Alterations of field potentials in isotropic cardiomyocyte cell layers induced by multiple endogenous pacemakers under normal and hypothermal conditions.

The use of autonomous contracting randomly grown cardiomyocyte monolayers cultivated on microelectrode arrays (MEAs) represents an accepted experimental setting for preclinical experimental research in the field of cardiac electrophysiology. A dominant pacemaker forces a monolayer to adhere to a regular and synchronized contraction. Randomly distributed multiple pacemakers interfere with this dominant center, resulting in more or less frequent changes of propagation direction. This study aims to characterize the impact of changing propagation directions at single electrodes of the MEA on the four intrinsic parameters of registered field potentials (FPs) FPrise, FPMIN, FPpre, and FPdur and conduction velocity (CV) under normal and hypothermal conditions. Primary cultures of chicken cardiomyocytes (n = 18) were plated directly onto MEAs and FPs were recorded in a temperature range between 37 and 29°C. The number and spatiotemporal distribution of biological and artificial pacemakers of each cell layer inside and outside of the MEA registration area were evaluated using an algorithm developed in-house. In almost every second myocardial cell layer, interfering autonomous pacemakers were detected at stable temperatures, showing random spatial distributions with similar beating rates. Additionally, a temperature-dependent change of the dominant pacemaker center was observed in n = 16 experiments. A significant spread-direction-dependent variation of CV, FPrise, FPMIN, and FPpre up to 14% could be measured between different endogenous pacemakers. In conclusion, based on our results, disregarding the spatial origin of excitation may lead to misinterpretations and erroneous conclusions of FP parameters in the verification of research hypotheses in cellular electrocardiology.

Atrial and ventricular myocardium extraction using model-based techniques.

OBJECTIVES: This paper presents an efficient approach for extracting myocardial structures from given atrial and ventricular blood masses to enable non-invasive estimation of electrical excitation in human atria and ventricles. METHODS: Based on given segmented atrial and ventricular blood masses, the approach constructs the myocardial structure directly, in the case that the myocardium can be detected in the volume data, or by using mean model information, in the case that the myocardium cannot be seen in the volume data due to image modalities or artefacts. The approach employs mathematical and gray-value morphology operations. Regulated by the spatial visibility of the myocardial structure in the medical image data especially the atrial myocardium needs to be estimated repeatedly using the a-priori knowledge given by the anatomy. RESULTS: The approach was tested using eight patient data sets. The reconstruction process yielded satisfying results with respect to an efficient generation of a volume conductor model which is essential when trying to implement the estimation of electrical excitation in clinical application. CONCLUSION: The approach yields ventricular and atrial models that qualify for cardiac source imaging in a clinical setting.

Computationally efficient noninvasive cardiac activation time imaging.

OBJECTIVE: The computer model-based computation of the cardiac activation sequence in humans has been recently subject of successful clinical validation. This method is of potential interest for guiding ablation therapy of arrhythmogenic substrates. However, computation times of almost an hour are unattractive in a clinical setting. Thus, the objective is the development of a method which performs the computation in a few minutes run time. METHODS: The computationally most expensive part is the product of the lead field matrix with a matrix containing the source pattern on the cardiac surface. The particular biophysical properties of both matrices are used for speeding up this operation by more than an order of magnitude. A conjugate gradient optimizer was developed using C++ for computing the activation map. RESULTS: The software was tested on synthetic and clinical data. The increase in speed with respect to the previously used Fortran 77 implementation was a factor of 30 at a comparable quality of the results. As an additional finding the coupled regularization strategy, originally introduced for saving computation time, also reduced the sensitivity of the method to the choice of the regularization parameter. CONCLUSIONS: As it was shown for data from a WPWpatient the developed software can deliver diagnostically valuable information at a much shorter span of time than current clinical routine methods. Its main application could be the localization of focal arrhythmogenic substrates.

A signal processing pipeline for noninvasive imaging of ventricular preexcitation.

OBJECTIVES: Noninvasive imaging of the cardiac activation sequence in humans could guide interventional curative treatment of cardiac arrhythmias by catheter ablation. Highly automated signal processing tools are desirable for clinical acceptance. The developed signal processing pipeline reduces user interactions to a minimum, which eases the operation by the staff in the catheter laboratory and increases the reproducibility of the results. METHODS: A previously described R-peak detector was modified for automatic detection of all possible targets (beats) using the information of all leads in the ECG map. A direct method was applied for signal classification. The algorithm was tuned for distinguishing beats with an adenosine induced AV-nodal block from baseline morphology in Wolff-Parkinson-White (WPW) patients. Furthermore, an automatic identification of the QRS-interval borders was implemented. RESULTS: The software was tested with data from eight patients having overt ventricular preexcitation. The R-peak detector captured all QRS-complexes with no false positive detection. The automatic classification was verified by demonstrating adenosine-induced prolongation of ventricular activation with statistical significance (p <0.001) in all patients. This also demonstrates the performance of the automatic detection of QRS-interval borders. Furthermore, all ectopic or paced beats were automatically separated from sinus rhythm. Computed activation maps are shown for one patient localizing the accessory pathway with an accuracy of 1 cm. CONCLUSIONS: The implemented signal processing pipeline is a powerful tool for selecting target beats for noninvasive activation imaging in WPW patients. It robustly identifies and classifies beats. The small beat to beat variations in the automatic QRS-interval detection indicate accurate identification of the time window of interest.

Lead field computation for the electrocardiographic inverse problem--finite elements versus boundary elements.

In order to be able to solve the inverse problem of electrocardiography, the lead field matrix (transfer matrix) has to be calculated. The two methods applied for computing this matrix, which are compared in this study, are the boundary element method (BEM) and the finite element method (FEM). The performance of both methods using a spherical model was investigated. For a comparable discretization level, the BEM yields smaller relative errors compared to analytical solutions. The BEM needs less computation time, but a larger amount of memory. Inversely calculated myocardial activation times using either the FEM or BEM computed lead field matrices give similar activation time patterns. The FEM, however, is also capable of considering anisotropic conductivities. This property might have an impact for future development, when also individual myocardial fiber architecture can be considered in the inverse formulation.

Ventricular surface activation time imaging from electrocardiogram mapping data.

Non-invasive imaging of cardiac electrophysiology provides a non-invasive way of obtaining information about electrical excitation. An iterative algorithm based on a general regularisation scheme for non-linear, ill-posed problems in Hilbert scales was applied to the electrocardiographic inverse problem, imaging the ventricular surface activation time (AT) map. This method was applied to electrocardiographic data from a 31-year-old healthy volunteer and a 24-year-old patient suffering from a Wolff-Parkinson-White (WPW) syndrome. The objective was to evaluate non-invasive AT imaging of an autonomous sinus rhythm and to quantify the localisation error of non-invasive AT imaging by localising the accessory pathway of the WPW syndrome and a pacing site for left ventricle pacing. The distances between the invasive and non-invasive localisation of the pacing site and the accessory pathway were 8 mm and 5 mm. The clinical case presented, shows that this non-invasive AT imaging approach may enable the reconstruction of single focal events with sufficient accuracy for potential clinical application.

An epidemiological modeling and data integration framework.

OBJECTIVES: In this work, a cellular automaton software package for simulating different infectious diseases, storing the simulation results in a data warehouse system and analyzing the obtained results to generate prediction models as well as contingency plans, is proposed. The Brisbane H3N2 flu virus, which has been spreading during the winter season 2009, was used for simulation in the federal state of Tyrol, Austria. METHODS: The simulation-modeling framework consists of an underlying cellular automaton. The cellular automaton model is parameterized by known disease parameters and geographical as well as demographical conditions are included for simulating the spreading. The data generated by simulation are stored in the back room of the data warehouse using the Talend Open Studio software package, and subsequent statistical and data mining tasks are performed using the tool, termed Knowledge Discovery in Database Designer (KD3). RESULTS: The obtained simulation results were used for generating prediction models for all nine federal states of Austria. CONCLUSION: The proposed framework provides a powerful and easy to handle interface for parameterizing and simulating different infectious diseases in order to generate prediction models and improve contingency plans for future events.

Patient-specific volume conductor modeling for non-invasive imaging of cardiac electrophysiology.

We propose a general workflow to numerically estimate the spread of electrical excitation in the patients' hearts. To this end, a semi-automatic segmentation pipeline for extracting the volume conductor model of structurally normal hearts is presented. The cardiac electrical source imaging technique aims to provide information about the spread of electrical excitation in order to assist the cardiologist in developing strategies for the treatment of cardiac arrhythmias. The volume conductor models of eight patients were extracted from cine-gated short-axis magnetic resonance imaging (MRI) data. The non-invasive estimation of electrical excitation was compared with the CARTO maps. The development of a volume conductor modeling pipeline for constructing a patient-specific volume conductor model in a fast and accurate way is one essential step to make the technique clinically applicable.

Ultraviolet spectrophotometer for measuring columnar atmospheric ozone from aircraft.

An ultraviolet spectrophotometer (UVS) to measure downward solar fluxes from an aircraft or other high altitude platform is described. The UVS uses an ultraviolet diffuser to obtain large angular response with no aiming requirement, a twelve-position filter wheel with narrow (2-nm) and broad (20-nm) bandpass filters, and an ultraviolet photodiode. The columnar atmospheric ozone above the UVS (aircraft) is calculated from the ratios of the measured ultraviolet fluxes. Comparison with some Dobson station measurements gives agreement to 2%. Some UVS measured ozone profiles over the Pacific Ocean for November 1976 are shown to illustrate the instrument's performance.

Treatment of laser-induced thermal acoustics in the framework of discrete kinetic theory

The physics behind the laser-induced thermal acoustics technique is dealt with on a microscopic level. A discrete velocity model of the Boltzmann equation for inelastically interacting gas mixtures in the presence of two counterpropagating laser beams is established. The collisional scheme for the model is developed by taking into account elastic and inelastic interactions between the gas particles, on the one hand, and the interactions between monochromatic laser photons and gas particles, on the other hand. The formation and evolution of laser-pulse-driven thermal and density gratings are simulated by numerically solving the discrete kinetic equations based on the fractional step method. Numerical results are provided for a wide scope of Knudsen numbers.

Calibration of an extreme-ultraviolet transmission grating spectrometer with synchrotron radiation.

The responsivity of an extreme-ultraviolet transmission grating spectrometer with silicon photodiode detectors was measured with synchrotron radiation. The spectrometer was designed to record the absolute radiation flux in a wavelength bandpass centered at 30 nm. The transmission grating had a period of 200 nm and relatively high efficiencies in the +1 and the -1 diffraction orders that were dispersed on either side of the zero-order beam. Three photodiodes were positioned to measure the signals in the zero order and in the +1 and -1 orders. The photodiodes had aluminum overcoatings that passed the desired wavelength bandpass centered at 30 nm and attenuated higher-order radiation and wavelengths longer than approximately 80 nm. The spectrometer's responsivity, the ratio of the photodiode current to the incident radiation power, was determined as a function of the incident wavelength and the angle of the spectrometer with respect to the incident radiation beam. The spectrometer's responsivity was consistent with the product of the photodiode responsivity and the grating efficiency, both of which were separately measured while removed from the spectrometer.