Involuntary childlessness represents a sensitive and emotionally moving topic. Depending on the method, reproductive treatments are associated with significant physical, psychological and financial burdens. Female sterility is caused by Fallopian tube occlusions in one of three cases. Our previously described microstent technology opens up new therapeutic possibilities to restore the lumen of the Fallopian tube without surgery. In this work, Finite Element Analysis was performed for design optimization of a polymeric selfexpanding microstent which had a limited crimping diameter by self-contact resulting in challenging loading behavior during application preparation. Three different stent designs were investigated. A bilinear constitutive material model considering isotropic hardening was used for modeling of the microstent. To evaluate the stent variations, the following criteria were defined: self-contact, maximum stresses (von Mises stress) and volume of stress above 45 MPa. All microstent designs were crimped to a diameter of 1.0 mm using Finite Element Analysis. Stent design version 1 and 2 were limited to crimping diameter considering self-contact. The wave-shaped cell design of version 3 completely prevented self-contact up to a diameter of 1.0 mm. Consequently, stent design version 3 offers the greatest potential for a self-expanding polymeric microstent for minimally invasive treatment of Fallopian tube occlusions.

Due to promising results, the patient cohort for transcather aortic valve replacement (TAVR) has been extended in recent years to include patients with a bicuspid aortic valve (BAV). There are different types of BAV. One variant is the tricommisural bicuspid aortic valve (TBAV). BAV have an increased risk of post-TAVR complications such as paravalvular leakage. In the case of paravalvular leakage, blood flows past the prosthesis back into the ventricle during diastole. Clinically, patients with BAV are often pre-dilated. For this reason, we want to investigate how pre-dilatation of BAV can affect the leakage rate. A simplified model is used for pre-dilatation, where the calcification nodule is cut along the free edge of the leaflets before the deployment. In order to evaluate the effects of this method, a deployment simulation was carried out for both geometries using an explicit calculation. A flow simulation was then performed to determine the paravalvular leakage. The pre-dilatation allows the leaflets to move independently of each other. Without pre-dilatation, the TAVR cannot fully expanded. The leakage rate is higher for the BAV than for the pre-dilated geometry (53.1mLs−1 vs. 19.4mLs−1). In this model, we have shown the effect of pre-dilatation on implantation results.

In silico simulations can be used to evaluate and optimize the safety, quality, efficacy and applicability of medical devices. Furthermore, in silico modeling is a powerful tool in therapy planning to optimally tailor treatment for each patient. For this purpose, a workflow to perform fast preoperative risk assessment of paravalvular leakage (PVL) after transcatheter aortic valve replacement (TAVR) is presented in this paper. To this end, a novel, efficient method is introduced to calculate the regurgitant volume in a simplified, but sufficiently accurate manner. A proof of concept of the method is obtained by comparison of the calculated results with results obtained from in vitro experiments. Furthermore, computational fluid dynamics (CFD) simulations are used to validate more complex stenosis scenarios. Comparing the simplified leakage model to CFD simulations reveals its potential for procedure planning and qualitative preoperative risk assessment of PVL. Finally, a 3D device deployment model and the efficient leakage model are combined to showcase the application of the presented leakage model, by studying the effect of stent size and the degree of stenosis on the regurgitant volume. The presented leakage model is also used to visualize the leakage path. To generalize the leakage model to a wide range of clinical applications, further validation on a large cohort of patients is needed to validate the accuracy of the model’s prediction under various patient-specific conditions.

Transcatheter aortic valve replacement (TAVR) has become the standard treatment of multimorbid patients with severe aortic valve stenosis. One frequently observed complication after TAVR procedure is the occurence of paravalvular leakage (PVL). PVL is caused by a gap between the vessel wall and the TAVR stent, enabling blood to flow from the aorta back to the ventricle during diastolic phase. A high PVL rate leads to increased mortality of TAVR patients. To avoid this complication, pericardial skirts were developed by manufacturers to seal the leakage gap. Furthermore, the aim is to improve the conforming expansion of the TAVR stent to the vessel wall, especially for the self-expanding TAVR consisting of nitinol. One factor for the expansion is the size and shape of the TAVR stent cells, which vary between 9 and 15 cells in the circumferential direction for established TAVR devices. To quantify the impact of different cell sizes on the occurence of PVL, we performed numerical studies with different TAVR designs and investigated the PVL for each TAVR design. For this purpose, we developed three different TAVR designs with 9, 12 and 15 stent cells in the circumferential direction of the TAVR. These were deployed into a generic aortic root model with standardized calcification in the annulus region using finite element simulations. Afterwards, the PVL was calculated using numerical flow simulations. We found that the TAVR stent design with nine cells had the highest PVL rate (11.2mLs−1). In contrast, the TAVR stent design with 15 cells had the lowest PVL (4.8mLs−1). Our study thus showed a decisive impact of cell size on the sealing behavior of the TAVR stent and, accordingly, the PVL.

Minimally invasive transcatheter aortic valve replacement (TAVR) procedure has become the preferred procedure for patients with aortic valve stenosis or insufficiency with high risk for conventional open surgery. The favorable clinical outcomes of high-risk patients led to an expansion of the cohort including intermediate and low-risk patients. A critical aspect of advancing TAVR procedures lies in preoperative planning, integrating patient-specific in-silico deployment simulation and post-deployment fluid mechanics assessments. This study introduces a novel approach to calcified TAVR patient shape modeling, addressing this problems. The model integrates an extended mesh generated by DeepCarve, encompassing the aortic arch, and a novel deep learning-based volumetric shape model of calcifications. The key innovation lies in the utilization of a conditional Convolutional Variational Autoencoder (cCVAE) to generate realistic calcification patterns, demonstrating promising preliminary results in matching actual cohort data. Future investigations should focus on data collection from diverse medical centers to validate and refine the proposed methodology. This study showcases significant progress in generating synthetic TAVR patient geometries, incorporating detailed anatomical structures such as the aortic root, valve, and arch, along with volumetric calcification patterns. These findings represent a crucial step towards enabling real-time preoperative TAVR planning, inclusive of patient- specific in-silico deployment simulation and comprehensive fluid mechanics assessments.

Transcatheter aortic valve replacement (TAVR) has become the standard therapy for aortic valve stenosis in patients with high surgical risk. Understanding the flow dynamics in TAVR is crucial for its evaluation and optimization. Experimental flow measurement by means of Particle Image Velocimetry (PIV) is increasingly applied alongside numerical analyses. This study introduces a novel test rig concept enabling the determination of velocity fields using Stereo-PIV under steady forward flow conditions through a TAVR during the peak systole matching the ISO 5840-1:2021 requirements. The experimental setup utilized an impeller pump to generate steady forward flow through a silicone aortic root model with implanted TAVR. A Stereo-PIV setup captured velocity fields in both ventricular inflow and aortic outflow regions. Test conditions were based on physiological flow rates determined from pulsatile measurements. Illumination of the added particles in the test fluid was achieved using an Nd:YAG laser. Fluorescent polystyrol particles (size: 50 μm) were used for flow visualization. Results showed characteristic flow patterns: a central jet flow entering the TAVR in the ventricular flow field. A jet flow directed towards the sinus side and a recirculation zone forming on the opposite side of the sinus could be detected in the aortic outflow. The width of the recirculation zone increases with distance from the TAVR. Maximum flow velocities were detected at 0.78 m/s for the ventricular flow field and 0.94 m/s for the aortic flow field. This study provides a comprehensive approach for fluid dynamic analysis of TAVR under steady flow conditions, offering insights into flow mechanics performance crucial for device optimization. Further investigations could enhance the PIV - measurement procedure by increasing both the spatial resolution and the tracer particle density within the acquired images for a comprehensive characterization of TAVR flow dynamics.

Abstract Due to excellent clinical results, transcatheter aortic valve replacement (TAVR) has evolved to a treatment option for patients with low surgical risk, resulting in an increasing demand for durable heart valve prostheses. Durability of TAVR could be limited by leaflet thrombosis. Thrombus formation in the aortic root is mainly affected by the hemodynamic situation, which is dependent on the positioning of the implant. We investigated the flow field in the aortic root after TAVR implantation by means of particle image velocimetry. To quantify the influence of the implant-position with respect to an alignment or misalignment of the leaflet commissures on the thrombogenic potential, we used a transport equation for residence time (RT) to consider washout behavior. Furthermore, we introduced a shear effect criterion (SIE) to address platelet activation as a measure for a potential thrombus formation. Misaligned implantation of a TAVR resulted in a reversed direction of rotation of the occurring recirculation area. This led to fluid flow with comparable areas of increased relative blood RT (RTaligned: 97.6%, RTmisaligned: 88.0%) and a smaller area of low shear load for the misaligned TAVR (SIEaligned: 57.7%, SIEmisaligned: 3.70%) into the sinus region, indicating a higher potential for thrombus formation.

Implantation of a shunt system is the most common neurosurgical procedure for the treatment of hydrocephalus. Hydrodynamic parameters of hydrocephalus shunt systems are valuable variables to address patients' needs. In this report, we present a test setup to evaluate hydrodynamic parameters of hydrocephalus shunt systems. The test setup was validated using a stainless steel capillary and compared with the analytical solution according to Bernoulli's equation. It was demonstrated that the experimental setup is able to model the pressure in a physiologically relevant range. The measured and averaged flow resistance was 2.96 mmHg/(ml min-1). According to the analytical solution of Bernoulli's equation, the flow resistance is 2.86 mmHg/(ml min-1). Therefore, the measured flow resistance is 3.5% higher than the analytical solution. Moreover, the nonlinear characteristic of the pressure drop at the inlet and outlet of the capillary plays a minor role compared to the friction of the tube flow. As a result, the increase in flow rate with increasing pressure load can be well approximated by a linear function for the low flow rates measured here. The experimental setup presented will be used in the future to characterize commercially available shunt systems under various hydrodynamic conditions.

The minimally invasive therapy for the treatment of aortic valve regurgitation and stenosis, transcatheter aortic valve replacement (TAVR), is an alternative to surgical valve replacement. Promising clinical results led to the consideration of expanding the use of TAVR in younger patients with lower surgical risk. This implies a longer durability of the TAVR. In relation to the durability of the TAVR, thickening of TAVR leaflets, including reduced motion, has been clinically observed. The aim of this study was to analyse the effects of valve leaflet thickening with reduced leaflet kinematics on the hemodynamics. We measured the flow through a TAVR under pulsatile conditions by using phase-resolved particle image velocimetry (PIV). It has been shown that flow conditions alter in a pathological manner in a TAVR replica with thickened leaflets compared with thin leaflets. In detail, shear stress and Reynolds stress increased by up to a factor of two and additionally the washout behaviour was worse for thickened leaflets. This suggests that a thickened valve is at higher risk for platelet activation and aggregation. This could lead to a self-reinforcing process in which the formation of a thickened valve promotes thrombus formation, which in turn promotes further progression of the thickening.

Biofluid mechanics play an important role in the study of the mechanism of cardiovascular diseases and in the development of new implants. For the assessment of hydrodynamic parameters, experimental methods as well as in-silico approaches can be used, such as particle image velocimetry (PIV) and Deep Learning, respectively. Challenges for PIV are the optical access to the region of interest, and time consumption for measuring and post-processing analysis in particular for three dimensional flow. To overcome these limitations state-of-the-art deep learning algorithms could be utilized to augment spatially coarse resolved flow fields. In this study, we demonstrate the use of Physics Informed Neural Networks (PINN) to augment PIV measurement data. To demonstrate a combined workflow, we investigate the flow of a Newtonian fluid through a simplified aneurysm under laminar conditions. Generation of synthetic PIV particle images of a single measurement plane and the corresponding PIV vector calculations were performed as the basis for the PINN algorithm. Based on the Navier-Stokes equations the PINN reconstructs the entire 3D flow field and pressure distribution inside the aneurysm. We observed qualitative agreements between ground through data and PINN predictions. Nevertheless, there are substantial differences in the quantitative, locally resolved comparison of the flow metrics, despite the generally tendency for the PINN algorithm to correctly augment the flow field.

The promising results of transcatheter aortic valve replacement (TAVR) over the past two decades indicate an expansion of the patient cohort toward patients with intermediate or low surgical risk. Since some complications of TAVR have already been minimized, subclinical leaflet thrombosis (SLT) has gained importance in recent years. SLT is manifested by a thrombotic layer on the prosthetic leaflets that gradually reduces leaflet motion. The resulting decrease in functionality of the TAVR causes a need for re-intervention. The origin of SLT and approaches to prevent SLT are still unexplored. For this reason, we have developed an in silicomodel that can be used during the design development process of TAVR devices to estimate the thrombosis risk of the implant. Based on passive scalar transport, hemodynamic metrics are used to quantify platelet activation and aggregation which are associated with the formation of thrombosis. In conjunction with a numerical simulation model considering the fluid-structure interaction between the blood mimicking fluid and the TAVR implanted in an aortic root, the thrombosis risk can be modeled. The simulation model can be used to calculate the three-dimensional flow structures within the native sinus and neo-sinus and also provides the ability to derive metrics to assess the risk of thrombosis. We demonstrated that this in silicomodel is a time-effective tool to assess thrombosis risk in TAVR product development.

Zusammenfassung Die minimalinvasive Implantation einer Transkatheter-Aortenklappenprothese (TAVR) hat sich zur Standardtherapie für Patienten mit schwerer Aortenklappenstenose und erhöhtem Operationsrisiko etabliert. Postoperative Komplikationen, wie die subklinische Klappenthrombose, rufen langfristig eine Funktionsstörung der TAVR hervor, die ohne Revisionstherapie zum Tod des Patienten führen kann. Mit der Abschätzung des Thromboserisikos von TAVR werden strömungsmechanische Mechanismen assoziiert. Die Particle Image Velocimetry (PIV) bietet ein etabliertes Messverfahren zur Bestimmung des Geschwindigkeitsfeldes einer TAVR, aus dem beispielsweise die Verweilzeit von Blut im Umfeld einer TAVR abgeleitet werden kann. Ein traversierbarer stereo-PIV Aufbau, bei dem zwei CMOS-Kameras im 45 ° Winkel zur Lichtschnittebene positioniert wurden, ermöglichte die Detektion von Tracerpartikeln in den relevanten Bereichen im Umfeld des TAVR. Mit einer geeigneten Messkammer, die in die hydraulische Nachbildung eines kardiovaskulären Kreislaufs implementiert wurde, konnte eine quasi-volumetrische Messung des physiologischen Geschwindigkeitsfeldes durchgeführt werden. Dafür wurde anhand radiologischer Daten eine realistische Implantationsumgebung rekonstruiert. Mit einem Blutersatzfluid (NaCl-Glycerin-Gemisch) wurde die normativ (ISO 5840:2021) geforderte kinematische Viskosität von ν = 3,5 cSt realisiert. Phasengetriggerte Aufnahmen ermöglichten die Messung zu definierten Zeitpunkten im kardiologischen Zyklus. Insgesamt ist es gelungen die komplexe Strömungstopologie mit dem dargestellten Messaufbau in allen relevanten Bereichen zu erfassen und damit zukünftig das Thromboserisiko abschätzen zu können.

Minimally invasive implantation of transcatheter aortic valve replacement (TAVR) has become the standard therapy for patients with severe aortic valve stenosis and increased surgical risk. Postoperative complications, such as subclinical leaflet thrombosis, cause long-term dysfunction of the TAVR, which may lead to patient death without revision therapy. Fluid mechanics mechanisms are associated with the assessment of thrombosis risk of TAVR. Particle Image Velocimetry (PIV) is an established measurement technique for determining the velocity field of a TAVR, which can be used, for example, to infer the residence time of blood in the vicinity of a TAVR. A traversable stereo PIV setup, in which two CMOS cameras were positioned at an angle of 45 degrees to the light sheet plane, enabled the detection of tracer particles in the relevant areas around the TAVR. A quasi-volumetric measurement of the physiological velocity field could be performed using a suitable measurement chamber implemented in the hydraulic replica of a cardiovascular system. For this purpose, a realistic implantation environment was reconstructed using radiological data. Using a blood substitute fluid (NaCl-glycerol mixture), the normative (ISO 5840:2021) required kinematic viscosity of nu = 3.5 was realized. Phase-triggered recordings allowed measurements at defined time points in the cardiac cycle. Overall, it was possible to capture the complex flow topology in all relevant areas with the presented measurement setup and thus to estimate the risk of thrombosis in the future.

Cardiovascular diseases are among the most common diseases with high mortality, including aortic valve stenosis and insufficiency. Minimally invasive implantation of transcatheter aortic valve prosthesis (TAVI) has become the standard procedure for patients with increased risk for open surgery. It is commonly accepted that the long-term outcome of aortic valve replacement depends on hemodynamic performance. This motivates the analysis of the velocity field in the vicinity of the TAVI. Computational fluid dynamics (CFD) methods have been established in the past, but show limitations in terms of computational effort when rapid design optimization or patient-specific decision making in real time is required. In this study we show the usage of PINNs for predicting fluid flow through a TAVI device. We also show a method of enforcing boundary conditions for this specific problem. Due to the physics involved in the training process, this principle does in theory not require additional training data. To validate the method, we performed CFD simulations that solved the Navier-Stokes equations be means of finite volume methods. Besides the good estimation of the main flow components, discrepancies between CFD and PINN results are present. Nevertheless, the flow structures have certain similarities in the coarse spatial localization of the vortex patterns occurring in flow around the TAVI device.

Many real world problems involve fluid flow phenomena, typically be described by the Navier–Stokes equations. The Navier–Stokes equations are partial differential equations (PDEs) with highly nonlinear properties. Currently mostly used methods solve this differential equation by discretizing geometries. In the field of fluid mechanics the finite volume method (FVM) is widely used for numerical flow simulation, so-called computational fluid dynamics (CFD). Due to high computational costs and cumbersome generation of the discretization they are not widely used in real time applications. Our presented work focuses on advancing PDE-constrained deep learning frameworks for more real-world applications with irregular geometries without parameterization. We present a Deep Neural Network framework that generate surrogates for non-geometric boundaries by data free solely physics driven training, by minimizing the residuals of the governing PDEs (i.e., conservation laws) so that no computationally expensive CFD simulation data is needed. We named this method geometry aware physics informed neural network—GAPINN. The framework involves three network types. The first network reduces the dimensions of the irregular geometries to a latent representation. In this work we used a Variational-Auto-Encoder (VAE) for this task. We proposed the concept of using this latent representation in combination with spatial coordinates as input for PINNs. Using PINNs we showed that it is possible to train a surrogate model purely driven on the reduction of the residuals of the underlying PDE for irregular non-parametric geometries. Furthermore, we showed the way of designing a boundary constraining network (BCN) to hardly enforce boundary conditions during training of the PINN. We evaluated this concept on test cases in the fields of biofluidmechanics. The experiments comprise laminar flow (Re = 500) in irregular shaped vessels. The main highlight of the presented GAPINN is the use of PINNs on irregular non-parameterized geometries. Despite that we showed the usage of this framework for Navier Stokes equations, it should be feasible to adapt this framework for other problems described by PDEs.

Computational fluid dynamics (CFD) has enormous potential for the development of novel cardiovascular implants. In particular, the evaluation of the thrombogenic potential of implants is gaining importance. For this purpose, the numerical model must represent the essential properties of the real system, i.e., an implant in the human blood circulation, in a suitable form. Due to its complexity, the model building process is crucial for the successful application of the model. Currently, there is no structured guideline for the application of numerical flow simulation to which model developers can refer. Based on NASA and ASTM, we present key aspects of the model building process using CFD for stent flow as an example.

The implantation of a transcatheter aortic valve replacement (TAVR) in patients with severe aortic stenosis improves pathologic blood flow through the aortic valve, but still alters hemodynamics in comparison to a healthy native aortic valve. The hemodynamic characteristics of TAVR are associated with hypo-attenuating leaflet thickening and prosthetic leaflet thrombosis, which may reduce the durability of TAVR. For this reason we developed a numerical model to identify pro-thrombotic regions of TAVR based on the velocity field. In silico models have already been proven to be an effective tool for device optimization in other medical device applications. However, when using an in silico model, it is important to validate the model assumptions with experimental data or analytical solutions to confirm the accuracy of the model. In this study, we present an approach to validate a complex numerical Fluid Structure Interaction (FSI) model used to simulate leaflet kinematics and flow in the vicinity of a TAVR. Based on the recommendation of ISO 5840 (2021), a combined validation of the kinematic and fluid dynamic parameters was performed for this purpose. The leaflet kinematic was investigated via high-speed recordings and evaluated based on the Geometric Orifice Area (GOA). The velocity field of the TAVR was determined experimentally using Particle Image Velocimetry (PIV). The evaluation of the GOA showed a good agreement of the in silico model with the in vitro data for the systolic duration. The occurring velocities were qualitatively compared during peak systole for three planes and showed similar flow characteristics. The maximum velocity was 1.1 m/s in the in vitro and in silico model. Based on the results, it can be assumed that the numerical FSI model of the TAVR can be used for thrombosis risk assessment.

Mitral regurgitation (MR) is the second most frequent indication for heart valve surgery and catheter interventions. According to European and US-American guidelines, transcatheter mitral valve repair in general and transcatheter edge-to-edge repair (TEER) in particular may be considered as a treatment option for selected high-risk patients. However, the biomechanical impact of TEERdevices on the mitral valve (MV) has not yet been fully understood. To address this problem, a 3D-Fluid-Structure Interaction (FSI) framework utilizing non-linear Finite Element Analysis (FEA) for the MV apparatus and Smoothed Particle Hydrodynamics (SPH) for the pulsatile fluid flow was developed and validated against in vitro data. An artificial MV-model (MVM) with a prolapse in the A2-P2 region and a custom-made TEER device implanted in the A2-P2 region were used for the in vitro investigations. In accordance with ISO 5910, projected mitral orifice areas (PMOA), flow rates as well as atrial and ventricular pressures were measured under pulsatile flow conditions before and after TEER device implantation. For the FSI-model, the MVM geometry was reconstructed by means of microcomputed tomography in a quasi-stress-free configuration. Quasi-static tensile test data was utilized for the development of linear- and hyperelastic material models of the chordae tendineae and leaflets, respectively. The fluid flow was modelled assuming an incompressible, homogenous Newtonian behaviour. Time-varying in vitro transmitral pressure loading was applied as a boundary condition. In vitro investigations show that TEER device implantation in the A2-P2 region effectively reduces the regurgitation fraction (RF) from 55 % to 13 %. Moreover, the comparison of experimental and numerical data yields a deviation of 2.09 % for the RF and a deviation of 0.40 % and 6.47 % for the maximum and minimum PMOA, respectively. The developed FSI-framework is in good agreement with in vitro data and is therefore applicable for the characterization of the biomechanical impact of different TEER devices under pulsatile flow conditions.

Abstract Background Percutaneous coronary interventions (PCI) of bifurcation stenoses are both complex and challenging. Stenting strategies share that the stents’ side cells must be carefully explored and appropriately prepared using balloons or stents. So far, stent manufacturers have not provided any information regarding side-branch expansion capacity of their stent platforms. Aims Given that drug-eluting stent (DES) information regarding their mechanical capacity of side-branch expansion is not available, we aimed to evaluate contemporary DES (Orsiro, BIOTRONIK AG; Xience Sierra, Abbott Vascular; Resolute Integrity, Medtronic; Promus Premier Select, Boston Scientific; Supraflex Cruz, Sahajan and Medical Technologies) by their side-branch expansion behavior using in vitro bench testing. Methods In this in vitro study, we analyzed five commercially available DES (diameter 3.0 mm), measuring their side-branch expansion following inflation of different high-pressure non-compliant (NC) balloons (balloon diameter: 2.00–4.00 mm), thereby revealing the morphological characteristics of their side-branch expansion capacities. Results We demonstrated that all tested contemporary DES platforms could withstand large single-cell deformations, up to 4.0 mm. As seen in our side-branch experiments, DES designs consisting of only two connectors between strut rings did not only result in huge cell areas, but also in larger cell diameters following side-branch expansion compared with DES designs using three or more connectors. Furthermore, the stent cell diameter attained was below the balloon diameter at normal pressure. Conclusions We recommend that the expansion capacity of side-branches should be considered in stent selection for bifurcation interventions.