, and [procedural] follow-up). Utilizing inversion recovery CMR, fibrotic myocardium can be visualized and quantified 10–15 min after intravenous administration of Gadolinium contrast. This imaging technique is known as late Gadolinium enhancement (LGE) imaging. Experimental models have shown excellent agreement between size and shape in LGE CMR and areas of myocardial infarction by histopathology. Recent studies have also demonstrated how scar size, shape and location from pre-procedural LGE can be useful in guiding ventricular tachycardia’s (VT) ablation or atrial fibrillation (AF) ablation. These procedures are often time-consuming due to the preceding electrophysiological mapping study required to identify slow conduction zones involved in re-entry circuits. Post-processed LGE images provide scar maps, which could be integrated with electroanatomic mapping systems to facilitate these procedures. __Inverse potential mapping__ Through the years, various noninvasive electrocardiographic imaging techniques have emerged that estimate epicardial potentials or myocardial activation times from potentials recorded on the thorax. Utilizing an inverse procedure, the potentials on the heart surface or activation times of the myocardium are estimated with the recorded body surface potentials as source data. Although this procedure only estimates the time course of unipolar epicardial electrograms, several studies have demonstrated that the epicardial potentials and electrograms provide substantial information about intramyocardial activity and have great potential to facilitate risk-stratification and generate personalized ablation strategies. __Objectives of this thesis__ 1. To evaluate the utility of cardiac magnetic resonance derived geometrical and tissue characteristic information for patient stratification and guidance of AF ablation. 2. To design and evaluate the performance of a finite element model based inverse potential mapping in predicting the arrhythmogenic focus in idiopathic ventricular tachycardia using invasive electro-anatomical activation mapping as a reference standard

A priori model independent inverse potential mapping: the impact of electrode positioning

__Introduction:__ In inverse potential mapping, local epicardial potentials are computed from recorded body surface potentials (BSP). When BSP are recorded with only a limited number of electrodes, in general biophysical a priori models are applied to facilitate the inverse computation. This study investigated the possibility of deriving epicardial potential information using only 62 torso electrodes in the absence of an a priori model. __Methods:__ Computer simulations were used to determine the optimal in vivo positioning of 62 torso electrodes. Subsequently, three different electrode configurations, i.e., surrounding the thorax, concentrated precordial (30 mm inter-electrode distance) and super-concentrated precordial (20 mm inter-electrode distance) were used to record BSP from three healthy volunteers. Magnetic resonance imaging (MRI) was performed to register the electrode positions with respect to the anatomy of the patient. Epicardial potentials were inversely computed from the recorded BSP. In order to determine the reconstruction quality, the super-concentrated electrode configuration was applied in four patients with an implanted MRI-conditional pacemaker system. The distance between the position of the ventricular lead tip on MRI and the inversely reconstructed pacing site was determined. __Results:__ The epicardial potential distribution reconstructed using the super-concentrated electrode configuration demonstrated the highest correlation (R = 0.98; p < 0.01) with the original epicardial source model. A mean localization error of 5.3 mm was found in the pacemaker patients. __Conclusion:__ This study demonstrated the feasibility of deriving detailed anterior epicardial potential information using only 62 torso electrodes without the use of an a priori model

Integrated whole-heart computational workflow for inverse potential mapping and personalized simulations

Background: Integration of whole-heart activation simulations and inverse potential mapping (IPM) could benefit the guidance and planning of electrophysiological procedures. Routine clinical application requires a fast and adaptable workflow. These requirements limit clinical translation of existing simulation models. This study proposes a comprehensive finite element model (FEM) based whole-heart computational workflow suitable for IPM and simulations. Methods: Three volunteers and eight patients with premature ventricular contractions underwent body surface potential (BSP) acquisition followed by a cardiac MRI (CMR) scan. The cardiac volumes were segmented from the CMR images using custom written software. The feasibility to integrate tissue-characteristics was assessed by generating meshes with virtual edema and scar. Isochronal activation maps were constructed by identifying the fastest route through the cardiac volume using the Möller-Trumbore and Floyd-Warshall algorithms. IPM's were reconstructed from the BSP's. Results: Whole-heart computational meshes were generated within seconds. The first point of atrial activation on IPM was located near the crista terminalis of the superior vena cave into the right atrium. The IPM demonstrated the ventricular epicardial breakthrough at the attachment of the moderator band with the right ventricular free wall. Simulations of sinus rhythm were successfully performed. The conduction through the virtual edema and scar meshes demonstrated delayed activation or a complete conductional block respectively. Conclusion: The proposed FEM based whole-heart computational workflow offers an integrated platform for cardiac electrical assessment using simulations and IPM. This workflow can incorporate patient-specific electrical parameters, perform whole-heart cardiac activation simulations and accurately reconstruct cardiac activation sequences from BSP's

Non-invasive focus localization, right ventricular epicardial potential mapping in patients with an MRI-conditional pacemaker system ‐ a pilot study

Abstract Background With the advent of magnetic resonance imaging (MRI) conditional pacemaker systems, the possibility of performing MRI in pacemaker patients has been introduced. Besides for the detailed evaluation of atrial and ventricular volumes and function, MRI can be used in combination with body surface potential mapping (BSPM) in a non-invasive inverse potential mapping (IPM) strategy. In non-invasive IPM, epicardial potentials are reconstructed from recorded body surface potentials (BSP). In order to investigate whether an IPM method with a limited number of electrodes could be used for the purpose of non-invasive focus localization, it was applied in patients with implanted pacing devices. Ventricular paced beats were used to simulate ventricular ectopic foci. Methods Ten patients with an MRI-conditional pacemaker system and a structurally normal heart were studied. Patientspecific 3D thorax volume models were reconstructed from the MRI images. BSP were recorded during ventricular pacing. Epicardial potentials were inversely calculated from the BSP. The site of epicardial breakthrough was compared to the position of the ventricular lead tip on MRI and the distance between these points was determined. Results For all patients, the site of earliest epicardial depolarization could be identified. When the tip of the pacing lead was implanted in vicinity to the epicardium, i.e. right ventricular (RV) apex or RV outflow tract, the distance between lead tip position and epicardial breakthrough was 6.0±1.9 mm. Conclusions In conclusion, the combined MRI and IPM method is clinically applicable and can identify sites of earliest depolarization with a clinically useful accuracy

Algorithms for left atrial wall segmentation and thickness – Evaluation on an open-source CT and MRI image database

© 2018 The Authors Structural changes to the wall of the left atrium are known to occur with conditions that predispose to Atrial fibrillation. Imaging studies have demonstrated that these changes may be detected non-invasively. An important indicator of this structural change is the wall\u27s thickness. Present studies have commonly measured the wall thickness at few discrete locations. Dense measurements with computer algorithms may be possible on cardiac scans of Computed Tomography (CT) and Magnetic Resonance Imaging (MRI). The task is challenging as the atrial wall is a thin tissue and the imaging resolution is a limiting factor. It is unclear how accurate algorithms may get and how they compare in this new emerging area. We approached this problem of comparability with the Segmentation of Left Atrial Wall for Thickness (SLAWT) challenge organised in conjunction with MICCAI 2016 conference. This manuscript presents the algorithms that had participated and evaluation strategies for comparing them on the challenge image database that is now open-source. The image database consisted of cardiac CT (n=10) and MRI (n=10) of healthy and diseased subjects. A total of 6 algorithms were evaluated with different metrics, with 3 algorithms in each modality. Segmentation of the wall with algorithms was found to be feasible in both modalities. There was generally a lack of accuracy in the algorithms and inter-rater differences showed that algorithms could do better. Benchmarks were determined and algorithms were ranked to allow future algorithms to be ranked alongside the state-of-the-art techniques presented in this work. A mean atlas was also constructed from both modalities to illustrate the variation in thickness within this small cohort

Evaluation of state-of-the-art segmentation algorithms for left ventricle infarct from late Gadolinium enhancement MR images

Studies have demonstrated the feasibility of late Gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) imaging for guiding the management of patients with sequelae to myocardial infarction, such as ventricular tachycardia and heart failure. Clinical implementation of these developments necessitates a reproducible and reliable segmentation of the infarcted regions. It is challenging to compare new algorithms for infarct segmentation in the left ventricle (LV) with existing algorithms. Benchmarking datasets with evaluation strategies are much needed to facilitate comparison. This manuscript presents a benchmarking evaluation framework for future algorithms that segment infarct from LGE CMR of the LV. The image database consists of 30 LGE CMR images of both humans and pigs that were acquired from two separate imaging centres. A consensus ground truth was obtained for all data using maximum likelihood estimation. Six widely-used fixed-thresholding methods and five recently developed algorithms are tested on the benchmarking framework. Results demonstrate that the algorithms have better overlap with the consensus ground truth than most of the n-SD fixed-thresholding methods, with the exception of the FullWidth-at-Half-Maximum (FWHM) fixed-thresholding method. Some of the pitfalls of fixed thresholding methods are demonstrated in this work. The benchmarking evaluation framework, which is a contribution of this work, can be used to test and benchmark future algorithms that detect and quantify infarct in LGE CMR images of the LV. The datasets, ground truth and evaluation code have been made publicly available through the website: https://www.cardiacatlas.org/web/guest/challenges