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.
O. Dössel, G. Reinerth, T. M. Schmidt, G. Seemann, J. Albers, S. Hagl, and C. F. Vahl. Simulation of biventricular activity in ventricular pacing on 3D-echocardiographic images using the cellular automaton in a porcine model. In The Thoracic and Cardiovascular Surgeon, vol. 52(S1) , pp. 22, 2004
C. Kausch, B. Schreiber, F. Kreuder, R. Schmidt, and O. Dössel. Monte Carlo simulations of the imaging performance of metal plate/phosphor screens used in radiotherapy. In Medical Physics, vol. 26(10) , pp. 2113-2124, 1999
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.
T. Schmidt, and O. Dössel. Testprozeduren für die Qualitätskontrolle von Vielkanal-Biomagnetometersystemen. In Biomedizinische Technik, vol. 38(s1) , pp. 189-190, 1993
Abstract:
Mit zunehmendem Einsatz von Vielkanal-Biomagnetometersystemen im klinischen Bereich gewinnt auch die Frage nach einer verläßlichen Qualitätskontrolle an Bedeutung. Immer häufiger werden die Ergebnisse einer biomagnetischen Messung zur Grundlage einer medizinischen Entscheidung gemacht. Besonders bei der Verwendung als prächirurgische Zusatzinformation stellt dies aber hohe Anforderungen an die Präzision und die Reproduzierbarkeit der Meßergebnisse. Mit dieser Zielrichtung wurde ein Meßprogramm erarbeitet, das die leistungsbestimmenden Parameter eines Biomagnetometers erfaßt und die realistischen Bedingungen in der klinischen Umgebung berücksichtigt. Im Vordergrund stehen dabei Messungen zum Rauschverhalten des Systems und zur Lokalisierungsgenauigkeit. Mit den vorgestellten Testprozeduren ist eine einfache, reproduzierbare und die relevanten Qualitätsaspekte abdeckende Überprüfung eines Vielkanal-Magnetometersystems möglich. Regelmäßige Anwendung deckt Fehlerquellen und damit verbundene Ungenauigkeiten auf und erlaubt die Zuverlässigkeit medizinischer Meßergebnisse einzuschätzen. Darüberhinaus werden die Ergebnisse verschiedener Systeme besser vergleichbar, was insbesondere bei multizentrischen Studien von Bedeutung ist.
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 remodeled substrate induced by chronic AF (cAF) and patients suffering from familial AF. To date, the reasons for these phenomena are only incompletely understood. We analyzed the effects of these two drugs in a computational model of atrial electrophysiology. The Courtemanche-Ramirez-Nattel model was adapted to represent cAF remodeled 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 analyzed 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. 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.
Catheter ablation of atrial fibrillation (AF) is still challenging and the sustaining mechanisms are discussed controversially. Basket mapping has emerged to a promising technique to detect temporary events like focal impulses fast changing fibrillation waves or meandering rotors.The aim of this study was to evaluate the atrial coverage of the basket catheter with respect to the distance of the electrodes to the endocardial surface and inter spline separation.
A. Luik, C. Schilling, M. Merkel, K. Schmidt, O. Dössel, and C. Schmitt. Impact of energy and CFAE classification in patients with persistent atrial fibrillation - analysis by a newly developed automatic algorithm (fuzzy decision tree). In Clinical Research in Cardiology, vol. 101(s1) , 2012
Atrial myofiber orientation is complex and has multiple discrete layers and bundles. A novel robust semi-automatic method to incorporate atrial anisotropy and heterogeneities into patient-specific models is introduced. The user needs to provide 22 distinct seed-points from which a network of auxiliary lines is constructed. These are used to define fiber orientation and myocardial bundles. The method was applied to 14 patient-specific volumetric models derived from CT, MRI and photographic data. Initial electrophysiological simulations show a significant influence of anisotropy and heterogeneity on the excitation pattern and P-wave duration (20.7% shortening). Fiber modeling results show good overall correspondence with anatomical data. Minor modeling errors are observed if more than four pulmonary veins exist in the model. The method is an important step towards creating realistic patient-specific atrial models for clinical applications.
Atrial fibre architecture has complex patterns of bundles and layers and is known to impact on atrial electrophysiology, especially in fast-conducting bundles like Crista Terminalis, Bachmanns bundle and pectinate muscles. Based on a priori knowledge of atrial fibre structure, we incorporated rule-based fibre orientation in seven volumetric models of human atria using a semi-automatic approach. We were able to introduce multiple layers of myofibres and regional heterogeneities of ion channels in the models. We evaluated the influence of complete atrial fibre architecture on multiple modelling scales. First, we simulated atrial excitation in the isotropic and anisotropic models using the model of Courtemanche et al. in combination with the monodomain approach. Second, we computed body surface potentials from the simulated transmembrane voltages and compared these to measured ECGs from the respective patients. Temporal behaviour of the atrial excitation sequences was significantly altered in the anisotropic models compared to the sequences in the isotropic models. Complete atrial activation was achieved approximately 20% faster in the anisotropic models mostly due to fast conducting myofibre bundles. Electrophysiological heterogeneities influenced right atrial transmembrane voltage distribution over time due to a less negative action potential plateau in Crista Terminalis cells. P-wave duration was significantly shorted by the introduction of atrial anisotropy and the error to measured P-wave duration was reduced. Furthermore, a pattern change in body surface potential distribution over time was observed. The anisotropic patterns showed a better match to the measurements. Thus, the modelling error by using generalised fibre architecture for patient-specific models was smaller than by using isotropic models. The results highlight the necessity to incorporate atrial anisotropy in personalised models to produce more realistic simulations. The semi-automatic approach allows the use of these models for future clinical applications.
Motivation: Anatomical models of the heart can be used to conduct multi-physics simulations. These simulations can aid basic and clinical research and are being translated into clinical practice nowadays.Problem statement: The human myocardium has very complex fiber structure, which has a strong impact on cardiac physiology. To understand and evaluate 3D fiber orientation in volumetric cardiac models, it is often necessary to project these onto printed pictures.Approach: Images of myocardial fibers using color-coded cylinders, color-coded streamlines and anaglyph methods are compared. Results: Streamlines provide a good distinction of myocardial bundles. Cylinders show the most accurate results. Color-coded representations reveal abrupt changes in fiber direction. Anaglyph visualizations give an illusion of depth in 2D prints and can display overlaying bundles. Conclusions: Streamlines are superior in imaging global fiber orientation, whereas cylinders give better results for local structures. Color-coding increases information where fiber structure is very complex, e.g. in the atria. Anaglyph images cause a loss in color information but help the viewer to understand the 3D object. Overall, it is necessary to choose the appropriate method of picturing fibers for specific tasks.
V. Schmidt. Semi-automatische Methode zur Modellierung der Faserorientierung in patienten-spezifischen Vorhofgeometrien. Institut für Biomedizinische Technik, Karlsruher Institut für Technologie (KIT). Diplomarbeit. 2010
V. Schmidt. Entwicklung einer graphischen Benutzeroberfläche für rechnergestützte Modelle der zellulären Elektrophysiologie. Universität Karlsruhe. Diplomarbeit. 2008