Fluid–structure interaction analysis of eccentricity and leaflet rigidity on thrombosis biomarkers in bioprosthetic aortic valve replacements

This work intends to study the effect of aortic annulus eccentricity and leaflet rigidity on the performance, thrombogenic risk and calcification risk in bioprosthetic aortic valve replacements (BAVRs). To address these questions, a two-way immersed fluid–structure interaction (FSI) computational model was implemented in a high-performance computing (HPC) multi-physics simulation software, and validated against a well-known FSI benchmark. The aortic valve bioprosthesis model is qualitatively contrasted against experimental data, showing good agreement in closed and open states. Regarding the performance of BAVRs, the model predicts that increasing eccentricities yield lower geometric orifice areas (GOAs) and higher normalized transvalvular pressure gradients (TPGs) for healthy cardiac outputs during systole, agreeing with in vitro experiments. Regions with peak values of residence time are observed to grow with eccentricity in the sinus of Valsalva, indicating an elevated risk of thrombus formation for eccentric configurations. In addition, the computational model is used to analyze the effect of varying leaflet rigidity on both performance, thrombogenic and calcification risks with applications to tissue-engineered prostheses. For more rigid leaflets it predicts an increase in systolic and diastolic TPGs, and decrease in systolic GOA, which translates to decreased valve performance. The peak shear rate and residence time regions increase with leaflet rigidity, but their volume-averaged values were not significantly affected. Peak solid stresses are also analyzed, and observed to increase with rigidity, elevating risk of valve calcification and structural failure. To the authors' knowledge this is the first computational FSI model to study the effect of eccentricity or leaflet rigidity on thrombogenic biomarkers, providing a novel tool to aid device manufacturers and clinical practitioners.This project has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 713673. The research leading to these results has also received funding from “la Caixa” Foundation, with fellowship ID: LCF/BQ/DI18/11660044, and has been co-funded by the project CompBioMed2 (H2020-EU.1.4.1.3. Grant No. 823712)Peer ReviewedPostprint (published version

Ondas y turbulencia cuasi-geostrófica en flujos rotantes y estratificados

Fil:Oks, David. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina

High-performance computing fluid-structure interaction model of bioprosthetic aortic valve replacements

(English) Computational modeling and simulation (CM&S) provides a powerful cost- and time-efficient tool to access detailed mechanistic information of biomedical problems, which is not accessible in either clinical imaging or in vitro bench testing. This enables the efficient testing of medical devices for a wide range of design parameters and working conditions, dictated by patient-specific characteristics such as age, gender, ethnicity, or comorbidities. Furthermore, computational models can be used to simulate not only single patients or bench-test setups but also populations of virtual patients, from either clinical or synthetic databases to obtain informative statistics. These studies, known as in silico clinical trials, can be used to reduce, refine and augment both animal and bench tests. CM&S can thus reduce cost and accelerate the time-to-market of medical devices while improving their safety and efficacy before the first-in-human implantation. In this thesis, a predictive fluid-structure interaction (FSI) computational model of bioprosthetic heart valve replacements was developed to be used in supercomputing environments and applied to problems of biomedical and clinical interest. The end objective is to provide a framework to test and optimize valve prostheses. Given that transcatheter aortic valve replacements (TAVRs) are being implanted in lower-risk and younger patients, long-term effects such as leaflet thrombosis have become a critical concern for patients, doctors, and device manufacturers. This work is focused on predicting the thrombogenic risk and overall hemodynamic performance of bioprosthetic aortic valve replacements. Motivated by minimizing patient-device mismatch, the main questions of interest addressed involve evaluating the effect of multiple geometric and material parameters on prosthesis performance. Some of these parameters include aortic annulus eccentricity, the diameter of the sinotubular junction, coronary alignment, and leaflet rigidity. In this thesis, both in vitro and patient-specific settings were modeled, according to the application of interest. For the model to run in practical computational times, the immersed finite element FSI method developed was designed to meet high-performance computing (HPC) standards. The numerical method was validated against well-known FSI benchmarks, and its performance was analyzed using HPC tools and was deployed in Barcelona Supercomputing Center's in-house multi-physics code, Alya. The model solves the two-way coupling between fluid and solid mechanics, together with fluid-particle dynamics to model the risk of platelet activation. The completeness and efficiency of the tool open an array of possibilities for predicting the performance of devices in patient-specific settings. This thesis hence represents a step towards in silico medicine becoming the gold standard in R&D of novel medical devices, regulatory submissions, and clinical planning.(Español) El modelado y simulación computacional (CM&S por sus siglas en inglés) proporciona una poderosa herramienta para acceder a información mecanística detallada de problemas biomédicos, a la que no se puede acceder mediante imágenes clínicas o estudios in-vitro. Esto permite eficientemente evaluar el funcionamiento de dispositivos médicos en una amplio rango de parámetros de diseño y condiciones de trabajo, determinadas por las características específicas del paciente, como la edad, el sexo, el origen étnico o las comorbilidades. Además, los modelos computacionales se pueden utilizar para simular no solo pacientes individuales o configuraciones de prueba de banco, sino también poblaciones de pacientes virtuales, ya sea a partir de bases de datos clínicos o generados sintéticamente para obtener estadísticas informativas. Estos estudios, conocidos como ensayos clínicos in-silico, se pueden utilizar para reducir, refinar y aumentar las pruebas en animales y de banco. De este modo, CM&S permite reducir costos y acelerar los tiempos de comercialización de dispositivos médicos, al mismo tiempo mejorando su seguridad y eficacia antes de la primer implantación en un humano.En esta tesis, se desarrolló un modelo computacional predictivo de interacción fluido-estructura (FSI por sus siglas en inglés) de reemplazos de válvulas cardíacas bioprotésicas, diseñado para ser ejecutado eficientemente en superordenadores. Este modelo fue aplicado a problemas de interés biomédico y clínico. El objetivo final es proporcionar un marco para probar y optimizar diseños de prótesis de la válvula aórtica. Dado que los reemplazos de válvula aórtica transcatéter (TAVR por sus siglas en inglés) se están implantando en pacientes más jóvenes y de menor riesgo, los efectos a largo plazo, como la trombosis valvular, se han convertido en un problema crítico para pacientes, médicos y fabricantes de dispositivos. Este trabajo se centra en la predicción del riesgo trombogénico y el rendimiento hemodinámico general de los reemplazos bioprostéticos de la válvula aórtica. Motivados por minimizar el desajuste entre el paciente y el dispositivo, las principales preguntas de interés abordadas involucran la evaluación del efecto de múltiples parámetros geométricos y materiales sobre el desempeño de la prótesis. Algunos de estos parámetros incluyen la excentricidad del anillo aórtico, el diámetro de la unión sinotubular, la alineación coronaria y la rigidez de las valvas. En esta tesis se modelaron escenarios tanto in-vitro como paciente-específicos, según la aplicación de interés. Para que el modelo se ejecute en tiempos computacionales prácticos, el método FSI de elementos finitos inmersos fue diseñado para cumplir con los estándares de computación de alto rendimiento (HPC por sus siglas en inglés) y se implementó en el código multifísico interno de Barcelona Supercomputing Center, Alya. El método numérico se validó contra pruebas de referencia de FSI, y su rendimiento se analizó utilizando herramientas de HPC. El modelo resuelve el acoplamiento bidireccional entre la mecánica de fluidos y sólidos, junto con la dinámica de fluidos y partículas para modelar el riesgo de activación de plaquetas. La integridad y la eficiencia de la herramienta abren la puerta a una serie de posibilidades para predecir el rendimiento de los dispositivos en entornos específicos del paciente. Por lo tanto, esta tesis representa un paso para que la medicina in-silico se convierta en el estándar en I+D de nuevos dispositivos, procesos de aprobación regulatoria y en planificación clínicaDOCTORAT EN MATEMÀTICA APLICADA (Pla 2012

Suspension of large inertial particles in a turbulent swirling flow

International audienceWe present experimental observations of the spatial distribution of large inertial particles suspended in a turbulent swirling flow at high Reynolds number. The plastic particles, which are tracked using several high speed cameras, are heavier than the working fluid so that their dynamics results from a competition between gravitational effects and turbulent agitation. We observe two different regimes of suspension. At low rotation rate, particles are strongly confined close to the bottom and are not able to reach the upper region of the tank whatever their size or density. At high rotation rate, particles are loosely confined: small particles become nearly homogeneously distributed while very large objects are preferentially found near the top as if gravity was reversed. We discuss these observations in light of a minimal model of random walk accounting for particle inertia and show that large particles have a stronger probability to remain in the upper part of the flow because they are too large to reach descending flow regions. As a consequence particles exhibit random horizontal motions near the top until they reach the central region where the mean flow vanishes, or until a turbulent fluctuation gets them down

Performance assessment of an electrostatic filter-diverter stent cerebrovascular protection device. Is it possible not to use anticoagulants in atrial fibrilation elderly patients?

Stroke is the second leading cause of death worldwide. Nearly two-thirds of strokes are produced by cardioembolisms, and half of cardioembolic strokes are triggered by Atrial Fibrillation (AF), the most common type of arrhythmia. A more recent cause of cardioembolisms is Transcatheter Aortic Valve Replacements (TAVRs), which may onset post-procedural adverse events such as stroke and Silent Brain Infarcts (SBIs), for which no definitive treatment exists, and which will only get worse as TAVRs are implanted in younger and lower risk patients. It is well known that some specific characteristics of elderly patients may lower the safety and efficacy of anticoagulation therapy, making it a real urgency to find alternative therapies. We propose a device consisting of a strut structure placed at the base of the treated artery to model the potential risk of cerebral embolisms caused by dislodged debris of varying sizes. This work analyzes a design based on a patented medical device, intended to block cardioembolisms from entering the cerebrovascular system, with a particular focus on AF, and potentially TAVR patients. The study has been carried out in two stages. Both of them based on computational fluid dynamics (CFD) coupled with Lagrangian particle tracking method. The first stage of the work evaluates a variety of strut thicknesses and inter-strut spacings, contrasting with the device-free baseline geometry. The analysis is carried out by imposing flowrate waveforms characteristic of both healthy and AF patients. Boundary conditions are calibrated to reproduce physiological flowrates and pressures in a patient's aortic arch. In the second stage, the optimal geometric design from the first stage was employed, with the addition of lateral struts to prevent the filtration of particles and electronegatively charged strut surfaces, studying the effect of electrical forces on the clots if they are considered charged. Flowrate boundary conditions were used to emulate both healthy and AF conditions. Results from numerical simulations coming form the first stage indicate that the device blocks particles of sizes larger than the inter-strut spacing. It was found that lateral strut space had the highest impact on efficacy. Based on the results of the second stage, deploying the electronegatively charged device in all three aortic arch arteries, the number of particles entering these arteries was reduced on average by 62.6% and 51.2%, for the healthy and diseased models respectively, matching or surpassing current oral anticoagulant efficacy. In conclusion, the device demonstrated a two-fold mechanism for filtering emboli: while the smallest particles are deflected by electrostatic repulsion, avoiding microembolisms, which could lead to cognitive impairment, the largest ones are mechanically filtered since they cannot fit in between the struts, effectively blocking the full range of particle sizes analyzed in this study. The device presented in this manuscript offers an anticoagulant-free method to prevent stroke and SBIs, imperative given the growing population of AF and elderly patients

Sources of high-density gaseous plasma based on a discharge with electron injection

A novel technique of high-density gaseous plasma generation was explored, and several plasma sources based on this technique were developed. The sources utilize a DC high-current (up to 35 A) gaseous discharge with electron injection into the cathode region. Electron generation and injection is accomplished by using an additional arc discharge with a cold hollow cathode. Low contamination of plasma is achieved by low discharge voltage (avoidance of sputtering), as well as by special geometric configuration of the emitter discharge electrodes thereby filtering (removing) the erosion products stemming from the emitter cathode. The devices produce a uniform and stable gaseous plasmas with density up to 1011 cm-3 in a volume of 1 m3, at the pressure of 3x10-4 Torr and higher. The sources are characterized by high reliability, low maintenance and long lifetime. The specific electric power consumption is 140 eV per one generated ion. The sources operate with noble gases, nitrogen, oxygen and hydrocarbons, and can be used for plasma immersion ion implantation and other ion technologies

Validation and Sensitivity analysis for a nasal spray deposition computational model

info:eu-repo/semantics/publishe

Hardware platforms for MEMS gyroscope tuning based on evolutionary computation using open-loop and closed -loop frequency response

We propose a tuning method for MEMS gyroscopes based on evolutionary computation to efficiently increase the sensitivity of MEMS gyroscopes through tuning. The tuning method was tested for the second generation JPL/Boeing Post-resonator MEMS gyroscope using the measurement of the frequency response of the MEMS device in open-loop operation. We also report on the development of a hardware platform for integrated tuning and closed loop operation of MEMS gyroscopes. The control of this device is implemented through a digital design on a Field Programmable Gate Array (FPGA). The hardware platform easily transitions to an embedded solution that allows for the miniaturization of the system to a single chip

Tuning of MEMS Gyroscope using Evolutionary Algorithm and "Switched Drive-Angle" Method

We propose a tuning method for Micro-Electro-Mechanical Systems (MEMS) gyroscopes based on evolutionary computation that has the capacity to efficiently increase the sensitivity of MEMS gyroscopes through tuning and, furthermore, to find the optimally tuned configuration for this state of increased sensitivity. We present the results of an experiment to determine the speed and efficiency of an evolutionary algorithm applied to electrostatic tuning of MEMS micro gyros. The MEMS gyro used in this experiment is a pyrex post resonator gyro (PRG) in a closed-loop control system. A measure of the quality of tuning is given by the difference in resonant frequencies, or frequency split, for the two orthogonal rocking axes. The current implementation of the closed-loop platform is able to measure and attain a relative stability in the sub-millihertz range, leading to a reduction of the frequency split to less than 100 mHz