Abstract:

This review focuses on the computerized modeling of the electrophysiology of the human atria, emphasizing the simulation of common arrhythmias such as atrial flutter (AFlut) and atrial fibrillation (AFib). Which components of the model are necessary to accurately model arrhythmogenic tissue modifications, including remodeling, cardiomyopathy, and fibrosis, to ensure reliable simulations? The central question explored is the level of detail required for trustworthy simulations for a specific context of use. The review discusses the balance between model complexity and computational efficiency, highlighting the risks of oversimplification and excessive detail. It covers various aspects of atrial modeling, from cellular to whole atria levels, including the influence of atrial geometry, fiber direction, anisotropy, and wall thickness on simulation outcomes. The article also examines the impact of different modeling approaches, such as volumetric 3D models, bilayer models, and single surface models, on the realism of simulations. In addition, it reviews the latest advances in the modeling of fibrotic tissue and the verification and validation of atrial models. The intended use of these models in planning and optimization of atrial ablation strategies is discussed, with a focus on personalized modeling for individual patients and cohort-based approaches for broader applications. The review concludes by emphasizing the importance of integrating experimental data and clinical validation to enhance the utility of computerized atrial models to improve patient outcomes.

Abstract:

Computer modeling of the electrophysiology of the heart has undergone significant progress. A healthy heart can be modeled starting from the ion channels via the spread of a depolarization wave on a realistic geometry of the human heart up to the potentials on the body surface and the ECG. Research is advancing regarding modeling diseases of the heart. This article reviews progress in calculating and analyzing the corresponding electrocardiogram (ECG) from simulated depolarization and repolarization waves. First, we describe modeling of the P-wave, the QRS complex and the T-wave of a healthy heart. Then, both the modeling and the corresponding ECGs of several important diseases and arrhythmias are delineated: ischemia and infarction, ectopic beats and extrasystoles, ventricular tachycardia, bundle branch blocks, atrial tachycardia, flutter and fibrillation, genetic diseases and channelopathies, imbalance of electrolytes and drug-induced changes. Finally, we outline the potential impact of computer modeling on ECG interpretation. Computer modeling can contribute to a better comprehension of the relation between features in the ECG and the underlying cardiac condition and disease. It can pave the way for a quantitative analysis of the ECG and can support the cardiologist in identifying events or non-invasively localizing diseased areas. Finally, it can deliver very large databases of reliably labeled ECGs as training data for machine learning.

Abstract:

Cardiologists measure electric signals inside the human heart aiming at a better diagnosis and optimized therapy of atrial arrhythmias like atrial flutter and atrial fibrillation. The catheters that are used for this purpose are improving: now they are able to pick up the electric signals at up to 64 positions inside the heart simultaneously. The patterns of electric depolarization are sometimes very simple, comparable to plane waves. But in case of patients with severe atrial arrhythmias they can be quite complex: U-turns around a line of block, ectopic centres, break throughs, reentry circuits, rotors, fractionated signals and chaotic patterns are often observed. Methods of biosignal analysis can support the cardiologists in classifying the signals and extract information of high diagnostic relevance. Computer models of the electrophysiology of the human heart can serve to design better algorithms for data analysis and to test algorithms, because the ground truth is known.

Abstract:

Congenital Long-QT Syndrome (LQTS) is a genetic dis- order affecting the repolarization of the heart. The most prevalent subtypes of LQTS are LQT1-3. In this work, we aim to evaluate the differences in the T-waves of simu- lated LQT1-3 in order to identify markers in the ECG that might help to classify patients solely based on ECG mea- surements. For LQT1, mutation S277L was used to char- acterize IKs and mutation S818L in IKr for LQT2. Volt- age clamp data were used to parametrize the ion channel equations of the ten Tusscher and Panfilov model of hu- man ventricular electrophysiology. LQT3 was integrated using an existing mutant INa model. The monodomain model was used in a transmural and apico-basal heteroge- neous model of the ventricles to calculate ventricular exci- tation propagation. The forward calculation on a torso model was performed to determine body surface ECGs. Compared to the physiological case with a QT-time of 375 ms, this interval was prolonged in all LQTS (LQT1 423 ms; LQT2 394 ms; LQT3 405 ms). The T-wave ampli- tude was changed (Einthoven lead II: LQT1 108%; LQT2 91%; LQT3 103%). Also, the width of the T-wave was en- larged (full width at half maximum: LQT1 111%; LQT2 125%; LQT3 109%). At the current state of modeling and data analysis, the three LQTS have not been distinguish- able solely by ECG data.

Abstract:

Abstract Magnetic particle imaging (MPI) is a new imaging modality using oscillating magnetic fields in the frequency range of 10 kHz to 100 kHz. The duration of data acquisition becomes smaller, and signal-to-noise ratio improves if the amplitude of these fields is increased - technically amplitudes of up to 100 mT might be feasible for human-sized systems. On the other hand, with increasing field strength, adverse health effects must be expected: oscillating magnetic fields can stimulate nerves and muscle and heat up tissue. Thresholds for stimulation with magnetic fields in this frequency range are not precisely known, neither is the local temperature rise following exposure. The ICNIRP guidelines define reference levels for magnetic field exposure for the general public that contain large safety factors - for medical diagnostics, they might be exceeded for a short time. In this article, research and guidelines in this field are briefly reviewed, and new results are presented in order to contribute to a future definition of safety limits for oscillating magnetic fields in MPI.

Abstract:

Numerical and patient-specific models of the human atrial anatomy and electrophysiology have a high potential to enhance our knowledge regarding pathological conditions and to increase the outcome of diagnosis and therapy. This chapter briefly describes the current state of the art in modeling of generalized human atria. Furthermore, the chapter demonstrates ways to personalize human atrial anatomy and electrophysiology based on a variety of measurement data from, e.g. late enhancement magnetic resonance imaging (MRI), patch clamp technique, intracardiac electrograms and body surface potential maps. Wherever patient data cannot be collected, patient-group specific behavior can be integrated. Some examples of the personalization process are described and the validation process is discussed together with future options for personalization, validation and application.

Abstract:

This review article gives a comprehensive survey of the progress made in computa- tional 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 di- rection. 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 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.

Abstract:

In this work, a new framework is presented that is suitable to solve the cardiac bidomain equation efficiently using the scientific computing library PETSc. Furthermore, the framework is able to modularly combine different ionic channels and is flexible enough to include arbitrary heterogeneities in ionic or coupling channel density. The ability of this framework is demonstrated in an example simulation in which the three-dimensional electrophysiological heterogeneity was adjusted in order to get a positive T-wave in the body electrocardiogram (ECG).

Abstract:

Simulations of the electrophysiological behavior of the heart improve the comprehension of the mechanisms of the cardiovascular system. Furthermore, the mathematical modeling will support diagnosis and therapy of patients suffering from heart diseases. In this paper, the chain of modeling of the electrical function in the heart is described. The components are explained briefly, namely modeling of cardiac geometry, reconstructing the cardiac electrophysiology and excitation propagation. Additionally, the mathematical methods allowing to implement and solve these models are outlined. The three recently more investigated cases atrial fibrillation, ischemia and long-QT syndrome are described and show how cardiac modeling can support cardiologists in answering their open questions.

Abstract:

The message of this article is that patient safety must be an essential part of thinking and planning in research for medical technology. Which aspects must be considered already in an early phase of any project are presented. The most important standards are listed briefly. Then the topics technical safety and electromagnetic compatibility (EMC), clinical evaluation, risk analysis, biological evaluation of materials, ergonomics, the special aspects of medical devices that include pharmacological components, and the requirements of software packages and implemented algorithms are discussed.Im vorliegenden Beitrag wird begründet, warum die Patientensicherheit vom ersten Tag an ein wesentlicher Bestandteil der Überlegungen und Planungen in der medizintechnischen Forschung sein muss. Es wird dargestellt, welche Aspekte insbesondere schon in den frühen Phasen eines Projektes berücksichtigt werden müssen. Die wichtigsten Normen werden nur kurz angesprochen. Dann werden die Themen technische Sicherheit und Elektromagnetische Verträglichkeit (EMV), klinische Prüfung, Risikoanalyse, biologische Bewertung von Materialien, Ergonomie, die Problematik von Medizintechnik mit pharmakologischen Komponenten und die Anforderungen an reine Softwarepakete für die Medizin und an implementierte Algorithmen genauer betrachtet.

Abstract:

Ablation strategies to prevent episodes of paroxysmal atrial fibrillation (AF) have been subject to many clinical studies. The issues mainly concern pattern and transmurality of the lesions. This paper investigates ten different ablation strategies on a multilayered 3-D anatomical model of the atria with respect to 23 different setups of AF initiation in a biophysical computer model. There were 495 simulations carried out showing that circumferential lesions around the pulmonary veins (PVs) yield the highest success rate if at least two additional linear lesions are carried out. The findings compare with clinical studies as well as with other computer simulations. The anatomy and the setup of ectopic beats play an important role in the initiation and maintenance of AF as well as the resulting therapy. The computer model presented in this paper is a suitable tool to investigate different ablation strategies. By including individual patient anatomy and electrophysiological measurement, the model could be parameterized to yield an effective tool for future investigation of tailored ablation strategies and their effects on atrial fibrillation.

Abstract:

BackgroundMultiple wavelets and rotors are accused of maintaining atrial fibrillation (AF). However, snake-like excitation patterns have recently been observed in AF. So far, computer models have investigated AF in a simplified anatomical model. In this work, pulmonary vein firing is simulated to investigate the initiation and maintenance of AF in a realistic anatomical model.Methods and ResultsThirty-five ectopic foci situated around all pulmonary veins were simulated by a unidirectional conduction block. The excitation propagation was simulated by an adaptive cellular automaton on a realistic 3-dimensional atrial anatomy. Atrial fibrillation was initiated in 65.7% of the simulations. Stable excitation patterns were broken up in anatomically heterogeneous regions, creating a streak-like excitation pattern similar to snakes. Multiple wavelets and rotors could be observed in anatomically smooth areas at the atria's roofs.ConclusionsThe influence of macroscopic anatomical structures on the course of AF seems to play an important role in the excitation propagation in AF. The computer simulations indicate that multiple mechanisms contribute to the maintenance of AF.

Abstract:

An optimal electrode position, atrio-ventricular (AV) and interventricular (VV) delay in cardiac resynchronization therapy (CRT) improves its success. An optimization strategy does not yet exist. A computer model of the Visible Man and a patient heart was used to simulate an atrio-ventricular and a left bundle branch block with 0%, 20% and 40% reduction in interventricular conduction velocity, respectively. The minimum error between physiological excitation and pathology/therapy was automatically computed for 12 different electrode positions. AV and VV delay timing was adjusted accordingly. The results show the importance of individually adjusting the electrode position as well as the timing delays to the patient's anatomy and pathology, which is in accordance with current clinical studies. The presented methods and strategy offer the opportunity to carry out non-invasive, automatic optimization of CRT preoperatively. The model is subject to validation in future clinical studies.

Abstract:

Cardiac arrhythmia is currently investigated from two different points of view. One considers ECG bio-signal analysis and investigates heart rate variability, baroreflex control, heart rate turbulence, alternans phenomena, etc. The other involves building computer models of the heart based on ion channels, bio-domain models and forward calculations to finally reach ECG and body surface potential maps. Both approaches aim to support the cardiologist in better understanding of arrhythmia, improving diagnosis and reliable risk stratification, and optimizing therapy. This article summarizes recent results and aims to trigger new research to bridge the different views.

Abstract:

Investigating the mechanisms underlying the genesis and conduction of electrical excitation in the atria at physiological and pathological states is of great importance. To provide knowledge concerning the mechanisms of excitation, we constructed a biophysical detailed and anatomically accurate computer model of human atria that incorporates both structural and electrophysiological heterogeneities. The three-dimensional geometry was extracted from the visible female dataset. The sinoatrial node (SAN) and atrium, including crista terminalis (CT), pectinate muscles (PM), appendages (APG) and Bachmann's bundle (BB) were segmented in this work. Fibre orientation in CT, PM and BB was set to local longitudinal direction. Descriptions for all used cell types were based on modifications of the Courtemanche et al. model of a human atrial cell. Maximum conductances of Ito, IKr and ICa,L were modified for PM, CT, APG and atrioventricular ring to reproduce measured action potentials (AP). Pacemaker activity in the human SAN was reproduced by removing IK1, but including If, ICa,T, and gradients of channel conductances as described in previous studies for heterogeneous rabbit SAN. Anisotropic conduction was computed with a monodomain model using the finite element method. The transversal to longitudinal ratio of conductivity for PM, CT and BB was 1:9. Atrial working myocardium (AWM) was set to be isotropic. Simulation of atrial electrophysiology showed initiation of APs in the SAN centre. The excitation spread afterwards to the periphery near to the region of the CT and preferentially towards the atrioventricular region. The excitation extends over the right atrium along PM. Both CT and PM activated the right AWM. Earliest activation of the left atrium was through BB and excitation spread over to the APG. The conduction velocities were 0.6ms-1 for AWM, 1.2ms-1 for CT, 1.6ms-1 for PM and 1.1ms-1 for BB at a rate of 63bpm. The simulations revealed that bundles form dominant pathways for atrial conduction. The preferential conduction towards CT and along PM is comparable with clinical mapping. Repolarization is more homogeneous than excitation due to the heterogeneous distribution of electrophysiological properties and hence the action potential duration.

Abstract:

Computer models of the electrophysiological processes in the human heart become increasingly precise and detailed. The dream of supporting diagnosis of arrhythmias and planning of therapeutic interventions comes into reach. Recent progress in the field of cellular models (including e.g. pathological cases), in the field of coupled cell patches (including e.g. heterogeneity) and in the field of validation (including e.g. intracardial multi-channel recordings) are reported.

Abstract:

Computer models of the heart can improve the understanding of the electrophysiological processes in healthy and diseased heart. They become more and more important for detailled diagnosis of arrhythmias and for optimization of therapy. Models of myocardium cells known today are described - they are based on the properties of all relevant ion channels in the cell membrane. Then it is demonstrated, how many cells can be joined to form a cell patch and how finally the complete heart can be modelled. A simpler approach is using a so called cellular automaton that allows for a significant reduction of calculation time while sacrifying some accordance to reality. Adaptive cellular automatons allow for a fast simulation with acceptable accuracy. Using them some results were gained for the simulation of typical arrhythmias, in the field of validation using an animal model and for therapy planning with RF-ablation.

Abstract:

More than 20 years of research in imaging of bioelectric sources in the human heart have passed and a lot of effort has been devoted to the topic. In spite of that the method is not established in clinical practice but still just an interesting research topic of enthusiastic scientist. A review together with a comprehensive literature survey is given in this article. Recent developments and new trends are outlined.

Abstract:

A modular multichannel SQUID-system, in which every single channel can be optimized or replaced individually, is presented. The DC-SQUIDs based on the materials NbN/MgO are prepared by thin film technology and show noise values below 10μΦ0/√Hz. A simplified way of coupling the modulation and feedback current directly to the coupling coil is realized The complete SQUID module including the superconducting shield was miniaturized down to a diameter of 5mm. The gradiometers are wire wound and an as made balancing better than 10−3 is achieved. The cryogenic system was optimized with respect to low vibrations and low helium boil off rate. Simple conductive paint with precisely adjusted surface resistivity is used for RF-shielding. The complete SQUID-electronic of one channel has been realized on one single board and uses a new bias modulation scheme to completely suppress intrinsic 1/f noise. The noise level of the complete system is below 10fT/√Hz. Biomagnetic measurements of the human heart and brain are presented. Single current dipole reconstructions and current density imaging techniques can be used to find the underlying sources. Using a special coil positioning system an overlay of the functional current images with morphological MR-images can be carried out.

Abstract:

Current sources in the human body can be localized by measuring the biomagnetic fields with multichannel SQUID systems. Important system aspects are the noise level, the ambient field suppression, the dynamic range, the reliability, the number of channels, and the arrangement of gradiometers. From the users point of view the most important quality factor is the accuracy with which a current dipole can be localized. A test procedure is proposed to determine the localization power of the system. A 31-channel-SQUID system is presented together with the results of the test. The crucial parts of the system determining the accuracy are pointed out.

Abstract:

A 19-channel SQUID system for biomagnetic measurements has been developed. This system differs from standard instruments in its modular approach. Various gradiometers can be coupled to the SQUIDs, the cryogenic system allows the exchange of single channels and the electronics is based on a cassette system. Problems with thermal insulation, vibrations of the gradiometers and tilted gradiometer geometries are discussed and solutions are presented.

Abstract:

The gauge factor of strain gauges is calculated considering the longitudinal and transverse strain sensitivity of the resistivity. The general result is applied to free wire strain gauges, adhered foil strain gauges and thin film strain gauges. The relation between the gauge factor and the piezoresistive constant..

Abstract:

In time resolved luminescence spectra, taken within the temperature range of 1180 K, the two lowest excited states of rare gas crystals are observed. One of them, the long lived 3 state is identified as the initial state for transient absorption. The transient absorption spectra (1180 K) indicate strong similarities between self-trapped excitons in the crystals and free excimers, but only in the energy region up to 1.5 eV above the lowest excited state 3. Higher energy levels and the continuum states of the self-trapped exciton are strongly influenced by solid state effects. The Journal of Chemical Physics is copyrighted by The American Institute of Physics

Abstract:

Efficient personalized ablation strategies for treating atrial arrhythmias remain challenging. Discrepancies in identifying arrhythmogenic areas using characterization methods, such as late gadolinium enhanced magnetic resonance imaging (LGE-MRI) and electroanatomical mapping, require a comparative analysis of local impedance (LI) and LGE-MRI data. This study aims to analyze correlations as basis for im- provement of treatment strategies. 16 patients undergoing left atrium (LA) ablation with LGE-MRI acquisition and LI data recording were recruited. LGE-MRI data and LI measurements were normalized to patient- and modality-specific blood pool references. A global mean shape was generated based on all patient geometries, and normalized local impedance (LIN) and LGE-MRI image intensity ratio (IIR) data points were co- registered for comparison.Data analysis comprised intra-patient and inter-patient assess- ments, evaluating differences in LIN values among datasets categorized by their IIR. Due to substantial deviations in LIN values, even within the same patient and IIR-category, discern- ing the presence or absence of a correlation was challenging, and no statistically significant correlation could be identified. Our findings underscore the necessity for standardized proto- cols in data acquisition, processing, and comparison, to mini- mize unquantified confounding effects. While immediate substitution of LI for LGE-MRI seems improbable given the significant LIN variations, this preliminary study lays the ground- work for systematic data acquisition. By ensuring data quality, a meaningful comparison between LI and LGE-MRI data can be facilitated, potentially shaping future strategies for atrial ar- rhythmia treatment.

Abstract:

AIMS: The effective refractory period (ERP) is one of the main electrophysiological properties governing arrhythmia, yet ERP personalization is rarely performed when creating patient-specific computer models of the atria to inform clinical decision-making. This study evaluates the impact of integrating clinical ERP measurements into personalized in silico models on arrhythmia vulnerability. METHODS AND RESULTS: Clinical ERP measurements were obtained in seven patients from multiple locations in the atria. Atrial geometries from the electroanatomical mapping system were used to generate personalized anatomical atrial models. The Courtemanche M. et al. cellular model was adjusted to reproduce patient-specific ERP. Four modeling approaches were compared: homogeneous (A), heterogeneous (B), regional (C), and continuous (D) ERP distributions. Non-personalized approaches (A and B) were based on literature data, while personalized approaches (C and D) were based on patient measurements. Modeling effects were assessed on arrhythmia vulnerability and tachycardia cycle length, with sensitivity analysis on ERP measurement uncertainty. Mean vulnerability was 3.4 ± 4.0%, 7.7 ± 3.4%, 9.0 ± 5.1%, and 7.0 ± 3.6% for scenarios A-D, respectively. Mean tachycardia cycle length was 167.1 ± 12.6 ms, 158.4 ± 27.5 ms, 265.2 ± 39.9 ms, and 285.9 ± 77.3 ms for scenarios A-D, respectively. Incorporating perturbations to the measured ERP in the range of 2, 5, 10, 20, and 50 ms changed the vulnerability of the model to 5.8 ± 2.7%, 6.1 ± 3.5%, 6.9 ± 3.7%, 5.2 ± 3.5%, and 9.7 ± 10.0%, respectively. CONCLUSION: Increased ERP dispersion had a greater effect on re-entry dynamics than on vulnerability. Inducibility was higher in personalized scenarios compared with scenarios with uniformly reduced ERP; however, this effect was reversed when incorporating fibrosis informed by low-voltage areas. Effective refractory period measurement uncertainty up to 20 ms slightly influenced vulnerability. Electrophysiological personalization of atrial in silico models appears essential and requires confirmation in larger cohorts.

Abstract:

Feature importance methods promise to provide a ranking of features according to importance for a given classification task. A wide range of methods exist but their rankings often disagree and they are inherently difficult to evaluate due to a lack of ground truth beyond synthetic datasets. In this work, we put feature importance methods to the test on real-world data in the domain of cardiology, where we try to distinguish three specific pathologies from healthy subjects based on ECG features comparing to features used in cardiologists' decision rules as ground truth. We found that the SHAP and LIME methods and Chi-squared test all worked well together with the native Random forest and Logistic regression feature rankings. Some methods gave inconsistent results, which included the Maximum Relevance Minimum Redundancy and Neighbourhood Component Analysis methods. The permutation-based methods generally performed quite poorly. A surprising result was found in the case of left bundle branch block, where T-wave morphology features were consistently identified as being important for diagnosis, but are not used by clinicians.

Abstract:

Digital twins of patients' hearts are a promising tool to assess arrhythmia vulnerability and to personalize therapy. However, the process of building personalized computational models can be challenging and requires a high level of human interaction. We propose a patient-specific Augmented Atria generation pipeline (AugmentA) as a highly automated framework which, starting from clinical geometrical data, provides ready-to-use atrial personalized computational models. AugmentA identifies and labels atrial orifices using only one reference point per atrium. If the user chooses to fit a statistical shape model to the input geometry, it is first rigidly aligned with the given mean shape before a non-rigid fitting procedure is applied. AugmentA automatically generates the fiber orientation and finds local conduction velocities by minimizing the error between the simulated and clinical local activation time (LAT) map. The pipeline was tested on a cohort of 29 patients on both segmented magnetic resonance images (MRI) and electroanatomical maps of the left atrium. Moreover, the pipeline was applied to a bi-atrial volumetric mesh derived from MRI. The pipeline robustly integrated fiber orientation and anatomical region annotations in 38.4 ± 5.7 s. In conclusion, AugmentA offers an automated and comprehensive pipeline delivering atrial digital twins from clinical data in procedural time.

Abstract:

Cardiovascular diseases account for 17 million deaths per year worldwide. Of these, 25% are categorized as sudden cardiac death, which can be related to ventricular tachycardia (VT). This type of arrhythmia can be caused by focal activation sources outside the sinus node. Catheter ablation of these foci is a curative treatment in order to inactivate the abnormal triggering activity. However, the localization procedure is usually time-consuming and requires an invasive procedure in the catheter lab. To facilitate and expedite the treatment, we present two novel localization support techniques based on convolutional neural networks (CNNs) that address these clinical needs. In contrast to existing methods, our approaches were designed to be independent of the patient-specific geometry and directly applicable to surface ECG signals, while also delivering a binary transmural position. Moreover, one of the method's outputs can be interpreted as several ranked solutions. The CNNs were trained on a dataset containing only simulated data and evaluated both on simulated test data and clinical data. On a novel large and open simulated dataset, the median test error was below 3 mm. The median localization error on the unseen clinical data ranged from 32 mm to 41 mm without optimizing the pre-processing and CNN to the clinical data. Interpreting the output of one of the approaches as ranked solutions, the best median error of the top-3 solutions decreased to 20 mm on the clinical data. The transmural position was correctly detected in up to 82% of all clinical cases. These results demonstrate a proof of principle to utilize CNNs to localize the activation source without the intrinsic need for patient-specific geometrical information. Furthermore, providing multiple solutions can assist physicians in identifying the true activation source amongst more than one possible location. With further optimization to clinical data, these methods have high potential to accelerate clinical interventions, replace certain steps within these procedures and consequently reduce procedural risk and improve VT patient outcomes.

Abstract:

Atrial fibrillation (AF) is one of the most commoncardiac diseases. However, a complete understanding of howto treat patients suffering from AF is still not achieved. Asthe isolation of the pulmonary veins in the left atrium (LA)is the standard treatment for AF, the role of the right atrium(RA) in AF is rarely considered. We investigated the impactof including the RA on arrhythmia vulnerability in silico. Wegenerated a dataset of five mono-atrial (LA) and five bi-atrialmodels with three different electrophysiological (EP) setupseach, regarding different states of AF-induced remodelling.For every model, a pacing protocol was run to induce reen-tries from a set of stimulation points. The average share ofinducing points across all EP setups was 0.0, 0.8 and 6.7 %for the mono-atrial scenario, 0.5, 27.3 and 37.9 % for the bi-atrial scenario. The increase in inducibility of LA stimula-tion points from mono- to bi-atrial scenario was 0.91 ± 2.03%,34.55 ± 14.9 % and 44.2 ± 14.9 %, respectively. In this study,the RA had a marked impact on the results of the vulnerabilityassessment that needs to be further investigated.

Abstract:

Mechanistic cardiac electrophysiology models allow for personalized simulations of the electrical activity in the heart and the ensuing electrocardiogram (ECG) on the body surface. As such, synthetic signals possess known ground truth labels of the underlying disease and can be employed for validation of machine learning ECG analysis tools in addition to clinical signals. Recently, synthetic ECGs were used to enrich sparse clinical data or even replace them completely during training leading to improved performance on real-world clinical test data. We thus generated a novel synthetic database comprising a total of 16,900 12 lead ECGs based on electrophysiological simulations equally distributed into healthy control and 7 pathology classes. The pathological case of myocardial infraction had 6 sub-classes. A comparison of extracted features between the virtual cohort and a publicly available clinical ECG database demonstrated that the synthetic signals represent clinical ECGs for healthy and pathological subpopulations with high fidelity. The ECG database is split into training, validation, and test folds for development and objective assessment of novel machine learning algorithms.

Abstract:

AIMS: Electro-anatomical voltage, conduction velocity (CV) mapping, and late gadolinium enhancement (LGE) magnetic resonance imaging (MRI) have been correlated with atrial cardiomyopathy (ACM). However, the comparability between these modalities remains unclear. This study aims to (i) compare pathological substrate extent and location between current modalities, (ii) establish spatial histograms in a cohort, (iii) develop a new estimated optimized image intensity threshold (EOIIT) for LGE-MRI identifying patients with ACM, (iv) predict rhythm outcome after pulmonary vein isolation (PVI) for persistent atrial fibrillation (AF). METHODS AND RESULTS: Thirty-six ablation-naive persistent AF patients underwent LGE-MRI and high-definition electro-anatomical mapping in sinus rhythm. Late gadolinium enhancement areas were classified using the UTAH, image intensity ratio (IIR >1.20), and new EOIIT method for comparison to low-voltage substrate (LVS) and slow conduction areas <0.2 m/s. Receiver operating characteristic analysis was used to determine LGE thresholds optimally matching LVS. Atrial cardiomyopathy was defined as LVS extent ≥5% of the left atrium (LA) surface at <0.5 mV. The degree and distribution of detected pathological substrate (percentage of individual LA surface are) varied significantly (P < 0.001) across the mapping modalities: 10% (interquartile range 0-14%) of the LA displayed LVS <0.5 mV vs. 7% (0-12%) slow conduction areas <0.2 m/s vs. 15% (8-23%) LGE with the UTAH method vs. 13% (2-23%) using IIR >1.20, with most discrepancies on the posterior LA. Optimized image intensity thresholds and each patient's mean blood pool intensity correlated linearly (R2 = 0.89, P < 0.001). Concordance between LGE-MRI-based and LVS-based ACM diagnosis improved with the novel EOIIT applied at the anterior LA [83% sensitivity, 79% specificity, area under the curve (AUC): 0.89] in comparison to the UTAH method (67% sensitivity, 75% specificity, AUC: 0.81) and IIR >1.20 (75% sensitivity, 62% specificity, AUC: 0.67). CONCLUSION: Discordances in detected pathological substrate exist between LVS, CV, and LGE-MRI in the LA, irrespective of the LGE detection method. The new EOIIT method improves concordance of LGE-MRI-based ACM diagnosis with LVS in ablation-naive AF patients but discrepancy remains particularly on the posterior wall. All methods may enable the prediction of rhythm outcomes after PVI in patients with persistent AF.

Abstract:

INTRODUCTION: Improved sinus rhythm (SR) maintenance rates have been achieved in patients with persistent atrial fibrillation (AF) undergoing pulmonary vein isolation plus additional ablation of low voltage substrate (LVS) during SR. However, voltage mapping during SR may be hindered in persistent and long-persistent AF patients by immediate AF recurrence after electrical cardioversion. We assess correlations between LVS extent and location during SR and AF, aiming to identify regional voltage thresholds for rhythm-independent delineation/detection of LVS areas. (1) Identification of voltage dissimilarities between mapping in SR and AF. (2) Identification of regional voltage thresholds that improve cross-rhythm substrate detection. (3) Comparison of LVS between SR and native versus induced AF. METHODS: Forty-one ablation-naive persistent AF patients underwent high-definition (1 mm electrodes; >1200 left atrial (LA) mapping sites per rhythm) voltage mapping in SR and AF. Global and regional voltage thresholds in AF were identified which best match LVS < 0.5 mV and <1.0 mV in SR. Additionally, the correlation between SR-LVS with induced versus native AF-LVS was assessed. RESULTS: Substantial voltage differences (median: 0.52, interquartile range: 0.33-0.69, maximum: 1.19 mV) with a predominance of the posterior/inferior LA wall exist between the rhythms. An AF threshold of 0.34 mV for the entire left atrium provides an accuracy, sensitivity and specificity of 69%, 67%, and 69% to identify SR-LVS < 0.5 mV, respectively. Lower thresholds for the posterior wall (0.27 mV) and inferior wall (0.3 mV) result in higher spatial concordance to SR-LVS (4% and 7% increase). Concordance with SR-LVS was higher for induced AF compared to native AF (area under the curve[AUC]: 0.80 vs. 0.73). AF-LVS < 0.5 mV corresponds to SR-LVS < 0.97 mV (AUC: 0.73). CONCLUSION: Although the proposed region-specific voltage thresholds during AF improve the consistency of LVS identification as determined during SR, the concordance in LVS between SR and AF remains moderate, with larger LVS detection during AF. Voltage-based substrate ablation should preferentially be performed during SR to limit the amount of ablated atrial myocardium.

Abstract:

Machine learning (ML) methods for the analysis of electrocardiography (ECG) data are gaining importance, substantially supported by the release of large public datasets. However, these current datasets miss important derived descriptors such as ECG features that have been devised in the past hundred years and still form the basis of most automatic ECG analysis algorithms and are critical for cardiologists' decision processes. ECG features are available from sophisticated commercial software but are not accessible to the general public. To alleviate this issue, we add ECG features from two leading commercial algorithms and an open-source implementation supplemented by a set of automatic diagnostic statements from a commercial ECG analysis software in preprocessed format. This allows the comparison of ML models trained on clinically versus automatically generated label sets. We provide an extensive technical validation of features and diagnostic statements for ML applications. We believe this release crucially enhances the usability of the PTB-XL dataset as a reference dataset for ML methods in the context of ECG data.

Abstract:

AIMS: The long-term success rate of ablation therapy is still sub-optimal in patients with persistent atrial fibrillation (AF), mostly due to arrhythmia recurrence originating from arrhythmogenic sites outside the pulmonary veins. Computational modelling provides a framework to integrate and augment clinical data, potentially enabling the patient-specific identification of AF mechanisms and of the optimal ablation sites. We developed a technology to tailor ablations in anatomical and functional digital atrial twins of patients with persistent AF aiming to identify the most successful ablation strategy. METHODS AND RESULTS: Twenty-nine patient-specific computational models integrating clinical information from tomographic imaging and electro-anatomical activation time and voltage maps were generated. Areas sustaining AF were identified by a personalized induction protocol at multiple locations. State-of-the-art anatomical and substrate ablation strategies were compared with our proposed Personalized Ablation Lines (PersonAL) plan, which consists of iteratively targeting emergent high dominant frequency (HDF) regions, to identify the optimal ablation strategy. Localized ablations were connected to the closest non-conductive barrier to prevent recurrence of AF or atrial tachycardia. The first application of the HDF strategy had a success of >98% and isolated only 5-6% of the left atrial myocardium. In contrast, conventional ablation strategies targeting anatomical or structural substrate resulted in isolation of up to 20% of left atrial myocardium. After a second iteration of the HDF strategy, no further arrhythmia episode could be induced in any of the patient-specific models. CONCLUSION: The novel PersonAL in silico technology allows to unveil all AF-perpetuating areas and personalize ablation by leveraging atrial digital twins.

Abstract:

BACKGROUND: Electrical impedance measurements have become an accepted tool for monitoring intracardiac radio frequency ablation. Recently, the long-established generator impedance was joined by novel local impedance measurement capabilities with all electrical circuit terminals being accommodated within the catheter. OBJECTIVE: This work aims at in silico quantification of distinct influencing factors that have remained challenges due to the lack of ground truth knowledge and the superposition of effects in clinical settings. METHODS: We introduced a highly detailed in silico model of two local impedance enabled catheters, namely IntellaNav MiFi™ OI and IntellaNav Stablepoint™, embedded in a series of clinically relevant environments. Assigning material and frequency specific conductivities and subsequently calculating the spread of the electrical field with the finite element method yielded in silico local impedances. The in silico model was validated by comparison to in vitro measurements of standardized sodium chloride solutions. We then investigated the effect of the withdrawal of the catheter into the transseptal sheath, catheter-tissue interaction, insertion of the catheter into pulmonary veins, and catheter irrigation. RESULTS: All simulated setups were in line with in vitro experiments and in human measurements and gave detailed insight into determinants of local impedance changes as well as the relation between values measured with two different devices. CONCLUSION: The in silico environment proved to be capable of resembling clinical scenarios and quantifying local impedance changes. SIGNIFICANCE: The tool can assists the interpretation of measurements in humans and has the potential to support future catheter development.

Abstract:

Interatrial conduction block refers to a disturbance in the propagation of electrical impulses in the conduction pathways between the right and the left atrium. It is a risk factor for atrial fibrillation, stroke, and premature death. Clin- ical diagnostic criteria comprise an increased P wave dura- tion and biphasic P waves in lead II, III and aVF due to ret- rograde activation of the left atrium. Machine learning algo- rithms could improve the diagnosis but require a large-scale, well-controlled and balanced dataset. In silico electrocardio- gram (ECG) signals, optimally obtained from a statistical shape model to cover anatomical variability, carry the poten- tial to produce an extensive database meeting the requirements for successful machine learning application. We generated the first in silico dataset including interatrial conduction block of 9,800simulated ECG signals based on a bi-atrial statistical shape model. Automated feature analysis was performed to evaluate P wave morphology, duration and P wave terminal force in lead V1. Increased P wave duration and P wave ter- minal force in lead V1 were found for models with interatrial conduction block compared to healthy models. A wide vari- ability of P wave morphology was detected for models with in- teratrial conduction block. Contrary to previous assumptions, our results suggest that a biphasic P wave morphology seems to be neither necessary nor sufficient for the diagnosis of in- teratrial conduction block. The presented dataset is ready for a classification with machine learning algorithms and can be easily extended.

Abstract:

Atrial fibrillation is responsible for a significant and steadily rising burden. Simultaneously, the treatment options for atrial fibrillation are far from optimal. Personalized simulations of cardiac electrophysiology could assist clinicians in the risk stratification and therapy planning for atrial fibrillation. However, the use of personalized simulations in clinics is currently not possible due to either too high computational costs or non-sufficient accuracy. Eikonal simulations come with low computational costs but cannot replicate the influence of cardiac tissue geometry on the conduction velocity of the wave propagation. Consequently, they currently lack the required accuracy to be applied in clinics. Biophysically detailed simulations on the other hand are accurate but associated with too high computational costs. To tackle this issue, a regression model is created based on biophysically detailed bidomain simulation data. This regression formula calculates the conduction velocity dependent on the thickness and curvature of the heart wall. Afterwards the formula was implemented into the eikonal model with the goal to increase the accuracy of the eikonal model without losing its advantage of computational efficiency. The results of the modified eikonal simulations demonstrate that (i) the local activation times become significantly closer to those of the biophysically detailed bidomain simulations, (ii) the advantage of the eikonal model of a low sensitivity to the resolution of the mesh was reduced further, and (iii) the unrealistic occurrence of endo-epicardial dissociation in simulations was remedied. The results suggest that the accuracy of the eikonal model was significantly increased. At the same time, the additional computational costs caused by the implementation of the regression formula are neglectable. In conclusion, a successful step towards a more accurate and fast computational model of cardiac electrophysiology was achieved.

Abstract:

Conduction velocity (CV) slowing is associated with atrial fibrillation (AF) and reentrant ventricular tachycardia (VT). Clinical electroanatomical mapping systems used to localize AF or VT sources as ablation targets remain limited by the number of measuring electrodes and signal processing methods to generate high-density local activation time (LAT) and CV maps of heterogeneous atrial or trabeculated ventricular endocardium. The morphology and amplitude of bipolar electrograms depend on the direction of propagating electrical wavefront, making identification of low-amplitude signal sources commonly associated with fibrotic area difficulty. In comparison, unipolar electrograms are not sensitive to wavefront direction, but measurements are susceptible to distal activity. This study proposes a method for local CV calculation from optical mapping measurements, termed the circle method (CM). The local CV is obtained as a weighted sum of CV values calculated along different chords spanning a circle of predefined radius centered at a CV measurement location. As a distinct maximum in LAT differences is along the chord normal to the propagating wavefront, the method is adaptive to the propagating wavefront direction changes, suitable for electrical conductivity characterization of heterogeneous myocardium. In numerical simulations, CM was validated characterizing modeled ablated areas as zones of distinct CV slowing. Experimentally, CM was used to characterize lesions created by radiofrequency ablation (RFA) on isolated hearts of rats, guinea pig, and explanted human hearts. To infer the depth of RFA-created lesions, excitation light bands of different penetration depths were used, and a beat-to-beat CV difference analysis was performed to identify CV alternans. Despite being limited to laboratory research, studies based on CM with optical mapping may lead to new translational insights into better-guided ablation therapies.

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Aims Atrial flutter (AFlut) is a common re-entrant atrial tachycardia driven by self-sustainable mechanisms that cause excitations to propagate along pathways different from sinus rhythm. Intra-cardiac electrophysiological mapping and catheter ablation are often performed without detailed prior knowledge of the mechanism perpetuating AFlut, likely prolonging the procedure time of these invasive interventions. We sought to discriminate the AFlut location [cavotricuspid isthmus-dependent (CTI), peri-mitral, and other left atrium (LA) AFlut classes] with a machine learning-based algorithm using only the non-invasive signals from the 12-lead electrocardiogram (ECG). Methods and results Hybrid 12-lead ECG dataset of 1769 signals was used (1424 in silico ECGs, and 345 clinical ECGs from 115 patients—three different ECG segments over time were extracted from each patient corresponding to single AFlut cycles). Seventy-seven features were extracted. A decision tree classifier with a hold-out classification approach was trained, validated, and tested on the dataset randomly split after selecting the most informative features. The clinical test set comprised 38 patients (114 clinical ECGs). The classifier yielded 76.3% accuracy on the clinical test set with a sensitivity of 89.7%, 75.0%, and 64.1% and a positive predictive value of 71.4%, 75.0%, and 86.2% for CTI, peri-mitral, and other LA class, respectively. Considering majority vote of the three segments taken from each patient, the CTI class was correctly classified at 92%. Conclusion Our results show that a machine learning classifier relying only on non-invasive signals can potentially identify the location of AFlut mechanisms. This method could aid in planning and tailoring patient-specific AFlut treatments.

Abstract:

Left atrial enlargement (LAE) is one of the risk factors for atrial fibrillation (AF). A non-invasive and automated detection of LAE with the 12-lead electrocardiogram (ECG) could therefore contribute to an improved AF risk stratification and an early detection of new-onset AF incidents. However, one major challenge when applying machine learning techniques to identify and classify cardiac diseases usually lies in the lack of large, reliably labeled and balanced clinical datasets. We therefore examined if the extension of clinical training data by simulated ECGs derived from a novel bi-atrial shape model could improve the automated detection of LAE based on P waves of the 12-lead ECG. We derived 95 volumetric geometries from the bi-atrial statistical shape model with continuously increasing left atrial volumes in the range of 30 ml to 65 ml. Electrophysiological simulations with 10 different conduction velocity settings and 2 different torso models were conducted. Extracting the P waves of the 12-lead ECG thus yielded a synthetic dataset of 1,900 signals. Besides the simulated data, 7,168 healthy and 309 LAE ECGs from a public clinical ECG database were available for training and testing of an LSTM network to identify LAE. The class imbalance of the training data could be reduced from 1:23 to 1:6 when adding simulated data to the training set. The accuracy evaluated on the test dataset comprising a subset of the clinical ECG recordings improved from 0.91 to 0.95 if simulated ECGs were included as an additional input for the training of the classifier. Our results suggest that using a bi-atrial statistical shape model as a basis for ECG simulations can help to overcome the drawbacks of clinical ECG recordings and can thus lead to an improved performance of machine learning classifiers to detect LAE based on the 12-lead ECG.

Abstract:

The arrhythmogenesis of atrial fibrillation is associated with the presence of fibrotic atrial tissue. Not only fibrosis but also physiological anatomical variability of the atria and the thorax reflect in altered morphology of the P wave in the 12-lead electrocardiogram (ECG). Distinguishing between the effects on the P wave induced by local atrial substrate changes and those caused by healthy anatomical variations is important to gauge the potential of the 12-lead ECG as a non-invasive and cost-effective tool for the early detection of fibrotic atrial cardiomyopathy to stratify atrial fibrillation propensity. In this work, we realized 54,000 combinations of different atria and thorax geometries from statistical shape models capturing anatomical variability in the general population. For each atrial model, 10 different volume fractions (0-45%) were defined as fibrotic. Electrophysiological simulations in sinus rhythm were conducted for each model combination and the respective 12-lead ECGs were computed. P wave features (duration, amplitude, dispersion, terminal force in V1) were extracted and compared between the healthy and the diseased model cohorts. All investigated feature values systematically in- or decreased with the left atrial volume fraction covered by fibrotic tissue, however value ranges overlapped between the healthy and the diseased cohort. Using all extracted P wave features as input values, the amount of the fibrotic left atrial volume fraction was estimated by a neural network with an absolute root mean square error of 8.78%. Our simulation results suggest that although all investigated P wave features highly vary for different anatomical properties, the combination of these features can contribute to non-invasively estimate the volume fraction of atrial fibrosis using ECG-based machine learning approaches.

Abstract:

AIMS: The treatment of atrial fibrillation beyond pulmonary vein isolation has remained an unsolved challenge. Targeting regions identified by different substrate mapping approaches for ablation resulted in ambiguous outcomes. With the effective refractory period being a fundamental prerequisite for the maintenance of fibrillatory conduction, this study aims at estimating the effective refractory period with clinically available measurements. METHODS AND RESULTS: A set of 240 simulations in a spherical model of the left atrium with varying model initialization, combination of cellular refractory properties, and size of a region of lowered effective refractory period was implemented to analyse the capabilities and limitations of cycle length mapping. The minimum observed cycle length and the 25% quantile were compared to the underlying effective refractory period. The density of phase singularities was used as a measure for the complexity of the excitation pattern. Finally, we employed the method in a clinical test of concept including five patients. Areas of lowered effective refractory period could be distinguished from their surroundings in simulated scenarios with successfully induced multi-wavelet re-entry. Larger areas and higher gradients in effective refractory period as well as complex activation patterns favour the method. The 25% quantile of cycle lengths in patients with persistent atrial fibrillation was found to range from 85 to 190 ms. CONCLUSION: Cycle length mapping is capable of highlighting regions of pathologic refractory properties. In combination with complementary substrate mapping approaches, the method fosters confidence to enhance the treatment of atrial fibrillation beyond pulmonary vein isolation particularly in patients with complex activation patterns.

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The contraction of the human heart is a complex process as a consequence of the interaction of internal and external forces. In current clinical routine, the resulting deformation can be imaged during an entire heart beat. However, the active tension development cannot be measured in vivo but may provide valuable diagnostic information. In this work, we present a novel numerical method for solving an inverse problem of cardiac biomechanics-estimating the dynamic active tension field, provided the motion of the myocardial wall is known. This ill-posed non-linear problem is solved using second order Tikhonov regularization in space and time. We conducted a sensitivity analysis by varying the fiber orientation in the range of measurement accuracy. To achieve RMSE <20% of the maximal tension, the fiber orientation needs to be provided with an accuracy of 10°. Also, variation was added to the deformation data in the range of segmentation accuracy. Here, imposing temporal regularization led to an eightfold decrease in the error down to 12%. Furthermore, non-contracting regions representing myocardial infarct scars were introduced in the left ventricle and could be identified accurately in the inverse solution (sensitivity >0.95). The results obtained with non-matching input data are promising and indicate directions for further improvement of the method. In future, this method will be extended to estimate the active tension field based on motion data from clinical images, which could provide important insights in terms of a new diagnostic tool for the identification and treatment of diseased heart tissue.

Abstract:

BACKGROUND Atrial !brillation (AF) is the most common supra- ventricular arrhythmia, characterized by disorganized atrial electri- cal activity, maintained by localized arrhythmogenic atrial drivers. Pulmonary vein isolation (PVI) allows to exclude PV-related drivers. However, PVI is less effective in patients with additional extra-PV arrhythmogenic drivers. OBJECTIVES To discriminate whether AF drivers are located near the PVs vs extra-PV regions using the noninvasive 12-lead electro- cardiogram (ECG) in a computational and clinical framework, and to computationally predict the acute success of PVI in these cohorts of data. METHODS AFdriverswereinducedin2computerizedatrialmodels and combined with 8 torso models, resulting in 1128 12-lead ECGs (80 ECGs with AF drivers located in the PVs and 1048 in extra-PV areas). A total of 103 features were extracted from the signals. Bi- nary decision tree classi!er was trained on the simulated data and evaluated using hold-out cross-validation. The PVs were subse- quently isolated in the models to assess PVI success Finally, the classi!er was tested on a clinical dataset (46 patients: 23 PV- dependent AF and 23 with additional extra-PV sources). RESULTS The classi!er yielded 82.6% speci!city and 73.9% sensi- tivity for detecting PV drivers on the clinical data. Consistency analysis on the 46 patients resulted in 93.5% results match. Applying PVI on the simulated AF cases terminated AF in 100% of the cases in the PV class. CONCLUSION Machine learning–based classi!cation of 12-lead- ECG allows discrimination between patients with PV drivers vs those with extra-PV drivers of AF. The novel algorithm may aid to identify patients with high acute success rates to PVI. KEYWORDS Atrial !brillation; Atrial ablation; Machine learning; Noninvasive; 12-lead electrocardiogram; Pulmonary vein isolation; Cardiac simulations (Cardiovascular Digital Health Journal 2021;2:126–136) © 2021 Heart Rhythm Society. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc- nd/4.0/).

Abstract:

Background: Hypertrophic cardiomyopathy (HCM) is typically caused by mutations in sarcomeric genes leading to cardiomyocyte disarray, replacement fibrosis, impaired contractility, and elevated filling pressures. These varying tissue properties are associ- ated with certain strain patterns that may allow to establish a diagnosis by means of non-invasive imaging without the necessity of harmful myocardial biopsies or con- trast agent application. With a numerical study, we aim to answer: how the variability in each of these mechanisms contributes to altered mechanics of the left ventricle (LV) and if the deformation obtained in in-silico experiments is comparable to values reported from clinical measurements. Methods: We conducted an in-silico sensitivity study on physiological and pathologi- cal mechanisms potentially underlying the clinical HCM phenotype. The deformation of the four-chamber heart models was simulated using a finite-element mechanical solver with a sliding boundary condition to mimic the tissue surrounding the heart. Furthermore, a closed-loop circulatory model delivered the pressure values acting on the endocardium. Deformation measures and mechanical behavior of the heart mod- els were evaluated globally and regionally. Results: Hypertrophy of the LV affected the course of strain, strain rate, and wall thickening—the root-mean-squared difference of the wall thickening between control (mean thickness 10 mm) and hypertrophic geometries (17 mm) was >10%. A reduc- tion of active force development by 40% led to less overall deformation: maximal radial strain reduced from 26 to 21%. A fivefold increase in tissue stiffness caused a more homogeneous distribution of the strain values among 17 heart segments. Fiber disarray led to minor changes in the circumferential and radial strain. A combination of pathological mechanisms led to reduced and slower deformation of the LV and halved the longitudinal shortening of the LA. Conclusions: This study uses a computer model to determine the changes in LV deformation caused by pathological mechanisms that are presumed to underlay HCM. This knowledge can complement imaging-derived information to obtain a more accu- rate diagnosis of HCM.

Abstract:

In both clinical and computational studies, different pacing protocols are used to induce arrhythmia and non-inducibility is often considered as the endpoint of treatment. The need for a standardized methodology is urgent since the choice of the protocol used to induce arrhythmia could lead to contrasting results, e.g., in assessing atrial fibrillation (AF) vulnerabilty. Therefore, we propose a novel method-pacing at the end of the effective refractory period (PEERP)-and compare it to state-of-the-art protocols, such as phase singularity distribution (PSD) and rapid pacing (RP) in a computational study. All methods were tested by pacing from evenly distributed endocardial points at 1 cm inter-point distance in two bi-atrial geometries. Seven different atrial models were implemented: five cases without specific AF-induced remodeling but with decreasing global conduction velocity and two persistent AF cases with an increasing amount of fibrosis resembling different substrate remodeling stages. Compared with PSD and RP, PEERP induced a larger variety of arrhythmia complexity requiring, on average, only 2.7 extra-stimuli and 3 s of simulation time to initiate reentry. Moreover, PEERP and PSD were the protocols which unveiled a larger number of areas vulnerable to sustain stable long living reentries compared to RP. Finally, PEERP can foster standardization and reproducibility, since, in contrast to the other protocols, it is a parameter-free method. Furthermore, we discuss its clinical applicability. We conclude that the choice of the inducing protocol has an influence on both initiation and maintenance of AF and we propose and provide PEERP as a reproducible method to assess arrhythmia vulnerability.

Abstract:

Background: Rate-varying S1S2 stimulation protocols can be used for restitution studies to characterize atrial substrate, ionic remodeling, and atrial fibrillation risk. Clinical restitution studies with numerous patients create large amounts of these data. Thus, an automated pipeline to evaluate clinically acquired S1S2 stimulation protocol data necessitates consistent, robust, reproducible, and precise evaluation of local activation times, electrogram amplitude, and conduction velocity. Here, we present the CVAR-Seg pipeline, developed focusing on three challenges: (i) No previous knowledge of the stimulation parameters is available, thus, arbitrary protocols are supported. (ii) The pipeline remains robust under different noise conditions. (iii) The pipeline supports segmentation of atrial activities in close temporal proximity to the stimulation artifact, which is challenging due to larger amplitude and slope of the stimulus compared to the atrial activity. Methods and Results: The S1 basic cycle length was estimated by time interval detection. Stimulation time windows were segmented by detecting synchronous peaks in different channels surpassing an amplitude threshold and identifying time intervals between detected stimuli. Elimination of the stimulation artifact by a matched filter allowed detection of local activation times in temporal proximity. A non-linear signal energy operator was used to segment periods of atrial activity. Geodesic and Euclidean inter electrode distances allowed approximation of conduction velocity. The automatic segmentation performance of the CVAR-Seg pipeline was evaluated on 37 synthetic datasets with decreasing signal-to-noise ratios. Noise was modeled by reconstructing the frequency spectrum of clinical noise. The pipeline retained a median local activation time error below a single sample (1 ms) for signal-to-noise ratios as low as 0 dB representing a high clinical noise level. As a proof of concept, the pipeline was tested on a CARTO case of a paroxysmal atrial fibrillation patient and yielded plausible restitution curves for conduction speed and amplitude. Conclusion: The proposed openly available CVAR-Seg pipeline promises fast, fully automated, robust, and accurate evaluations of atrial signals even with low signal-to-noise ratios. This is achieved by solving the proximity problem of stimulation and atrial activity to enable standardized evaluation without introducing human bias for large data sets.

Abstract:

In patients with atrial fibrillation, intracardiac electrogram signal amplitude is known to decrease with increased structural tissue remodeling, referred to as fibrosis. In addition to the isolation of the pulmonary veins, fibrotic sites are considered a suitable target for catheter ablation. However, it remains an open challenge to find fibrotic areas and to differentiate their density and transmurality. This study aims to identify the volume fraction and transmurality of fibrosis in the atrial substrate. Simulated cardiac electrograms, combined with a generalized model of clinical noise, reproduce clinically measured signals. Our hybrid dataset approach combines and clinical electrograms to train a decision tree classifier to characterize the fibrotic atrial substrate. This approach captures different dynamics of the electrical propagation reflected on healthy electrogram morphology and synergistically combines it with synthetic fibrotic electrograms from experiments. The machine learning algorithm was tested on five patients and compared against clinical voltage maps as a proof of concept, distinguishing non-fibrotic from fibrotic tissue and characterizing the patient's fibrotic tissue in terms of density and transmurality. The proposed approach can be used to overcome a single voltage cut-off value to identify fibrotic tissue and guide ablation targeting fibrotic areas.

Abstract:

We aim to provide a critical appraisal of basic concepts underlying signal recording and processing technologies applied for (i) atrial fibrillation (AF) mapping to unravel AF mechanisms and/or identifying target sites for AF therapy and (ii) AF detection, to optimize usage of technologies, stimulate research aimed at closing knowledge gaps, and developing ideal AF recording and processing technologies. Recording and processing techniques for assessment of electrical activity during AF essential for diagnosis and guiding ablative therapy including body surface electrocardiograms (ECG) and endo- or epicardial electrograms (EGM) are evaluated. Discussion of (i) differences in uni-, bi-, and multi-polar (omnipolar/Laplacian) recording modes, (ii) impact of recording technologies on EGM morphology, (iii) global or local mapping using various types of EGM involving signal processing techniques including isochronal-, voltage- fractionation-, dipole density-, and rotor mapping, enabling derivation of parameters like atrial rate, entropy, conduction velocity/direction, (iv) value of epicardial and optical mapping, (v) AF detection by cardiac implantable electronic devices containing various detection algorithms applicable to stored EGMs, (vi) contribution of machine learning (ML) to further improvement of signals processing technologies. Recording and processing of EGM (or ECG) are the cornerstones of (body surface) mapping of AF. Currently available AF recording and processing technologies are mainly restricted to specific applications or have technological limitations. Improvements in AF mapping by obtaining highest fidelity source signals (e.g. catheter–electrode combinations) for signal processing (e.g. filtering, digitization, and noise elimination) is of utmost importance. Novel acquisition instruments (multi-polar catheters combined with improved physical modelling and ML techniques) will enable enhanced and automated interpretation of EGM recordings in the near future.

Abstract:

The human heart is a masterpiece of the highest complexity coordinating multi-physics aspects on a multi-scale range. Thus, modeling the cardiac function to reproduce physiological characteristics and diseases remains challenging. Especially the complex simulation of the blood's hemodynamics and its interaction with the myocardial tissue requires a high accuracy of the underlying computational models and solvers. These demanding aspects make whole-heart fully-coupled simulations computationally highly expensive and call for simpler but still accurate models. While the mechanical deformation during the heart cycle drives the blood flow, less is known about the feedback of the blood flow onto the myocardial tissue. To solve the fluid-structure interaction problem, we suggest a cycle-to-cycle coupling of the structural deformation and the fluid dynamics. In a first step, the displacement of the endocardial wall in the mechanical simulation serves as a unidirectional boundary condition for the fluid simulation. After a complete heart cycle of fluid simulation, a spatially resolved pressure factor (PF) is extracted and returned to the next iteration of the solid mechanical simulation, closing the loop of the iterative coupling procedure. All simulations were performed on an individualized whole heart geometry. The effect of the sequential coupling was assessed by global measures such as the change in deformation and-as an example of diagnostically relevant information-the particle residence time. The mechanical displacement was up to 2 mm after the first iteration. In the second iteration, the deviation was in the sub-millimeter range, implying that already one iteration of the proposed cycle-to-cycle coupling is sufficient to converge to a coupled limit cycle. Cycle-to-cycle coupling between cardiac mechanics and fluid dynamics can be a promising approach to account for fluid-structure interaction with low computational effort. In an individualized healthy whole-heart model, one iteration sufficed to obtain converged and physiologically plausible results.

Abstract:

Electrical impedance tomography is clinically used to trace ventilation related changes in electrical conductivity of lung tissue. Estimating regional pulmonary perfusion using electrical impedance tomography is still a matter of research. To support clinical decision making, reliable bedside information of pulmonary perfusion is needed. We introduce a method to robustly detect pulmonary perfusion based on indicator-enhanced electrical impedance tomography and validate it by dynamic multidetector computed tomography in two experimental models of acute respiratory distress syndrome. The acute injury was induced in a sublobar segment of the right lung by saline lavage or endotoxin instillation in eight anesthetized mechanically ventilated pigs. For electrical impedance tomography measurements, a conductive bolus (10% saline solution) was injected into the right ventricle during breath hold. Electrical impedance tomography perfusion images were reconstructed by linear and normalized Gauss-Newton reconstruction on a finite element mesh with subsequent element-wise signal and feature analysis. An iodinated contrast agent was used to compute pulmonary blood flow via dynamic multidetector computed tomography. Spatial perfusion was estimated based on first-pass indicator dilution for both electrical impedance and multidetector computed tomography and compared by Pearson correlation and Bland-Altman analysis. Strong correlation was found in dorsoventral (r = 0.92) and in right-to-left directions (r = 0.85) with good limits of agreement of 8.74% in eight lung segments. With a robust electrical impedance tomography perfusion estimation method, we found strong agreement between multidetector computed and electrical impedance tomography perfusion in healthy and regionally injured lungs and demonstrated feasibility of electrical impedance tomography perfusion imaging.

Abstract:

The electrocardiogram (ECG) is a standard cost-efficient and non-invasive tool for the early detection of various cardiac diseases. Quantifying different timing and amplitude features of and in between the single ECG waveforms can reveal important information about the underlying (dys-)function of the heart. Determining these features requires the detection of fiducial points that mark the on- and offset as well as the peak of each ECG waveform (P wave, QRS complex, T wave). Manually setting these points is time-consuming and requires a physician’s expert knowledge. Therefore, the highly modular ECGdeli toolbox for MATLAB was developed, which is capable of filtering clinically recorded 12-lead ECG signals and detecting the fiducial points, also called delineation. It is one of the few open toolboxes offering ECG delineation for P waves, T Waves and QRS complexes. The algorithms provided were evaluated with the QT database, an ECG database comprising 105 signals with fiducial points annotated by clinicians. The median difference between the fiducial points set by the boundary detection algorithm and the clinical annotations serving as a ground truth is less than 4 samples (16 ms) for the P wave and the QRS complex markers.

Abstract:

Large-scale electrophysiological simulations to obtain electrocardiograms (ECG) carry the potential to pro- duce extensive datasets for training of machine learning classifiers to, e.g., discriminate between different cardiac pathologies. The adoption of simulations for these purposes is limited due to a lack of ready-to- use models covering atrial anatomical variability. We built a bi-atrial statistical shape model (SSM) of the endocardial wall based on 47 segmented human CT and MRI datasets using Gaussian process morphable models. Generalization, specificity, and compact- ness metrics were evaluated. The SSM was applied to simulate atrial ECGs in 100 random volumetric instances. The first eigenmode of our SSM reflects a change of the total volume of both atria, the second the asym- metry between left vs. right atrial volume, the third a change in the prominence of the atrial appendages. The SSM is capable of generalizing well to unseen geometries and 95% of the total shape variance is cov- ered by its first 24 eigenvectors. The P waves in the 12-lead ECG of 100 random instances showed a duration of 109 . 7 ±12 . 2 ms in accordance with large cohort studies. The novel bi-atrial SSM itself as well as 100 exemplary instances with rule-based augmentation of atrial wall thickness, fiber orientation, inter-atrial bridges and tags for anatomical structures have been made publicly available. This novel, openly available bi-atrial SSM can in future be employed to generate large sets of realistic atrial geometries as a basis for in silico big data approaches.

Abstract:

During atrial fibrillation, cardiac tissue undergoes different remodeling processes at different scales from the molecular level to the tissue level. One central player that contributes to both electrical and structural remodeling is the myofibroblast. Based on recent experimental evidence on myofibroblasts’ ability to contract, we extended a biophysical myofibroblast model with Ca2+ handling components and studied the effect on cellular and tissue electrophysiology. Using genetic algorithms, we fitted the myofibroblast model parameters to the existing in vitro data. In silico experiments showed that Ca2+ currents can explain the experimentally observed variability regarding the myofibroblast resting membrane potential. The presence of an L-type Ca2+ current can trigger automaticity in the myofibroblast with a cycle length of 799.9 ms. Myocyte action potentials were prolonged when coupled to myofibroblasts with Ca2+ handling machinery. Different spatial myofibroblast distribution patterns increased the vulnerable window to induce arrhythmia from 12 ms in non-fibrotic tissue to 22 ± 2.5 ms and altered the reentry dynamics. Our findings suggest that Ca2+ handling can considerably affect myofibroblast electrophysiology and alter the electrical propagation in atrial tissue composed of myocytes coupled with myofibroblasts. These findings can inform experimental validation experiments to further elucidate the role of myofibroblast Ca2+ handling in atrial arrhythmogenesis.

Abstract:

Diseases caused by alterations of ionic concentrations are frequently observed challenges and play an important role in clinical practice. The clinically established method for the diagnosis of electrolyte concentration imbalance is blood tests. A rapid and non-invasive point-of-care method is yet needed. The electrocardiogram (ECG) could meet this need and becomes an established diagnostic tool allowing home monitoring of the electrolyte concentration also by wearable devices. In this review, we present the current state of potassium and calcium concentration monitoring using the ECG and summarize results from previous work. Selected clinical studies are presented, supporting or questioning the use of the ECG for the monitoring of electrolyte concentration imbalances. Differences in the findings from automatic monitoring studies are discussed, and current studies utilizing machine learning are presented demonstrating the potential of the deep learning approach. Furthermore, we demonstrate the potential of computational modeling approaches to gain insight into the mechanisms of relevant clinical findings and as a tool to obtain synthetic data for methodical improvements in monitoring approaches.

Abstract:

Background Radiofrequency ablation (RFA) is a common approach to treat cardiac arrhythmias. During this intervention, numerous strategies are applied to indirectly estimate lesion formation. However, the assessment of the spatial extent of these acute injuries needs to be improved in order to create well-defined and durable ablation lesions. Methods We investigated the electrophysiological characteristics of rat atrial myocardium during an ex vivo RFA procedure with fluorescence-optical and electrical mapping. By analyzing optical data, the temporal growth of punctiform ablation lesions was reconstructed after stepwise RFA sequences. Unipolar electrograms (EGMs) were simultaneously recorded by a multielectrode array (MEA) before and after each RFA sequence. Based on the optical results, we searched for electrical features to delineate these lesions from healthy myocardium. Results Several unipolar EGM parameters were monotonically decreasing when distances between the electrode and lesion boundary were smaller than 2 mm. The negative component of the unipolar EGM [negative peak amplitude (Aneg)] vanished for distances lesser than 0.4 mm to the lesion boundary. Median peak-to-peak amplitude (Vpp) was decreased by 75% compared to baseline. Conclusion Aneg and Vpp are excellent parameters to discriminate the growing lesion area from healthy myocardium. The experimental setup opens new opportunities to investigate EGM characteristics of more complex ablation lesions.

Abstract:

Identification of atrial sites that perpetuate atrial fibrillation (AF), and ablation thereof terminates AF, is challenging. We hypothesized that specific electrogram (EGM) characteristics identify AF-termination sites (AFTS). Twenty-one patients in whom low-voltage-guided ablation after pulmonary vein isolation terminated clinical persistent AF were included. Patients were included if short RF-delivery for <8sec at a given atrial site was associated with acute termination of clinical persistent AF. EGM-characteristics at 21 AFTS, 105 targeted sites without termination and 105 non-targeted control sites were analyzed. Alteration of EGM-characteristics by local fibrosis was evaluated in a three-dimensional high resolution (100 µm)-computational AF model. AFTS demonstrated lower EGM-voltage, higher EGM-cycle-length-coverage, shorter AF-cycle-length and higher pattern consistency than control sites (0.49 ± 0.39 mV vs. 0.83 ± 0.76 mV, p < 0.0001; 79 ± 16% vs. 59 ± 22%, p = 0.0022; 173 ± 49 ms vs. 198 ± 34 ms, p = 0.047; 80% vs. 30%, p < 0.01). Among targeted sites, AFTS had higher EGM-cycle-length coverage, shorter local AF-cycle-length and higher pattern consistency than targeted sites without AF-termination (79 ± 16% vs. 63 ± 23%, p = 0.02; 173 ± 49 ms vs. 210 ± 44 ms, p = 0.002; 80% vs. 40%, p = 0.01). Low voltage (0.52 ± 0.3 mV) fractionated EGMs (79 ± 24 ms) with delayed components in sinus rhythm ('atrial late potentials', respectively 'ALP') were observed at 71% of AFTS. EGMs recorded from fibrotic areas in computational models demonstrated comparable EGM-characteristics both in simulated AF and sinus rhythm. AFTS may therefore be identified by locally consistent, fractionated low-voltage EGMs with high cycle-length-coverage and rapid activity in AF, with low-voltage, fractionated EGMs with delayed components/ 'atrial late potentials' (ALP) persisting in sinus rhythm.

Abstract:

Therapeutic hypothermia (TH) is an approved neuroproctetive treatment to reduce neurological morbidity and mortality after hypoxic-ischemic damage related to cardiac arrest and neonatal asphyxia. Also in the treatment of acute ischemic stroke (AIS), which in Western countries still shows a very high mortality rate of about 25 %, selective mild TH by means of Targeted Temperature Management (TTM) could potentially decrease final infarct volume. In this respect, a novel intracarotid blood cooling catheter system has recently been developed, which allows for combined carotid blood cooling and mechanical thrombectomy (MT) and aims at selective mild TH in the affected ischemic brain (core and penumbra). Unfortunately, so far direct measurement and control of cooled cerebral temperature requires invasive or elaborate MRI-assisted measurements. Computational modeling provides unique opportunities to predict the resulting cerebral temperatures on the other hand. In this work, a simplified 3D brain model was generated and coupled with a 1D hemodynamics model to predict spatio-temporal cerebral temperature profiles using finite element modeling. Cerebral blood and tissue temperatures as well as the systemic temperature were analyzed for physiological conditions as well as for a middle cerebral artery (MCA) M1 occlusion. Furthermore, vessel recanalization and its effect on cerebral temperature was analyzed. The results show a significant influence of collateral flow on the cooling effect and are in accordance with experimental data in animals. Our model predicted a possible neuroprotective temperature decrease of 2.5 ℃ for the territory of MCA perfusion after 60 min of blood cooling, which underlines the potential of the new device and the use of TTM in case of AIS.

Abstract:

OBJECTIVE: Unipolar intracardiac electrograms (uEGMs) measured inside the atria during electro-anatomic mapping contain diagnostic information about cardiac excitation and tissue properties. The ventricular far field (VFF) caused by ventricular depolarization compromises these signals. Current signal processing techniques require several seconds of local uEGMs to remove the VFF component and thus prolong the clinical mapping procedure. We developed an approach to remove the VFF component using data obtained during initial anatomy acquisition. METHODS: We developed two models which can approximate the spatio-temporal distribution of the VFF component based on acquired EGM data: Polynomial fit, and dipole fit. Both were benchmarked based on simulated cardiac excitation in two models of the human heart and applied to clinical data. RESULTS: VFF data acquired in one atrium were used to estimate model parameters. Under realistic noise conditions, a dipole model approximated the VFF with a median deviation of 0.029mV, yielding a median VFF attenuation of 142. In a different setup, only VFF data acquired at distances of more than 5mm to the atrial endocardium were used to estimate the model parameters. The VFF component was then extrapolated for a layer of 5mm thickness lining the endocardial tissue. A median deviation of 0.082mV (median VFF attenuation of 49x) was achieved under realistic noise conditions. CONCLUSION: It is feasible to model the VFF component in a personalized way and effectively remove it from uEGMs. SIGNIFICANCE: Application of our novel, simple and computationally inexpensive methods allows immediate diagnostic assessment of uEGM data without prolonging data acquisition.

Abstract:

End-stage chronic kidney disease (CKD) patients are facing a 30% rise for the risk of lethal cardiac events (LCE) compared to non-CKD patients. At the same time, these patients undergoing dialysis experience shifts in the potassium concentrations. The increased risk of LCE paired with the concentration changes suggest a connection between LCE and concentration disbalances. To prove this link, a continuous monitoring device for the ionic concentrations, e.g. the ECG, is needed. In this work, we want to answer if an optimised signal processing chain can improve the result quantify the influence of a disbalanced training dataset on the final estimation result. The study was performed on a dataset consisting of 12-lead ECGs recorded during dialysis sessions of 32 patients. We selected three features to find a mapping from ECG features to [K+]o: T-wave ascending slope, T-wave descending slope and T-wave amplitude. A polynomial model of 3rd order was used to reconstruct the concentrations from these features. We solved a regularised weighted least squares problem with a weighting matrix dependent on the frequency of each concentration in the dataset (frequent concentration weighted less). By doing so, we tried to generate a model being suitable for the whole range of the concentrations.With weighting, errors are increasing for the whole dataset. For the data partition with [K+]o<5 mmol/l, errors are increasing, for [K+]o≥5 mmol/l, errors are decreasing. However, and apart from the exact reconstruction results, we can conclude that a model being valid for all patients and not only the majority, needs to be learned with a more homogeneous dataset. This can be achieved by leaving out data points or by weighting the errors during the model fitting. With increasing weighting, we increase the performance on the part of the [K+]o that are less frequent which was desired in our case.

Abstract:

The morphology of the electrocardiogram (ECG) varies among different healthy subjects due to anatomical and structural reasons, such as for example the shape of the heart geometry or the position and size of surrounding organs in the torso. Knowledge about these ECG morphology changes could be used to parameterize electrophysiological simula- tions of the human heart. In this work, we detected the boundaries of ECG waveforms, i.e. the P-wave, the QRS-complex and the T-wave, in 12- lead ECGs from 918 healthy subjects in the Physionet Com- puting in Cardiology Challenge 2020 Database with the IBT openECG toolbox. Subsequently, we obtained the onset, the peak and the offset of each P-wave, QRS-complex and T-wave in the signal. In this way, the duration of the P-wave, the QRS- complex and the T-wave, the PQ-, RR- and the QT-interval as well as the amplitudes of the P-wave, the Q-, R- and S- peak and the T-wave in each lead were extracted from the 918 healthy ECGs. Their statistical distributions and correlation between each other were assessed. The highest variabilities among the 918 healthy subject were found for the RR interval and the amplitudes of the QRS- complex. The highest correlation was observed for feature pairs that represent the same feature in different leads. Es- pecially the R-peak amplitudes showed a strong correlation across different leads. The calculated feature distributions can be used to optimize the parameters of populations of cardiac electrophysiological models. In this way, realistic in-silico generated surface ECGs can be simulated in large scale and could be used as input data for machine learning algorithms for a classification of cardio- vascular diseases.

Abstract:

BACKGROUND: Electrical impedance tomography (EIT) with indicator dilution may be clinically useful to measure relative lung perfusion, but there is limited information on the performance of this technique. METHODS: Thirteen pigs (50-66 kg) were anaesthetised and mechanically ventilated. Sequential changes in ventilation were made: (i) right-lung ventilation with left-lung collapse, (ii) two-lung ventilation with optimised PEEP, (iii) two-lung ventilation with zero PEEP after saline lung lavage, (iv) two-lung ventilation with maximum PEEP (20/25 cm HO to achieve peak airway pressure 45 cm HO), and (v) two-lung ventilation under unilateral pulmonary artery occlusion. Relative lung perfusion was assessed with EIT and central venous injection of saline 3%, 5%, and 10% (10 ml) during breath holds. Relative perfusion was determined by positron emission tomography (PET) using Gallium-labelled microspheres. EIT and PET were compared in eight regions of equal ventro-dorsal height (right, left, ventral, mid-ventral, mid-dorsal, and dorsal), and directional changes in regional perfusion were determined. RESULTS: Differences between methods were relatively small (95% of values differed by less than 8.7%, 8.9%, and 9.5% for saline 10%, 5%, and 3%, respectively). Compared with PET, EIT underestimated relative perfusion in dependent, and overestimated it in non-dependent, regions. EIT and PET detected the same direction of change in relative lung perfusion in 68.9-95.9% of measurements. CONCLUSIONS: The agreement between EIT and PET for measuring and tracking changes of relative lung perfusion was satisfactory for clinical purposes. Indicator-based EIT may prove useful for measuring pulmonary perfusion at bedside.

Abstract:

Local brain hypothermia is an attractive method for providing cerebral neuroprotection for ischemic stroke patients and at the same time reducing systemic side effects of cooling. In acute ischemic stroke patients with large vessel occlusion, combination with endovascular mechanical recanalization treatment could potentially allow for an alleviation of inflammatory and apoptotic pathways in the critical phase of reperfusion. The direct cooling of arterial blood by means of an intra-carotid heat exchange catheter compatible with recanalization systems is a novel promising approach. Focusing on the concept of "cold reperfusion", we developed an energetic model to calculate the rate of temperature decrease during intra-carotid cooling in case of physiological as well as decreased perfusion. Additionally, we discussed and considered the effect and biological significance of temperature decrease on resulting brain perfusion. Our model predicted a 2 °C brain temperature decrease in 8.3, 11.8 and 26.2 min at perfusion rates of 50, 30 and 10ml100g⋅min, respectively. The systemic temperature decrease - caused by the venous blood return to the main circulation - was limited to 0.5 °C in 60 min. Our results underline the potential of catheter-assisted, intracarotid blood cooling to provide a fast and selective brain temperature decrease in the phase of vessel recanalization. This method can potentially allow for a tissue hypothermia during the restoration of the physiological flow and thus a "cold reperfusion" in the setting of mechanical recanalization.

Abstract:

Atypical atrial flutter (AFlut) is a reentrant arrhythmia which patients frequently develop after ablation for atrial fibrillation (AF). Indeed, substrate modifications during AF ablation can increase the likelihood to develop AFlut and it is clinically not feasible to reliably and sensitively test if a patient is vulnerable to AFlut. Here, we present a novel method based on personalized computational models to identify pathways along which AFlut can be sustained in an individual patient. We build a personalized model of atrial excitation propagation considering the anatomy as well as the spatial distribution of anisotropic conduction velocity and repolarization characteristics based on a combination of a priori knowledge on the population level and information derived from measurements performed in the individual patient. The fast marching scheme is employed to compute activation times for stimuli from all parts of the atria. Potential flutter pathways are then identified by tracing loops from wave front collision sites and constricting them using a geometric snake approach under consideration of the heterogeneous wavelength condition. In this way, all pathways along which AFlut can be sustained are identified. Flutter pathways can be instantiated by using an eikonal-diffusion phase extrapolation approach and a dynamic multifront fast marching simulation. In these dynamic simulations, the initial pattern eventually turns into the one driven by the dominant pathway, which is the only pathway that can be observed clinically. We assessed the sensitivity of the flutter pathway maps with respect to conduction velocity and its anisotropy. Moreover, we demonstrate the application of tailored models considering disease-specific repolarization properties (healthy, AF-remodeled, potassium channel mutations) as well as applicabiltiy on a clinical dataset. Finally, we tested how AFlut vulnerability of these substrates is modulated by exemplary antiarrhythmic drugs (amiodarone, dronedarone). Our novel method allows to assess the vulnerability of an individual patient to develop AFlut based on the personal anatomical, electrophysiological, and pharmacological characteristics. In contrast to clinical electrophysiological studies, our computational approach provides the means to identify all possible AFlut pathways and not just the currently dominant one. This allows to consider all relevant AFlut pathways when tailoring clinical ablation therapy in order to reduce the development and recurrence of AFlut.

Abstract:

Chronic kidney disease (CKD) affects 13% of the worldwide population and end stage patients often receive haemodialysis treatment to control the electrolyte concentrations. The cardiovascular death rate increases by 10% - 30% in dialysis patients than in general population. To analyse possible links between electrolyte concentration variation and cardiovascular diseases, a continuous non-invasive monitoring tool enabling the estimation of potassium and calcium concentration from features of the ECG is desired. Although the ECG was shown capable of being used for this purpose, the method still needs improvement. In this study, we examine the influence of lead reduction techniques on the estimation results of serum calcium and potassium concentrations.We used simulated 12 lead ECG signals obtained using an adapted Himeno et al. model. Aiming at a precise estimation of the electrolyte concentrations, we compared the estimation based on standard ECG leads with the estimation using linearly transformed fusion signals. The transformed signals were extracted from two lead reduction techniques: principle component analysis (PCA) and maximum amplitude transformation (Max- Amp). Five features describing the electrolyte changes were calculated from the signals. To reconstruct the ionic concentrations, we applied a first and a third order polynomial regression connecting the calculated features and concentration values. Furthermore, we added 30 dB white Gaussian noise to the ECGs to imitate clinically measured signals. For the noisefree case, the smallest estimation error was achieved with a specific single lead from the standard 12 lead ECG. For example, for a first order polynomial regression, the error was 0.0003±0.0767 mmol/l (mean±standard deviation) for potassium and -0.0036±0.1710 mmol/l for calcium (Wilson lead V1). For the noisy case, the PCA signal showed the best estimation performance with an error of -0.003±0.2005 mmol/l for potassium and -0.0002±0.2040 mmol/l for calcium (both first order fit). Our results show that PCA as ECG lead reduction technique is more robust against noise than MaxAmp and standard ECG leads for ionic concentration reconstruction.

Abstract:

Under persistent atrial fibrillation (peAF), cardiac tissue experiences electrophysiological and structural remodeling. Fibrosis in the atrial tissue has an important impact on the myocyte action potential and its propagation. The objective of this work is to explore the effect of heterogeneities present in the fibrotic tissue and their impact on the intracardiac electrogram (EGM). Human atrial myocyte and fibroblast electrophysiology was simulated using mathematical models proposed by Koivumäki et al. to represent electrical remodeling under peAF and the paracrine effect of the transforming grow factor 1 (TGF-1). 2D tissue simulations were computed varying the density of fibrosis (10%, 20% and 40%), myofibroblasts and collagen were randomly distributed with different ratios (0%-100%, 50%-50% and 100%- 0%). Results show that increasing the fibrosis density changes the re-entry dynamics from functional to anatomical due to a block in conduction in regions with high fibrosis density (40%). EGM morphology was affected by different ratios of myofibroblasts-collagen. For low myofibroblast densities (below 50%) the duration of active segments was shorter compared to higher myofibroblasts densities (above 50%). Our results show that fibrosis heterogeneities can alter the dynamics of the re-entry and the morphology of the EGM.

Abstract:

Aims Chronic left atrial enlargement (LAE) increases the risk of atrial fibrillation. Electrocardiogram (ECG) criteria might provide a means to diagnose LAE and identify patients at risk; however, current criteria perform poorly. We seek to characterize the potentially differential effects of atrial dilation vs. hypertrophy on the ECG P-wave. Methods and results We predict effects on the P-wave of (i) left atrial dilation (LAD), i.e. an increase of LA cavity volume without an increase in myocardial volume, (ii) left atrial concentric hypertrophy (LACH), i.e. a thickened myocardial wall, and (iii) a combination of the two. We performed a computational study in a cohort of 72 anatomical variants, derived from four human atrial anatomies. To model LAD, pressure was applied to the LA endocardium increasing cavity volume by up to 100%. For LACH, the LA wall was thickened by up to 3.3 mm. P-waves were derived by simulating atrial excitation propagation and computing the body surface ECG. The sensitivity regarding changes beyond purely anatomical effects was analysed by altering conduction velocity by 25% in 96 additional model variants. Left atrial dilation prolonged P-wave duration (PWd) in two of four subjects; in one subject a shortening, and in the other a variable change were seen. Left atrial concentric hypertrophy, in contrast, consistently increased P-wave terminal force in lead V1 (PTF-V1) in all subjects through an enlarged amplitude while PWd was unaffected. Combined hypertrophy and dilation generally enhanced the effect of hypertrophy on PTF-V1. Conclusion Isolated LAD has moderate effects on the currently used P-wave criteria, explaining the limited utility of PWd and PTF-V1 in detecting LAE in clinical practice. In contrast, PTF-V1 may be a more sensitive indicator of LA myocardial hypertrophy.

Abstract:

Electrocardiographic imaging (ECGI) reconstructs the electrical activity of the heart from a dense array of body-surface electrocardiograms and a patient-specific heart-torso geometry. Depending on how it is formulated, ECGI allows the reconstruction of the activation and recovery sequence of the heart, the origin of premature beats or tachycardia, the anchors/hotspots of re-entrant arrhythmias and other electrophysiological quantities of interest. Importantly, these quantities are directly and noninvasively reconstructed in a digitized model of the patient’s three-dimensional heart, which has led to clinical interest in ECGI’s ability to personalize diagnosis and guide therapy. Despite considerable development over the last decades, validation of ECGI is challenging. Firstly, results depend considerably on implementation choices, which are necessary to deal with ECGI’s ill-posed character. Secondly, it is challenging to obtain (invasive) ground truth data of high quality. In this review, we discuss the current status of ECGI validation as well as the major challenges remaining for complete adoption of ECGI in clinical practice. Specifically, showing clinical benefit is essential for the adoption of ECGI. Such benefit may lie in patient outcome improvement, workflow improvement, or cost reduction. Future studies should focus on these aspects to achieve broad adoption of ECGI, but only after the technical challenges have been solved for that specific application/pathology. We propose ‘best’ practices for technical validation and highlight collaborative efforts recently organized in this field. Continued interaction between engineers, basic scientists and physicians remains essential to find a hybrid between technical achievements, pathological mechanisms insights, and clinical benefit, to evolve this powerful technique towards a useful role in clinical practice.

Abstract:

Electrocardiographic imaging (ECGI) strongly relies on a priori assumptions and additional information to overcome ill-posedness. The major challenge of obtaining good reconstructions consists in finding ways to add information that effectively restricts the solution space without violating properties of the sought solution. In this work, we attempt to address this problem by constructing a spatio-temporal basis of body surface potentials (BSP) from simulations of many focal excitations. Measured BSPs are projected onto this basis and reconstructions are expressed as linear combinations of corresponding transmembrane voltage (TMV) basis vectors. The novel method was applied to simulations of 100 atrial ectopic foci with three different conduction velocities. Three signal-to-noise ratios (SNR) and bases of six different temporal lengths were considered. Reconstruction quality was evaluated using the spatial correlation coefficient of TMVs as well as estimated local activation times (LAT). The focus localization error was assessed by computing the geodesic distance between true and reconstructed foci. Compared with an optimally parameterized Tikhonov-Greensite method, the BSP basis reconstruction increased the mean TMV correlation by up to 22, 24, and 32% for an SNR of 40, 20, and 0 dB, respectively. Mean LAT correlation could be improved by up to 5, 7, and 19% for the three SNRs. For 0 dB, the average localization error could be halved from 15.8 to 7.9 mm. For the largest basis length, the localization error was always below 34 mm. In conclusion, the new method improved reconstructions of atrial ectopic activity especially for low SNRs. Localization of ectopic foci turned out to be more robust and more accurate. Preliminary experiments indicate that the basis generalizes to some extent from the training data and may even be applied for reconstruction of non-ectopic activity.

Abstract:

Optical mapping is widely used as a tool to investigate cardiac electrophysiology in ex vivo preparations. Digital filtering of fluorescence-optical data is an important requirement for robust subsequent data analysis and still a challenge when processing data acquired from thin mammalian myocardium. Therefore, we propose and investigate the use of an adaptive spatio-temporal Gaussian filter for processing optical mapping signals from these kinds of tissue usually having low signal-to-noise ratio (SNR). We demonstrate how filtering parameters can be chosen automatically without additional user input. For systematic comparison of this filter with standard filtering methods from the literature, we generated synthetic signals representing optical recordings from atrial myocardium of a rat heart with varying SNR. Furthermore, all filter methods were applied to experimental data from an ex vivo setup. Our developed filter outperformed the other filter methods regarding local activation time detection at SNRs smaller than 3 dB which are typical noise ratios expected in these signals. At higher SNRs, the proposed filter performed slightly worse than the methods from literature. In conclusion, the proposed adaptive spatio-temporal Gaussian filter is an appropriate tool for investigating fluorescence-optical data with low SNR. The spatio-temporal filter parameters were automatically adapted in contrast to the other investigated filters.

Abstract:

Promising results have been reported in noninvasive estimation of cardiac activation times (AT) using the equivalent dipole layer (EDL) source model in combination with the boundary element method (BEM). However, the assumption of equal anisotropy ratios in the heart that underlies the EDL model does not reflect reality. In the present study, we quantify the errors of the nonlinear AT imaging based on the EDL approximation. Nine different excitation patterns (sinus rhythm and eight ectopic beats) were simulated with the monodomain model. Based on the bidomain theory, the body surface potential maps (BSPMs) were calculated for a realistic finite element volume conductor with an anisotropic heart model. For the forward calculations, three cases of bidomain conductivity tensors in the heart were considered: isotropic, equal, and unequal anisotropy ratios in the intra- and extracellular spaces. In all inverse reconstructions, the EDL model with BEM was employed: AT were estimated by solving the nonlinear optimization problem with the initial guess provided by the fastest route algorithm. Expectedly, the case of unequal anisotropy ratios resulted in larger localization errors for almost all considered activation patterns. For the sinus rhythm, all sites of early activation were correctly estimated with an optimal regularization parameter being used. For the ectopic beats, all but one foci were correctly classified to have either endo- or epicardial origin with an average localization error of 20.4 mm for unequal anisotropy ratio. The obtained results confirm validation studies and suggest that cardiac anisotropy might be neglected in clinical applications of the considered EDL-based inverse procedure.

Abstract:

OBJECTIVE: Atrial tachycardia (AT) still pose a major challenge in catheter ablation. Although state-of-the-art electroanatomical mapping systems allow to acquire several thousand intracardiac electrograms (EGMs), algorithms for diagnostic analysis are mainly limited to the amplitude of the signal (voltage map) and the local activation time~(LAT map). We applied spatio-temporal analysis of EGM activity to generate maps indicating reentries and diastolic potentials, thus identifying and localizing the driving mechanism of AT. METHODS: First, the time course of active surface area (ASA) is determined during one basic cycle length (BCL). The global cycle length coverage (gCLC) reflects the relative duration within one BCL for which activity was present in each individual atrium. A local cycle length coverage (lCLC) is computed for circular sub-areas with 20mm diameter. The simultaneous active surface area sASA is determined to indicate the spatial extent of depolarizing tissue. RESULTS: Combined analysis of these spatial scales allowed to correctly identify and localize the driving mechanism: gCLC values of 100% were indicative for atria harbouring a reentrant driver. lCLC could detect micro reentries within an area of 1.651.28cm in simulated data and differentiate them against focal sources. Mid-diastolic potentials, being potential targets for catheter ablation, were identified as the areas showing confined activity based on sASA values. CONCLUSION: The concept of spatio-temporal activity analysis proved successful and correctly indicated the tachycardia mechanism in 20 simulated AT scenarios and three clinical data sets. SIGNIFICANCE: Automatic interpretation of intracardiac mapping data could help to improve the treatment strategy in complex cases of AT.

Abstract:

Background: During atrial fibrillation, heterogeneities and anisotropies result in a chaotic propagation of the depolarization wavefront. The electrophysiological parameter called conduction velocity (CV) influences the propagation pattern over the atrium. We present a method that determines the regional CV for deformed catheter shapes, which result due to the catheter movement and changing wall contact.Methods: The algorithm selects stable catheter positions, finds the local activation times (LAT), considers the wall contact and calculates all CV estimates within the area covered by the catheter. The method is evaluated with simulated data and then applied to four clinical data sets. Both sinus rhythm activity as well as depolarization wavefronts initiated by stimulation are analyzed. The regional CV is compared with the fractionation duration (FD) and peak-to-peak (P2P) voltages. A speed of 0.5 m/s was defined to create the simulated LAT.Results: After analyzing the simulated LAT with clinical catheter spatial coordinates, the median CV of 0.5 m/s with an interquartile range of 0.22 and exact CV direction vectors were obtained. For clinical cases, the CV magnitude range of 0.08 m/s to 1.0 m/s was obtained. The P2P amplitude of 0.7 mV to 3.7 mV and the mean FD from 40.79ms to 48.66ms was obtained. The correlation of 0.86 was observed between CV and P2P amplitude, and 0.62 between CV and FD.Conclusion: In this paper, a method is presented and validated which calculates the CV for the deformed catheter and changing wall contact. In an exemplary clinical data set correlation between regional CV with FD and the P2P voltage was observed.

Abstract:

Objectives: This study hypothesized that P-wave morphology and timing under left atrial appendage (LAA) pacing change characteristically immediately upon anterior mitral line (AML) block. Background: Perimitral flutter commonly occurs following ablation of atrial fibrillation and can be cured by an AML. However, confirmation of bidirectional block can be challenging, especially in severely fibrotic atria. Methods: The study analyzed 129 consecutive patients (66 ± 8 years, 64% men) who developed perimitral flutter after atrial fibrillation ablation. We designed electrocardiography criteria in a retrospective cohort (n = 76) and analyzed them in a validation cohort (n = 53). Results: Bidirectional AML block was achieved in 110 (85%) patients. For ablation performed during LAA pacing without flutter (n = 52), we found a characteristic immediate V1 jump (increase in LAA stimulus to P-wave peak interval in lead V1) as a real-time marker of AML block (V1 jump ≥30 ms: sensitivity 95%, specificity 100%, positive predictive value 100%, negative predictive value 88%). As V1 jump is not applicable when block coincides with termination of flutter, absolute V1 delay was used as a criterion applicable in all cases (n = 129) with a delay of 203 ms indicating successful block (sensitivity 92%, specificity 84%, positive predictive value 90%, negative predictive value 87%). Furthermore, an initial negative P-wave portion in the inferior leads was observed, which was attenuated in case of additional cavotricuspid isthmus ablation. Computational P-wave simulations provide mechanistic confirmation of these findings for diverse ablation scenarios (pulmonary vein isolation ± AML ± roof line ± cavotricuspid isthmus ablation). Conclusions: V1 jump and V1 delay are novel real-time electrocardiography criteria allowing fast and straightforward assessment of AML block during ablation for perimitral flutter.

Abstract:

Catheter ablation is a curative therapeutic approach for atrial fibrillation (AF). Ablation of rotational sources based on basket catheter measurements has been proposed as a promising approach in patients with persistent AF to complement pulmonary vein isolation. However, clinically reported success rates are equivocal calling for a mechanistic investigation under controlled conditions. We present a computational framework to benchmark ablation strategies considering the whole cycle from excitation propagation to electrogram acquisition and processing to virtual therapy. Fibrillation was induced in a patient-specific 3D volumetric model of the left atrium, which was homogeneously remodelled to sustain reentry. The resulting extracellular potential field was sampled using models of grid catheters as well as realistically deformed basket catheters considering the specific atrial anatomy. Virtual electrograms were processed to compute phase singularity density maps to target rotor tips with up to three circular ablations. Stable rotors were successfully induced in different regions of the homogeneously remodelled atrium showing that rotors are not constrained to unique anatomical structures or locations. Phase singularity density maps correctly identified and located the rotors (deviation < 10 mm) based on catheter recordings only for sufficient resolution (inter-electrode distance = 3 mm) and proximity to the wall (< 10 mm). Targeting rotor sites with ablation did not stop reentries in the homogeneously remodelled atria independent from lesion size (1-7 mm radius), from linearly connecting lesions with anatomical obstacles, and from the number of rotors targeted sequentially (up to 3). Our results show that phase maps derived from intracardiac electrograms can be a powerful tool to map atrial activation patterns, yet they can also be misleading due to inaccurate localization of rotor tips depending on electrode resolution and distance to the wall. This should be considered to avoid ablating regions that are in fact free of rotor sources of AF. In our experience, ablation of rotor sites was not successful to stop fibrillation. Our comprehensive simulation framework provides the means to holistically benchmark ablation strategies in silico under consideration of all steps invol

Abstract:

Patients suffering from end stage of chronic kid- ney disease (CKD) often undergo haemodialysis to normalize the electrolyte concentrations. Moreover, cardiovascular disease (CVD) is the main cause of death in CKD patients. To study the connection between CKD and CVD, we investi- gated the effects of an electrolyte variation on cardiac signals (action potential and ECG) using a computational model. In a first step, simulations with the Himeno et al. ventricular cell model were performed on cellular level with different extra- cellular sodium ([Na+]o), calcium ([Ca2+]o) and potassium ([K+]o) concentrations as occurs in CKD patients. [Ca2+]o and [K+]o changes caused variations in different features describ- ing the morphology of the AP. Changes due to a [Na+]o varia- tion were not as prominent. Simulations with [Ca2+]o varia- tions were also carried out on ventricular ECG level and a 12-lead ECG was computed. Thus, a multiscale simulator from ion channel to ECG reproducing the calcium-dependent inactivation of ICaL was achieved. The results on cellular and ventricular level agree with results from literature. Moreover, we suggest novel features representing electrolyte changes that have not been described in literature. These results could be helpful for further studies aiming at the estimation of ionic concentrations based on ECG recordings.

Abstract:

Multi-scale computational modeling of cardiac electrophysiology has fostered our understanding of the genesis of the ECG. While current models capture the relevant processes under physiological and many disease conditions with high fidelity, proper representation of the conditions in the extracellular milieu remains challenging. The recent human ventricular myocyte model by Himeno et al. is one of the first biophysical models which faithfully represents the dependence of the action potential (AP) duration on the extracellular calcium concentration ([Ca2+]o). Here, we present a heterogeneous formulation of the Himeno et al. cellular model and integrate it into a multi-scale framework to compute body surface ECGs. We propose three variants of the Himeno et al. model to account for transmural heterogeneity. The ionic current level parameter sets representing subendocardial, M, and subepicardial cell types were informed by the experimental data presented with the O’Hara-Rudy model and tuned to match AP level features such as repolarization stability. As shown in a previous work by Keller et al., an apico-basal gradient of IKs conductance is a likely mechanism causing concordant T-waves. Therefore, we increased the IKs conductance in the Himeno et al. model at the apex by a factor of 3.5 compared to the base to obtain an APD shortening of 12.5%. The model setup comprising transmural and apico-basal heterogeneity yielded a physiological ventricular ECG comparable to previous setups building on the ten Tusscher et al. cellular model. Our novel setup allows to study, for the first time, how realistic changes of the AP under hypo- and hypercalcaemic conditions translate to changes in the ECG. Resulting QT prolongation under hypocalcaemic conditions quantitatively matched human experimental data. In conclusion, the setup presented here provides a tool to study the effect of altered calcium levels in the extracellular milieu of the heart, as e. g. occurring during renal failure, across multiple spatial scales mechanistically.

Abstract:

The Purkinje system is part of the fast-conducting ventricular excitation system. The anatomy of the Purkinje system varies from person to person and imposes a unique excitation pattern on the ventricular myocardium, which defines the morphology of the QRS complex of the ECG to a large degree. While it cannot be imaged in-vivo, it plays an important role for personalizing computer simulations of cardiac electrophysiology. Here, we present a new method to automatically model and customize the Purkinje system based on the measured electrocardiogram (ECG) of a patient. A graphbased algorithm was developed to generate Purkinje systems based on the parameters fibre density, minimal distance from the atrium, conduction velocity, and position and timing of excitation sources mimicking the bundle branches. Based on the resulting stimulation profile, the activation times of the ventricles were calculated using the fast marching approach. Predescribed action potentials and a finite element lead field matrix were employed to obtain surface ECG signals. The root mean square error (RMSE) between the simulated and measured QRS complexes of the ECGs was used as cost function to perform optimization of the Purkinje parameters. One complete evaluation from Purkinje tree generation to the simulated ECG could be computed in about 10 seconds on a standard desktop computer. The measured ECG of the patient used to build the anatomical model was matched via parallel simplex optimization with a remaining RMSE of 4.05 mV in about 16 hours. The approach presented here allows to tailor the structure of the Purkinje system through the measured ECG in a patient-specific way. The computationally efficient implementation facilitates global optimization.

Abstract:

This study examines the effect of mental workload on the electrocardiogram (ECG) of participants driving the Lane Change Task (LCT). Different levels of mental workload were induced by a secondary task (n-back task) with three levels of difficulty. Subjective data showed a significant increase of the experienced workload over all three levels. An exploratory approach was chosen to extract a large number of rhythmical and morphological features from the ECG signal thereby identifying those which differentiated best between the levels of mental workload. No single rhythmical or morphological feature was able to differentiate between all three levels. A group of parameters were extracted which were at least able to discriminate between two levels. For future research, a combination of features is recommended to achieve best diagnosticity for different levels of mental workload.

Abstract:

Heart rate variability (HRV) plays an important role in medicine and psychology because it is used to quantify imbalances of the autonomic nervous system (ANS). An important manifestations of the ANS on HRV is also directly related to respiration and it is called respiratory sinus arrhythmia (RSA). This is a controlled phenomenon that leads to a synchronized coupling between respiration and instantaneous heart rate. Thus, the portion of HRV that is not related to respiration, and could potentially contain undiscovered diagnostic value, is overlapped and remains hidden in a standard HRV analysis. In such cases, a decoupling procedure would deliver a discriminated HRV analysis and possible new insights about the regulation of the cardiovascular system. In this work, we propose an algorithm based on Granger's causality to measure coupling between respiration and HRV. In the case of significant coupling, we estimate and cancel the respiration driven HRV component using a linear filtering approach. We tested the method using synthetic signals and prove it to deliver a reliable coupling measurement in 96.3% of the cases and reconstruct respiration free signals with a median correlation coefficient of 0.992. Afterwards, we applied our method to signals recorded during paced respiration and during natural breathing. We demonstrated that coupling is dependent on respiratory frequency and that it maximizes at 0.3 Hz. Furthermore, the HRV parameters measured during paced respiration tend to level among subjects after decoupling. The intersubject variability of HRV parameter is also decreased after the separation process. During natural breathing, coupling is notoriously lower to non-existing and decoupling has little impact on HRV. We conclude that the method proposed here can be used to investigate the diagnostic value of respiration independent HRV parameters.

Abstract:

The most important ECG marker for the diagnosis of ischemia or infarction is a change in the ST segment. Baseline wander is a typical artifact that corrupts the recorded ECG and can hinder the correct diagnosis of such diseases. For the purpose of finding the best suited filter for the removal of baseline wander, the ground truth about the ST change prior to the corrupting artifact and the subsequent filtering process is needed. In order to create the desired reference, we used a large simulation study that allowed us to represent the ischemic heart at a multiscale level from the cardiac myocyte to the surface ECG. We also created a realistic model of baseline wander to evaluate five filtering techniques commonly used in literature. In the simulation study, we included a total of 5.5 million signals coming from 765 electrophysiological setups. We found that the best performing method was the wavelet-based baseline cancellation. However, for medical applications, the Butterworth high-pass filter is the better choice because it is computationally cheap and almost as accurate. Even though all methods modify the ST segment up to some extent, they were all proved to be better than leaving baseline wander unfiltered.

Abstract:

Radiofrequency ablation has become a first-line approach for curative therapy of many cardiac arrhythmias. Various existing catheter designs provide high spatial resolution to identify the best spot for performing ablation and to assess lesion formation. However, creation of transmural and nonconducting ablation lesions requires usage of catheters with larger electrodes and improved thermal conductivity, leading to reduced spatial sensitivity. As trade-off, an ablation catheter with integrated mini electrodes was introduced. The additional diagnostic benefit of this catheter is still not clear. In order to solve this issue, we implemented a computational setup with different ablation scenarios. Our in silico results show that peak-to-peak amplitudes of unipolar electrograms from mini electrodes are more suitable to differentiate ablated and nonablated tissue compared to electrograms from the distal ablation electrode. However, in orthogonal mapping position, no significant difference was observed between distal electrode and mini electrodes electrograms in the ablation scenarios. In conclusion, catheters with mini electrodes bring about additional benefit to distinguish ablated tissue from nonablated tissue in parallel position with high spatial resolution. It is feasible to detect conduction gaps in linear lesions with this catheter by evaluating electrogram data from mini electrodes.

Abstract:

In den Lebenswissenschaften ist die Individualisierte Medizin aktuell ein zentrales Thema, vielleicht ein Hype. Das bestätigen auch synonyme, erweiternde und klärende Begriffe wie Personalisierte Medizin, Customized Medicine, Stratifizierende Medizin oder Präzisionsmedizin. In einer State of the Union Address an die Bevölkerung der Vereinigten Staaten von Amerika hat Präsident Barack Obama 2015 die Bedeutung der Präzisionsmedizin hervorgehoben [1]. Diese Initiative wurde inhaltlich wesentlich vom Direktor des National Institute of Health, dem Genetiker Francis Collins, vorangetrieben [2]. Individualisierte Medizin, das ist eine gute Botschaft, betont sie doch die Wertigkeit des einzelnen Patienten. Für klinisch tätige Ärzte ist das bereits eine Selbstverständlichkeit. Die Bedeutung eines Wortes, und das sei mit einem Lächeln hinzugefügt, zeigt sich nach Wittgenstein im Gebrauch der Sprache [3].Die Nationale Akademie der Wissenschaften Leopoldina, die acatech Deutsche Akademie der Technikwissenschaften und die Union der Deutschen Akademien der Wissenschaften haben im Dezember 2014 eine Stellungnahme über Voraussetzungen und Konsequenzen der Individualisierten Medizin publiziert. Darin wird der Fokus, wie im Vorwort ausgeführt, auf molekulare, genetische und pharmakologische Aspekte der Onkologie gelegt, einen Bereich, in dem die Individualisierung am weitesten fortgeschritten ist. Diese Beschränkung bedeutet, dass andere eng assoziierte Themen, wie die Patienten- und Versorgungsperspektiven, der Bereich der Medizintechnik oder neue Erkrankungen, beispielsweise in der Psychiatrie, in dieser Studie nicht beleuchtet werden. Die Behandlung dieser Gebiete bedarf einer separaten nachfolgenden Betrachtung. [4].Vor einer Betrachtung wesentlicher Beiträge allein der Bildgebung in der Individualisierten Medizin seien wenige vorausschickende Bemerkungen zu zwei Grenz-Fragen der Wissenschaft gemacht. Was steht für und gegen Stellungnahmen der genannten Akademien? Erfüllt die Beschäftigung mit der Bildgebung Kriterien der Wissenschaft?Eine der Aufgaben der Akademien ist es, Ordnung in die vorhandenen Aussagen und auch damit vorhandene Daten zu bringen, die in unterschiedlichen Disziplinen hervorgebracht werden, um daraus ein Gesamtbild zu formen. Weiterhin sollen Empfehlungen gegeben werden, wie die Entwicklungen günstig zu beeinflussen sind [5]. Wichtige Grenzen der wissenschaftlichen Politik- bzw. Gesellschaftsberatung bilden etwa Katastrophenwarnungen und Heilsverheißungen, andererseits nicht-altruistische, sondern dem Eigeninteresse dienende, wie auch politisierende Verlautbarungen. Das setzt eine Selbstbegrenzung voraus.Wünschenswert ist bei wissenschaftlichem Handeln der Respekt von und vor Grenzen, ist die Distanz zur Macht. Diese Macht kann der Politik, der Ökonomie und auch den Medien zugeschrieben werden; fatal sind Nähe oder gar Einfluss von Ideologien. Dabei wird nicht nur ein behutsamer Umgang mit Empfehlungen angesprochen; im wissenschaftlichen Handeln sind gerade beim Gegenstand der Bildgebung Berührungen mit der und sogar Überlappungen mit Interessen der Industrie möglich, teilweise gewünscht und fruchtbar. Letztlich ist es ja immer die Industrialisierung, die medizinischen Fortschritt, sei er pharmakologisch oder technologisch abbildbar, breiten Bevölkerungsgruppen und entlegenen Standorten zugänglich macht. Das bedarf immer einer gegenseitigen kritischen Begleitung.Die Wissenschaft dient dem Erkenntnisgewinn. Dazu gehört eine methodische Suche nach Wahrheit, die alle Befähigten überprüfen und nachvollziehen können. Wenn dieses angenommen, akzeptiert werden kann, dann sind die Technikwissenschaften Wissenschaften, dann betreiben Radiologie und Nuklearmedizin Wissenschaft (science). Dann bedarf es nicht der Aufzählung von Nobelpreisen oder ähnlichen Anerkennungen in der Scientific Community. Dann bedarf es nicht der Aufzählung fachlicher Beispiele; die Methoden und die Technologien fallen nicht vom Himmel. Wissenschaft wird von Menschen betrieben und getragen. An Pioniere der Bildgebung, an Personen, wie Wilhelm Conrad Röntgen, Marie Curie, Godfrey Hounsfield, Peter Mansfield, Paul Lauterbur oder Stephan Hell sei erinnert.* Dieses Editorial wird zeitgleich in Nuklearmedizin publiziert. Schober O, Dössel O, Ermert H et al. Bildgebung in Klinik und Forschung: Beitrag zur Individualisierten Medizin? Nuklearmedizin 2017; 56: 157-161; https://doi.org/10.3413/2017-05-0002.

Abstract:

Electrocardiographic imaging (ECGI) has recently gained attention as a viable diagnostic tool for reconstructing cardiac electrical activity in normal hearts as well as in cardiac arrhythmias. However, progress has been limited by the lack of both standards and unbiased comparisons of approaches and techniques across the community, as well as the consequent difficulty of effective collaboration across research groups.. To address these limitations, we created the Consortium for Electrocardiographic Imaging (CEI), with the objective of facilitating collaboration across the research community in ECGI and creating standards for comparisons and reproducibility. Here we introduce CEI and describe its two main efforts, the creation of EDGAR, a public data repository, and the organization of three collaborative workgroups that address key components and applications in ECGI. Both EDGAR and the workgroups will facilitate the sharing of ideas, data and methods across the ECGI community and thus address the current lack of reproducibility, broad collaboration, and unbiased comparisons.

Abstract:

Robust and exact automatic P wave detection and delineation in the electrocardiogram (ECG) is still an interesting but challenging research topic. The early prognosis of cardiac afflictions such as atrial fibrillation and the response of a patient to a given treatment is believed to improve if the P wave is carefully analyzed during sinus rhythm. Manual annotation of the signals is a tedious and subjective task. Its correctness depends on the experience of the annotator, quality of the signal, and ECG lead. In this work, we present a wavelet-based algorithm to detect and delineate P waves in individual ECG leads. We evaluated a large group of commonly used wavelets and frequency bands (wavelet levels) and introduced a special phase free wavelet transformation. The local extrema of the transformed signals are directly related to the delineating points of the P wave. First, the algorithm was studied using synthetic signals. Then, the optimal parameter configuration was found using intracardiac electrograms and surface ECGs measured simultaneously. The reverse biorthogonal wavelet 3.3 was found to be optimal for this application. In the end, the method was validated using the QT database from PhysioNet. We showed that the algorithm works more accurately and more robustly than other methods presented in literature. The validation study delivered an average delineation error of the P wave onset of -0.32+/-12.41 ms when compared to manual annotations. In conclusion, the algorithm is suitable for handling varying P wave shapes and low signal-to-noise ratios.

Abstract:

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.

Abstract:

Computational models of cardiac electrophysiology provided insights into arrhythmogenesis and paved the way toward tailored therapies in the last years. To fully leverage in silico models in future research, these models need to be adapted to reflect pathologies, genetic alterations, or pharmacological effects, however. A common approach is to leave the structure of established models unaltered and estimate the values of a set of parameters. Today's high-throughput patch clamp data acquisition methods require robust, unsupervised algorithms that estimate parameters both accurately and reliably. In this work, two classes of optimization approaches are evaluated: gradient-based trust-region-reflective and derivative-free particle swarm algorithms. Using synthetic input data and different ion current formulations from the Courtemanche et al. electrophysiological model of human atrial myocytes, we show that neither of the two schemes alone succeeds to meet all requirements. Sequential combination of the two algorithms did improve the performance to some extent but not satisfactorily. Thus, we propose a novel hybrid approach coupling the two algorithms in each iteration. This hybrid approach yielded very accurate estimates with minimal dependency on the initial guess using synthetic input data for which a ground truth parameter set exists. When applied to measured data, the hybrid approach yielded the best fit, again with minimal variation. Using the proposed algorithm, a single run is sufficient to estimate the parameters. The degree of superiority over the other investigated algorithms in terms of accuracy and robustness depended on the type of current. In contrast to the non-hybrid approaches, the proposed method proved to be optimal for data of arbitrary signal to noise ratio. The hybrid algorithm proposed in this work provides an important tool to integrate experimental data into computational models both accurately and robustly allowing to assess the often non-intuitive consequences of ion channel-level changes on higher levels of integration.

Abstract:

BACKGROUND AND OBJECTIVE: Progress in biomedical engineering has improved the hardware available for diagnosis and treatment of cardiac arrhythmias. But although huge amounts of intracardiac electrograms (EGMs) can be acquired during electrophysiological examinations, there is still a lack of software aiding diagnosis. The development of novel algorithms for the automated analysis of EGMs has proven difficult, due to the highly interdisciplinary nature of this task and hampered data access in clinical systems. Thus we developed a software platform, which allows rapid implementation of new algorithms, verification of their functionality and suitable visualization for discussion in the clinical environment. METHODS: A software for visualization was developed in Qt5 and C++ utilizing the class library of VTK. The algorithms for signal analysis were implemented in MATLAB. Clinical data for analysis was exported from electroanatomical mapping systems. RESULTS: The visualization software KaPAVIE (Karlsruhe Platform for Analysis and Visualization of Intracardiac Electrograms) was implemented and tested on several clinical datasets. Both common and novel algorithms were implemented which address important clinical questions in diagnosis of different arrhythmias. It proved useful in discussions with clinicians due to its interactive and user-friendly design. Time after export from the clinical mapping system to visualization is below 5min. CONCLUSION: KaPAVIE(2) is a powerful platform for the development of novel algorithms in the clinical environment. Simultaneous and interactive visualization of measured EGM data and the results of analysis will aid diagnosis and help understanding the underlying mechanisms of complex arrhythmias like atrial fibrillation.

Abstract:

Whole-chamber mapping using a 64-pole basket catheter (BC) has become a featured approach for the analysis of excitation patterns during atrial fibrillation. A flexible catheter design avoids perforation but may lead to spline bunching and influence coverage. We aim to quantify the catheter deformation and endocardial coverage in clinical situations and study the effect of catheter size and electrode arrangement using an in silico basket model. Atrial coverage and spline separation were evaluated quantitatively in an ensemble of clinical measurements. A computational model of the BC was implemented including an algorithm to adapt its shape to the atrial anatomy. Two clinically relevant mapping positions in each atrium were assessed in both clinical and simulated data. The simulation environment allowed varying both BC size and electrode arrangement. Results showed that interspline distances of more than 20&#8201;mm are common, leading to a coverage of less than 50% of the left atrial (LA) surface. In an ideal in silico scenario with variable catheter designs, a maximum coverage of 65% could be reached. As spline bunching and insufficient coverage can hardly be avoided, this has to be taken into account for interpretation of excitation patterns and development of new panoramic mapping techniques.

Abstract:

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.

Abstract:

One promising application of electrocardiographic (ECG) imaging is noninvasive reconstruction of atrial activities. However, despite numerous clinical studies, which are mostly concerned with complex irregular excitation patterns, there are relatively few in silico investigations on the imaging of ectopic activation. In the present work, we explore the localization accuracy of ECG imaging regarding atrial focal sites. For the forward calculations, we used four realistic geometrical models with complex anatomical structure and a rule-based fiber orientation embedded into the atrial model. Excitation propagation was simulated with the monodomain model. For each geometrical model, 20 activation sequences originating from the posterior wall of the left atrium were simulated. Based on the bidomain theory, the body surface potential maps resulting from these focal events were computed. For the inverse reconstructions, we employed a full-search procedure based on the fastest route algorithm assuming uniform excitation propagation. Localization errors were revealed to be dependent on the model-specific atrial geometry. We also performed similarity analysis for the first halves of the P wave duration, which improved the results in three models.

Abstract:

INTRODUCTION: The "Experimental Data and Geometric Analysis Repository", or EDGAR is an Internet-based archive of curated data that are freely distributed to the international research community for the application and validation of electrocardiographic imaging (ECGI) techniques. The EDGAR project is a collaborative effort by the Consortium for ECG Imaging (CEI, ecg-imaging.org), and focused on two specific aims. One aim is to host an online repository that provides access to a wide spectrum of data, and the second aim is to provide a standard information format for the exchange of these diverse datasets. METHODS: The EDGAR system is composed of two interrelated components: 1) a metadata model, which includes a set of descriptive parameters and information, time signals from both the cardiac source and body-surface, and extensive geometric information, including images, geometric models, and measure locations used during the data acquisition/generation; and 2) a web interface. This web interface provides efficient, search, browsing, and retrieval of data from the repository. RESULTS: An aggregation of experimental, clinical and simulation data from various centers is being made available through the EDGAR project including experimental data from animal studies provided by the University of Utah (USA), clinical data from multiple human subjects provided by the Charles University Hospital (Czech Republic), and computer simulation data provided by the Karlsruhe Institute of Technology (Germany). CONCLUSIONS: It is our hope that EDGAR will serve as a communal forum for sharing and distribution of cardiac electrophysiology data and geometric models for use in ECGI research.

Abstract:

Background: Intracardiac electrograms are an indispensable part during diagnosis of supraventriculararrhythmias, but atrial activity (AA) can be obscured by ventricular far-fields (VFF). Concepts based onstatistical independence like principal component analysis (PCA) cannot be applied for VFF removalduring atrial tachycardia with stable conduction.Methods: A database of realistic electrograms containing AAand VFF was generated. Both PCA and thenew technique periodic component analysis (&#960;CA) were implemented, benchmarked, and applied toclinical data.Results: The concept of &#960;CA was successfully verified to retain compromised AA morphology,showing high correlation (cc = 0.98 ± 0.01) for stable atrial cycle length (ACL). Performance ofPCA failed during temporal coupling (cc = 0.03 ± 0.08) but improved for increasing conductionvariability (cc = 0.77 ± 0.14). Stability of ACL was identified as a critical parameter for &#960;CAapplication. Analysis of clinical data confirmed these findings.Conclusion: &#960;CA is introduced as a powerful new technique for artifact removal in periodic signals.Its concept and performance were benchmarked against PCA using simulated data and demonstratedon measured electrograms.

Abstract:

PURPOSE: To evaluate two commonly used respiratory motion correction techniques for coronary magnetic resonance angiography (MRA) regarding their dependency on motion estimation accuracy and final image quality and to compare both methods to the respiratory gating approach used in clinical practice. MATERIALS AND METHODS: Ten healthy volunteers were scanned using a non-Cartesian radial phase encoding acquisition. Respiratory motion was corrected for coronary MRA according to two motion correction techniques, image-based (IMC) and reconstruction-based (RMC) respiratory motion correction. Both motion correction approaches were compared quantitatively and qualitatively against a reference standard navigator-based respiratory gating (RG) approach. Quantitative comparisons were performed regarding visible vessel length, vessel sharpness, and total acquisition time. Two experts carried out a visual scoring of image quality. Additionally, numerical simulations were performed to evaluate the effect of motion estimation inaccuracy on RMC and IMC. RESULTS: RMC led to significantly better image quality than IMC (P's paired Student's t-test were smaller than 0.001 for vessel sharpness and visual scoring). RMC did not show a statistically significant difference compared to reference standard RG (vessel length [99% confidence interval]: 86.913 [83.097-95.015], P = 0.107; vessel sharpness: 0.640 [0.605-0.802], P = 0.012; visual scoring: 2.583 [2.410-3.424], P = 0.018) in terms of vessel visualization and image quality while reducing scan times by 56%. Simulations showed higher dependencies for RMC than for IMC on motion estimation inaccuracies. CONCLUSION: RMC provides a similar image quality as the clinically used RG approach but almost halves the scan time and is independent of subjects' breathing patterns. Clinical validation of RMC is now desirable. J. Magn. Reson. Imaging 2015.

Abstract:

Over the last decades, the information content derived from cardiac electric and magnetic field measurements has been debated. Our co-workers Wilhelms et al. inves- tigated electrically silent acute ischemia in human ven- tricles caused by occlusion of a coronary artery. In the present work, we extend the previous study by calculating associated magnetic fields produced by early stage acute ischemia with varying transmural extent. Multiscale com- putational simulations were performed for calculations of body surface potential maps (BSPM) and magnetocardio- grams (MCG) on a magnetometer sensor matrix situated above the anterior chest wall. Depending on the ischemia size, the ST-segments of the simulated electrocardiograms (ECG) experienced depression for subendocardial cases and elevation for transmural ischemia. One intermedi- ate extent resulted in a zero ST-segment which makes it diagnostically indistinguishable from the healthy case. Magnetic field calculations for this electrically silent is- chemia also revealed no difference compared to the control case. Otherwise, both ECG and MCG signals during ST- segments showed either depression or elevation from zero line. In this simulation study, MCG did not deliver addi- tional information to uncover electrically silent ischemia. For a general conclusion, further in-silico investigations with different ischemia shapes, sizes and positions should be performed and clinical studies with recordings of both ECG and MCG signals have to be conducted.

Abstract:

Catheter ablation has emerged as an effective treatment strategy for atrial fibrillation (AF) in recent years. During AF, complex fractionated atrial electrograms (CFAE) can be recorded and are known to be a potential target for ablation. Automatic algorithms have been developed to simplify CFAE detection, but they are often based on a single descriptor or a set of descriptors in combination with sharp decision classifiers. However, these methods do not reflect the progressive transition between CFAE classes. The aim of this study was to develop an automatic classification algorithm, which combines the information of a complete set of descriptors and allows for progressive and transparent decisions. We designed a method to automatically analyze CFAE based on a set of descriptors representing various aspects, such as shape, amplitude and temporal characteristics. A fuzzy decision tree (FDT) was trained and evaluated on 429 predefined electrograms. CFAE were classified into four subgroups with a correct rate of 81+/-3%. Electrograms with continuous activity were detected with a correct rate of 100%. In addition, a percentage of certainty is given for each electrogram to enable a comprehensive and transparent decision. The proposed FDT is able to classify CFAE with respect to their progressive transition and may allow objective and reproducible CFAE interpretation for clinical use.

Abstract:

The fiber orientation in the atria has a significant contribution to the electrophysiologic behavior of the heart and to the genesis of arrhythmia. Atrial fiber orientation has a direct effect on excitation propagation, activation patterns and the P-wave. We present a rule-based algorithm that works robustly on different volumetric meshes composed of either isotropic hexahedra or arbitrary tetrahedra as well as on 3-dimensional triangular surface meshes in patient-specific geometric models. This method fosters the understanding of general pro-arrhythmic mechanisms and enhances patient-specific modeling approaches.

Abstract:

AIMS: The clinical efficacy in preventing the recurrence of atrial fibrillation (AF) is higher for amiodarone than for dronedarone. Moreover, pharmacotherapy with these drugs is less successful in patients with remodelled substrate induced by chronic AF (cAF) and patients suffering from familial AF. To date, the reasons for these phenomena are only incompletely understood. We analyse the effects of the drugs in a computational model of atrial electrophysiology. METHODS AND RESULTS: The Courtemanche-Ramirez-Nattel model was adapted to represent cAF remodelled tissue and hERG mutations N588K and L532P. The pharmacodynamics of amiodarone and dronedarone were investigated with respect to their dose and heart rate dependence by evaluating 10 descriptors of action potential morphology and conduction properties. An arrhythmia score was computed based on a subset of these biomarkers and analysed regarding circadian variation of drug concentration and heart rate. Action potential alternans at high frequencies was observed over the whole dronedarone concentration range at high frequencies, while amiodarone caused alternans only in a narrow range. The total score of dronedarone reached critical values in most of the investigated dynamic scenarios, while amiodarone caused only minor score oscillations. Compared with the other substrates, cAF showed significantly different characteristics resulting in a lower amiodarone but higher dronedarone concentration yielding the lowest score. CONCLUSION: Significant differences exist in the frequency and concentration-dependent effects between amiodarone and dronedarone and between different atrial substrates. Our results provide possible explanations for the superior efficacy of amiodarone and may aid in the design of substrate-specific pharmacotherapy for AF.

Abstract:

During the contraction of the ventricles, the ventricles interact with the atria as well as with the pericardium and the surrounding tissue in which the heart is embedded. The atria are stretched, and the atrioventricular plane moves toward the apex. The atrioventricular plane displacement (AVPD) is considered to be a major contributor to the ventricular function, and a reduced AVPD is strongly related to heart failure. At the same time, the epicardium slides almost frictionlessly on the pericardium with permanent contact. Although the interaction between the ventricles, the atria and the pericardium plays an important role for the deformation of the heart, this aspect is usually not considered in computational models. In this work, we present an electromechanical model of the heart, which takes into account the interaction between ventricles, pericardium and atria and allows to reproduce the AVPD. To solve the contact problem of epicardium and pericardium, a contact handling algorithm based on penalty formulation was developed, which ensures frictionless and permanent contact. Two simulations of the ventricular contraction were conducted, one with contact handling of pericardium and heart and one without. In the simulation with contact handling, the atria were stretched during the contraction of the ventricles, while, due to the permanent contact with the pericardium, their volume increased. In contrast to that, in the simulations without pericardium, the atria were also stretched, but the change in the atrial volume was much smaller. Furthermore, the pericardium reduced the radial contraction of the ventricles and at the same time increased the AVPD.

Abstract:

Tracking the location of medical devices in interventional X-ray data solves different problems. For example the motion information of the devices is used to determine cardiac or respiratory motion during X-ray guided procedures or device features are used as landmarks to register images. In this publication an approach using a 3D deformable catheter model is presented and used to track a coronary sinus (CS) catheter in 3D plus time through a complete rotational angiography sequence. The benefits of using voxel based models with attenuation information for 2D/3D registration are investigated in comparison to binary catheter models. The 2D/3D registration of the model allows to extract a 3D catheter shape from every individual 2D projection. The tracking accuracy is evaluated on simulated and clinical rotational angiography data of the contrast enhanced left atrium. The quantitative evaluation of the experiments delivers an average registration accuracy for all catheter electrodes of 0.23 mm in 2D and 0.95 mm in 3D when using an attenuation model of the catheter. The overall tracking accuracy is lower when using binary catheter models.

Abstract:

Cardiac ablation procedures during electrophysiology interventions are performed under x-ray guidance with a C-arm imaging system. Some procedures require catheter navigation in complex anatomies like the left atrium. Navigation aids like 3D road maps and external tracking systems may be used to facilitate catheter navigation. As an alternative to external tracking a fully automatic method is presented here that enables the calculation of the 3D location of the ablation catheter from individual 2D x-ray projections. The method registers a high resolution, deformable 3D attenuation model of the catheter to a 2D x-ray projection. The 3D localization is based on the divergent beam projection of the catheter. On an individual projection, the catheter tip is detected in 2D by image filtering and a template matching method. The deformable 3D catheter model is adapted using the projection geometry provided by the C-arm system and 2D similarity measures for an accurate 2D/3D registration. Prior to the tracking and registration procedure, the deformable 3D attenuation model is automatically extracted from a separate 3D cone beam CT reconstruction of the device. The method can hence be applied to various cardiac ablation catheters. In a simulation study of a virtual ablation procedure with realistic background, noise, scatter and motion blur an average 3D registration accuracy of 3.8 mm is reached for the catheter tip. In this study four different types of ablation catheters were used. Experiments using measured C-arm fluoroscopy projections of a catheter in a RSD phantom deliver an average 3D accuracy of 4.5 mm.

Abstract:

Cardiac C-arm CT imaging delivers a tomographic region-of-interest reconstruction of the patient's heart during image guided catheter interventions. Due to the limited size of the flat detector a volume image is reconstructed, which is truncated in the cone-beam (along the patient axis) and the fan-beam (in the transaxial plane) direction. To practically address this local tomography problem correction methods, like projection extension, are available for first pass image reconstruction. For second pass correction methods, like metal artefact reduction, alternative correction schemes are required when the field of view is limited to a region-of-interest of the patient. In classical CT imaging metal artefacts are corrected by metal identification in a first volume reconstruction and generation of a corrected projection data set followed by a second reconstruction. This approach fails when the metal structures are located outside the reconstruction field of view. When a C-arm CT is performed during a cardiac intervention pacing leads and other cables are frequently positioned on the patients skin, which results in propagating streak artefacts in the reconstruction volume. A first pass approach to reduce this type of artefact is introduced and evaluated here. It makes use of the fact that the projected position of objects outside the reconstruction volume changes with the projection perspective. It is shown that projection based identification, tracking and removal of high contrast structures like cables, only detected in a subset of the projections, delivers a more consistent reconstruction volume with reduced artefact level. The method is quantitatively evaluated based on 50 simulations using cardiac CT data sets with variable cable positioning. These data sets are forward projected using a C-arm CT system geometry and generate artefacts comparable to those observed in clinical cardiac C-arm CT acquisitions. A C-arm CT simulation of every cardiac CT data set without cables served as a ground truth. The 3D root mean square deviation between the simulated data set with and without cables could be reduced for 96% of the simulated cases by an average of 37% (min -9%, max 73%) when using the first pass correction method. In addition, image quality improvement is demonstrated for clinical whole heart C-arm CT data sets when the cable removal algorithm was applied.

Abstract:

Radiofrequency ablation (RFA) therapy is the gold standard in interventional treatment of many cardiac arrhythmias. A major obstacle are non transmural lesions, leading to recurrence of arrhythmias. Recent clinical studies have suggested intracardiac electrogram (EGM) criteria as a promising marker to evaluate lesion development. Seeking for a deeper understanding of underlying mechanisms, we established a simulation approach for acute RFA lesions. Ablation lesions were modeled by a passive necrotic core surrounded by a borderzone with properties of heated myocardium. Herein, conduction velocity and electrophysiological properties were altered. We simulated EGMs during RFA to study the relation between lesion formation and EGM changes using the bidomain model. Simulations were performed on a three dimensional setup including a geometrically detailed representation of the catheter with highly conductive electrodes. For validation, EGMs recorded during RFA procedures in five patients were analyzed and compared to simulation results. Clinical data showed major changes in the distal unipolar EGM. During RFA, the negative peak amplitude decreased up to 104% and maximum negative deflection was up to 88% smaller at the end of the ablation sequence. These changes mainly occurred in the first 10 s after ablation onset. Simulated unipolar EGM reproduced the clinical changes, reaching up to 83% negative peak amplitude reduction and 80% decrease in maximum negative deflection for transmural lesions. In future work, the established model may enable the development of further EGM criteria for transmural lesions even for complex geometries in order to support clinical therapy.

Abstract:

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.

Abstract:

In case of chest pain, immediate diagnosis of myocardial ischemia is required to respond with an appropriate treatment. The diagnostic capability of the electrocardiogram (ECG), however, is strongly limited for ischemic events that do not lead to ST elevation. This computational study investigates the potential of different electrode setups in detecting early ischemia at 10 minutes after onset: standard 3-channel and 12-lead ECG as well as body surface potential maps (BSPMs). Further, it was assessed if an additional ECG electrode with optimized position or the right-sided Wilson leads can improve sensitivity of the standard 12-lead ECG. To this end, a simulation study was performed for 765 different locations and sizes of ischemia in the left ventricle. Improvements by adding a single, subject specifically optimized electrode were similar to those of the BSPM: 211% increased detection rate depending on the desired specificity. Adding right-sided Wilson leads had negligible effect. Absence of ST deviation could not be related to specific locations of the ischemic region or its transmurality. As alternative to the ST time integral as a feature of ST deviation, the K point deviation was introduced: the baseline deviation at the minimum of the ST-segment envelope signal, which increased 12-lead detection rate by 7% for a reasonable threshold.

Abstract:

AIMS: Human ether-a-go-go-related gene (hERG) missense mutations N588K and L532P are both associated with atrial fibrillation (AF). However, the underlying gain-of-function mechanism is different. The aim of this computational study is to assess and understand the arrhythmogenic mechanisms of these genetic disorders on the cellular and tissue level as a basis for the improvement of therapeutic strategies. METHODS AND RESULTS: The IKr formulation of an established model of human atrial myocytes was adapted by using the measurement data of wild-type and mutant hERG channels. Restitution curves of the action potential duration and its slope, effective refractory period (ERP), conduction velocity, reentry wavelength (WL), and the vulnerable window (VW) were determined in a one-dimensional (1D) tissue strand. Moreover, spiral wave inducibility and rotor lifetime in a 2D tissue patch were evaluated. The two mutations caused an increase in IKr regarding both peak amplitude and current integral, whereas the duration during which IKr is active was decreased. The WL was reduced due to a shorter ERP. Spiral waves could be initiated by using mutation models as opposed to the control case. The frequency dependency of the VW was reversed. CONCLUSION: Both mutations showed an increased arrhythmogenicity due to decreased refractory time in combination with a more linear repolarization phase. The effects were more pronounced for mutation L532P than for N588K. Furthermore, spiral waves presented higher stability and a more regular pattern for L532P. These in silico investigations unveiling differences of mutations affecting the same ion channel may help to advance genotype-guided AF prevention and therapy strategies.

Abstract:

BACKGROUND: Investigations on adverse biological effects of nanoparticles (NPs) in the lung by in vitro studies are usually performed under submerged conditions where NPs are suspended in cell culture media. However, the behaviour of nanoparticles such as agglomeration and sedimentation in such complex suspensions is difficult to control and hence the deposited cellular dose often remains unknown. Moreover, the cellular responses to NPs under submerged culture conditions might differ from those observed at physiological settings at the air-liquid interface. RESULTS: In order to avoid problems because of an altered behaviour of the nanoparticles in cell culture medium and to mimic a more realistic situation relevant for inhalation, human A549 lung epithelial cells were exposed to aerosols at the air-liquid interphase (ALI) by using the ALI deposition apparatus (ALIDA). The application of an electrostatic field allowed for particle deposition efficiencies that were higher by a factor of more than 20 compared to the unmodified VITROCELL deposition system. We studied two different amorphous silica nanoparticles (particles produced by flame synthesis and particles produced in suspension by the Stober method). Aerosols with well-defined particle sizes and concentrations were generated by using a commercial electrospray generator or an atomizer. Only the electrospray method allowed for the generation of an aerosol containing monodisperse NPs. However, the deposited mass and surface dose of the particles was too low to induce cellular responses. Therefore, we generated the aerosol with an atomizer which supplied agglomerates and thus allowed a particle deposition with a three orders of magnitude higher mass and of surface doses on lung cells that induced significant biological effects. The deposited dose was estimated and independently validated by measurements using either transmission electron microscopy or, in case of labelled NPs, by fluorescence analyses. Surprisingly, cells exposed at the ALI were less sensitive to silica NPs as evidenced by reduced cytotoxicity and inflammatory responses. CONCLUSION: Amorphous silica NPs induced qualitatively similar cellular responses under submerged conditions and at the ALI. However, submerged exposure to NPs triggers stronger effects at much lower cellular doses. Hence, more studies are warranted to decipher whether cells at the ALI are in general less vulnerable to NPs or specific NPs show different activities dependent on the exposure method.

Abstract:

The goal of ECG-imaging (ECGI) is to reconstruct heart electrical activity from body surface potential maps. The problem is ill-posed, which means that it is extremely sensitive to measurement and modeling errors. The most commonly used method to tackle this obstacle is Tikhonov regularization, which consists in converting the original problem into a well-posed one by adding a penalty term. The method, despite all its practical advantages, has however a serious drawback: The obtained solution is often over-smoothed, which can hinder precise clinical diagnosis and treatment planning. In this paper, we apply a binary optimization approach to the transmembrane voltage (TMV)-based problem. For this, we assume the TMV to take two possible values according to a heart abnormality under consideration. In this work, we investigate the localization of simulated ischemic areas and ectopic foci and one clinical infarction case. This affects only the choice of the binary values, while the core of the algorithms remains the same, making the approximation easily adjustable to the application needs. Two methods, a hybrid metaheuristic approach and the difference of convex functions (DC), algorithm were tested. For this purpose, we performed realistic heart simulations for a complex thorax model and applied the proposed techniques to the obtained ECG signals. Both methods enabled localization of the areas of interest, hence showing their potential for application in ECGI. For the metaheuristic algorithm, it was necessary to subdivide the heart into regions in order to obtain a stable solution unsusceptible to the errors, while the analytical DC scheme can be efficiently applied for higher dimensional problems. With the DC method, we also successfully reconstructed the activation pattern and origin of a simulated extrasystole. In addition, the DC algorithm enables iterative adjustment of binary values ensuring robust performance.

Abstract:

Electrocardiographic imaging (ECG imaging) is a method to depict electrophysiological processes in the heart. It is an emerging technology with the potential of making the therapy of cardiac arrhythmia less invasive, less expensive, and more precise. A major challenge for integrating the method into clinical workflow is the seamless and correct identification and localization of electrodes on the thorax and their assignment to recorded channels. This work proposes a camera-based system, which can localize all electrode positions at once and to an accuracy of approximately 1+/-1 mm. A system for automatic identification of individual electrodes is implemented that overcomes the need of manual annotation. For this purpose, a system of markers is suggested, which facilitates a precise localization to subpixel accuracy and robust identification using an error-correcting code. The accuracy of the presented system in identifying and localizing electrodes is validated in a phantom study. Its overall capability is demonstrated in a clinical scenario.

Abstract:

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.

Abstract:

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.

Abstract:

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.

Abstract:

Ventricular ectopic beats (VEBs) trigger a characteristic response of the heart called heart rate turbulence (HRT). The HRT can be used to predict sudden cardiac death in patients with a history of myocardial infarction. In this work, we present a reliable algorithm to detect and classify ectopic beats. Every electrocardiogram (ECG) is processed with innovative filtering techniques, artifact detection methods, and a robust multichannel analysis to produce accurate annotation results. For the classification task, a support vec- tor machine was used. Furthermore, a new approach to the analysis of HRT is proposed. The HRT is interpreted as the response of a second-order system to an external perturbation. The system theoretical parameters were estimated. The influence of VEB on the morphology of subsequent T waves was also analyzed. A strong influence was detected in the study with 14 patients experiencing frequent VEB. The evolution of the morphology of the T wave with every new beat was studied, and it could be concluded that an exponential shape underlies this dynamic process and was called morphological heart rate turbulence (MHRT). Parameters were defined to quantify the MHRT. The analysis of the MHRT could help to understand the influence of an ectopic beat on the repolarization processes of the heart and more accurately stratify the risk of sudden cardiac death.

Abstract:

Inhibition of the atrial ultra-rapid delayed rectifier potassium current (I Kur) represents a promising therapeutic strategy in the therapy of atrial fibrillation. However, experimental and clinical data on the antiarrhythmic efficacy remain controversial. We tested the hypothesis that antiarrhythmic effects of I Kur inhibitors are dependent on kinetic properties of channel blockade. A mathematical description of I Kur blockade was introduced into Courtemanche-Ramirez-Nattel models of normal and remodeled atrial electrophysiology. Effects of five model compounds with different kinetic properties were analyzed. Although a reduction of dominant frequencies could be observed in two dimensional tissue simulations for all compounds, a reduction of spiral wave activity could be only be detected in two cases. We found that an increase of the percent area of refractory tissue due to a prolongation of the wavelength seems to be particularly important. By automatic tracking of spiral tip movement we find that increased refractoriness resulted in rotor extinction caused by an increased spiral-tip meandering. We show that antiarrhythmic effects of I Kur inhibitors are dependent on kinetic properties of blockade. We find that an increase of the percent area of refractory tissue is the underlying mechanism for an increased spiral-tip meandering, resulting in the extinction of re-entrant circuits.

Abstract:

Mathematical modeling of cardiac electrophysiology is an insightful method to investigate the underlying mechanisms responsible for arrhythmias such as atrial fibrillation. In past years, five models of human atrial electrophysiology with different formulations of ionic currents, and consequently diverging properties, have been published. The aim of this work is to give an overview of strengths and weaknesses of these models depending on the purpose and the general requirements of simulations. Therefore, these models were systematically benchmarked with respect to general mathematical properties and their ability to reproduce certain electrophysiological phenomena, such as action potential alternans. To assess the models ability to replicate modified properties of human myocytes and tissue in cardiac disease, electrical remodeling in chronic atrial fibrillation was chosen as test case. The healthy and remodeled model variants were compared with experimental results in single-cell, 1D and 2D tissue simulations to investigate action potential and restitution properties, as well as the initiation of reentrant circuits.

Abstract:

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.

Abstract:

Tissue heating during magnetic resonance measurements is a potential hazard at high-field MRI, and particularly, in the framework of parallel radiofrequency transmission. The heating is directly related to the radiofrequency energy absorbed during an magnetic resonance examination, that is, the specific absorption rate (SAR). SAR is a pivotal parameter in MRI safety regulations, requiring reliable estimation methods. Currently used methods are usually based on models which are neither patient-specific nor taken into account patient position and posture, which typically leads to the need for large safety margins. In this work, a novel approach is presented, which measures local SAR in a patient-specific manner. Using a specific formulation of Maxwell's equations, the local SAR is estimated via postprocessing of the complex transmit sensitivity of the radiofrequency antenna involved. The approximations involved in the proposed method are investigated. The presented approach yields a sufficiently accurate and patient-specific local SAR measurement of the brain within a scan time of less than 5 min.

Abstract:

Introduction: Atrial fibrillation (AF) is the most common cardiac arrhythmia affecting around 1% of the population. Several anti-arrhythmic drugs such as e.g. amiodarone or dronedarone influence cardiac electrophysiology reducing arrhythmias. However, the electrophysiological mechanisms underlying the initiation and persistence of AF are not completely understood yet.Methods: A mathematical model of atrial electrophysiology was modified to simulate the effects of chronic AF (cAF). Furthermore, ion channel conductivities were reduced according to the inhibition caused by two different concentrations of amiodarone and dronedarone. The resulting drug effects were investigated in healthy and cAF single-cells as well as in tissue. In a 1D tissue strand, restitution curves of the effective refractory period (ERP), the conduction velocity (CV) and the wavelength (WL) were computed. Furthermore, persistence of rotors in a 2D tissue patch was analyzed. For this purpose, four rotors were initiated in the cAF patch and then the drug effects were incorporated.Results: Dronedarone and amiodarone prolonged the atrial action potential duration of cAF cells, whereas high concentration of amiodarone slightly shortened it in healthy cells. Furthermore, both drugs increased the ERP and slowed the CV. Dronedarone shows the longer ERP and also a higher CV. As a result, the WL was prolonged by dronedarone and shortened by high concentration of amiodarone. Low concentration of amiodarone did not change the WL. In the 2D tissue patch, dronedarone altered significantly the trajectory of rotors, but did not terminate them.Conclusion: Computer simulations of the effects of antiarrhythmic drugs on cardiac electrophysiology are a helpful tool to better understand the mechanisms responsible for persistence and termination of AF. However, ion current measurement data available in literature show great variability of values depending on the species or temperature. Therefore, integration of drug effects into models of cardiac electrophysiology still needs to be improved.

Abstract:

Aims Amiodarone and cisapride are both known to prolong the QT interval, yet the two drugs have different effects on arrhythmia. Cisapride can cause torsades de pointes while amiodarone is found to be anti-arrhythmic. A computational model was used to investigate the action of these two drugs.Methods and results In a biophysically detailed model, the ion current conductivities affected by both drugs were reduced in order to simulate the pharmacological effects in healthy and ischaemic cells. Furthermore, restitution curves of the action potential duration (APD), effective refractory period, conduction velocity, wavelength, and the vulnerable window were determined in a one-dimensional (1D) tissue strand. Moreover, cardiac excitation propagation was computed in a 3D model of healthy ventricles. The corresponding body surface potentials were calculated and standard 12-lead electrocardiograms were derived. Both cisapride and amiodarone caused a prolongation of the QT interval and the refractory period. However, cisapride did not significantly alter the conduction-related properties, such as e.g. the wavelength or vulnerable window, whereas amiodarone had a larger impact on them. It slightly flattened the APD restitution slope and furthermore reduced the conduction velocity and wavelength.Conclusion Both drugs show similar prolongation of the QT interval, although they present different electrophysiological properties in the single-cell as well as in tissue simulations of cardiac excitation propagation. These computer simulations help to better understand the underlying mechanisms responsible for the initiation or termination of arrhythmias caused by amiodarone and cisapride.

Abstract:

The specific absorption rate (SAR) is a limiting constraint in sequence design for high-field MRI. SAR estimation is typically performed by numerical simulations using generic human body models. This entails an intrinsic uncertainty in present SAR prediction. This study first investigates the required detail of human body models in terms of spatial resolution and the number of soft tissue classes required, based on finite-differences time-domain simulations of a 3 T body coil. The numerical results indicate that a resolution of 5 mm is sufficient for local SAR estimation. Moreover, a differentiation between fatty tissues, water-rich tissues, and the lungs was found to be essential to represent eddy current paths inside the human body. This study then proposes a novel approach for generating individualized body models from whole-body water-fat-separated MR data and applies it to volunteers. The SAR hotspots consistently occurred in the arms due to proximity to the body coil as well as in narrow regions of the muscles. An initial in vivo validation of the simulated fields in comparison with measured B(1) -field maps showed good qualitative and quantitative agreement. Magn Reson Med, 2011. (c) 2011 Wiley-Liss, Inc.

Abstract:

OBJECT: Parallel transmission facilitates a relatively direct control of the RF transmit field. This is usually applied to improve the RF field homogeneity but might also allow a reduction of the specific absorption rate (SAR) to increase freedom in sequence design for high-field MRI. However, predicting the local SAR is challenging as it depends not only on the multi-channel drive but also on the individual patient. MATERIALS AND METHODS: The potential of RF shimming for SAR management is investigated for a 3 T body coil with eight independent transmit elements, based on Finite-Difference Time-Domain (FDTD) simulations. To address the patient-dependency of the SAR, nine human body models were generated from volunteer MR data and used in the simulations. A novel approach to RF shimming that enforces local SAR constraints is proposed. RESULTS: RF shimming substantially reduced the local SAR, consistently for all volunteers. Using SAR constraints, a further SAR reduction could be achieved with only minor compromises in RF performance. CONCLUSION: Parallel transmission can become an important tool to control and manage the local SAR in the human body. The practical use of local SAR constraints is feasible with consistent results for a variety of body models.

Abstract:

The specific absorption rate (SAR) is an important safety criterion, limiting many MR protocols with respect to the achievable contrast and scan duration. Parallel transmission enables control of the radiofrequency field in space and time and hence allows for SAR management. However, a trade-off exists between radiofrequency pulse performance and SAR reduction. To overcome this problem, in this work, parallel transmit radiofrequency pulses are adapted to the position in sampling k-space. In the central k-space, highly homogeneous but SAR-intensive radiofrequency shim settings are used to achieve optimal performance and contrast. In the outer k-space, the homogeneity requirement is relaxed to reduce the average SAR of the scan. The approach was experimentally verified on phantoms and volunteers using field echo and spin echo sequences. A reduction of the SAR by 25-50% was achieved without compromising image quality.

Abstract:

Ventricular wall deformation is widely assumed to have an impact on the morphology of the T-wave that can be measured on the body surface. This study aims at quantifying these effects based on an in silico approach. To this end, we used a hybrid, static-dynamic approach: action potential propagation and repolarization were simulated on an electrophysiologically detailed but static 3-D heart model while the forward calculation accounted for ventricular deformation and the associated movement of the electrical sources (thus, it was dynamic). The displacement vectors that describe the ventricular motion were extracted from cinematographic and tagged MRI data using an elastic registration procedure. To probe to what extent the T-wave changes depend on the synchrony/asynchrony of mechanical relaxation and electrical repolarization, we created three electrophysiological configurations, each with a unique QT time: a setup with physiological QT time, a setup with pathologically short QT time (SQT), and pathologically long QT time (LQT), respectively. For all three electrophysiological configurations, a reduction of the T-wave amplitude was observed when the dynamic model was used for the forward calculations. The largest amplitude changes and the lowest correlation coefficients between the static and dynamic model were observed for the SQT setup, followed by the physiological QT and LQT setups.

Abstract:

BACKGROUND: The prevalence of atrial fibrillation is increased in patients with end-stage renal disease. Previous studies suggested that extracellular electrolyte alterations caused by hemodialysis (HD) therapy could be proarrhythmic. METHODS: Multiscale models were used for a consequent analysis of the effects of extracellular ion concentration changes on atrial electrophysiology. Simulations were based on measured electrolyte concentrations from patients with end-stage renal disease. RESULTS: Simulated conduction velocity and effective refractory period are decreased at the end of an HD session, with potassium having the strongest influence. P-wave is prolonged in patients undergoing HD therapy in the simulation as in measurements. CONCLUSIONS: Electrolyte concentration alterations impact atrial electrophysiology from the action potential level to the P-wave and can be proarrhythmic, especially because of induced hypokalemia. Analysis of blood electrolytes enables patient-specific electrophysiology modeling. We are providing a tool to investigate atrial arrhythmias associated with HD therapy, which, in the future, can be used to prevent such complications.

Abstract:

The electric properties of human tissue can potentially be used as an additional diagnostic parameter, e.g., in tumor diagnosis. In the framework of radiofrequency safety, the electric conductivity of tissue is needed to correctly estimate the local specific absorption rate distribution during MR measurements. In this study, a recently developed approach, called electric properties tomography (EPT) is adapted for and applied to in vivo imaging. It derives the patient's electric conductivity and permittivity from the spatial sensitivity distributions of the applied radiofrequency coils. In contrast to other methods to measure the patient's electric properties, EPT does not apply externally mounted electrodes, currents, or radiofrequency probes, which enhances the practicability of the approach. This work shows that conductivity distributions can be reconstructed from phase images and permittivity distributions can be reconstructed from magnitude images of the radiofrequency transmit field. Corresponding numerical simulations using finite-difference time-domain methods support the feasibility of this phase-based conductivity imaging and magnitude-based permittivity imaging. Using this approximation, three-dimensional in vivo conductivity and permittivity maps of the human brain are obtained in 5 and 13 min, respectively, which can be considered a step toward clinical feasibility for EPT. Magn Reson Med, 2011. (c) 2011 Wiley-Liss, Inc.

Abstract:

In this paper, we present an efficient method to estimate changes in forward-calculated body surface potential maps (BSPMs) caused by variations in tissue conductivities. For blood, skeletal muscle, lungs, and fat, the influence of conductivity variations was analyzed using the principal component analysis (PCA). For each single tissue, we obtained the first PCA eigenvector from seven sample simulations with conductivities between ±75% of the default value. We showed that this eigenvector was sufficient to estimate the signal over the whole conductivity range of ±75%. By aligning the origins of the different PCA coordinate systems and superimposing the single tissue effects, it was possible to estimate the BSPM for combined conductivity variations in all four tissues. Furthermore, the method can be used to easily calculate confidence intervals for the signal, i.e., the minimal and maximal possible amplitudes for given conductivity uncertainties. In addition to that, it was possible to determine the most probable conductivity values for a given BSPM signal. This was achieved by probing hundreds of different conductivity combinations with a numerical optimization scheme. In conclusion, our method allows to efficiently predict forward-calculated BSPMs over a wide range of conductivity values from few sample simulations.

Abstract:

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 8 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 7 of 8 pacing sequences. On average, local CV decreased by 2015% and global CV by 1713%. 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.

Abstract:

Acute cardiac ischemia, which is caused by the occlusion of a coronary artery, often leads to lethal ventricular arrhythmias or heart failure. The early diagnosis of this pathology is based on changes of the electrocardiogram (ECG), i.e. mainly shifts of the ST segment. However, the underlying mechanisms responsible for these shifts are not completely understood. Furthermore, clinical observations indicate that some acute ischemia cases can hardly be detected using standard 12-lead ECG only. Therefore, multi-scale computer simulations of cardiac ischemia using realistic models of human ventricles were carried out in this work. For this purpose, the transmembrane voltage distributions in the heart and the corresponding body surface potentials were computed with varying transmural extent of the ischemic region at different ischemia stages. Some of the simulated ischemia cases were electrically silent, i.e. they could hardly be identified in the 12-lead ECG.

Abstract:

Purpose: Three-dimensional (3-D) reconstruction of the coronary arteries during a cardiac catheter-based intervention can be performed from a C-arm based rotational x-ray angiography sequence. It can support the diagnosis of coronary artery disease, treatment planning, and intervention guidance. 3-D reconstruction also enables quantitative vessel analysis, including vessel dynamics from a time-series of reconstructions.Methods: The strong angular undersampling and motion effects present in gated cardiac reconstruction necessitate the development of special reconstruction methods. This contribution presents a fully automatic method for creating high-quality coronary artery reconstructions. It employs a sparseness-prior based iterative reconstruction technique in combination with projection-based motion compensation.Results: The method is tested on a dynamic software phantom, assessing reconstruction accuracy with respect to vessel radii and attenuation coefficients. Reconstructions from clinical cases are presented, displaying high contrast, sharpness, and level of detail.Conclusions: The presented method enables high-quality 3-D coronary artery imaging on an interventional C-arm system.

Abstract:

This paper examined the effects that different tissue conductivities had on forward-calculated ECGs. To this end, we ranked the influence of tissues by performing repetitive forward calculations while varying the respective tissue conductivity. The torso model included all major anatomical structures like blood, lungs, fat, anisotropic skeletal muscle, intestine, liver, kidneys, bone, cartilage, and spleen. Cardiac electrical sources were derived from realistic atrial and ventricular simulations. The conductivity rankings were based on one of two methods: First, we considered fixed percental conductivity changes to probe the sensitivity of the ECG regarding conductivity alterations. Second, we set conductivities to the reported minimum and maximum values to evaluate the effects of the existing conductivity uncertainties. The amplitudes of both atrial and ventricular ECGs were most sensitive for blood, skeletal muscle conductivity and anisotropy as well as for heart, fat, and lungs. If signal morphology was considered, fat was more important whereas skeletal muscle was less important. When comparing atria and ventricles, the lungs had a larger effect on the atria yet the heart conductivity had a stronger impact on the ventricles. The effects of conductivity uncertainties were significant. Future studies dealing with electrocardiographic simulations should consider these effects.

Abstract:

Biventricular pacing (BVP) could be improved by identifying the patient-specific optimal electrode positions. Body surface potential map (BSPM) is a non-invasive technique for obtaining the electrophysiology and pathology of a patient. The study proposes the use of BSPM as input for an automated non-invasive strategy based on a personalized computer model of the heart, to identify the patient pathology and specific optimal treatment with BVP devices. The anatomy of a patient suffering from left bundle branch block and myocardial infarction is extracted from a series of MR data sets. The clinical measurements of BSPM are used to parameterize the computer model of the heart to represent the individual pathology. Cardiac electrophysiology is simulated with ten Tusscher cell model and excitation propagation is calculated with adaptive cellular automaton, at physiological and pathological conduction levels. The optimal electrode configurations are identified by evaluating the QRS error between healthy and pathology case with/without pacing. Afterwards, the simulated ECGs for optimal pacing are compared to the post-implantation clinically measured ECGs. Both simulation and clinical optimization methods identified the right ventricular (RV) apex and the LV posterolateral regions as being the optimal electrode configuration for the patient. The QRS duration is reduced both in measured and simulated ECG after implantation with 20 and 14%, respectively. The optimized electrode positions found by simulation are comparable to the ones used in hospital. The similarity in QRS duration reduction between measured and simulated ECG signals indicates the success of the method. The computer model presented in this work is a suitable tool to investigate individual pathologies. The personalized model could assist therapy planning of BVP in patients with congestive heart failure. The proposed method could be used as prototype for further clinically oriented investigations of computerized optimization of biventricular pacing.

Abstract:

OBJECT: Most functional magnetic resonance imaging (fMRI) experiments use gradient-echo echo planar imaging (GE EPI) to detect the blood oxygenation level-dependent (BOLD) effect. This technique may fail in the presence of anatomy-related susceptibility-induced field gradients in the human head. In this work, we present a novel 3D compensation method in combination with a template-based correction that can be optimized over particular regions of interest to recover susceptibility-induced signal loss without acquisition time penalty. MATERIALS AND METHODS: Based on an evaluation of B(0) field maps of eight subjects, slice-dependent gradient compensation moments are derived for maximal BOLD sensitivity in two compromised regions: the orbitofrontal cortex and the amygdala areas. A modified EPI sequence uses these additional gradient moments in all three imaging directions. The method is compared to non-compensated, template-based and subject-specific correction gradients and also in a breath-holding experiment. RESULTS: The slice-dependent gradient compensation method significantly improves signal intensity/BOLD sensitivity by about 35/43% in the orbitofrontal cortex and by 17/30% in the amygdala areas compared to a conventional acquisition. Template-based correction and subject-specific correction perform equally well. The BOLD sensitivity in the breath hold experiment is effectively increased in compensated regions. CONCLUSION: The new method addresses the problem of susceptibility-induced signal loss, without compromising temporal resolution. It can be used for event-related functional experiments without requiring additional subject-specific calibration or calculation time.

Abstract:

This work presents a new approach toward a fast, simultaneous amplitude of radiofrequency field (B(1)) and T(1) mapping technique. The new method is based on the "actual flip angle imaging" (AFI) sequence. However, the single pulse repetition time (TR) pair used in the standard AFI sequence is replaced by multiple pulse repetition time sets. The resulting method was called "multiple TR B(1)/T(1) mapping" (MTM). In this study, MTM was investigated and compared to standard AFI in simulations and experiments. Feasibility and reliability of MTM were proven in phantom and in vivo experiments. Error propagation theory was applied to identify optimal sequence parameters and to facilitate a systematic noise comparison to standard AFI. In terms of accuracy and signal-to-noise ratio, the presented method outperforms standard AFI B(1) mapping over a wide range of T(1). Finally, the capability of MTM to determine T(1) was analyzed qualitatively and quantitatively, yielding good agreement with reference measurements. Magn Reson Med, 2010. (c) 2010 Wiley-Liss, Inc.

Abstract:

Atrial arrhythmias, such as atrial flutter or fibrillation, are frequent indications for catheter ablation. Recorded intracardiac electrograms (EGMs) are, however, mostly evaluated subjectively by the physicians. In this paper, we present a method to quantitatively extract the wave direction and the local conduction velocity from one single beat in a circular mapping catheter signal. We simulated typical clinical EGMs to validate the method. We then showed that even with noise, the average directional error was below 10(°) and the average velocity error was below 5.4 cm/s. In a realistic atrial simulation, the method could clearly distinguish between stimuli from different pulmonary veins. We further analyzed eight clinical data segments from three patients in normal sinus rhythm and with stimulation. We obtained stable wave directions for each segment and conduction velocities between 70 and 115 cm/s. We conclude that the method allows for easy quantitative analysis of single macroscopic wavefronts in intracardiac EGMs, such as during atrial flutter or in typical clinical stimulation procedures after termination of atrial fibrillation. With corresponding simulated data, it can provide an interface to personalize electrophysiological (EP) models. Furthermore, it could be integrated into EP navigation systems to provide quantitative data of high diagnostic value to the physician

Abstract:

Non-invasive localization of premature ventricular beat (PVB) foci is very important for medical treatment of numerous cardiac diseases. In this work a model-based method of reconstruction of ectopic center locations is investigated.Within the scope of this method patient's multichannel ECG is used as a reference for optimization of an electrophysiological cardiac model. This model is based on the cellular automaton principle and utilizes anatomical data of the patient. Optimized are coordinates of the ectopic focus as well as excitation conduction velocity of ventricular myocardium. Initial values for these parameters are obtained by solving the linearized problem of electrocardiography in terms of activation times. Optimization is performed by minimization of discrepancy between the simulated and reference ECGs.The aim of the current work is to estimate the quality of ectopic focus localization delivered by this method. Four sample ectopic beats have been simulated, with their foci located in different regions of the left ventricle. 1% Gaussian noise has been introduced into the resulting ECGs. In this way the "measured" ECG signals for this investigation have been obtained. Afterwards the origin of each ectopic beat has been reconstructed using the model-based approach. The method has demonstrated reliable localization of PVB foci, reconstruction errors have not exceeded 6.1 mm.

Abstract:

The distributions of transmembrane voltage (TMV) within the cardiac tissue are linearly connected with the patient's body surface potential maps (BSPMs) at every time instant. The matrix describing the relation between the respective distributions is referred to as the transfer matrix. This matrix can be employed to carry out forward calculations in order to find the BSPM for any given distribution of TMV inside the heart. Its inverse can be used to reconstruct the cardiac activity non-invasively, which can be an important diagnostic tool in the clinical practice.The computation of this matrix using the finite element method can be quite time-consuming. In this work, a method is proposed allowing to speed up this process by computing an approximate transfer matrix instead of the precise one. The method is tested on three realistic anatomical models of real-world patients. It is shown that the computation time can be reduced by 50% without loss of accuracy.

Abstract:

Over the last years, nonfluoroscopic in vivo cardiac mapping and navigation systems have been developed and successfully applied in clinical electrophysiology. Clearly, a trend can be observed to introduce more sensors into the measurement system so that physiological information can be gathered simultaneously and more efficiently and the duration of procedure can be shortened significantly. However, it would not be realistic to equip each catheter electrode with a localizer, e.g., by embedding a miniature magnetic location sensor. Therefore, in this paper, an alternate approach has been worked out to efficiently localize multiple catheter electrodes by considering the impedance between electrodes in the heart and electrode patches on the body surface. In application of the new technique, no additional expensive and sophisticated hardware is required other than the currently existing cardiac navigation system. A tank model and a computerized realistic human model are employed to support the development of the positioning system. In the simulation study, the new approach achieves an average localization error of less than 1 mm, which proves the feasibility of the impedance-based catheter positioning system. Consequently, the new positioning system can provide an inexpensive and accurate solution to improve the efficiency and efficacy of catheter ablation.

Abstract:

The electric conductivity can potentially be used as an additional diagnostic parameter, e.g., in tumour diagnosis. Moreover, the electric conductivity, in connection with the electric field, can be used to estimate the local SAR distribution during MR measurements. In this study, a new approach, called electric properties tomography (EPT) is presented. It derives the patient's electric conductivity, along with the corresponding electric fields, from the spatial sensitivity distributions of the applied RF coils, which are measured via MRI. Corresponding numerical simulations and initial experiments on a standard clinical MRI system underline the principal feasibility of EPT to determine the electric conductivity and the local SAR. In contrast to previous methods to measure the patient's electric properties, EPT does not apply externally mounted electrodes, currents, or RF probes, thus enhancing the practicability of the approach. Furthermore, in contrast to previous methods, EPT circumvents the solution of an inverse problem, which might lead to significantly higher spatial image resolution.

Abstract:

An improvement of biventricular pacing (BVP) could be possible by detecting the patient specific optimal pacemaker parameters. Body surface potential map (BSPM) is used to obtain the electrophysiology and pathology of an individual patient non-invasively. The clinical measurements of BSPM are used to parameterize the computer model of the heart to represent the individual pathology. The computer model of the heart is used to simulate the dyssynchrony of the ventricles and myocardial infarction (MI). Cardiac electrophysiology is simulated with ten Tusscher cell model, while excitation propagation is intended with adaptive cellular automaton at physiological and pathological conduction stages. The optimal electrode configurations are identified by minimizing the QRS duration error of healthy and pathology case with/without pacing between pre and post-implantation. Afterwards, the simulated ECGs for optimal pacing are compared to the post implantation clinically measured ECGs. The optimal electrode positions found by simulation are comparable to the ones meausured in hospital. The QRS duration reduction error between measured and simulated 12 ECG signals are similar with a constant offset of 15 ms. The personalized model present in this research is an effective tool for therapy planning of BVP in patients with congestive heart failure.

Abstract:

BACKGROUND: The efficacy of cardiac resynchronization therapy through biventricular pacing (BVP) has been demonstrated by numerous studies in patients suffering from congestive heart failure. In order to achieve a guideline for optimal treatment with BVP devices, an automated non-invasive strategy based on a computer model of the heart is presented. MATERIALS AND METHODS: The presented research investigates an off-line optimization algorithm regarding electrode positioning and timing delays. The efficacy of the algorithm is demonstrated in four patients suffering from left bundle branch block (LBBB) and myocardial infarction (MI). The computer model of the heart was used to simulate the LBBB in addition to several MI allocations according to the different left ventricular subdivisions introduced by the American Heart Association. Furthermore, simulations with reduced interventricular conduction velocity were performed in order to model interventricular excitation conduction delay. More than 800,000 simulations were carried out by adjusting a variety of 121 pairs of atrioventricular and interventricular delays and 36 different electrode positioning set-ups. Additionally, three different conduction velocities were examined. The optimization measures included the minimum root mean square error (E(RMS)) between physiological, pathological and therapeutic excitation, and also the difference of QRS-complex duration. Both of these measures were computed automatically. RESULTS: Depending on the patient's pathology and conduction velocity, a reduction of E(RMS) between physiological and therapeutic excitation could be reached. For each patient and pathology, an optimal pacing electrode pair was determined. The results demonstrated the importance of an individual adjustment of BVP parameters to the patient's anatomy and pathology. CONCLUSION: This work proposes a novel non-invasive optimization algorithm to find the best electrode positioning sites and timing delays for BVP in patients with LBBB and MI. This algorithm can be used to plan an optimal therapy for an individual patient.

Abstract:

The motion of the heart is a major challenge for cardiac imaging using CT. A novel approach to decrease motion blur and to improve the signal to noise ratio is motion compensated reconstruction which takes motion vector fields into account in order to correct motion. The presented work deals with the determination of local motion vector fields from high contrast objects and their utilization within motion compensated filtered back projection reconstruction. Image registration is applied during the quiescent cardiac phases. Temporal interpolation in parameter space is used in order to estimate motion during strong motion phases. The resulting motion vector fields are during image reconstruction. The method is assessed using a software phantom and several clinical cases for calcium scoring. As a criterion for reconstruction quality, calcium volume scores were derived from both, gated cardiac reconstruction and motion compensated reconstruction throughout the cardiac phases using low pitch helical cone beam CT acquisitions. The presented technique is a robust method to determine and utilize local motion vector fields. Motion compensated reconstruction using the derived motion vector fields leads to superior image quality compared to gated reconstruction. As a result, the gating window can be enlarged significantly, resulting in increased SNR, while reliable Hounsfield units are achieved due to the reduced level of motion artefacts. The enlargement of the gating window can be translated into reduced dose requirements.

Abstract:

A ray-based approach that models the geometric mapping properties of a flat optical detector based on a microlens array is presented. The investigated optical detector substitutes a single-aperture lens optic for planar and tomographic data acquisition in space-constrained small-animal imaging applications. The formalism implements forward mapping of a three-dimensional object volume onto a two-dimensional sensor surface as well as the backprojection (inverse mapping) of acquired sensor data sets. The object focus distance is the sole free parameter for the inverse mapping. By variation of the object focus distance, arbitrary object surface areas within the computed object images can be focused. The inverse mapping algorithm was applied to an experimentally acquired sensor data set from a three-dimensional phantom. The results are compared with focal point image formation.

Abstract:

Cardiac tissue exhibits spatially heterogeneous electrophysiological properties. In cardiac diseases, these properties also change in time. This study introduces a framework to investigate their role in cardiac ischemia using mathematical modeling and computational simulations at cellular and tissue level. Ischemia was incorporated by reproducing effects of hyperkalemia, acidosis, and hypoxia with a human electrophysiological model. In tissue, spatial heterogeneous ischemia was described by central ischemic (CIZ) and border zone. Anisotropic conduction was simulated with a bidomain approach in an anatomical ventricle model including realistic fiber orientation and transmural, apico-basal, and interventricular electrophysiological heterogeneities. A model of electrical conductivity in a human torso served for ECG calculations. Ischemia increased resting but reduced peak voltage, action potential duration, and upstroke velocity. These effects were strongest in subepicardial cells. In tissue, conduction velocity decreased towards CIZ but effective refractory period increased. At 10 min of ischemia 19% of subepi- and 100% of subendocardial CIZ cells activated with a delay of 34.6+/-7.8 ms and 55.9+/-18.8 ms, respectively, compared to normal. Significant ST elevation and premature T wave end appeared only with the subepicardial CIZ. The model reproduced effects of ischemia at cellular and tissue level. The results suggest that the presented in silico approach can complement experimental studies, e.g., in understanding the role of ischemia or the onset of arrhythmia.

Abstract:

A 3-D reconstruction of the coronary arteries offers great advantages in the diagnosis and treatment of cardiovascular disease, compared to 2-D X-ray angiograms. Besides improved roadmapping, quantitative vessel analysis is possible. Due to the heart's motion, rotational coronary angiography typically provides only 5-10 projections for the reconstruction of each cardiac phase, which leads to a strongly undersampled reconstruction problem. Such an ill-posed problem can be approached with regularized iterative methods. The coronary arteries cover only a small fraction of the reconstruction volume. Therefore, the minimization of the mbiL(1) norm of the reconstructed image, favoring spatially sparse images, is a suitable regularization. Additional problems are overlaid background structures and projection truncation, which can be alleviated by background reduction using a morphological top-hat filter. This paper quantitatively evaluates image reconstruction based on these ideas on software phantom data, in terms of reconstructed absorption coefficients and vessel radii. Results for different algorithms and different input data sets are compared. First results for electrocardiogram-gated reconstruction from clinical catheter-based rotational X-ray coronary angiography are presented. Excellent 3-D image quality can be achieved.

Abstract:

The quality of three-dimensional (3D) reconstructions of the coronary arteries from rotational coronary angiography depends on the selected phase point. Inconsistencies in the projection data, due to heart motion, degrade the image quality. Here, a method for the automatic selection of the optimum phase points for reconstruction is presented.The method aims at determining heart phases with minimum inconsistency of the motion state in the selected projection data. This is achieved by calculating an error measure which describes the inconsistency of the vessel centerline geometry in three dimensions for all cardiac phases. The phases with minimum inconsistency are then selected as optimum reconstruction phases. The method's feasibility was tested on 22 clinical cases. One late-diastolic and one end-systolic optimum phase were determined automatically for each case. For comparison, three observers visually determined the optimum phases.Overall, 82% of the 44 automatically determined phases delivered optimum image quality, only 5% showed considerably lower quality than the visually determined optimum phase. For all 22 cases at least one of the two automatically determined phases yielded optimum quality.In a first test the method proved to robustly determine optimum reconstruction phase points.

Abstract:

Three-dimensional reconstruction of coronary arteries can be performed during x-ray-guided interventions by gated reconstruction from a rotational coronary angiography sequence. Due to imperfect gating and cardiac or breathing motion, the heart's motion state might not be the same in all projections used for the reconstruction of one cardiac phase. The motion state inconsistency causes motion artefacts and degrades the reconstruction quality. These effects can be reduced by a projection-based 2D motion compensation method. Using maximum-intensity forward projections of an initial uncompensated reconstruction as reference, the projection data are transformed elastically to improve the consistency with respect to the heart's motion state. A fast iterative closest-point algorithm working on vessel centrelines is employed for estimating the optimum transformation. Motion compensation is carried out prior to and independently from a final reconstruction. The motion compensation improves the accuracy of reconstructed vessel radii and the image contrast in a software phantom study. Reconstructions of human clinical cases are presented, in which the motion compensation substantially reduces motion blur and improves contrast and visibility of the coronary arteries.

Abstract:

In this paper, a new method for QRS complex analysis and estimation based on principal component analysis (PCA) and polynomial fitting techniques is presented. Multi-channel ECG signals were recorded and QRS complexes were obtained from every channel and aligned perfectly in matrices. For every channel, the covariance matrix was calculated from the QRS complex data matrix of many heartbeats. Then the corresponding eigenvectors and eigenvalues were calculated and reconstruction parameter vectors were computed by expansion of every beat in terms of the principal eigenvectors. These parameter vectors show short-term fluctuations that have to be discriminated from abrupt changes or long-term trends that might indicate diseases. For this purpose, first-order poly-fit methods were applied to the elements of the reconstruction parameter vectors. In healthy volunteers, subsequent QRS complexes were estimated by calculating the corresponding reconstruction parameter vectors derived from these functions. The similarity, absolute error and RMS error between the original and predicted QRS complexes were measured. Based on this work, thresholds can be defined for changes in the parameter vectors that indicate diseases.

Abstract:

Reduced cardiac output, dysfunction of the conduction system, atrio-ventricular block, bundle branch blocks and remodeling of the chambers are results of congestive heart failure (CHF). Biventricular pacing as Cardiac Resynchronization Therapy (CRT) is a recognized therapy for the treatment of heart failure. The present paper investigates an automated non-invasive strategy to optimize CRT with respect to electrode positioning and timing delays based on a complex threedimensional computer model of the human heart. The anatomical model chosen for this study was the segmented data set of the Visible Man and a set of patient data with dilated ventricles and left bundle branch block. The excitation propagation and intra-ventricular conduction were simulated with Ten Tusscher electrophysiological cell model and adaptive cellular automaton. The pathologies simulated were a total atrioventricular (AV) block and a left bundle branch block (LBBB) in conjunction with reduced interventricular conduction velocities. The simulated activation times of different myocytes in the healthy and diseased heart model are compared in terms of root mean square error. The outcomes of the investigation show that the positioning of the electrodes, with respect to proper timing delay influences the efficiency of the resynchronization therapy. The proposed method may assist the surgeon in therapy planning.

Abstract:

OBJECTIVE: Optimization of cardiac resynchronization therapy (CRT) is still unsolved. It has been shown that optimal electrode position,atrioventricular (AV) and interventricular (VV) delays improve the success of CRT and reduce the number of non-responders. However, no automatic, noninvasive optimization strategy exists to date. METHODS: Cardiac resynchronization therapy was simulated on the Visible Man and a patient data-set including fiber orientation and ventricular heterogeneity. A cellular automaton was used for fast computation of ventricular excitation. An AV block and a left bundle branch block were simulated with 100%, 80% and 60% interventricular conduction velocity. A right apical and 12 left ventricular lead positions were set. Sequential optimization and optimization with the downhill simplex algorithm (DSA) were carried out. The minimal error between isochrones of the physiologic excitation and the therapy was computed automatically and leads to an optimal lead position and timing. RESULTS: Up to 1512 simulations were carried out per pathology per patient. One simulation took 4 minutes on an Apple Macintosh 2 GHz PowerPC G5. For each electrode pair an optimal pacemaker delay was found. The DSA reduced the number of simulations by an order of magnitude and the AV-delay and VV - delay were determined with a much higher resolution. The findings are well comparable with clinical studies. CONCLUSION: The presented computer model of CRT automatically evaluates an optimal lead position and AV-delay and VV-delay, which can be used to noninvasively plan an optimal therapy for an individual patient. The application of the DSA reduces the simulation time so that the strategy is suitable for pre-operative planning in clinical routine. Future work will focus on clinical evaluation of the computer models and integration of patient data for individualized therapy planning and optimization.

Abstract:

Aims This computational study examined the influence of fibre orientation on the electrical processes in the heart. In contrast to similar previous studies, human diffusion tensor magnetic resonance imaging measurements were used.Methods The fibre orientation was extracted from distinctive regions of the left ventricle. It was incorporated in a single tissue segment having a fixed geometry. The electrophysiological model applied in the computational units considered transmural heterogeneities. Excitation was computed by means of the monodomain model; the accompanying pseudo-electrocardiograms (ECGs) were calculated.Results The distribution of fibre orientation extracted from the same transversal section showed only small variations. The fibre information extracted from the equal circumferential but different longitudinal positions showed larger differences, mainly in the imbrication angle. Differences of the endocardial myocyte orientation mainly affected the beginning of the activation sequence. The transmural propagation was faster in areas with larger imbrication angles leading to a narrower QRS complex in pseudo-ECGs.Conclusion The model can be expanded to simulate electrophysiology and contraction in the whole heart geometry. Embedded in a torso model, the impact of fibre orientation on body surface ECGs and their relation to local pseudo-ECGs can be identified.

Abstract:

In dynamic magnetic resonance imaging (MRI) studies, the motion kinetics or the contrast variability are often hard to predict, hampering an appropriate choice of the image update rate or the temporal resolution. A constant azimuthal profile spacing (111.246 degrees), based on the Golden Ratio, is investigated as optimal for image reconstruction from an arbitrary number of profiles in radial MRI. The profile order is evaluated and compared with a uniform profile distribution in terms of signal-to-noise ratio (SNR) and artifact level. The favorable characteristics of such a profile order are exemplified in two applications on healthy volunteers. First, an advanced sliding window reconstruction scheme is applied to dynamic cardiac imaging, with a reconstruction window that can be flexibly adjusted according to the extent of cardiac motion that is acceptable. Second, a contrast-enhancing k-space filter is presented that permits reconstructing an arbitrary number of images at arbitrary time points from one raw data set. The filter was utilized to depict the T1-relaxation in the brain after a single inversion prepulse. While a uniform profile distribution with a constant angle increment is optimal for a fixed and predetermined number of profiles, a profile distribution based on the Golden Ratio proved to be an appropriate solution for an arbitrary number of profiles.

Abstract:

The paper is addressed to detect the parameters of a sphere-center coordinates and radius based on a stack of CT slices. It is proposing a new hierarchical Hough transform approach. In the first step, all slices are taken into consideration sequentially and a 2D accumulator array is used to obtain the coordinates (x"0,y"0), the projecting value of the sphere center into every X-Y-plane. In this step, also a new type of 2D Hough transform for circle or circular detection is proposed based on an effective point filtering. In the second step, the radii of the circles in the different slices are obtained using 1D accumulator arrays. In the last step, the coordinate z"0 and the radius R of the sphere are acquired using a 2D planar Hough transform based on the correlation between the radii of circles, the coordinates z of the slice and the sphere radius. The hierarchical Hough transform is applied to analyze the structure of femoral head of human hip joints. Compared to the established Hough transform techniques for 3D object detection, the hierarchical Hough transform reduces storage space and calculation time significantly and it has a good robustness to noise in the images.

Abstract:

OBJECT: Multiple contrasts are often helpful for a comprehensive diagnosis. In 3D abdominal MRI, breath-hold techniques are preferred for single contrast acquisitions to avoid respiratory artifacts. In this paper, highly accelerated parallel MRI is used to acquire large 3D abdominal volumes with two different contrasts within a single breath-hold. MATERIAL AND METHODS: In vivo studies have been performed on six healthy volunteers, combining T (1)- and T (2)-weighted, gradient- or spin-echo based scans, as well as water/fat resolved imaging in a single breath-hold. These 3D scans were acquired with an acceleration factor of six, using a prototype 32-element receive array. RESULTS: The presented approach was tested successfully on all volunteers. The whole liver area was covered by a FOV of 350 x 250 x 200 mm(3) for all scans with reasonable spatial resolution. Arbitrary scan protocols generating different contrasts have been shown to be combinable in this single breath-hold approach. Good spatial correspondence with negligible spatial offset was achieved for all different scan combinations acquired in overall breath-hold times between 15 and 25 s. CONCLUSION: Enabled by highly parallel imaging technology, this study demonstrates the technical feasibility and the promising image quality of single breath-hold dual contrast MRI.

Abstract:

PURPOSE: To demonstrate a rapid MR technique that combines imaging and R2* mapping based on a single radial multi-gradient-echo (rMGE) data set. The technique provides a fast method for online monitoring of the administration of (super-)paramagnetic contrast agents as well as image-guided drug delivery. MATERIALS AND METHODS: Data are acquired using an rMGE sequence, resulting in interleaved undersampled radial k-spaces representing different echo times (TEs). These data sets are reconstructed separately, yielding a series of images with different TEs used for pixelwise R2* mapping. A fast numerical algorithm implemented on a real-time reconstruction platform provides online estimation of the relaxation rate R2*. Simultaneously the images are summed for the computation of a high-resolution image. RESULTS: Convenient high-resolution R2* maps of phantoms and the liver of a healthy volunteer were obtained. In addition to stable intrinsic baseline maps, the proposed technique provides particularly accurate results for the high relaxation rates observed during the presence of (super-)paramagnetic contrast agents. Assuming that the change in R2* is proportional to the concentration of the agent, the technique offers a rough estimate for dynamic dosage. CONCLUSION: The simultaneous online display of morphological and parametric information permits convenient, quantitative surveillance of contrast-agent administration.

Abstract:

In this work an optimization-based method of modeling the cardiac activity is presented. The method employs a personalized anatomical 3D model of the patients thorax provided by the segmentation of MRI data as well as an electrophysiological model of the heart.Cellular automaton is used to model the propagation of depolarization and repolarization fronts through the myocardium. The form of action potential (AP) curves was previously derived from the coupled myocardium cell models developed by Noble, Priebe-Beuckelmann and ten Tusscher. The results provided by these three cell models are compared.A series of body surface potential maps (BSPMs) is calculated, the signals on the nodes representing the electrodes are recorded, providing thus a simulated multichannel ECG. A root-mean-square of the difference between simulated and measured ECGs is taken as a criterion for optimization of heart model parameters.The method provides a time-dependent distribution of transmembrane voltages within the heart muscle of a patient.

Abstract:

The application of strong electrical stimuli is a common method used for terminating irregular cardiac behaviour. The study presents the influence of electrophysiological heterogeneity on the response of human hearts to electrical stimulation. The human electrophysiology was simulated using the ten Tusscher-Noble-Noble-Panfilov cell model. The anisotropic propagation of depolarisation in three-dimensional virtual myocardial preparations was calculated using bidomain equations. The research was carried out on different types of virtual cardiac wedge. The selection of the modelling parameters emphasises the influence of cellular electrophysiology on the response of the human myocardium to electrical stimulation. The simulations were initially performed on a virtual cardiac control model characterised by electrophysiological homogeneity. The second preparation incorporated the transmural electrophysiological heterogeneity characteristic of the healthy human heart. In the third model type, the normal electrophysiological heterogeneity was modified by the conditions of heart failure. The main currents responsible for repolarisation (Ito, IKs and IKI) were reduced by 25%. Successively, [Na+]i was increased by the regulation of the Na+-Ca2+ exchange function, and fibrosis was represented by decreasing electrical conductivity. Various electrical stimulation configurations were used to investigate the differences in the responses of the three different models. Monophasic and biphasic electrical stimuli were applied through rectangular paddles and needle electrodes. A whole systolic period was simulated. The distribution of the transmembrane voltage indicated that the modification of electrophysiological heterogeneity induced drastic changes during the repolarisation phase. The results illustrated that each of the heart failure conditions amplifies the modification of the response of the myocardium to electrical stimulation. Therefore a theoretical model of the failing human heart must incorporate all the characteristic features.

Abstract:

In this study the performance of a planar array for magnetic induction tomography (MIT) was investigated and the results of measurements to determine the precision and sensitivity of the sensor were undertaken. A planar-array MIT system utilizing flux-linkage minimization for the primary field has been constructed and evaluated. The system comprises 4 printed excitation coils of 4 turns which were shielded, 8 surface-mount inductors of inductance 10 microH as sensor, mounted such that in principle no primary-field flux threads them, and a calibration coil to produce a strong primary field. The excitation current was multiplexed via relays to drive the excitation and reference coils. The noise values were similar in real and imaginary components in the lower frequencies and the factor to which the primary field could be reduced was greatest in the nearest coil. Methods for determining the true real and imaginary components and for flux-linkage minimization for the primary field for variations in channel sensitivities are described and the results of measurements of the system's noise and drift are given. A SNR of 47 dB was observed at 4 MHz when a 0.3 Sm-1 saline filled tank of dimensions 20 cmx20 cmx10 cm was placed centrally over the array. Finally, images were reconstructed from measurements of saline samples in a free space background, with the samples moved past the array in 21 1 cm steps to emulate mechanical scanning of the array. The image reconstruction characteristics of the planar array in conjunction with the reconstruction technique employed are discussed.

Abstract:

A shortcoming of today's coronary magnetic resonance angiography (MRA) is its low total scan efficiency (<5%), as only small well-defined fractions of the respiratory (50%) and cardiac (10%) cycle are used for data acquisition. These precautions are necessary to prevent blurring and artifacts related to respiratory and cardiac motion. Hence, scan times range from 4 to 9 min, which may not be tolerated by patients. To overcome this drawback, an ECG-triggered, navigator-gated free breathing radial 3D balanced FFE sequence with intra-RR motion correction is investigated in this study. Scan efficiency is increased by using a long cardiac acquisition window during the RR interval. This allows the acquisition of a number of independent k-space segments during each cardiac cycle. The intersegment motion is corrected using a self-guided epicardial fat tracking procedure in a postprocessing step. Finally, combining the motion-corrected segments forms a high-resolution image. Experiments on healthy volunteers are presented to show the basic feasibility of this approach.

Abstract:

In magnetic induction tomography reducing the influence of the primary excitation field on the sensors can provide a significant improvement in SNR and/or allow the operating frequency to be reduced. For the purposes of imaging, it would be valuable if all, or a useful subset, of the detection coils could be rendered insensitive to the primary field for any excitation coil activated. Suitable schemes which have been previously suggested include the use of axial gradiometers and coil-orientation methods (Bx sensors). This paper examines the relative performance of each method through computer simulation of the sensitivity profiles produced by a single sensor, and comparison of reconstructed images produced by sensor arrays. A finite-difference model was used to determine the sensitivity profiles obtained with each type of sensor arrangement. The modelled volume was a cuboid of dimensions 50 cmx50 cmx12 cm with a uniform conductivity of 1 S m-1. The excitation coils were of 5 cm diameter and the detection coils of 5 mm diameter. The Bx sensors provided greater sensitivity than the axial gradiometers at all depths, other than on the surface layer of the volume. Images produced using a single-planar array were found to contain distortion which was reduced by the addition of a second array.

Abstract:

Parallel imaging techniques, which use several receive coils simultaneously, have been shown to enable a significant scan time reduction by subsampling k-space. Nevertheless, the data acquired with multiple coils in parallel exhibit some redundancy if the number of receive coils exceeds the subsampling factor. This redundancy leads to an overdetermination of the reconstruction problem, which is generally used to optimize the signal-to-noise ratio (SNR). However, it can yield further information about the quality of the reconstructed image, and can thus be used to identify and correct image artifacts. While some known approaches try to solve this problem in k-space, this study addresses it in the spatial domain and uses a modified SENSE reconstruction to reduce or completely remove ghost-type artifacts arising from processes such as motion or flow during data acquisition. Phantom and in vivo studies show significant improvements in image quality after correction, and serve as a basis for the discussion of the performance and limitations of this new approach.

Abstract:

Parallel imaging techniques, which in principle represent procedures of unfolding a reduced dataset, are well known and well established in MR imaging. This paper presents a further application of one particular reconstruction method, the SENSE algorithm, considered from a different point of view to remove potential foldover in conventional images acquired with multiple receive coils. Based on the coil sensitivity information, a body coverage map in the excited plane is calculated. This is used together with the measured raw data in a SENSE-type reconstruction to optimize the signal-to-noise ratio (SNR) as well as to remove foldover reliably by unfolding the image to a larger field of view. The reconstruction is performed automatically, without any user interaction, and does not affect data acquisition. Based on phantom and in vivo studies, which retain high image quality after the removal, the potential and limits of this approach are discussed, also taking into account future scanner hardware that will support a large number of parallel receiver channels.

Abstract:

The steady-state free precessing (SSFP) sequences, widely used in MRI today, acquire data only during a short fraction of the repetition time (TR). Thus, they exhibit a poor scan efficiency. In this paper, a novel approach to extending the acquisition window for a given TR without considerably modifying the basic sequence is explored for radial SSFP sequences. The additional data are primarily employed to increase the signal-to-noise ratio, rather than to improve the temporal resolution of the imaging. The approach is analyzed regarding its effect on the image SNR (signal to noise ratio) and the reconstruction algorithm. Results are presented for phantom experiments and cardiac functions studies. The gain in SNR is most notable in rapid imaging, since SNR enhancement for a constant repetition time may be used to compensate for the increase in noise resulting from angular undersampling.

Abstract:

Die kurzzeitige Kalzium-Akkumulation im myokardialen Gewebe bei isotoner Kontraktion ist von klinischer Bedeutung, da die Kalziumüberladung des Zytosols ursächlich an der Entstehung von Rhythmusstörungen beteiligt ist. Unklar ist derzeit, woher das überschüssige Kalzium stammt, ob aus intrazellulären Speichern, modifizierten Membranströmen oder von Seiten des kontraktilen Apparates. Ziel dieser Arbeit ist es zu klären, 1) an welcher Stelle in der Zelle das Kalzium freigesetzt wird und 2) ob das Ausmaß der Aktin-Myosin- Überlappung oder die Anzahl angelagerter Querbrücken die Pufferkapazität des kontraktilen Apparates für Kalzium mitbestimmen.Methoden Muskeltrabekel von 18 Patienten, die sich einer Herzoperation unterzogen, wurden untersucht. Während isometrischer Kontraktion der Präparate setzte kurzzeitige, sinusoidale Längenvibration (Frequenz: 125 Hz, Amplitude: 14% ML) ein. Besonderes Augenmerk lag hierbei auf der Reaktion des Kalzium-Signals (Indikator: Fura-2/AM). In einer zweiten Messreihe wurde dieser Versuch nach Zugabe von 10 mM BDM wiederholt, das bekannt ist für seine Kraftminderung durch Senkung der Kalzium-Sensitivität des Troponin C. Im dritten Versuchsblock wurde permanente Vibration angewandt.Ergebnisse 1) Induzierte Vibration reduzierte die aktive Kraft auf das Niveau der Ruhekraft. Zeitgleich kam es zu einer messbaren Zunahme des Kalziums im Zytosol. 2) Bei subtotaler Inhibition der elektromechanischen Kopplung durch BDM erreichte die aktive Kraft 10,4% der Kontrolle bei nahezu unverändertem Kalziumsignal (Kalzium-Zeit-Integral unter BDM: 91,9±3,2% der Kontrolle). Vibration führte unter diesen Bedingungen zu einer Kraftinhibition, ohne dass eine zusätzliche Kalzium-Freisetzung erreicht wurde. 3) Permanente Vibration reduzierte die Kraftamplitude des supramaximal aktivierten Präparates auf 28% (1,3±0,4 mN). Gleichzeitig stieg das Kalzium-Zeit-Integral auf 114,5±4,7%.Schlussfolgerung Die Befunde sprechen dafür, dass die Reduktion der Anzahl angelagerter Querbrücken beim Verkürzungsvorgang zu einer Verminderung der Empfindlichkeit des kontraktilen Apparates für Kalzium führt. Die verminderte Pufferkapazität des kontraktilen Apparates für Kalzium wird messbar durch eine Zunahme der Kalziumkonzentration im Zytosol, wenn bereits angelagerte Querbrücken durch Vibration mechanisch gelöst werden oder wenn die Anlagerung von Querbrücken durch permanente Vibration verhindert wird. Dieser Befund erklärt die klinische Beobachtung, dass die akute Nachlastsenkung häufig mit dem Auftreten von Rhythmusstörungen verbunden ist.

Abstract:

BACKGROUND: This article presents a study, which examines the effects of biphasic electrical shocks on human ventricular tissue. The effects of this type of shock are not yet fully understood. Animal experiments showed the superiority of biphasic shocks over monophasic ones in defibrillation. A mathematical computer simulation can increase the knowledge of human heart behavior. METHODS: The research presented in this article was done with different models representing a three-dimensional wedge of ventricular myocardium. The electrophysiology was described with Priebe-Beuckelmann model. The realistic fiber twist, which is specific to human myocardium was included. Planar electrodes were placed at the ends of the longest side of the virtual cardiac wedge, in a bath medium. They were sources of electrical shocks, which varied in magnitude from 0.1 to 5 V. In a second arrangement ring electrodes were placed directly on myocardium for getting a better view on secondary electrical sources. The electrical reaction of the tissue was generated with a bidomain model. RESULTS: The reaction of the tissue to the electrical shock was specific to the initial imposed characteristics. Depolarization appeared in the first 5 ms in different locations. A further study of the cardiac tissue behavior revealed, which features influence the response of the considered muscle. It was shown that the time needed by the tissue to be totally depolarized is much shorter when a biphasic shock is applied. Each simulation ended only after complete repolarization was achieved. This created the possibility of gathering information from all states corresponding to one cycle of the cardiac rhythm. CONCLUSIONS: The differences between the reaction of the homogeneous tissue and a tissue, which contains cleavage planes, reveals important aspects of superiority of biphasic pulses.

Abstract:

A shortcoming of current coronary MRA methods with thin-slab 3D acquisitions is the time-consuming examination necessitated by extensive scout scanning and precise slice planning. To improve ease of use and cover larger parts of the anatomy, it appears desirable to image the entire heart with high spatial resolution instead. For this purpose, an isotropic 3D-radial acquisition was employed in this study. This method allows undersampling of k-space in all three spatial dimensions, and its insensitivity to motion enables extended acquisitions per cardiac cycle. We present initial phantom and in vivo results obtained in volunteers that demonstrate large volume coverage with high isotropic spatial resolution. We were able to visualize all major parts of the coronary arteries retrospectively from the volume data set without compromising the image quality. The scan time ranged from 10 to 14 min during free breathing at a heart rate of 60 bpm, which is comparable to that of a thin-slab protocol comprising multiple scans for each coronary artery.

Abstract:

Numerical field calculations and experimental investigations were performed to examine the heating of the surface of human skin during the application of a new electrode design for the patient return electrode. The new electrode is characterised by an equipotential ring around the central electrode pads. A multi-layer thigh model was used, to which the patient return electrode and the active electrode were connected. The simulation geometry and the dielectric tissue parameters were set according to the frequency of the current. The temperature rise at the skin surface due to the flow of current was evaluated using a two-step numerical solving procedure. The results were compared with experimental thermographical measurements that yielded a mean value of maximum temperature increase of 3.4 degrees C and a maximum of 4.5 degrees C in one test case. The calculated heating patterns agreed closely with the experimental results. However, the calculated mean value in ten different numerical models of the maximum temperature increase of 12.5 K (using a thermodynamic solver) exceeded the experimental value owing to neglect of heat transport by blood flow and also because of the injection of a higher test current, as in the clinical tests. The implementation of a simple worst-case formula that could significantly simplify the numerical process led to a substantial overestimation of the mean value of the maximum skin temperature of 22.4 K and showed only restricted applicability. The application of numerical methods confirmed the experimental assertions and led to a general understanding of the observed heating effects and hotspots. Furthermore, it was possible to demonstrate the beneficial effects of the new electrode design with an equipotential ring. These include a balanced heating pattern and the absence of hotspots.

Abstract:

PURPOSE: To assess respiratory motion models for coronary magnetic resonance angiography (CMRA). In this study various motion models that describe the respiration-induced 3D displacements and deformations of the main coronary arteries were compared.MATERIALS AND METHODS: Multiple high-resolution 3D coronary MR images were acquired in healthy volunteers using navigator-based respiratory gating, each depicting the coronary vessels at different respiratory motion states. In the images representing the different inspiratory states the displacements and deformations of the main coronary vessels with respect to the end-expiratory state were determined, by means of elastic registration. Several correction models (superior-inferior (SI) translation, 3D translation, and 3D affine transformation) were tested and compared with respect to their ability to map a selected inspiratory to the end-expiratory motion state.RESULTS: 3D translation was found to be superior over SI translation, which is commonly used for prospective motion correction in CMRA. The 3D affine transformation was found to be the best correction model considered in this study. Furthermore, a large intersubject variability of the model parameters was observed.CONCLUSION: The results of this study indicate that a patient-adapted 3D correction model (3D translation or better 3D affine) will considerably improve prospective motion correction in CMRA.

Abstract:

Image processing was used as a fundamental tool to derive motion information from magnetic resonance (MR) images, which was fed back into prospective respiratory motion correction during subsequent data acquisition to improve image quality in coronary MR angiography (CMRA) scans. This reduces motion artifacts in the images and, in addition, enables the usage of a broader gating window than commonly used today to increase the scan efficiency. The aim of the study reported in this paper was to find a suitable motion model to be used for respiratory motion correction in cardiac imaging and to develop a calibration procedure to adapt the motion model to the individual patient. At first, the performance of three motion models [one-dimensional translation in feet-head (FH) direction, three-dimensional (3-D) translation, and 3-D affine transformation] was tested in a small volunteer study. An elastic image registration algorithm was applied to 3-D MR images of the coronary vessels obtained at different respiratory levels. A strong intersubject variability was observed. The 3-D translation and affine transformation model were found to be superior over the conventional FH translation model used today. Furthermore, a new approach is presented, which utilizes a fast model-based image registration to extract motion information from time series of low-resolution 3-D MR images, which reflects the respiratory motion of the heart. The registration is based on a selectable global 3-D motion model (translation, rigid, or affine transformation). All 3-D MR images were registered with respect to end expiration. The resulting time series of model parameters were analyzed in combination with additionally acquired motion information from a diaphragmatic MR pencil-beam navigator to calibrate the respiratory motion model. To demonstrate the potential of a calibrated motion model for prospective motion correction in coronary imaging, the approach was tested in CMRA examinations in five volunteers.

Abstract:

The implementation and first in vivo results of a novel coronary magnetic resonance angiography (MRA) protocol allowing simultaneous acquisition of multiple geometrically independent 3D imaging stacks are presented. Each imaging stack is acquired in a separate cardiac phase using an individual magnetization preparation and navigator-based gating and prospective motion correction. Each stack covers one of the main coronary vessels. Thus, an improvement of scan efficiency was achieved, which was used in this study to reduce total scan time at standard image quality. Experiments performed in healthy volunteers and in patients using a two-stack approach yielded a total scan time reduction of 50% with an image quality equivalent to standard single-stack coronary MRA.

Abstract:

Mapping of electrical endocardial activity is an important task for cardiac diagnosis and surgical treatment planning. Different kinds of catheters measure this activity with a limited number of electrodes. In recent years an increasing number of mapping systems is used in clinical routine. Various systems have been introduced and discussed in literature. This work deals with the localization of catheter electrodes in the heart with advanced techniques of digital image processing. The catheters - developed by various enterprises - differ in shape, handling and amount of electrodes. They are specified and presented in detail. Digital image analysis techniques like filters, Fourier and Hough transformation build the background and basics for this work. The main part describes the methods for the detection of the electrodes and the catheter strings. With these methods, it is possible to setup computer models for each catheter. The computer models can be used e. g. in numerical field calculation together with medical tomographic datasets.

Abstract:

Motion is one major problem of magnetic resonance imaging (MRI) of the coronary vessels. Despite of cardiac motion of the beating heart itself respiratory motion has to be considered (see MR movie of respiratory motion of the heart). Respiratory motion is commonly suppressed by gating techniques, which reduce scan efficiency. In principle modern MR scanners are able to correct those motion patterns prospectively, which can be described by a 3D affine transformation. A prospective motion correction approach could be used to increase the respiratory gating window and in consequence to reduce scan time. However, in order to achieve a sufficient correction the motion must be described quantitatively. In this initial study the respiratory motion of the heart (coronary vessels) was analysed and a new motion model described by an affine transformation was compared to two rigid motion models. The affine transformation model achieved a better fit (mean error < 1 mm for coronary vessels) than a rigid motion model describing translation in all directions (mean error < 2 mm) and a rigid motion model covering only superior-inferior motion (mean error <6 mm).

Abstract:

A model of the electromechanical behavior of a myocardial region is presented. The model combines an electrophysiological, a force development and an excitation propagation model. All of these models incorporate the effects of deformation of the myocardium. An extension of the traditional bidomain model for excitation propagation is proposed. The extension describes the stretch dependency of the conductivity tensor of the intra- and extracellular space and is constructed outgoing from physically motivated assumptions, which simplify the behavior of the conductivity tensor. The extension makes usage of the deformation gradient tensor, which is a foundation in the theory of continuums mechanics. The performed simulations illustrate some effects of myocardial electromechanical behavior.

Abstract:

Knowledge of the distribution of electrical fields in the human body is of importance for scientists, engineers and physicians. This paper shows one way to achieve this knowledge by numerical calculation based on macroscopic models of the human body. An anatomical model is created by preprocessing, segmentation and classification of the digital images within the Visible Man data set. Conductivity models are derived, which describe the distribution of electrical conductivity in the human body. A conductivity model is applied to solve an exemplary forward problem in electrophysiology, which consist of the calculation of the electrical field distribution arising from cardiac sources. The cardiac sources are obtained by a model of the excitation process within the heart. The calculation of electrical fields is carried out numerically by employing the finite difference method.

Abstract:

This paper describes the measurement of a data set used to create a three-dimensional (3-D) parametric model of atrial anatomy. A short introduction to porcine and human atrial anatomy is given and important anatomical differences are noted. The data acquisition techniques are described. A pig heart was arrested in diastole and perfusion fixed in-situ at physiological pressures with the chest open but the pericardium intact, then excised, cast and mounted. A six-degree-of-freedom measurement arm was used to measure three-dimensional epicardial surface geometry and fiber angles. An epicardial surface model was created using a computer aided design (CAD ) software program for reverse engineering. The model was used to direct the dissection of the heart into small tissue blocks from which endocardial fiber angles and wall thicknesses were measured. Tissue blocks were then cryo-sectioned for histology and the identification of conducting system structures. Figures and images illustrate the resulting surface model, the acquired fiber angles and wall thickness. This preliminary work provides a foundation for building a three-dimensional anatomically detailed model suitable as a mesh for computational analysis of atrial mechanics and electrophysiology.

Abstract:

This work deals with the simulation of the electrical cardiac excitation propagation based on anatomical models of the human heart and body. The generation of anatomical models applying different techniques of digital image processing to medical image data is described as well as the generation of electrophysiological models based on these anatomical models. Different spatial and temporal physical field distributions, e.g. the transmembrane potential, the current sources and the extracellular potentials, are calculated and visualized in sinus rhythm case as well as in pathological cases.

Abstract:

The imaging performance of metal plate/phosphor screens which are used for the creation of portal images in radiotherapy is investigated by using Monte Carlo simulations. To this end the modulation transfer function, the noise power spectrum and the detective quantum efficiency [DQE(f)] are calculated for different metals and phosphors and different thicknesses of metal and phosphor for a range of spatial resolutions. The interaction of x-rays with the metal plate/phosphor screen is modeled with the EGS4 electron gamma shower code. Optical transport in the phosphor is modeled by simulating scattering and reabsorption events of individual optical photons. It is shown that metals with a high atomic number perform better than lighter metals in maximizing the DQE(f). It is furthermore shown that the DQE(f) for the metal plate/phosphor screen alone is nearly x-ray quantum absorption limited up to spatial frequencies of 0.4 cycles/mm. In addition, it is argued that the secondary quantum sink of optical photons imposed by the optical chain (mirror, lenses and video camera) leads to a significant degradation of the signal-to-noise ratio at spatial frequencies which are most important for successful registration of portal images. Therefore, the conclusion is that a replacement of the optical chain by a flat array of photodiodes placed directly under the phosphor will lead to a substantial improvement in image quality of portal images.

Abstract:

In radiotherapy, portal images are used to ensure a correct patient position during every radiation session. A reliable on-line verification is of clinical interest to interrupt the radiation in time in case the patient is not at the right position. A great problem for successful image registration is the poor image quality of portal images. They are corrupted by noise and of very low contrast. A method directly based on the grey levels is not sufficient. Therefore a structure-based method was developed which is almost insensitive to distrubances (air bubbles, noise, slowly varying grey levels). In most cases the selection of a region of interest (ROI) can be omitted. Besides the automatical segmentation of the radiation field, only the structures relevant for matching the anatomy are enhanced by using a bandpass filter. It is possible to detect the maximum correlation between different image modalities reliably (simulator image, digitally reconstructed radiograph, portal image). By using Fast Fourier Transformation (FFT), the calculation time is smaller than five seconds, which enables a clinical on-line verification. We have matched 1139 pairs of images of different modalities and various regions of the body (pelvis, nasopharyngeal space, head, lung). The success rate is greater than 95%.

Abstract:

The noise of two integrated YBa2Cu3O7-SrTiO3-YBa2Cu3O7 multilayer magnetometers in static magnetic fields up to 110 µT is investigated: An inductively coupled magnetometer with integrated flux transformer and a multiloop magnetometer. In both samples, only a moderate increase of the low frequency flux noise is found in high fields, due to the high epitaxial quality of the involved multilayer films. So for moderately shielded or unshielded applications in the earth's magnetic field, high-quality integrated YBa2Cu3O7 magnetometers can be operated with low excess noise.

Abstract:

We have designed and fabricated three types of high- SQUID (superconducting quantum interference device) magnetometers based on step-edge Josephson junctions using three different concepts of coupling magnetic flux into the SQUID: (i) a single pickup loop galvanically coupled to the SQUID, (ii) a flux transformer inductively coupled to the SQUID and (iii) a multiloop pickup loop used directly as the SQUID inductance. On a substrate we achieved an effective flux capture area of and for the inductively coupled and multiloop devices, respectively. Due to the low white noise levels of for the inductively coupled magnetometer and for the multiloop device high quality magnetocardiograms were recorded inside a magnetically shielded room without signal averaging.

Abstract:

Three magnetometers based on dc superconducting quantum interference devices (SQUIDs) fabricated from YBa2Cu3O7 x have been operated in a magnetically shielded room using a flux-locked loop involving additional positive feedback with bias current reversal. Two of these devices, integrated multiloop dc SQUIDs with outer diameters of 7 mm, achieved white noise levels of 10 fT/&#8730;Hz for bicrystal junctions and 30 fT/&#8730;Hz for step&#8208;edge junctions. The third magnetometer involved a flux transformer with a 10×10 mm2 pickup coil connected to a 16-turn input coil which was inductively coupled to a bicrystal SQUID. This device achieved a white noise of 16.2 fT/&#8730;Hz. High quality magnetocardiograms were obtained without signal averaging.

Abstract:

We have fabricated YBa2Cu3O7 ramp-type junctions incorporating a barrier layer of NdGaO3 with a nominal thickness of 2 nm. The junctions exhibit pronounced Josephson effects and operate up to 82 K. The characteristics are well described within the resistively shunted junction model. We observe large hysteresis parameters &#946;c even at elevated temperatures. The output voltage of a high-Tc dc SQUID is found to benefit from the intrinsic junction capacitance.

Abstract:

At the current state of technology, multichannel simultaneous recording of combined electric potentials and magnetic fields should constitute the most powerful tool for separation and localization of focal brain activity. We performed an explorative study of multichannel simultaneous electric SEPs and magnetically recorded SEFs. MEG only sees tangentially oriented sources, while EEG signals include the entire activity of the brain. These characteristics were found to be very useful in separating multiple sources with overlap of activity in time. The electrically recorded SEPs were adequately modelled by three equivalent dipoles located: (1) in the region of the brainstem, modelling the P14 peak at the scalp, (2) a tangentially oriented dipole, modelling the N20-P20 and N30-P30 peaks, and part of the P45, and (3) a radially oriented dipole, modelling the P22 peak and part of the P45, both located in the region of the somatosensory cortex. Magnetically recorded SEFs were adequately modelled by a single equivalent dipole, modelling the N20-P20 and N30-P30 peaks, located close to the posterior bank of the central sulcus, in area 3b (mean deviation: 3 mm). The tangential sources in the electrical data were located 6 mm on average from the area 3b. MEG and EEG was able to locate the sources of finger stimulated SEFs in accordance with the somatotopic arrangement along the central fissure. A combined analysis demonstrated that MEG can provide constraints to the orientation and location of sources and helps to stabilize the inverse solution in a multiple-source model of the EEG.

Abstract:

A multi-layer technology, based on YBaCuO as the superconducting material and SrTiO3 as the insulating material, is described. Patterning is performed by photolithography and Ar-ion-beam etching under fiat incidence. Using a resist bake-out prior to the etching, step angles in the patterned lower film of less than 20 degrees are obtained. Superconducting 10-turn thin-film coils have been fabricated with transition temperatures of up to 83 K and critical current densities at 77 K of 2*105 A cm-2. Furthermore we have fabricated a thin-film flux transformer and combined it in flip-chip configuration with a low-noise YBCO step-edge DC SQUID. We measured a magnetic field resolution of the complete magnetometer of 200 fT Hz-1/2 at 1 Hz, dominated by the SQUID noise itself.

Abstract:

We have fabricated ramp-type Josephson junctions and SQUIDs (superconducting quantum interference devices) using an ultrathin barrier layer of NdGaO3 as weak contact between the YBa2Cu3O7 electrodes. The junctions operate up to 82 K, exhibiting current-voltage characteristics of the resistively-hunted-unction type. A normal-state resistance of up to....

Abstract:

A fully oxygen-compatible ion-beam sputter deposition process (IBS) has been implemented for investigation of four film/substrate couples: (103)/(110)YBCO on (110)SrTiO3 (STO) and on (100)NdGaO3 (NGO), and (100)/(010)YBCO on (110)NGO and on (100)STO. For comparison, some (103)/(110)YBCO films have also been prepared by off-axis rf-magnetron sputtering. Below about 600 °C semiconducting, sub-nm flat, and perfectly single-crystalline YBCO films crystallize on these substrates with a crystallographic unit cell of about 1/3 of the Cu-O subcell of YBCO and perfect registration with the Ti4+-O and Ga3+-O sublattice of STO and NGO, respectively. At higher temperature superconducting YBCO films grow coherently epitaxially in the first....

Abstract:

Neuromagnetic imaging is a relatively new diagnostic tool for examination of electrical activities in the nervous system. It is based on the non-invasive detection of extremely weak magnetic fields around the human body with superconducting quantum interference device (SQUID) detectors. Often the equivalent current dipole model is used to describe the centre of the electrical activity. New current density reconstruction methods enable the imaging of the spatial extent and structure of neuronal activities. For practical use in medical diagnosis a combination of the abstract neuromagnetic images with MR or CT images is required in order to match the functional activity with anatomy and morphology. The neuromagnetic images can be overlaid onto three-dimensional morphological images with spatially arbitrarily selectable slices. The matching of both imaging modalities is discussed. On the basis of the detection of auditory evoked magnetic fields, neuromagnetic images are reconstructed with linear estimation theory algorithms. The MR images are used as a priori information of the volume conductor geometry and allow an attachment of functional and morphological properties.

Abstract:

We have designed and fabricated a thin-film flux transformer by a YBa2Cu3O7/SrTiO3 (YBCO/STO) multilayer process. The flux transformer consists of a 20-turn input coil of.....

Abstract:

We have fabricated Y1Ba2Cu3O7-x step-edge junction dc superconducting quantum interference devices (SQUIDs) and characterized their noise performance. The current-voltage characteristics of our SQUIDs are of resistively shunted junction type with critical current densities jc of about 104 A/cm2 and maximum flux to voltage transfer functions...

Abstract:

Currently, linear estimation reconstruction is the only feasible method for extracting information about spatially distributed current sources from measurements of neural magnetic fields. We present the results of a systematic study of the effect of the signal-to-noise ratio on the imaging quality of one such algorithm in over-as well as undetermined circumstances. In particular, we will discuss the necessary trade-off between the contradictory goals of a minimum norm of the reconstructed current density distribution and of a minimal deviation of the reconstructed fields from the measured fields. As an example, we show the reconstruction of a simple arrangement of two nearly parallel dipoles in two different depths inside a spherical volume conductor, discussing the differences between the computer simulation without noise and simulation with a realistic noise level.

Abstract:

NbN/MgO/NbN Josephson tunnel junctions have been prepared using various barrier preparation conditions. The energy of the sputtered MgO particles arriving at the substrate was found to be the most important parameter. Tunnel junctions (10*10 mu m2) with Vm values of up to 23 mV have been fabricated. The optimized NbN/MgO/NbN junction process is extended to a reliable whole-wafer process for DC SQUID fabrication.

Abstract:

Ziel dieses neuen medizinischen Diagnoseverfahren ist es, mit sog. supraleitenden Quanten-Intererenz-Detektoren (SQUIDs), die durch neuronale Ströme im Gehirn hervorgerufen magnetischen Felder außerhalb des menschlichen Kopfes zu messen, um so ein Bild von der Funktion des Gehirns zu erstellen.

Abstract:

A continuum light emission extending from the infrared to the ultraviolet has been observed in highly excited Xe and Kr crystals. The light is emitted by an electron plasma with an electron density of about 10 to the 18th per cu cm. The kinetic energies of the electrons correspond to an electron temperature of about 2000 K for a lattice temperature of 15 K (Kr) and 60 K (Xe). This electron plasma represents a case of an extreme thermal nonequilibrium between electrons and the lattice consisting of neutrals and ions.

Abstract:

A density of 1 × 1017cm-3 excited centers has been created in Ar crystals by excitation with an intense electron pulse. The crystals emit the Ar*2 excimer band at 9.8 eV from the...

Abstract:

Die Vorteile der Datennutzung im Gesundheitswesen sind mittler- weile so offensichtlich, dass es fahrlässig wäre, diese nicht umzu- setzen. Der vorliegende IMPULS will Anstoß für eine sichere und souveräne Nutzung von Gesundheitsdaten geben. Dazu werden Chancen, Hemmnisse sowie Diskussionspunkte und Handlungs- felder aufgezeigt und in Bezug gesetzt zu aktuellen Gesetzesvor- haben in diesem Bereich. Das Papier richtet sich vor allem an politische Entscheidungsträgerinnen und Entscheidungsträger und soll Wege aufzeigen, wie der Datenschatz zum Wohle der Patientinnen und Patienten gehoben werden kann.Aufbauend auf einer Bestandsaufnahme des heutigen Gesund- heitssystems und einer Analyse der bestehenden Hürden und Hindernisse haben wir Handlungsfelder identifiziert, in denen die zuständigen Akteure aktiv werden müssen:Die Datenfreigabe ist die alles entscheidende Grundlage für die Datennutzung. In einem dermaßen komplexen System wie dem Gesundheitswesen reicht eine binäre Entweder-oder-Entscheidung nicht aus; ein abgestuftes, differenziertes Einwilligungsverfahren ist nötig, um einen souveränen Umgang mit den Gesundheitsdaten jeder und jedes Einzelnen zu ermöglichen. Es gibt heute Möglich- keiten, die feingranulare Einwilligung zur Nutzung der Daten so zu gestalten, dass sie relativ schnell und gut informiert durchgeführt werden kann, zum Beispiel mithilfe des Mobiltelefons.Nur Daten mit einer hinreichenden Datenqualität sind für die Nutzung sowohl in der medizinischen Versorgung als auch in Forschung und Entwicklung verwendbar. Daher sind einheitliche Standards und Formate dringend nötig.Alle öffentlichen und privaten Akteure, die Gesundheitsdaten erheben, sollten durch die Datenbereitstellung an gemeinsamen Gesundheitsdatenräumen beteiligt sein. Dabei braucht es neben einer möglichst weitreichenden Veröffentlichung von Daten auch klare Regelungen zum Schutz von geistigem Eigentum und damit der Wettbewerbsfähigkeit der Beteiligten. Zudem müssen neben staatlichen Forschungseinrichtungen wie der Universitäts- medizin auch Unternehmen der Pharma- und der Medizintechnik- branche Zugriff auf die Daten erhalten, damit die Ergebnisse der Forschung bei den Millionen von Patientinnen und Patienten auch tatsächlich ankommen.Die Datenweitergabe sollte im Sinne der Sicherheit soweit möglich in anonymisierter und aggregierter Form erfolgen;gleichzeitig sollten angesichts des potenziellen medizinischen Mehrwerts unter bestimmten Umständen auch eine Nutzung pseudonymisierter und personalisierter Daten möglich sein. Einrichtungen und Unternehmen, die Gesundheitsdaten für die allgemeine Nutzung zur Verfügung stellen, sollten auch einen besseren Zugang zu solchen Daten erhalten. Die Publikation datenbasierter Forschungsergebnisse sollte die Regel sein.Für den Bereich Infrastruktur und Datensicherheit ist darauf zu achten, dass Datengewinnung, Datenbereitstellung und Datenfreigabe konsequent getrennt, also in unterschiedlichen Einrichtungen angesiedelt werden, um Datenmissbrauch so gut wie möglich zu verhindern. Eine schnellere, robuste und sichere Infrastruktur für Gesundheitsdaten ist hierfür Grund- voraussetzung; bei deren Erarbeitung müssen alle Beteiligten konsequent eingebunden werden, auch im Hinblick auf gute Benutzerschnittstellen.Die Datennutzung sollte im Sinne einer Value-based Healthcare erfolgen und den Fokus zudem auch auf präventive Angebote und den Ausbau von telemedizinischen Leistungen legen. Dazu braucht es neue Metriken zur umfassenden Bewertung von Gesundheit und zur Integration neuer Leistungen in die Ver- sorgung.Die digitale Gesundheitskompetenz muss durch Aus- und Weiter- bildung auf allen Ebenen – von den Patientinnen und Patienten über die Ärzteschaft und das Pflegepersonal bis hin zu Presse und anderen Medien – besser werden. Wir benötigen dringend mehr und exzellent ausgebildete IT-Expertinnen und -Experten für den Gesundheitsbereich, zum Beispiel Medical Data Scientists.Die öffentliche Meinungsbildung über das Thema Datennutzung im Gesundheitswesen sollte neben den berechtigten Datenschutz- anliegen auch die Vorteile berücksichtigen und einen öffentlichen Diskurs über Datenschutzmöglichkeiten und den Mehrwert der Datennutzung anregen.Zur Innovationsförderung auf Basis von Datennutzung braucht es einheitliche Rahmenbedingungen auf nationaler und europäischer Ebene, um Rechtssicherheit zu schaffen. Gleich- zeitig müssen datengetriebene Ansätze und neue Diagnose- und Therapiemöglichkeiten, zum Beispiel durch KI, in der Zulassung gleichwertig mit klassischen Verfahren berücksichtigt werdenDigitalisierung und Datennutzung erlauben durch Auto- matisierung und Personalisierung ein nachhaltiges und zu- kunftsfähiges Gesundheitswesen, welches das Patientenwohl ins Zentrum stellt und Gesundheit ganzheitlich betrachtet.

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Lernende Systeme oder Machine Learning, so sind sich Fachleute einig, werden auch in der Medizin und der Medizintechnik zukünftig eine große Bedeutung erlangen – mit Vorteilen aber auch mit Risiken für Patientinnen und Patienten, Unternehmen und Fachpersonal. Dabei ergeben sich verschiedenste Herausforderungen im Umgang mit Machine-Learning-Systemen – unter anderem für praktische Behandlungssituationen, für die Qualitätskontrolle, für die Sicherheit in Notfallsituationen oder die Bewertung der vom Computer vorgeschlagenen Diagnosen und Therapiepfade. Die vorliegende acatech POSITION ist das Ergebnis einer Arbeitsgruppe von Wissenschaftlerinnen und Wissenschaftlern aus Medizin und Technik. Die Projektgruppe gibt einen Überblick über heutige Anwendungen von Machine Learning in der Medizintechnik und beleuchtet wichtige zukünftige Anwendungsfelder. Im Fokus stehen darüber hinaus ethische, rechtliche und regulatorische Aspekte sowie kritische Fragen zum Datenschutz und mögliche Veränderungen im Arzt-Patienten-Verhältnis. Neben Vorschlägen zum Aufbau großer medizinischer Datenbanken gibt diese Position auch Handlungsempfehlungen für Ärztinnen und Ärzte, Einrichtungen der Forschungsförderung und die Politik.

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Umfassende Darstellung der Bandbreite bildgebender Modalitäten in der Medizin (z. B. Projektionsröntgen, Computertomographie und Magnetresonanztomographie)Detaillierte Information zu jedem Verfahren über das physikalische Grundprinzip, die gerätetechnische Umsetzung, die Qualitätsparameter und die medizinischen Applikationen.Für Studierende technischer Diplom-, Bachelor- und Masterstudiengänge an Universitäten und Fachhochschulen auf dem Gebiet der Biomedizinischen Technik aber auch für Studierende der Medizin sowie für Praktiker in der medizintechnischen Industrie und im medizinischen Bereich

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VERTRAUEN IN DIE / IN DER WISSENSCHAFT?Streitgespräche in den Wissenschaftlichen Sitzungen der Versammlung der Akademiemitglieder am 30. November 2012 und am 14. Juni 2013

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Die großen Trends der Medizintechnik Biomolekularisierung, Miniaturisierung, Computerisierung werden beschrieben und die gesellschaftlichen Rahmenbedingungen, unter denen in Zukunft Innovationen der Medizintechnik entstehen, werden analysiert. Einige Fokusthemen der Medizintechnik werden etwas detaillierter betrachtet: Was sind die interessanten Forschungsvorhaben von heute, die möglicherweise morgen Wirklichkeit werden?

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Es wird eine Methode beschrieben, wie medizinische Bilder des Herzens modellbasiert mit EKG-Daten verknüpft werden können, um damit zu einer spezifischen Diagnostik und zu einer besseren Therapieplanung in der Kardiologie zu gelangen. Zunächst wird aus MRT- oder CT-Bildern des Patienten die Geometrie seines Herzens ermittelt. Elektrokardiographische Messungen an der Körperoberfläche (EKG oder Body Surface Potential Mapping) und aus dem Inneren des Herzens (intracardial mapping) werden aufgenommen und die Orte der Messung in den Bilddatensatz eingetragen (registration). Ein elektrophysiologisches Computermodell vom Herzen des Patienten wird mit Hilfe der elektrophysiologischen Messdaten iterativ angepasst. Schließlich entsteht im Computer ein virtuelles Herz des Patienten, welches sowohl die Geometrie als auch die Elektrophysiologie wiedergibt. Ein Modell der Vorhöfe hat beispielsweise das Potenzial, die Ursachen von Vorhofflimmern zu erkennen und die Radiofrequenz-Ablationsstrategie zu optimieren. Ein Modell der Ventrikel des Herzens kann helfen, genetisch bedingte Rhythmusstörungen besser zu verstehen oder auch die Parameter bei der kardialen Resynchronisationstherapie zu optimieren. Die Modellierung des Herzens mit einem Infarktgebiet könnte die elektrophysiologischen Auswirkungen des Infarktes beschreiben und die Risikostratifizierung für gefährliche ventrikuläre Arrhythmien unterstützen oder die Erfolgsrate bei ventrikulären Ablationen erhöhen.

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Vorträge im Rahmen der wissenschaftlichen Sitzungen der Technikwissenschaftlichen Klasse am 24. Februar, 5. Mai und 18. Oktober 2006

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Mathematisierung der NaturStreitgespräche in den Wissenschaftlichen Sitzungen der Versammlung der Berlin-Brandenburgischen Akademie der Wissenschaftenam 10. Dezember 2004 und 27. Mai 2005

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Papers from the 4th International Conference on Superconducting and Quantum Effect Devices and their Applications held in Berlin, Germany, June 18-21, 1991.Detailliertere InformationenSuperconducting devices and their applications: proceedings of the 4th international conference SQUID '91 (session on superconducting devices), Berlin, Fed. Rep. of Germany, June 18-21, 1991Von Hans Koch, H. LübbigMitwirkende Personen Hans KochEdition: illustratedVeröffentlicht von Springer-Verlag, 1992Original von University of MichiganDigitalisiert am 10. Dez. 2007ISBN 0387553967, 9780387553962603 Seiten

Abstract:

Due to forthcoming use of MPI on humans there is an urgent need for a thorough research on possible adverse effects of this technique on patients health. However, the health impact of exposure to time-varying magnetic fields in a frequency range between 10 kHz and 100 MHz, such as the MPI drive field, are still poorly investigated.The current paper intends to give an overview on an in-silico approach to investigation of stimulating effects that could be caused by the MPI drive field. For this purpose, cell models of myocardiocyte, myocyte and neurocyte, as well as a suitable setup for the simulation of the exposure to time-varying magnetic fields have been developed. The evaluation of performed simulations was carried out on the basis of transmembrane voltage elevation and induced current densities.

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This article presents three success stories that show how the coaction of mathematics and medicine has pushed a development towards patient specific models on the basis of modern medical imaging and virtual labs, which, in the near future, will play an increasingly important role. Thereby the interests of medicine and mathematics seem to be consonant: either discipline wants the results fast and reliably. As for the medical side, this means that the necessary computations must run in shortest possible times on a local PC in the clinics and that their results must be accurate and resilient enough so that they can serve as a basis for medical decisions. As for the mathematical side, this means that highest level requirements for the efficiency of the applied algorithms and the numerical and visualization software have to be met. Yet there is still a long way to go, until anatomically correct and medically useful individual functional models for the essential body parts and for the most frequent.

Abstract:

Atrial tachycardia and atrial flutter are frequent arrhythmia that occur spontaneously and after ablation of atrial fibrillation. Depolarization waves that differ significantly from sinus rhythm propagate across the atria with high frequency (typically 140 to 220 beats per minute). A detailed and personalized analysis of the spread of depolarization is imperative for a successful ablation therapy. Thus, catheters with several electrodes are employed to measure multichannel electrograms inside the atria. Here we propose a new concept for spatio-temporal analysis of multichannel electrograms during atrial tachycardia and atrial flutter. It is based on the calculation of simultaneously active areas. The method allows to identify atrial tachycardia and to automatically distinguish between subtypes of focal activity, micro-reentry and macro-reentry.

Abstract:

Today, patients suffering from atrial arrhythmias like atrial flutter (AFlut) or atrial fibrillation (AFib) are examined in the EP-lab (electrophysiology lab) in order to understand and treat the disease. Multichannel catheters are advanced into the atria in order to measureelectric signals at manyintracardiacpositions simultaneously. Complementary to clinical learning,comprehension of the disease and therapeutic strategies can be improved with computer modeling of the heart. This way, hypotheses about initiation and perpetuation of the arrhythmia can be tested and ablation strategies can be assessed in-silico. Modeling and biosignal analysis can benefit from mutual fertilization. On the one hand, modeling can be improved and personalization can be achieved via high density mapping of the atria. On the other hand, new algorithms for the interpretation of multichannel electrograms can be developed and evaluated with synthetic signals from computer models of the atria. This article illustrates the synergetic potential by examples and highlights challenges to be addressed in the future.

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By means of computer modeling general comprehension of electrophysiology (EP) of human atria can be improved and simulated patterns of ectopic foci, reentry and rotors can be created. On the other hand atrial electrograms are measured in the EP lab of many hospitals every day. In this contribution simulated and measured clinical signals are compared critically aiming at better understanding of atrial fibrillation and validation of computer modeling.

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Heterogeeities of the ventricular electrophysiol- ogy play a major role in the generation of the T-wave mor- phology and amplitude. The exact way of the distribution of electrophysiological differences is not known. In this work, a numerical approach is presented in which the excitation propagation of different heterogeneity distributions of IKs are simulated and the multi-channel ECG is calculated. The ECG data are evaluated against measured ECGs. The most realistic configuration is a combination of transmural and apico-basal heterogeneity with 35% of Endo, 30% of M and 35% of Epi cells and an apico-basal gradient with a factor of 2. This specific setup has a correlation of around 90% and a root mean square error of around 0.0795.

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The heart rate is mediated by the G protein-coupled muscarinic receptor (M2R) activating the acetylcholine (ACh)-dependent K+ current (IKACh). Here, a novel model for IKACh gating is presented based on recent findings that M2R agonist binding is voltage-sensitive. Furthermore, ACh and pilocarpine (Pilo) manifest opposite voltage-dependent IKACh modulation. In a previous work, a 4-state Markov model of M2R reconstructing the voltage-dependent change in agonist affinity was proposed. In this work, a 2-state Markov model of IKACh gating purely dependent on the G&#946;&#947; concentration is proposed. IKACh is modeled based on the description of Zhang et al. Measurement data are used to parametrize the combined M2R and IKACh model for both ACh and Pilo. The channel model has a linear G&#946;&#947; dependent forward and a constant backward rate. For ACh and Pilo, optimal values of model parameters are found reconstructing the measured opposite voltage-dependent change in agonist affinity. The combined model is able to reconstruct the measured data regarding the agonist and voltage-dependent properties of the M2R-IKACh channel complex. In future studies, this channel will be integrated in a sinus node model to investigate the effect of the channel properties on heart rate

Abstract:

A method to reconstruct integrals of transmembrane voltages in the heart from measured integrals of Body Surface Potential Maps (BSPM) is proposed. It is applied to localize the origin of premature beats in the heart (extrasystoles). In contrast to other proposals no specific assumption about the slope of the transmembrane voltage during depolarization is made, in particular it must not be a step function. This way the non-linear problem of localizing ectopic foci based on activation times is translated into a linear inverse problem. A Maximum-A-Posteriori (MAP) estimator is applied to solve the ill-posed linear inverse problem. Successful localization of ventricular extrasystoles is demonstrated using computer simulations. Even endocardial, midmyocardial and epicardial foci can be separated.

Abstract:

The objective of personalised modelling of the atria is to improve comprehension of the etiology of atrial arrhythmias, to enable specific diagnosis and to optimise therapy. We start with CT or MR datasets and use adapted segmentation procedures to build a patient-specific 3D-model of the atria. Then we include fibre direction based on the rules of atrial anatomy. Work in progress is also considering late enhancement MRI in order to add areas of fibrotic tissue. Next we can use BSPM data of the P-wave and solve the inverse problem of ECG to get a hypothesis about the spread of depolarisation. Finally we use intracardiac catheter signals (e.g. using a circular catheter) to measure direction and conduction velocity of depolarisation waves (sinus rhythm, atrial flutter, or following stimulation). All this is integrated into a personalised model of the atria of an individual patient. Our next goal will be to properly add ablation lines into the model.The research leading to these results has partly received funding from the European Communitys Seventh Framework Programme (FP7/2007-2013) under grant agreement n 224495 (euHeart project).

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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.

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Atrial fibrillation (AF) is a common pathology. AF modifies the electrophysiological properties of cells (remodeling) promoting the occurrence and maintenance of AF.Electrical remodeling includes changes in ICa,L, Ito, IK1 and IK,ACh. These effects were integrated in a human atrial computer model. Gap junction remodeling was considered in the conductivity of the monodomain equation calculating excitation. Specific features were calculated to determine the risk of AF initiation and perpetuation.ERP was reduced from 330ms to 103ms. CV was lowered from 755mm/s to 608mm/s. The WL reduction was even higher (from 249mm to 63mm) leading to a higher probability of occurrence and maintenance of AF. A maximum of 7 spirals waves were initiated leading to a peak in the power spectrum at 10.32Hz.The computer model underlines the relevance of remodeling in AF chronification. The results add to the knowledge of AF maintenance. Our model might prove to be a tool for the development of novel therapeutic strategies.

Abstract:

Orthogonal recursive bisection (ORB) algorithm can be used as data decomposition strategy to distribute a large data set of a cardiac model to a distributed memory supercomputer. It has been shown previously that good scaling results can be achieved using the ORB algorithm for data decomposition. However, the ORB algorithm depends on the distribution of computational load of each element in the data set. In this work we investigated the dependence of data decomposition and load balancing on different rotations of the anatomical data set to achieve optimization in load balancing. The anatomical data set was given by both ventricles of the Visible Female data set in a 0.2 mm resolution. Fiber orientation was included. The data set was rotated by 90 degrees around x, y and z axis, respectively. By either translating or by simply taking the magnitude of the resulting negative coordinates we were able to create 14 data sets of the same anatomy with different orientation and position in the overall volume. Computation load ratios for non tissue vs. tissue elements used in the data decomposition were 1:1, 1:2, 1:5, 1:10, 1:25, 1:38.85, 1:50 and 1:100 to investigate the effect of different load ratios on the data decomposition. The ten Tusscher et al. (2004) electrophysiological cell model was used in monodomain simulations of 1 ms simulation time to compare performance using the different data sets and orientations. The simulations were carried out for load ratio 1:10, 1:25 and 1:38.85 on a 512 processor partition of the IBM Blue Gene/L supercomputer. The results show that the data decomposition does depend on the orientation and position of the anatomy in the global volume. The difference in total run time between the data sets is 10 s for a simulation time of 1 ms. This yields a difference of about 28 h for a simulation of 10 s simulation time. However, given larger processor partitions, the difference in run time decreases and becomes less significant. Depending on the processor partition size, future work will have to consider the orientation of the anatomy in the global volume for longer simulation runs.

Abstract:

The output data generated in whole heart simula- tions are usually single or multiple parameters at each point in the simulation space. Visualizing data sets of gigabyte size puts great stress on the hardware and can be slow and tedious. Creating animated movies to analyze the excitation propaga- tion can take hours on standard systems. We present two par- allel visualization techniques to improve rendering of large datasets from cardiac simulations.The Scalable Parallel Visualization Networking (SPVN) toolkit provides the ability to assist in optimizing the utility and functionality of the aggregate resources in visualization clusters. Run time visualization offers the opportunity to visu- alize the results of cardiac simulations on the fly on High Per- formance Computers. Parallel visualization techniques enable fast manipulation of high resolution whole heart data sets and simulation results. The SPVN system has the potential to be linked with the simulation environment similar to the run time visualization described.Future efforts will focus on creating a simulation and visu- alization environment with appropriate characteristics for clinical setting. Specifically, speed, intuitive control and the ability to render diverse signals will likely be critical to drive adoption in the clinical setting.

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Atrial fibrillation (AF) is the most common cardiac arrhythmia in the western world. Genetic variants in the cardiac I Kr channel have been identified to influence ventricular repolarization. The aim of this work is to investigate the effect of the mutation N588K on atrial repolarization and the predisposition to AF. Experimental data of N588K mutated hERG channel were incorporated in an atrial ionic model using parameter fitting. The effects of the mutation were analyzed in cell and tissue. N588K showed a gain of function effect, causing a rapid repolarization and a shortening of the action potential duration. Computer simulations of a schematic right atrial geometry were used to investigate the excitation conduction properties. The effective refractory period of mutant cells were reduced from 317 to 233 ms at 1 Hz. The conduction velocity is not significantly influenced by the mutation. Nevertheless, the wavelength of mutant cells is for all frequencies smaller, indicating that the mutation N588K predisposes the initiation and perpetuation of AF.

Abstract:

Cisapride is a drug to help gastric problems. It is limited because of reports of the side-effect long QT syndrome which predisposes to arrhythmias. In this computatinal study, the effects of Cisapride on human ventricular myocytes are investigated in-silico. From literature reported effects of the drug on ion channel level are included into a virtual human ventricular cell. Cisapride has the most dominating effect on the rapid delayed rectifier current IKr. A shift in the activation and inactivation and mainly a reduction of conductivity is seen. This leads to the prolongation of the APD comparable to the long QT syndrome. In future studies, the stability of the heart under the influence of this drug will be evaluated

Abstract:

After mathematical modeling of the healthy heart now modeling of diseases comes into the focus of research. Modeling of arrhythmias already shows a large degree of realism. This offers the chance of more detailed diagnosis and computer assisted therapy planning. Options for genetic diseases (channelopathies like Long-QT-syndrome), infarction and infarction-induced ventricular fibrillation, atrial fibrillation (AF) and cardiac resynchronization therapy are demonstrated.

Abstract:

Multi-scale, multi-physical heart models have not yet been able to include a high degree of accuracy and resolution with respect to model detail and spatial resolution due to computational limitations of current systems. We propose a framework to compute large scale cardiac models. Decomposition of anatomical data in segments to be distributed on a parallel computer is carried out by optimal recursive bisection (ORB). The algorithm takes into account a computational load parameter which has to be adjusted according to the cell models used. The diffusion term is realized by the monodomain equations. The anatomical data-set was given by both ventricles of the Visible Female data-set in a 0.2 mm resolution. Heterogeneous anisotropy was included in the computation. Model weights as input for the decomposition and load balancing were set to (a) 1 for tissue and 0 for non-tissue elements; (b) 10 for tissue and 1 for non-tissue elements. Scaling results for 512, 1024, 2048, 4096 and 8192 computational nodes were obtained for 10 ms simulation time. The simulations were carried out on an IBM Blue Gene/L parallel computer. A 1 s simulation was then carried out on 2048 nodes for the optimal model load. Load balances did not differ significantly across computational nodes even if the number of data elements distributed to each node differed greatly. Since the ORB algorithm did not take into account computational load due to communication cycles, the speedup is close to optimal for the computation time but not optimal overall due to the communication overhead. However, the simulation times were reduced form 87 minutes on 512 to 11 minutes on 8192 nodes. This work demonstrates that it is possible to run simulations of the presented detailed cardiac model within hours for the simulation of a heart beat.

Abstract:

The classic tool of assessing learning progress are written tests and assignments. In large groups of students the workload often does not allow in depth evaluation during the course. Thus our aim was to modify the course to include active learning methods and student centered teaching. We changed the course structure only slightly and established new assessment methods like minute papers, short tests, mini-projects and a group project at the end of the semester. The focus was to monitor the learning progress during the course so that problematic issues could be addressed immediately. The year before the changes 26.76 % of the class failed the course with a grade average of 3.66 (Pass grade is 4.0/30 % of achievable marks). After introducing student centered teaching, only 14 % of students failed the course and the average grade was 3.01. Grades were also distributed more evenly with more students achieving better results. We have shown that even in large groups of students with > 100 participants student centered and active learning is possible. Although it requires a great work overhead on the behalf of the teaching staff, the quality of teaching and the motivation of the students is increased leading to a better learning environment.

Abstract:

Electrophysiological modeling of the heart enable quantitative description of electrical processes during normal and abnormal excitation. Cell models describe e.g. the properties of the cell membrane and the gating process of ionic channels. New measurement data is available for these channels for physiological and some pathological states. These data should be included in the models to enhance their features. In this work we describe a framework adapting ion channel models to measurement data by using a particle swarm optimization (PSO). Models of ion channels can be described by Hogdkin-Huxley equations or by Markovian models. They consider rate constants that are complex functions depending on the transmembrane voltage. Each transition has two rate constants described by several parameters. These parameters need to be varied in order to minimize the difference between measured and simulated ion channel kinetics. Since this minimization procedure is multidimensional and the function can have several local minima, conventional optimization strategies like Powells algorithm and conjugate gradient do not ensure to find the global minimum. To overcome this, a PSO was implemented that inserts several dependent particles randomly into the search space. It is based on the social behavior of swarms. As the particles are independent during each iteration the procedure can be calculated in parallel. The measurement data used for this work were current traces of a voltage-clamp protocol of reggae mutant hERG channels. The same protocol as for the measurement was assigned to the model of Lu et al. describing hERG function with a Markovian model. The value to be minimized was the sum of mean square errors between measured and simulated currents at certain time instances. Both Powell and PSO were started several times with random starting values. In 94% of the cases PSO found the minimum compared to 16% for Powell. On the other hand PSO needed approximately 100 times more function evaluations. The parallelization decreased the overall time needed by the PSO to about the same amount Powell needed. Therefore, the parallel PSO is a fast and reliable approach for adapting ion channel models to measured data.

Abstract:

The sinus node (SN) is the primary pacemaker of the heart. It is a heterogeneous structure in the right atrium composed of two types of cells with different electrophysiological properties. One type is distributed more densely in the periphery the other in the center. Different gap junction types and densities exist leading to a heterogeneity in conduction. It is supposed that this complex interplay of heterogeneities is the basic mechanism that the small SN is able to electrically drive the surrounding atrial muscle. If this interplay is disturbed, the function of the SN can be effected massively. In this simulation study we want to demonstrate the effects of the L532P mutation in hERG called reggae on SN electrophysiology.Mutant hERG channels were expressed in xenopus oocytes and the channel properties were measured with voltage-clamp technique. The data showed mainly a shift of the steady-state inactivation to more positive potentials. This leads to an increase of the ionic current during the depolarized phase. The data was integrated in the heterogeneous rabbit SN model of Zhang et al. by adapting the parameters of the IKr channel with aid of optimization methods using the same stimulation protocol as in the measurements.The most sensitive parameter was the shift voltage of the steady-state inactivation from -19.2 mV in the physiological case to 10.1 mV in the mutant model. When inserting this mutant IKr in the central SN model the ability of the central cells to depolarize spontaneously was eliminated. Peripheral cell still beat but are affected by the mutation. The slope of the pre-potential and the upstroke velocity were not changed. The maximum diastolic potential was increased by 2 mV and the maximum systolic potential decreased by 1.5 mV. The diastolic interval was shortened slightly by 3 ms. The main effect was a reduction of the action potential duration from 108 ms to 84 ms leading to a frequency increase from 6.37 Hz to 7.62 Hz.These effects lead to a changing SN function. The increase of the shift voltage is in good agreement with the measured changes. Especially the loss of auto-rhythmicity in the central zone is expected to change the overall SN activity. Although peripheral SN cells beat faster we expect a bradycardial function of the complete SN because of electrotonic interactions with the silent central SN cells and the low resting membrane voltage of surrounding atrial muscle cells. In a further study this suggestion has to be investigated in an anisotropic and heterogeneous 3D model.

Abstract:

A computer model of the human heart is presented, that starts with the electrophysiology of single myocardial cells including all relevant ion channels, spans the de- and repolarization of the heart including the generation of the Electrocardiogram (ECG) and ends with the contraction of the heart that can be measured using 4D Magnetic Resonance Imaging (MRI). The model can be used to better understand physiology and pathophysiology of the heart, to improve diagnostics of infarction and arrhythmia and to enable quantitative therapy planning. It can also be used as a regularization tool to gain better solutions of the ill-posed inverse problem of ECG. Movies of the evolution of electrophysiology of the heart can be reconstructed from Body Surface Potential Maps (BSPM) and MRI, leading to a new non-invasive medical imaging technique.

Abstract:

Heart Failure is the most common cardiac disease worldwide; supraventricular arrhythmia the most common cardiac arrhythmia. The understanding of these diseases advances treatment options. Ablation therapy is a well accepted non-pharmacological option in the treatment of atrial fibrillation. Cardiac resynchronization therapy with biventricular pacing devices has been shown successful in patients with severe heart failure. However, an optimization or even individual therapy planning is not standard or not even carried out today. These non-pharmacological treatments can be investigated and optimized with the help of computer models of the heart. Different ablation strategies are applied to terminate the arrhythmia in the virtual environment and a comparison of strategies can be carried out. With respect to cardiac resynchronization therapy, the computer model allows for automatic and non-invasive optimization of electrode positions and timing delays. With clinical validation, the presented computer models and methods have the potential to contribute to individualized therapy planning.

Abstract:

Nachdem in der Vergangenheit statische Computermodelle von der Anatomie des Patienten entwickelt wurden, stehen heute funktionelle Modelle im Vordergrund der Forschung, in denen beispielsweise Bewegungsabläufe oder physiologische Prozesse im Körper modelliert werden. Zielsetzung ist das bessere Verständnis der funktionellen Prozesse (Grundlagenforschung), die vertiefende Diagnose (Etiologie, Erkennen der Ursachen einer Erkrankung) und die systematische Optimierung der Therapie. Daneben können auch Lern-Werkzeuge für Ärzte daraus abgeleitet werden (Learning and Training). Um zu diesen Zielen zu gelangen, müssen funktionelle Vorgänge im Körper quantitativ verstanden und modelliert werden (Mathematical Physiology, Computational Biology). Erst die mathematische Beschreibung erlaubt die sichere Vorhersage. Vor Erreichen dieses Zieles ist viel Grundlagenforschung nötig, da viele funktionelle Abläufe im Körper noch nicht quantitativ bekannt sind. Oft bedeutet dies, dass Erkrankungen bis zur zellulären Ursache und bis zu den komplexen biologischen Regelkreisen mathematisch beschrieben werden müssen

Abstract:

Atrial fibrillation (AF) is the most common cardiac arrhythmia leading to a high rate of stroke. The underlying mechanisms of initiation and maintenance of AF are not fully understood. Several findings suggest a multitude of factors to leave the atria vulnerable to AF. In this work, a rule-based approach is taken to simulate the initiation of AF in a computer model for the purpose of generating a model with which the influence of anatomical structures, electrophysiological properties of the atria and arrhythmogenic activity can be evaluated. Pulmonary vein firing has been simulated leading to AF in 65.7 % of all simulations. The excitation pattern generated resemble chaotic excitation behavior, which is characteristic for AF as well as stable reentrant circuits responsible for atrial flutter. The findings compare well with literature. In future, the presented computer model of AF can be used in therapy planning such as ablation therapy or overdrive pacing.

Abstract:

Question: The mechanisms responsible for atrial fibrillation (AF) are not completely understood. Various conduction velocities and realistic anatomical structures of the atria are implemented into a computer model showing the influence of complex anatomical structures on the initiation and maintenance of AF.Method Used: In a computer model of the Visible Female heart (National Library of Medicine, Bethseda, Maryland, USA), the initiation of AF was simulated by pulmonary vein (PV) firing. The anatomical model had a resolution of 1,696,740 tissue voxel with 0.33 mm voxel side length. 32 foci around all pulmonary veins were set. The excitation propagation was simulated using an adaptive cellular automaton. Electrophysiological parameters depending on different tissue types can be set. In this work, only the conduction velocity was reduced compared to physiological data.Results: The initiation of AF through ectopic foci creates re-entrant circuits and quasi-chaotic excitation pattern in the computer model. 8 of 16 foci in the left superior, 3 of 4 foci in the left inferior, 5 of 8 foci in the right superior and 4 of 4 foci in the right inferior PV created AF after only 1.5 s. The excitation pattern shows stable re-entrant circuits as well as chaotic behavior. A breakup of stable re-entrant circuits was also observed when simulating the pathology for 17.5 s. The other foci caused self-terminating rotors.Conclusion: Computer models of the excitation propagation of the heart can be used to simulate AF initiated by triggers in the PV. A reduction in conduction velocity caused the establishment of re-entrant circuits and quasi-chaotic behavior. The complex model of the Visible Female heart showed the importance of anatomical structures in the maintenance of AF. Future work will include an improvement of the computer model by incorporating heterogeneities of atrial tissue and an implementation of individual patient models for therapy planning.

Abstract:

The approach to solve the inverse problem of electrocardiography presented here is using a computer model of the individual heart of a patient. It is based on a 3D-MRI dataset. Electrophysiologically important tissue classes are incorporated using rules. Source distributions inside the heart are simulated using a cellular automaton. Finite Element Method is used to calculate the corresponding body surface potential map. Characteristic parameters like duration and amplitude of transmembrane potential or velocity of propagation are optimized for selected tissue classes or regions in the heart so that simulated data fit to the measured data. This way the source distribution and its time course of an individual patient can be reconstructed.

Abstract:

The purpose of this study is to develop a computer model-based planning environment for therapeutically cardiac interventions, i.e. surgical or catheter ablation procedures in atrial cases and placing pacemaker electrodes in biventricular pacing. Existing mathematical models are used to simulate the electrophysiology on an anatomical pig model during a heart cycle. The results of these models were validated in multiple domestic pig animal experiments. We found that the models created enable us to simulate the electrical behaviour of the heart nearly in real time and that it reproduces the properties of the heart in atrial flutter and in ventricular pacing with different pacing locations. The results of computer-based simulations may lead to a better understanding of cardiac rhythm disorders and the development of new, less invasive operative techniques.

Abstract:

Atrial fibrillation (AF) is a critical pathology due to the risk of secondary diseases like thromboemboli and ventricular arrhythmia. A recent study identified a familial type of AF based on a mutation influencing the cardiac IKs channel. The mutant channel is characterized by a gain-of-function and a nearly linear current-voltage relationship. The kinetics and density of IKs in a model of atrial myocytes was adjusted to the measured characteristic to describe the mechanisms and effects of the mutation. A schematic anatomical model of the right atrium was designed to simulate the excitation propagation. The action potential duration of the mutant cell was reduced to 105 ms and the effective refractory period to 148 ms. Both factors lead to a reduction in wavelength and thus the risk of an initiation and perpetuation of AF rises. The results support the understanding of the complex behavior of cardiac cells. The described model will be used to investigate AF and potential treatments.

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The spatial resolution of Bioelectric Imaging of the Heart was investigated. Based on the measurement of a multichannel Electrocardiogram (ECG) or Magnetocardiogram (MCG) images of epicardial potential distributions can be reconstructed. The imaging properties of this method have been investigated using Computer simulations. The spatial resolution depends strongly on the number and arrangement of electrodes and magnetometers, on the noise level of the sensors and on the individual morphology of the patient. Artefacts show up if errors in the torso model (geometry and/or impedance values) occur.

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A procedure to find the optimal electrode positions for multichannel electrocardiography is presented. The criterion is the ability to reconstruct images of the electrical activity of the heart. Singular value decomposition of the lead field matrix is the chosen approach. The finite element method is used for numerical field calculation to determine the lead field matrix. Estimates on the expected measurement error play an important role in the optimization procedure. The optimal arrangement of electrodes is compared with other electrode positions reported in the literature using different optimization criteria. Body surface potential maps (BSPM) are measured on a healthy volunteer using the optimized electrode arrangement and preliminary epicardial potential patterns are reconstructed

Abstract:

A modular multichannel superconducting quantum interference device (SQUID) system, in which every channel can be optimized or replaced individually, was further improved. The number of channels was increased to 31. The noise level is better than 10 fT/&#8730;Hz. A novel way of RF shielding using conductive paint avoids degradation of the SQUID characteristics due to RF interference without introducing significant extra noise, so that the system works without any Faraday cage. A simplified way of coupling the modulation and feedback signal directly to the SQUID was developed and tested successfully. The SQUID module with superconducting connections to the gradiometer and its superconducting shield was miniaturized to an outer diameter of 5 mm, so that it can be placed near the gradiometer without introducing significant unbalance. Tests have demonstrated that the accuracy of the system with respect to the localization of a single current dipole is better than 2 mm

Abstract:

A modular low-noise seven-channel SQUID-magnetometer for biomagnetic measurements was developed. The DC-SQUIDs are prepared by thin film technology based on the materials NbN-MgO-NbN, and show a flux noise below 10 &#956;&#934;0/&#8730;Hz. The signal is picked up with first-order wire-wound gradiometers of 2-cm diameter and coupled to the SQUIDs by integrated coupling coils. Individual channels can be replaced from the system, and various gradiometers can be used giving a flexible modular system. The electronics are based on the flux-locked-loop method extended by a bias modulation technique to reduce 1/f noise. The overall system noise is below 20 fT/&#8730;Hz. Biomagnetic measurements on auditory evoked fields have been carried out

Abstract:

The different principles of sensor error correction are classified with respect to intrinsic or extrinsic compensation techniques, analog or digital techniques, and integrated or discrete techniques, and typical examples are given. Advantages and disadvantages of the different methods are analyzed, and future trends are outlined. One logical continuation of these trends is the application-specific IC for sensor signal amplification and error correction. On the other hand, inexpensive multipurpose ICs (e.g. an A/D converter and a microprocessor together with a small primary electronics to adapt the IC to the individual sensor type) should also find applications

Abstract:

IntroductionThe role of the right atrium (RA) in atrial fibrillation (AF) has long been overlooked. Computer models of the atria can aid in assessing how the RA influences arrhythmia vulnerability and in studying the role of RA drivers in the induction of AF, both aspects challenging to assess in living patients until now. It remains unclear whether the incorporation of the RA influences the propensity of the model to reentry induction. As personalized ablation strategies rely on non-inducibility criteria, the adequacy of left atrium (LA)-only models for developing such ablation tools is uncertain.AimTo evaluate the effect of incorporating the RA in 3D patient-specific computer models on arrhythmia vulnerability.MethodsImaging data from 8 subjects were obtained to generate patient-specific computer models. For each subject, we created 2 models: one monoatrial consisting only of the LA, and one biatrial model consisting of both the RA and LA. We considered 3 different states of substrate remodeling: healthy (H), mild (M), and severe (S). The Courtemanche et al. cellular model was modified from control conditions to a setup representing AF-induced remodeling with 0%, 50%, and 100% changes for H, M, and S, respectively. Conduction velocity along the myocyte preferential direction was set to 1.2, 1.0, and 0.8m/s for each remodeling level. To incorporate fibrotic substrate, we manually placed six seeds on each biatrial model, 3 in the LA and 3 in the RA, corresponding to regions with the most frequent enhancement (IIR>1.2) in LGE-MRI. The extent of the fibrotic substrate corresponded to the Utah 2 (5-20%) and Utah 4 (>35%) stages, for M and S respectively, while the H state was modeled without fibrosis. Electrical propagation in the atria was modeled using the monodomain equation solved with openCARP. Arrhythmia vulnerability was assessed by virtual S1S2 pacing from different points separated by 2cm. A point was classified as inducing arrhythmia if reentry was initiated and maintained for at least 1s. The vulnerability ratio was defined as the number of inducing points divided by the number of stimulation points. The mean tachycardia cycle length (TCL) of the induced arrhythmia was assessed at the stimulation site. We compared the vulnerability ratio of the LA in monoatrial and biatrial configurations.ResultsThe incorporation of the RA increased the mean LA vulnerability ratio by 115.79% (0.19±0.13 to 0.41±0.22, p=0.033) in state M, and 29.03% in state S (0.31±0.14 to 0.40±0.15, p=0.219) as illustrated in Figure 1. No arrhythmia was induced in the H models. RA inclusion increased the TCL of LA reentries by 5.51% (186.9±13.3ms to 197.2±18.3ms, p=0.006) in M scenario, and decreased it by 7.17% (224.3±27.6ms to 208.2±34.8ms, p=0.010) in scenario S. RA inclusion resulted in an elevated LA inducibility, revealing 4.9±3.3 additional points per patient in the LA for the biatrial model that did not induce reentry in the monoatrial model. ConclusionsThe LA vulnerability in a biatrial model differs from the LA vulnerability in a monoatrial model. Incorporating the RA in patient-specific computational models unmasked potential inducing points in the LA. The RA had a substrate-dependent effect on reentry dynamics, altering the TCL of LA-induced reentries. Our results provide evidence for an important role of the RA in the maintenance and induction of arrhythmia in patient-specific computational models, thus suggesting the use of biatrial models.

Abstract:

Atrial fibrillation (AF) is the most common sus- tained arrhythmia posing a significant burden to patients and leading to an increased risk of stroke and heart failure. Additional ablation of areas of arrhythmogenic substrate in the atrial body detected by either late gadolinium enhance- ment magnetic resonance imaging (LGE-MRI) or electro- anatomical mapping (EAM) may increase the success rate of restoring and maintaining sinus rhythm compared to the stan- dard treatment procedure of pulmonary vein isolation (PVI). To evaluate if LGE-MRI and EAM identify equivalent sub- strate as potential ablation targets, we divided the left atrium (LA) into six clinically important regions in ten patients. Then, we computed the correlation between both modalities by ana- lyzing the regional extents of identified pathological tissue. In this regional analysis, we observed no correlation between late gadolinium enhancement (LGE) and low voltage areas (LVA), neither in any region nor with regard to the entire atrial surface (−0.3 < 𝑟 < 0.3). Instead, the regional extents identified as pathological tissue varied significantly between both modali- ties. An increased extent of LVA compared to LGE was ob- served in the septal wall of the LA (𝑎 ̃sept.,LVA = 19.63 % and 𝑎 ̃sept.,LGE = 3.94 %, with 𝑎 ̃ = median of the extent of patho- logical tissue in the corresponding region). In contrast, in the inferior and lateral wall, the extent of LGE was higher than the extent of LVA for most geometries (𝑎 ̃inf.,LGE = 27.22% and 𝑎 ̃lat.,LGE = 32.70 % compared to 𝑎 ̃inf .,LVA = 9.21 % and 𝑎 ̃lat.,LVA = 6.69 %). Since both modalities provided dis- crepant results regarding the detection of arrhythmogenic sub- strate using clinically established thresholds, further investiga- tions regarding their constraints need to be performed in order to use these modalities for patient stratification and treatment planning.

Abstract:

Introduction: Although the effective refractory period (ERP) is one of the main electrophysiological properties governing atrial tachycardia (AT) maintenance, ERP personalization is rarely performed when creating patient-specifi c computer models of the atria to inform clinical decision-making. State-of-the-art models usually do not consider physiological ERP gradients but assume a homogeneous ERP distribution. This assumption might have an influence on the ability to induce reentries in the model.Aim: To evaluate the impact of incorporating clinical ERP measurements when creating in silico personalized models to predict vulnerability to atrial fibrillation (AF).Methods: Clinical ERP measurements were obtained from three patients from multiple locations in the atria. The protocol for ERP identification consisted of trains of 7 S1 stimuli with a basic cycle length of 500ms followed by an S2 stimulus with a coupling interval between 300 and 200ms in decrements of 10ms until loss of capture. The atrial geometries from the electroanatomical mapping system were used to generate personalized atrial models. To reproduce patient-specific ERP, the established Courtemanche cellular model was gradually reparameterized from control conditions to a setup representing AF-induced remodeling. Three different approaches were studied:1) a control scenario with no ERP personalization 2) a discrete split where each region had a single ERP value and3) a continuous ERP distribution by interpolation of measured ERP data (Fig. 1). Arrhythmia vulnerability was assessed by virtual S1S2 pacing from different locations separated by 3cm. The number and location of inducing points and type of arrhythmia were determined for the three approaches. The mean conduction velocity was setto 0.7 m/s and the electrical propagation in the atria was modeled by the monodomain equation and solved withopenCARP.Results: Incorporating patient-specific ERP as a continuous distribution did not induce any reentrant activity. A summary of induced ATs is shown in Table 1. For patient A, AF was induced from 3 different locations with the control setup, whereas 9 ATs were induced with the regional method, of which 4 were AF and 5 macro reentries. For patient B, AF was induced from 1 point with the control setup; whereas with the regional approach, AF was induced at 4 points. For patient C, only one macro reentry was induced with the regional method.Conclusion: The incorporation of patient-specifi c ERP values has an impact on the assessment of AF vulnerability. Furthermore, the type of personalization affects the likelihood of AF inducibility. The incorporation of more detailed ERP distributions may lead to a more accurate prediction of AF trigger points and could in the future inform patient-specifi c therapy planning. Larger cohorts need to follow to demonstrate the role of incorporating clinical patient-specifi c ERP values into personalized models for predicting AF vulnerability.

Abstract:

Regions with pathologically altered substrate have been identified as potentially proarrhythmic for atrial fibrillation. Mapping techniques, such as voltage mapping, are currently used to estimate the location of these fibrotic areas. Recently, local impedance (LI) has gained attention as another modality for atrial substrate assessment as it does not rely on the dynamically changing electrical activity of the heart. However, its limits for assessing non-transmural and complex fibrosis patterns have not yet been studied in detail. In this work, the ability of EGMs and LI to identify non-transmural fibrosis at different transmural levels using in silico experiments is explored. A pseudo-bidomain model was used to recover the extracellular potential on the surface of the tissue while LI reconstruction was calculated by a time-difference imaging approach with an homogeneous tissue background conductivity. Four fibrosis configurations were modeled to compare the two modalities using Pearson correlation coefficient. Only one transmural structure was detected by voltage whereas non-transmural structures, namely endo-, midmyo-, and epicardial, yielded zero. The correlation for LI maps ranged from -0.02 to 0.74. We conclude that LI, together with EGMs, can be expected to distinguish between healthy and fibrotic tissue, paving the way towards its use as a surrogate for non-transmural atrial substrate.

Abstract:

Computational models of the fluid dynamics in the human heart are a powerful tool to investigate disease mechanisms and their impact on the blood flow patterns. These models can for example be used to assess alterations occurring in hypertrophic cardiomyopathy, which is a genetic disease that increases the risk of sudden cardiac death. To overcome the challenges of a moving mesh approach, we modeled the movement of the endocardial surface based on an immersed boundary method. The verification on a simple moving 2D geometry proved plausible results. The application to the dis- eased, hypertrophic heart geometry confirmed that the computation of the mesh movement is made possible with this approach.

Abstract:

Clinical and computational studies highlighted the role of atrial anatomy for atrial fibrillation vulnerability. However, personalized computational models are often generated from electroanatomical maps, which might lack important anatomical structures like the appendages, or from imaging data which are potentially affected by segmentation uncertainty. A bi-atrial statistical shape model (SSM) covering relevant structures for electrophysiological simulations was shown to cover atrial shape variability. We hypothesized that it could, therefore, also be used to infer the shape of missing structures and deliver ready-to-use models to assess atrial fibrillation vulnerability in silico. We implemented a highly automatized pipeline to generate a personalized computational model by fitting the SSM to the clinically acquired geometries. We applied our framework to a geometry coming from an electroanatomical map and one derived from magnetic resonance images (MRI). Only landmarks belonging to the left atrium and no information from the right atrium were used in the fitting process. The left atrium surface-to-surface distance between electroanatomical map and a fitted instance of the SSM was 2.26+-1.95 mm. The distance between MRI segmentation and SSM was 2.07+-1.56 mm and 3.59+-2.84 mm in the left and right atrium, respectively. Our semi-automatic pipeline provides ready-to-use personalized computational models representing the original anatomy well by fitting a SSM. We were able to infer the shape of the right atrium even in the case of using information only from the left atrium.

Abstract:

Individualized computer models of the geometry of the human heart are often based on mag- netic resonance images (MRI) or computed tomography (CT) scans. The stress distribution in the imaged state cannot be measured but needs to be estimated from the segmented geometry, e.g. by an iterative algorithm. As the convergence of this algorithm depends on different geometrical conditions, we system- atically studied their influence. Beside various shape alterations, we investigated the chamber volume, as well as the effect of material parameters. We found a marked influence of passive material parameters: increasing the model stiffness by a factor of ten halved the residual norm in the first iteration. Flat and concave areas led to a reduced robustness and convergence rate of the unloading algorithm. With this study, the geometric effects and modeling aspects governing the unloading algorithm’s convergence are identified and can be used as a basis for further improvement.

Abstract:

Mitral regurgitation alters the flow conditions in the left ventricle. To account for quantitative changes and to investigate the behavior of different flow components, a realistic computational model of the whole human heart was employed in this study. While performing fluid dynamics simulations, a scalar transport equation was solved to analyze vortex formation and ventricular wash-out for different regurgitation severities. Additionally, a particle tracking algorithm was implemented to visualize single components of the blood flow. We confirmed a significantly lowered volume of the direct flow component as well as a higher vorticity in the diseased case.

Abstract:

Today a variety of models describe the physiological behavior of the heart on a cellular level. The intracellular calcium concentration plays an important role, since it is the main driver for the active contraction of the heart. Due to different implementations of the calcium dynamics, simulating cardiac electromechanics can lead to severely different behaviorsof the active tension when coupling the same tension model with different electrophysiological models. To handle these variations, we present an optimization tool that adapts the parameters of the most recent, human based tension model. The goal is to generate a physiologically valid tension development when coupled to an electrophysiological cellular model independent of the specifics of that model's calcium transient. In this work, we focus ona ventricular cell model. In order to identify the calcium-sensitive parameters, a sensitivity analysis of the tension model was carried out. In a further step, the cell model was adapted to reproduce the sarcomere length-dependent behavior of troponin C. With a maximum relative deviationof 20.3% per defined characteristic of the tension development, satisfactory results could be obtained for isometric twitch tension. Considering the length-dependent troponin handling, physiological behavior could be reproduced. In conclusion, we propose an algorithm to adapt the tension development model to any calcium transient input toachieve a physiologically valid active contraction on a cellular level. As a proof of concept, the algorithm is successfully applied to one of the most recent human ventricular cell models. This is an important step towards fullycoupled electromechanical heart models, which are a valuable tool in personalized health care

Abstract:

In order to be used in a clinical context, numerical simulation tools have to strike a balance between accuracy and low computational effort. For re- producing the pumping function of the human heart numerically, the physical domains of cardiac continuum mechanics and fluid dynamics have a significant relevance. In this context, fluid-structure interaction between the heart muscle and the blood flow is particularly important: Myocardial tension development and wall deformation drive the blood flow. However, the degree to which the blood flow has a retrograde effect on the cardiac mechanics in this multi-physics problem remains unclear up to now. To address this question, we implemented a cycle-to-cycle coupling based on a finite element model of a patient-specific whole heart geometry. The deforma- tion of the cardiac wall over one heart cycle was computed using our mechanical simulation framework. A closed loop circulatory system model as part of the simulation delivered the chamber pressures. The displacement of the endo- cardial surfaces and the pressure courses of one cycle were used as boundary conditions for the fluid solver. After solving the Navier-Stokes equations, the relative pressure was extracted for all endocardial wall elements from the three dimensional pressure field. These local pressure deviations were subsequently returned to the next iteration of the continuum mechanical simulation, thus closing the loop of the iterative coupling procedure. Following this sequential coupling approach, we simulated three iterations of mechanic and fluid simulations. To characterize the convergence, we evaluated the time course of the normalized pressure field as well as the euclidean distance between nodes of the mechanic simulation in subsequent iterations. For the left ventricle (LV), the maximal euclidean distance of all endocardial wall nodes was smaller than 2mm between the first and second iteration. The maximal distance between the second and third iteration was 70μm, thus the limit of necessary cycles was already reached after two iterations. In future work, this iterative coupling approach will have to prove its abil- ity to deliver physiologically accurate results also for diseased heart models. Altogether, the sequential coupling approach with its low computational effort delivered promising results for modeling fluid-structure interaction in cardiac simulations.

Abstract:

Atrial flutter (AFl) is a common heart rhythm disorder driven by different self-sustaining electrophysiological atrial mechanisms. In the present work, we sought to discriminate which mechanism is sustaining the arrhythmia in an individual patient using non-invasive 12-lead electrocardiogram (ECG) signals. Specifically, we analyse the influence of atrial and torso geometries for the success of such discrimination. 2,512 ECG were simulated and 151 features were extracted from the signals. Three classification scenarios were investigated: random set classification; leave-one-atrium-out (LOAO); and leave-one-torso-out (LOTO). A radial basis neural network classifier achieved test accuracies of 89.84%, 88.98%, and 59.82% for the random set classification, LOTO, and LOAO, respectively. The most discriminative single feature was the F-wave duration (74% test accuracy). Our results show that a machine learning approach can potentially identify a high number of different AFl mechanisms using the 12-lead ECG. More than the 8 atrial models used in this work should be included during training due to the significant influence that the atrial geometry has on the ECG signals and thus on the resulting classification. This non-invasive classification can help to identify the optimal ablation strategy, reducing time and resources required to conduct invasive cardiac mapping and ablation procedures.