Left atrial appendage occlusion: On the need of a numerical model to simulate the implant procedure.

Left atrial appendage occlusion (LAAO) is a percutaneous procedure to prevent thromboembolism in patients affected by atrial fibrillation. Despite its demonstrated efficacy, the LAA morphological complexity hinders the procedure, resulting in postprocedural drawbacks (device-related thrombus and peri-device leakage). Local anatomical features may cause difficulties in the device's positioning and affect the effectiveness of the device's implant. The current work proposes a detailed FE model of the LAAO useful to investigate implant scenarios and derive clinical indications. A high-fidelity model of the Watchman FLX device and simplified parametric conduits mimicking the zone of the LAA where the device is deployed were developed. Device-conduit interactions were evaluated by looking at clinical indicators such as device-wall gap, possible cause of leakage, and device protrusion. As expected, the positioning of the crimped device before the deployment was found to significantly affect the implant outcomes: clinician's choices can be improved if FE models are used to optimize the pre-operative planning. Remarkably, also the wall mechanical stiffness plays an important role. However, this parameter value is unknown for a specific LAA, a crucial point that must be correctly defined for developing an accurate FE model. Finally, numerical simulations outlined how the device's configuration on which the clinician relies to assess the implant success (i.e., the deployed configuration with the device still attached to the catheter) may differ from the actual final device's configuration, relevant for achieving a safe intervention.

Computational Analysis of the Effects of Fiber Deformation on the Microstructure and Permeability of Blood Oxygenator Bundles.

Mechanical loads on the polymeric fibers of oxygenating bundles are commonly present due to bundle press-fitting during device assembly and blood pressure load. However, computational fluid dynamics (CFD) simulations for fiber bundle optimization neglect possible changes in microstructure due to such deformations. The aim of this study is to investigate the impact of fiber deformability on bundle microstructure and fluid dynamics mainly in terms of permeability. Fibers from commercial mats typically used for blood oxygenators were mechanically tested and based on these experimental data, a material model was developed to simulate the structural deformations the fibers undergo under press-fitting and blood pressure loads. Then, CFD simulations were performed on deformed bundle repetitive units to investigate permeability under varying loading conditions. The effects of different bundle geometric parameters on the variation of bundle permeability due to press-fitting were evaluated. Bundle press-fitting results in significant changes in microstructure that are reflected in a bundle permeability more than halved for a 15% press-fitting. This impact on permeability is present in all the simulated fiber bundles and becomes more pronounced as the pitch between fibers and thus bundle porosity decreases. Instead, the analyses on pressurized bundle show only small deformations caused by pressure load, with permeability changes below 1%. While blood pressure effects could be neglected, bundle press-fitting turns out to have a significant impact on bundle microstructure and permeability. Neglecting such microstructure variations during CFD simulations could also lead to incorrect assessment of the local fluid dynamics within the bundle.

Investigating Balloon-Vessel Contact Pressure Patterns in Angioplasty: In Silico Insights for Drug-Coated Balloons.

Drug-Coated Balloons have shown promising results as a minimally invasive approach to treat stenotic arteries, but recent animal studies have revealed limited, non-uniform coating transfer onto the arterial lumen. In vitro data suggested that local coating transfer tracks the local Contact Pressure (CP) between the balloon and the endothelium. Therefore, this work aimed to investigate in silico how different interventional and device parameters may affect the spatial distribution of CP during the inflation of an angioplasty balloon within idealized vessels that resemble healthy femoral arteries in size and compliance. An angioplasty balloon computational model was developed, considering longitudinal non-uniform wall thickness, due to its forming process, and the folding procedure of the balloon. To identify the conditions leading to non-uniform CP, sensitivity finite element analyses were performed comparing different values for balloon working length, longitudinally varying wall thickness, friction coefficient on the balloon-vessel interface, vessel wall stiffness and thickness, and balloon-to-vessel diameter ratio. Findings indicate a significant irregularity of contact between the balloon and the vessel, mainly affected by the balloon's unfolding and longitudinal thickness variation. Mirroring published data on coating transfer distribution in animal studies, the interfacial CP distribution was maximal at the middle of the balloon treatment site, while exhibiting a circumferential pattern of linear peaks as a consequence of the particular balloon-vessel interaction during unfolding. A high ratio of balloon-to-vessel diameter, higher vessel stiffness, and thickness was found to increase significantly the amplitude and spatial distribution of the CP, while a higher friction coefficient at the balloon-to-vessel interface further exacerbated the non-uniformity of CP. Evaluation of balloon design effects revealed that the thicker tapered part caused CP reduction in the areas that interacted with the extremities of the balloon, whereas total length only weakly impacted the CP. Taken together, this study offers a deeper understanding of the factors influencing the irregularity of balloon-tissue contact, a key step toward uniformity in drug-coating transfer and potential clinical effectiveness.

Relevant Choices Affecting the Fatigue Analysis of Ni-Ti Endovascular Devices.

Ni-Ti alloys are widely used for biomedical applications due to their superelastic properties, which are especially convenient for endovascular devices that require minimally invasive insertion and durable effects, such as peripheral/carotid stents and valve frames. After crimping and deployment, stents undergo millions of cyclic loads imposed by heart/neck/leg movements, causing fatigue failure and device fracture that can lead to possibly severe consequences for the patient. Standard regulations require experimental testing for the preclinical assessment of such devices, which can be coupled with numerical modeling to reduce the time and costs of such campaigns and to obtain more information regarding the local state of stress and strain in the device. In this frame, this review aimed to enlighten the relevant choices that can affect the outcome of the fatigue analysis of Ni-Ti devices, both from experimental and numerical perspectives.

On the need of a scale-dependent material characterization to describe the mechanical behavior of 3D printed Ti6Al4V custom prostheses using finite element models.

Additive manufacturing is widely used in the orthopaedic industry for the high freedom and flexibility in the design and production of personalized custom implants made of Ti6Al4V. Within this context, finite element modeling of 3D printed prostheses is a robust tool both to guide the design phase and to support clinical evaluations, possibly virtually describing the in-vivo behavior of the implant. Given realistic scenarios, a suitable description of the overall implant's mechanical behavior is unavoidable. Considering typical custom prostheses' designs (i.e. acetabular and hemipelvis implants), complex designs involving solid and/or trabeculated parts, and material distribution at different scales hinder a high-fidelity modeling of the prostheses. Moreover, uncertainties in the production and in the material characterization of small parts approaching the accuracy limit of the additive manufacturing technology still exist. While recent works suggest that the mechanical properties of thin 3D-printed parts may be peculiarly affected by specific processing parameters (i.e. powder grain size, printing orientation, samples' thickness) as compared to conventional Ti6Al4V alloy, the current numerical models make gross simplifications in describing the complex material behavior of each part at different scales. The present study focuses on two patient-specific acetabular and hemipelvis prostheses, with the aim of experimentally characterizing and numerically describing the dependency of the mechanical behavior of 3D printed parts on their peculiar scale, therefore, overcoming one major limitation of current numerical models. Coupling experimental activities with finite element analyses, the authors initially characterized 3D printed Ti6Al4V dog-bone samples at different scales, representative of the main material components of the investigated prostheses. Afterwards, the authors implemented the characterized material behaviors into finite element models to compare the implications of adopting scale-dependent vs. conventional scaleindependent approaches in predicting the experimental mechanical behavior of the prostheses in terms of their overall stiffness and the local strain distribution. The material characterization results highlighted the need for a scale-dependent reduction of the elastic modulus for thin samples compared to the conventional Ti6Al4V, which is fundamental to properly describe the overall stiffness and local strain distribution on the prostheses. The presented works demonstrate how an appropriate material characterization and a scale-dependent material description is needed to develop reliable FE models of 3D printed implants characterized by a complex material distribution at different scales.

Global stiffness and residual stresses in spinal fixator systems: A validated finite element study on the interconnection mechanism.

Posterior spinal fixation systems are the gold standard to treat different column disorders using rods and screws. The proper connection between them is guaranteed by the Interconnection Mechanism (IM), consisting of different metallic subcomponents held together through the application of tightening torque. The response of the fixation system is defined by its overall stiffness, which in turn is governed by the local residual stress field arising during tightening. Although literature computational models for studying spinal fixation are becoming increasingly anatomically complex, most studies disregard completely the realistic modeling of the IM, namely choosing elastic-plastic material models and proper contact interactions. In this frame, the present study aims at increasing awareness in the field of spinal fixation modeling by investigating the mechanical response of the IM in terms of overall stiffness and local residual stresses. Once validated through dedicated experiments, the results of the proposed model have been compared with the current literature, highlighting the key role of the IM in the reliable modeling of spinal fixation.

A proof-of-concept study for the simulation of blood flow in a post arterial segment for different blood rheology models.

Cardiovascular disease (CVD) and especially atherosclerosis are chronic inflammatory diseases which cause the atherosclerotic plaque growth in the arterial vessels and the blood flow reduction. Stents have revolutionized the treatment of this disease to a great extent by restoring the blood flow in the vessel. The present study investigates the performance of the blood flow after stent implantation in patient-specific coronary artery and demonstrates the effect of using Newtonian vs. non-Newtonian blood fluid models in the distribution of endothelial shear stress. In particular, the Navier-Stokes and continuity equations were employed, and three non-Newtonian fluid models were investigated (Carreau, Carreau-Yasuda and the Casson model). Computational finite elements models were used for the simulation of blood flow. The comparison of the results demonstrates that the Newtonian fluid model underestimates the calculation of Endothelial Shear Stress, while the three non-Newtonian fluids present similar distribution of shear stress. Keywords: Blood flow dynamics, stented artery, non-Newtonian fluid. Clinical Relevance- This work demonstrates that when blood flow modeling is performed at stented arteries and predictive models are developed, the non-Newtonian nature of blood must be considered.

An in silico trials platform for the evaluation of stent design effect in post-implantation outcomes.

Bioresorbable Vascular Scaffolds (BVS), developed to allow drug deliver and mechanical support, followed by complete resorption, have revolutionized atherosclerosis treatment. InSilc is a Cloud platform for in silico clinical trials (ISCT) used in the design, development and evaluation pipeline of stents. The platform integrates beyond the state-of-the-art multi-disciplinary and multiscale models, which predict the scaffold's performance in the short/acute and medium/long term. In this study, a use case scenario of two Bioabsorbable Vascular Stents (BVSs) implanted in the same arterial anatomy is presented, allowing the whole InSilc in silico pipeline to be applied and predict how the different aspects of this intervention affect the success of stenting process.

Reliable Numerical Models of Nickel-Titanium Stents: How to Deduce the Specific Material Properties from Testing Real Devices.

The current interest of those dealing with medical research is the preparation of digital twins. In this frame, the first step to accomplish is the preparation of reliable numerical models. This is a challenging task since it is not common to know the exact device geometry and material properties unless in studies performed in collaboration with the manufacturer. The particular case of modeling Ni-Ti stents can be highlighted as a worst-case scenario due to both the complex geometrical features and non-linear material response. Indeed, if the limitations in the description of the geometry can be overcome, many difficulties still exist in the assessment of the material, which can vary according to the manufacturing process and requires many parameters for its description. The purpose of this work is to propose a coupled experimental and computational workflow to identify the set of material properties in the case of commercially-resembling Ni-Ti stents. This has been achieved from non-destructive tensile tests on the devices compared with results from Finite Element Analysis (FEA). A surrogate modeling approach is proposed for the identification of the material parameters, based on a minimization problem on the database of responses of Ni-Ti materials obtained with FEA with a series of different parameters. The reliability of the final result was validated through the comparison with the output of additional experiments.

An in silico trials platform for the evaluation of effect of the arterial anatomy configuration on stent implantation.

The introduction of Bioresorbable Vascular Scaffolds (BVS) has revolutionized the treatment of atherosclerosis. InSilc is an in silico clinical trial (ISCT) platform in a Cloud-based environment used for the design, development and evaluation of BVS. Advanced multi-disciplinary and multiscale models are integrated in the platform towards predicting the short/acute and medium/long term scaffold performance. In this study, InSilc platform is employed in a use case scenario and demonstrates how the whole in silico pipeline allows the interpretation of the effect of the arterial anatomy configuration on stent implantation.

Applications of computational fluid dynamics to congenital heart diseases: a practical review for cardiovascular professionals.

INTRODUCTION: The increased survival rate of patients with congenital heart disease (CHD) has made it likely that 70%-95% of infants with CHDs surviving into adulthood often require careful follow-up and (repeat) interventions. Patients with CHDs often have abnormal blood flow patterns, due to both primary cardiac defect and the consequent surgical or endovascular repair. AREA COVERED: Computational fluid dynamics (CFD) alone or coupled with advanced imaging tools can assess blood flow patterns of CHDs to both understand their pathophysiology and anticipate the results of surgical or interventional repair. EXPERT OPINION: CFD is a mathematical technique that quantifies and describes the characteristics of fluid flow using the laws of physics. Through dedicated software based on virtual reconstruction and simulation and patients' real data coming from computed tomography, magnetic resonance imaging, and 3/4 D-ultrasound, reconstruction of models of circulation of most CHD can be accomplished. CFD can provide insights about the pathophysiology of coronary artery anomalies, interatrial shunts, coarctation of the aorta and aortic bicuspid valve, tetralogy of Fallot and univentricular heart, with the capability in some cases of simulating different types of surgical or interventional repair and tailoring the treatment on the basis of these findings.

Comprehensive computational analysis of the crimping procedure of PLLA BVS: effects of material viscous-plastic and temperature dependent behavior.

Recently, researchers focused their attention on the use of polymeric bioresorbable vascular scaffolds (BVSs) as alternative to permanent metallic drug-eluting stents (DESs) for the treatment of atherosclerotic coronary arteries. Due to the different mechanical properties, polymeric stents, if compared to DESs, are characterized by larger strut size and specific design. It implies that during the crimping phase, BVSs undergo higher deformation and the packing of the struts, making this process potentially critical for the onset of damage. In this work, a computational study on the crimping procedure of a PLLA stent, inspired by the Absorb GT1 (Abbott Vascular) design, is performed, with the aim of evaluating how different strategies (loading steps, velocities and temperatures) can influence the results in terms of damage risk and final crimped diameter. For these simulations, an elastic-viscous-plastic model was adopted, based on experimental results, obtained from tensile testing of PLLA specimens loaded according to ad hoc experimental protocols. Furthermore, the results of these simulations were compared with those obtained by neglecting strain rate and temperature dependence in the material model (as often done in the literature), showing how this lead to significant differences in the prediction of the crimped diameter and internal stress state.

Validation of the computational model of a coronary stent: a fundamental step towards in silico trials.

The proof of the reliability of a numerical model is becoming of paramount importance in the era of in silico clinical trials. When dealing with a coronary stenting procedure, the virtual scenario should be able to replicate the real device, passing through the different stages of the procedure, which has to maintain the atherosclerotic vessel opened. Nevertheless, most of the published studies adopted commercially resembling geometries and generic material parameters, without a specific validation of the employed numerical models. In this work, a workflow for the generation and validation of the computational model of a coronary stent was proposed. Possible sources of variability in the results, such as the inter-batches variability in the material properties and the choice of proper simulation strategies, were accounted for and discussed. Then, a group of in vitro tests, representative of the device intended use was used as a comparator to validate the model. The free expansion simulation, which is the most used simulation in the literature, was shown to be only partially useful for stent model validation purposes. On the other hand, the choice of proper additional experiments, as the suggested uniaxial tensile tests on the stent and deployment tests into a deformable tube, could provide further suitable information to prove the efficacy of the numerical approach.

From the real device to the digital twin: A coupled experimental-numerical strategy to investigate a novel bioresorbable vascular scaffold.

The purpose of this work is to propose a workflow that couples experimental and computational activities aimed at developing a credible digital twin of a commercial coronary bioresorbable vascular scaffold when direct access to data about material mechanical properties is not possible. Such a situation is be faced when the manufacturer is not involved in the study, thus directly investigating the actual device is the only source of information available. The object of the work is the Fantom® Encore polymeric stent (REVA Medical) made of Tyrocore™. Four devices were purchased and used in mechanical tests that are easily reproducible in any mechanical laboratory, i.e. free expansion and uniaxial tension testing, the latter performed with protocols that emphasized the rate-dependent properties of the polymer. Given the complexity of the mechanical behaviour observed experimentally, it was chosen to use the Parallel Rehological Framework material model, already used in the literature to describe the behaviour of other polymers, such as PLLA. Calibration of the material model was based on simulations that replicate the tensile test performed on the device. Given the high number of material parameters, a plan of simulations was done to find the most suitable set, varying each parameter value in a feasible range and considering a single repetitive unit of the stent, neglecting residual stresses generated by crimping and expansion. This strategy resulted in a significant reduction of computational cost. The performance of the set of parameters thus identified was finally evaluated considering the whole delivery system, by comparing the experimental results with the data collected simulating free expansion and uniaxial tension testing. Moreover, radial force testing was numerically performed and compared with literature data. The obtained results demonstrated the effectiveness of the digital twin development pipeline, a path applicable to any commercial device whose geometric structure is based on repetitive units.

Analytical methods for braided stents design and comparison with FEA.

Braiding technology is nowadays commonly adopted to build stent-like devices. Indeed, these endoprostheses, thanks to their typical great flexibility and kinking resistance, find several applications in mini-invasive treatments, involving but not limiting to the cardiovascular field. The design process usually involves many efforts and long trial and error processes before identifying the best combination of manufacturing parameters. This paper aims to provide analytical tools to support the design and optimization phases: the developed equations, based on few geometrical parameters commonly used for describing braided stents and material stiffness, are easily implementable in a worksheet and allow predicting the radial rigidity of braided stents, also involving complex features such as multiple twists and looped ends, and the diameter variation range. Finite element simulations, previously validated with respect to experimental tests, were used as a comparator to prove the reliability of the analytical results. The illustrated tools can assess the impact of each selected parameter modification and are intended to guide the optimal selection of geometrical and mechanical stent proprieties to obtain the desired radial rigidity, deliverability (minimum diameter), and, if forming processes are planned to modify the shape of the stent, the required diameter variations (maximum and minimum diameters).

Finite Element Simulations of the ID Venous System to Treat Venous Compression Disorders: From Model Validation to Realistic Implant Prediction.

The ID Venous System is an innovative device proposed by ID NEST MEDICAL to treat venous compression disorders that involve bifurcations, such as the May-Thurner syndrome. The system consists of two components, ID Cav and ID Branch, combined through a specific connection that prevents the migration acting locally on the pathological region, thereby preserving the surrounding healthy tissues. Preliminary trials are required to ensure the safety and efficacy of the device, including numerical simulations. In-silico models are intended to corroborate experimental data, providing additional local information not acquirable by other means. The present work outlines the finite element model implementation and illustrates a sequential validation process, involving seven tests of increasing complexity to assess the impact of each numerical uncertainty separately. Following the standard ASME V&V40, the computational results were compared with experimental data in terms of force-displacement curves and deformed configurations, testing the model reliability for the intended context of use (differences < 10%). The deployment in a realistic geometry confirmed the feasibility of the implant procedure, without risk of rupture or plasticity of the components, highlighting the potential of the present technology.

How to Validate in silico Deployment of Coronary Stents: Strategies and Limitations in the Choice of Comparator.

This study aims at proposing and discussing useful indications to all those who need to validate a numerical model of coronary stent deployment. The proof of the reliability of a numerical model is becoming of paramount importance in the era of in silico trials. Recently, the ASME V&V Standard Committee for medical devices prepared the V&V 40 standard document that provides a framework that guides users in establishing and assessing the relevance and adequacy of verification and validation activities performed for proving the credibility of models. To the knowledge of the authors, only a few examples of the application of the V&V 40 framework to medical devices are available in the literature, but none about stents. Specifically, in this study, the authors wish to emphasize the choice of a relevant set of experimental activities to provide data for the validation of computational models aiming to predict coronary stent deployment. Attention is focused on the use of ad hoc 3D-printed mock vessels in the validation plan, which could allow evaluating aspects of clinical relevance in a representative but controlled environment.

Nickel-Titanium peripheral stents: Which is the best criterion for the multi-axial fatigue strength assessment?

Ni-Ti stents fatigue strength assessment requires a multi-factorial complex integration of applied loads, material and design and is of increasing interest. In this work, a coupled experimental-numerical method for the multi-axial fatigue strength assessment is proposed and verified for two different stent geometries that resemble commercial products. Particular attention was paid to the identification of the material fatigue limit curve. The common approach for the Ni-Ti stents fatigue assessment based on the von Mises yield criterion was proven unsuitable for a realistic fatigue strength assessment. On the other hand, critical plane-based criteria were more representative of the experimental outcomes regardless of stent design.

Design and implementation of in silico clinical trial for Bioresorbable Vascular Scaffolds.

In the recent years, Bioresorbable Vascular Scaffolds (BVS) for the treatment of atherosclerosis have been introduced. InSilc is a cloud based in silico clinical trial (ISCT) platform for drug-eluting BVS. The platform integrates multidisciplinary and multiscale models predicting the BVS performance. In this study, we present a use case scenario and demonstrate the functioning of the individual modules and of the whole pipeline and the ability to predict BVS short, medium, long-term outcomes.