The influence of bicuspid aortic valves on the dynamic pressure distribution in the ascending aorta: a porcine ex vivo model †

OBJECTIVES The aim of the study was to simulate the effect of different bicuspid aortic valve configurations on the dynamic pressure distribution in the ascending aorta. METHODS Aortic specimens were harvested from adult domestic pigs. In Group 1, bicuspidalization was created by a running suture between the left and the right coronary leaflets (n = 6) and in Group 2 by a running suture between the left and the non-coronary leaflets (n = 6). Eleven tricuspid specimens served as controls. Two intraluminal pressure catheters were positioned at the concavity and the convexity of the ascending aorta. The specimens were connected to a mock circulation (heart rate: 60 bpm, target pressure: 95 mmHg). A comparison of the different conditions was also done in a numerical simulation. RESULTS At a distal mean aortic pressure of 94 ± 10 mmHg, a mean flow rate of 5.2 ± 0.3 l/min was achieved. The difference of maximal dynamic pressure values (which occurred in systole) between locations at the convexity and the concavity was 7.8 ± 2.9 mmHg for the bicuspid and 1.0 ± 0.9 mmHg for the tricuspid specimens (P < 0.001). The numerical simulation revealed an even higher pressure difference between convexity and concavity for bicuspid formation. CONCLUSIONS In this hydrodynamic mock circulation model, we were able to demonstrate that bicuspid aortic valves are associated with significant pressure differences in different locations within the ascending aorta compared with tricuspid aortic valves. These altered pressure distributions and flow patterns may further add to the understanding of aneurismal development in patients with bicuspid aortic valves and might serve to anticipate adverse aortic events due to a better knowledge of the underlying mechanism

Differences in biocompatibility of microneedles from cyclic olefin polymers with human endothelial and epithelial skin cells

Microneedles are promising devices for transdermal delivery and diagnostic applications, due to their minimally invasive and painless nature of application. However, so far, applications are limited to small scale research projects. Material selection and production for larger projects remain a challenge. In vitro testing using human cell culture could bridge the gap between cost effective screening of suitable materials and concerns for safety and ethics. In this study, materials were tested for effects on viability and morphology of human endothelial cells and keratinocytes. In addition, materials were assessed for their potential to influence cellular differentiation and barrier formation. Elution-based testing of inflammatory markers revealed no negative effects in all applied tests, whereas the assessment of differentiation markers on cells in direct contact with the material showed differences and allowed the selection of candidate materials for future medical device applications. This study illustrates that elution-based biocompatibility testing can paint an incomplete picture. Advanced staining techniques and cell types specific for the application of the medical device improve material selection to reduce and replace animal testing at an early stage in the development process. © 2018 The Authors. journal Of Biomedical Materials Research Part A Published By Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 505–512, 2019

Piezoelectric inkjet coating of injection moulded, reservoir-tipped microneedle arrays for transdermal delivery

Coated microneedles have significant potential for use in transdermal delivery applications. In this paper, we describe the fabrication of microneedle master templates using microstereolithography techniques and subsequently use a commercial injection moulding process to replicate these microneedles in biocompatible cyclic olefin polymer (COP) materials. Notably, the 475 μm-tall needle designs feature a shallow pit or reservoir at the tip, thereby providing both a target and holder for incoming droplets that are deposited using a piezoelectric inkjet printer. Using this design, no tilting or rotation of the needle array is required during the filling process. In the preliminary tests reported here, the reservoir is filled with a FITC-labelled dye that acts as a model drug, and ex vivo skin tests are used to verify skin penetration, the transfer of this model drug to the skin and to measure the reliability of the needles themselves. To our knowledge, this is the first time that such an inkjet-filled, reservoir-tipped microneedle has been demonstrated

A combined CFD and structural analysis of blood flow in pathologic aortic geometries

Zsfassung in dt. SpracheZahlreiche klinische Studien belegen durch das gemeinsame gehäufte Auftreten einen kausalen Zusammenhang zwischen stenosierten bikuspidalen Aortenklappen und DeBakey Typ I Aortendissektionen. Neben histo-pathologischen Faktoren werden eventuelle biomechanische Gründe als potentielle Auslöser dieser Krankheit angenommen. Mit Hilfe von numerischen CFD Simulationen untersuchten wir potentielle Effekte des durch die Klappenstenose veränderten Strömungsfeldes auf die Aortenwand. Methoden: Das pulsatile Geschwindigkeitsfeld der Blutströmung durch die menschliche Aorta in Ruhe und unter Arbeitsbedingungen wurde numerisch für normale Klappen und verschiedene Typen von bikuspidalen Aortenklappen zusammen mit 3 verschiedenen Größen von Aortendissektionen simuliert. Ein steifes Modell des links-ventrikulären Ausflusstrakts, der jeweils offenen Klappe und des Aortenbogens wurde durch ein Netz mit ca. 1.5Mio Zellen diskretisiert. Das Blut wurde als Newtonsche Flüssigkeit approximiert, Turbulenz wurde mit Hilfe des Transition-SST-k-omega-Solvers von ANSYS® modelliert. Neben globalen hemodynamischen Observablen wurden die Geschwindigkeit des Blut-Jets, Wanddruck, Wandschubspannung und der Staudruck zwischen den bereits dissektierten Arterienlamellen berechnet und visualisiert. Anschließend wurde basierend auf den berechneten Druckwerten unter Ausnutzung des generalisierten Hooke´schen Gesetzes mit Hilfe einer inkrementellen Prozedur eine vergleichende Festigkeitsüberprüfung der Aortenwand und unter Zuhilfenahme von elementaren hydrostatischen Überlegungen die potentielle Dissektionskraft auf die verschieden großen Lamellen durchgeführt um diese dann im Kontext mit experimentellen Materialversagenswerten diskutieren zu können. Resultate: Normale Aortenklappen erreichen systolische Blutgeschwindigkeiten von ca. 1.2m/s, Wanddrücke von 117mmHg und Staudrücke welche allesamt nicht größer als 8mmHg werden, stenosierte bikuspidale Aortenklappen mit einem ellipsoiden Öffnungsverhältnis von 21:6mm hingegen belasten die Wand der aorta ascendens proximal des truncus brachiocephalicus mit systolischen Jets von bis zu 4.4m/s, Wanddrücken um 160mmHg und Staudrücken bis zu 45mmHg. Das Resultat im bikuspidalen Fall sind pulsatile Kraftspitzen von 0.288N auf die delaminierten Wandschichten mit einer Fläche von 48mm 2. Im Falle normaler Aortenklappen fallen die Kraftspitzen mit 0,051N deutlich geringer aus. Ein Vergleich zwischen quantitativen und qualitativen Zusammenhängen zwischen physiologischen und pathologischen Wandspannungen mit belastungsinduzierten Ermüdungserscheinungen der Aortenwand lässt ein signifikant erhöhtes Dissektionsrisiko der Aortenwand im bikuspidalen Fall vermuten. Schlussfolgerungen: Die durch stenosierte bikuspidale Aortenklappen verursachte erhöhte Strömungsgeschwindigkeit des Blutes führt zu signifikant erhöhten Wanddrücken und Staudrücken, was mit hoher Wahrscheinlichkeit die Ursache, zumindest aber einen begünstigenden Faktor bei Bildung und Vergrößerung von Dissektionen der aorta ascendends darstellt.It is known from clinical practice that stenotic bicuspid aortic valves (BAV) are frequently associated with DeBakey Type I aortic dissections. Beside eventual histopathologic reasons, biomechanical causes are considered as potential reason. We investigated the potential effects of the disturbed flow field on the aortic wall by CFD simulation. Methods: Pulsatile blood flow distribution through the human aorta at rest and exercise was numerically assessed for normal valves and different BAV configurations, together with 3 sizes of aortic dissected layers. A stiff model of the ventricular outflow tract, the open valve and the aortic arch was digitized with 1.5mio cells. Newtonian conditions were assumed, using the Transition-SST-k-omega-solver of ANSYS®. Besides global hemodynamic values, jet velocity, wall pressure, wall shear stress and ram pressure within the dissected area were calculated. Subsequently, a comparative durability approval analysis and assessment of potential dissection force based on predicted blood pressure values and incremental solutions of generalized Hooke´s law of elasticity is discussed in context with aortic failure stress data. Results: Whereas a normal AV provides systolic jet velocities of 1.2m/s, wall pressures of only 117mmHg and a ram pressure of less than 8mmHg, BAV with an opening relation of 21:6mm show systolic jet velocities of 4.4m/s, wall pressures of 160mmHg and ram pressures of up to 45mmHg ram pressure at the ascending aorta proximal of the brachiocephalic trunk.This resulted e.g. in a pulsatile peak force of 0,288N on the delaminated wall layer of an assumed size of 48mm 2. For the normal AV, this force would be only 0,051N. Comparison of quantitative interrelations between physiologic and increased aortic wall stress with tissue weakening processes reveal significantly increased risk of dissection. Conclusion: The increase of jet velocity caused by stenotic BAV leads to a significantly increased wall pressure and ram pressure, which may be a cause or at least a promoting factor of development and propagation of ascending aortic dissection.12

Development and improvement of parallel Optical Coherence Tomography modalities for biomedical imaging

Das Ziel dieser Arbeit war es zu zeigen, mit einer alternativen, parallelen Beleuchtungs- und Aufnahmemethode die Aufnahmegeschwindigkeit zu erhöhen ohne an Sensitivität, Auflösung und Kontrast einzubüßen und den technologischen Aufwand auf einem Minimum zu halten. Zu diesem Zwecke wurde ein neuartiges medizinisches Diagnosegerät (LPSI) entwickelt und in vivo getestet, welches auf paralleler Beleuchtung des Auges mit einer fokussierten Linie anstatt eines einzelnen Punktes basiert. Das vom Auge rückgestreute Licht der gesamten Linienbeleuchtung wird in paralleler Weise mit einer Linienkamera aufgenommen und erlaubt daher sehr schnelle Aufnahmegeschwindigkeit ohne dass man auf komplexe durchstimmbare Laser mit ultraschneller Wiederholrate, teure Datenerfassung und resonante mechanische Scanner zurückgreifen muss. Zusätzliche erlaubt die Linienbeleuchtung mehr Lichtleistung pro Zeiteinheit in das Auge einzustrahlen, was bei Erhöhung der Aufnahmegeschwindigkeit zu einer höheren Sensitivität im Vergleich zu Geräten mit Punktfokus führt. Im Vergleich zu viel langsameren Geräten basierend auf Punktfokusbeleuchtung zeigen die in vivo Resultate eine vergleichbare oder bessere Performance hinsichtlich Kontrast, Auflösung und Sensitivität. Die Ergebnisse dieser Arbeit untermauern das große diagnostische, wissenschaftliche und wirtschaftliche Potential, das in Geräten mit paralleler Linienbeleuchtung steckt und könnten sogar zu einem Paradigmenwechsel in der Augendiagnose führen.Despite the advances in imaging speed of Optical Coherence Tomography (OCT) modalities it is necessary to further increase the 3D imaging speed especially for applications requiring large field of view and increased sampling rate. The central objective of the presented thesis was to manifest the theoretical advantages of parallel OCT paradigm for in vivo retinal diagnosis. For this purpose, a novel high-speed medical imaging modality based on the parallel OCT paradigm was developed and demonstrated for in vivo imaging. The presented method uses line-field swept source illumination at a central wavelength of 840 nm and parallel detection of the spectral signal with a fast linear array detector. Line-field parallel swept source interferometric imaging (LPSI) permits higher retinal exposure and therefore enables high-speed imaging at higher sensitivity. LPSI utilizes an off-axis alignment of the reference arm to create a spatial modulation of the interferometric signal for full range imaging. This enables doubling the imaging speed as compared to conventional swept source OCT approaches with cost-effective and commercially available technology. The in vivo results obtained in human nailfold and the retina demonstrate competitive sensitivity, speed, image contrast and penetration depth when compared to much slower point scanning OCT modalities. Based on a theoretical prelude explaining the optical imaging properties and the interferometric signal of the LPSI system, the schematic of the bench-top setup, image acquisition and the post-processing routines for structural imaging, optical angiography and digital refocusing are described. The presented results appreciate the potential of LPSI for retinal diagnosis and might even lead to a change in paradigm in ophthalmic OCT imaging.Abweichender Titel laut Übersetzung der Verfasserin/des VerfassersZsfassung in dt. SpracheWien, Med. Univ., Diss., 2015OeBB(VLID)171522

Wide-Field OCT Angiography at 400 KHz Utilizing Spectral Splitting

Optical angiography systems based on optical coherence tomography (OCT) require dense sampling in order to maintain good vascular contrast. We demonstrate a way to gain acquisition speed and spatial sampling by using spectral splitting with a swept source OCT system. This method splits the recorded spectra into two to several subspectra. Using continuous lateral scanning, the lateral sampling is then increased by the same factor. This allows increasing the field of view of OCT angiography, while keeping the same transverse resolution and measurement time. The performance of our method is demonstrated in vivo at different locations of the human retina and verified quantitatively. Spectral splitting can be applied without any changes in the optical setup, thus offering an easy way to increase the field of view of OCT in general and in particular for OCT angiography

The influence of bicuspid aortic valves on the dynamic pressure distribution in the ascending aorta: A porcine ex vivo model

OBJECTIVES: The aim of the study was to simulate the effect of different bicuspid aortic valve configurations on the dynamic pressure distribution in the ascending aorta. METHODS: Aortic specimens were harvested from adult domestic pigs. In Group 1, bicuspidalization was created by a running suture between the left and the right coronary leaflets (n = 6) and in Group 2 by a running suture between the left and the non-coronary leaflets (n = 6). Eleven tricuspid specimens served as controls. Two intraluminal pressure catheters were positioned at the concavity and the convexity of the ascending aorta. The specimens were connected to a mock circulation (heart rate: 60 bpm, target pressure: 95 mmHg). A comparison of the different conditions was also done in a numerical simulation. RESULTS: At a distal mean aortic pressure of 94 ± 10 mmHg, a mean flow rate of 5.2 ± 0.3 l/min was achieved. The difference of maximal dynamic pressure values (which occurred in systole) between locations at the convexity and the concavity was 7.8 ± 2.9 mmHg for the bicuspid and 1.0 ± 0.9 mmHg for the tricuspid specimens (P < 0.001). The numerical simulation revealed an even higher pressure difference between convexity and concavity for bicuspid formation. CONCLUSIONS: In this hydrodynamic mock circulation model, we were able to demonstrate that bicuspid aortic valves are associated with significant pressure differences in different locations within the ascending aorta compared with tricuspid aortic valves. These altered pressure distributions and flow patterns may further add to the understanding of aneurismal development in patients with bicuspid aortic valves and might serve to anticipate adverse aortic events due to a better knowledge of the underlying mechanisms

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Visualization in the Einstein Year 2005: A Case Study on Explanatory and Illustrative Visualization of Relativity and Astrophysics

with relativistic and astrophysical visualization, which has been culminating in a substantial engagement for visualization in the Einstein Year 2005---the 100 anniversary of Einstein&apos;s publications on special relativity, the photoelectric effect, and Brownian motion. This paper focuses on explanatory and illustrative visualizations used to communicate aspects of the difficult theories of special and general relativity, their geometric structure, and of the related fields of cosmology and astrophysics. We discuss visualization strategies, motivated by physics education and didactics of mathematics, and describe what kind of visualization methods have proven to be useful for different types of media, such as still images in popular-science magazines, film contributions to TV shows, oral presentations, or interactive museum installations. Although our visualization tools build upon existing methods and implementations, these techniques have been improved by several novel technical contributions like image-based special relativistic rendering on GPUs, an extension of general relativistic ray tracing to manifolds described by multiple charts, GPU-based interactive visualization of gravitational light deflection, as well as planetary terrain rendering. The usefulness and effectiveness of our visualizations are demonstrated by reporting on experiences with, and feedback from, recipients of visualizations and collaborators