Bernhard Pfeifer

A new rule-based algorithm for identifying metabolic markers in prostate cancer using tandem mass spectrometry

MOTIVATIONnProstate cancer is the most prevalent tumor in males and its incidence is expected to increase as the population ages. Prostate cancer is treatable by excision if detected at an early enough stage. The challenges of early diagnosis require the discovery of novel biomarkers and tools for prostate cancer management.nnnRESULTSnWe developed a novel feature selection algorithm termed as associative voting (AV) for identifying biomarker candidates in prostate cancer data measured via targeted metabolite profiling MS/MS analysis. We benchmarked our algorithm against two standard entropy-based and correlation-based feature selection methods [Information Gain (IG) and ReliefF (RF)] and observed that, on a variety of classification tasks in prostate cancer diagnosis, our algorithm identified subsets of biomarker candidates that are both smaller and show higher discriminatory power than the subsets identified by IG and RF. A literature study confirms that the highest ranked biomarker candidates identified by AV have independently been identified as important factors in prostate cancer development.nnnAVAILABILITYnThe algorithm can be downloaded from the following http://biomed.umit.at/page.cfm?pageid=516.

Cardiac anisotropy: is it negligible regarding noninvasive activation time imaging?

The aim of this study was to quantify the effect of cardiac anisotropy in the activation-based inverse problem of electrocardiography. Differences of the patterns of simulated body surface potential maps for isotropic and anisotropic conditions were investigated with regard to activation time (AT) imaging of ventricular depolarization. AT maps were estimated by solving the nonlinear inverse ill-posed problem employing spatio-temporal regularization. Four different reference AT maps (sinus rhythm, right-ventricular and septal pacing, accessory pathway) were calculated with a bidomain theory based anisotropic finite-element heart model in combination with a cellular automaton. In this heart model a realistic fiber architecture and conduction system was implemented. Although the anisotropy has some effects on forward solutions, effects on inverse solutions are small indicating that cardiac anisotropy might be negligible for some clinical applications (e.g., imaging of focal events) of our AT imaging approach. The main characteristic events of the AT maps were estimated despite neglected electrical anisotropy in the inverse formulation. The worst correlation coefficient of the estimated AT maps was 0.810 in case of sinus rhythm. However, all characteristic events of the activation pattern were found. The results of this study confirm our clinical validation studies of noninvasive AT imaging in which cardiac anisotropy was neglected.

A Finite Element Formulation for Atrial Tissue Monolayer

OBJECTIVESnUsing computer models for the study of complex atrial arrhythmias such as atrial fibrillation is computationally demanding as long observation periods in the order of tens of seconds are required. A well established approach for reducing computational workload is to approximate the thin atrial walls by curved monolayers. On the other hand, the finite element method (FEM) is a well established approach to solve the underlying partial differential equations.nnnMETHODSnA generalized 2D finite element method (FEM) is presented which computes the corresponding stiffness and coupling matrix for arbitrarily shaped monolayers (ML). Compared to standard 2D FEM, only one additional coordinate transformation is required. This allows the use of existing FEM software with minor modifications. The algorithm was tested to simulate wave propagation in benchmark geometries and in a model of atrial anatomy.nnnRESULTSnThe ML model was able to simulate electric activation in curved tissue with anisotropic conductivity. Simulations in branching tissue yielded slightly different patterns when compared to a volumetric model with finite thickness. In the model of atrial anatomy the computed activation times for five different pacing protocols displayed a correlation of 0.88 compared to clinical data.nnnCONCLUSIONSnThe presented method provides a useful and easily implemented approach to model wave propagation in MLs with a few restrictions to volumetric models.

Multi-lead ECG electrode array for clinical application of electrocardiographic inverse problem

Methods for noninvasive imaging of electric function of the heart might become clinical standard procedure the next years. Thus, the overall procedure has to meet clinical requirements as easy and fast application. In this study we propose a new electrode array which improves the information content in the ECG map, considering clinical constraints such as easy to apply and compatibility with routine leads. A major challenge is the development of an electrode array which yields a high information content even for a large interindividual variation in torso shape. For identifying regions of high information content we introduce the concept of a locally applied virtual electrode array. As a result of our analysis we constructed a new electrode array consisting of two L-shaped regular spaced parts and compared it to the electrode array we use for clinical studies upon activation time imaging. We assume that one side effect caused by the regular shape and spacing of the new array be that the reconstruction of electrodes placed on the patients back is simplified. It may be sufficient to record a few characteristic electrode positions and merge them with a model of the posterior array.

A training whole-heart model for simulating propagation and ECG patterns

Abstract The forward problem of electrocardiography describes the spatio-temporal source–field relationship generating the body surface potential (BSP) and, thus, the electrocardiogram (ECG). The paper presents a ventricular and atrial model for simulating cardiac de- and repolarization and the P-, QRS- and T-wave. The atria and the ventricles are coupled, so that electroanatomical function can be simulated at ones. Movement and contraction are not taken into account while an individual geometry, fibre architecture and ECG sensor arrangement including the Wilson central terminal (WCT) as common reference were considered. This in silico whole-heart model can be used for detailed investigations of the nature of the ECG for the normal beat, arrhythmias, ischemia and infarction. In addition, this model was used as a reference tool for developing and testing different electrocardiographic inverse approaches.

An Epidemiological Modeling and Data Integration Framework

OBJECTIVESnIn 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.nnnMETHODSnThe 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).nnnRESULTSnThe obtained simulation results were used for generating prediction models for all nine federal states of Austria.nnnCONCLUSIONnThe 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.

Combining active appearance models and morphological operators using a pipeline for automatic myocardium extraction

A geometrical model of the human heart is of interest in many fields of biophysics. The myocardium contains the electrical sources responsible for the generation of the body-surface ECG. An accurate geometric knowledge of these sources is crucial when dealing with the electrocardiographic forward and inverse problem. We developed a semiautomatic approach for segmenting the myocardium in order to deal with the electrocardiographic problem. The approach can be divided into two main steps. The first step extracts the atrial and ventricular blood masses by employing Active Appearance Models (AAM). The ventricular blood masses are segmented automatically after providing the positions of the apex cordis and the base of the heart. Due to the complex geometry of the atria the segmentation process of the atrial blood masses requires more information. We divided, therefore, the left and the right atrium into three divisions of appearance: the base of the heart, the lower pulmonary veins from its first up to the last appearance in the image stack, and the upper pulmonary veins. After successful extraction of the blood masses the second step involves morphologically-based operations in order to extract the myocardium either directly by detecting the myocardium in the volume block, or by reconstructing the myocardium using mean model information, in case the algorithm fails to detect the myocardium.

Simulation of atrial electrophysiology and body surface potentials for normal and abnormal rhythm

The effect of different atrial electrical activation sequences (sinus rhythm and atrial flutter circling in the right atrium) on the body surface potentials is investigated in this study. A realistic volume conductor model consisting of atria, lungs, chest and blood masses is generated from image stacks recorded by magnetic resonance imaging. The electrical sources-the transmembrane potentials-within the atrial volumetric model are simulated for different atrial rhythms employing a cellular automaton capable of considering different parameters depending on the specific properties of the tissues. The potentials on the torso surface are computed applying the finite element method for solving the differential equations derived from the bidomain theory. Both the simulated atrial activation patterns and the computed torso potentials for atrial sinus rhythm and atrial flutter are in qualitatively and quantitatively good agreement with data measured in humans. The simulation of body surface potentials generated by different electrical activation sequences in the atria or ventricles allows testing and assessing noninvasive imaging of cardiac electrophysiology, as both the potentials on the body surface and the reference activation in the heart are available.

Quantification of blood flow velocity in stenosed arteries by the use of finite elements: an observer-independent noninvasive method

Interventions for peripheral arterial disease should be designed to treat a physiological rather than an anatomic defect. Thus, for vascular surgeons, functional information about stenoses is as important as the anatomic one. In case of finding a stenosis by the use of magnetic resonance angiography, it would be a matter of particular interest to derive automatically and directly objective information about the hemodynamic influence on blood flow, caused by patient-specific stenoses. We developed a methodology to noninvasively perform numerical simulations of a patients hemodynamic state on the basis of magnetic resonance images and by the means of the finite element method. We performed patient-specific three-dimensional simulation studies of the increase in systolic blood flow velocity due to stenoses using the commercial computational fluid dynamic software package FIDAP 8.52. The generation of a mesh defining the flow domain with a stenosis and some simulation results are shown.

KOPPLUNG VON KERNSPIN-TOMOGRAPHIE UND EKG-MAPPING ZUR AKTIVIERUNGSSEQUENZBESTIMMUNG DES HERZENS

S I M M A K Y : Nonmvusive imaging of cardiac electroplusiolot y (NIC l · ) provides detailed Information about clcctrical propagation through the heart during cardi.iv.· arrhytlunuis. NICE can be accomplished by the l us io n öl data from magnetic resonance imaging and ckvtrocardiographie mapping. Io dato, only some studies of clinical validation of nonimas ive activation lime imaging has been reported, lnch results from the complexity of data acquisition in the catheier laboratory. l kvtrophysiology studies in all 4 chambers were perlormed in K) patients. Activation time maps on the ondoand cpicardium of the heart were calculated and validated vvith catheter-based electroanatomical data (( ARTO ). The mean error localizing characteristic evcnts (pacing sites, accessory pathways, or first endocurdial breakthroughs) was 8.5 mni (5mm to 18mm). The eorrelation coefficient of the activation time maps of the target chamber ranged between 0.7 and 0.95. Clmical validation studies of cardiac arrhythmias in the atria (e.g. flutter and fibrillation) by means of catheter mapping techniques are the focus of further research.