Shape Optimization of hemolysis for shear thinning flows in moving domains

We consider the $3$D problem of hemolysis minimization in blood flows, namely the minimization of red blood cells damage, through the shape optimization of moving domains. Such a geometry is adopted to take into account the modeling of rotating systems and blood pumps. The blood flow is described by generalized Navier-Stokes equations, in the particular case of shear thinning flows. The velocity and stress fields are then used as data for a transport equation governing the hemolysis index, aimed to measure the red blood cells damage rate. For a sequence of converging moving domains, we show that a sequence of associated solutions to blood equations converges to a solution of the problem written on the limit moving domain. Thus, we extended the result given in (Soko\l{}owski, Stebel, 2014, in \textit{Evol. Eq. Control Theory}) for $q \geq 11/5$, to the range $6/5< q < 11/5$, where $q$ is the exponent of the rheological law. We then show that the sequence of hemolysis index solutions also converges to the limit solution. This shape continuity properties allows us to show the existence of minimal shapes for a class of functionals depending on the hemolysis index

Numerical modelling of additive manufacturing process for stainless steel tension testing samples

Nowadays additive manufacturing (AM) technologies including 3D printing grow rapidly and they are expected to replace conventional subtractive manufacturing technologies to some extents. During a selective laser melting (SLM) process as one of popular AM technologies for metals, large amount of heats is required to melt metal powders, and this leads to distortions and/or shrinkages of additively manufactured parts. It is useful to predict the 3D printed parts to control unwanted distortions and shrinkages before their 3D printing. This study develops a two-phase numerical modelling and simulation process of AM process for 17-4PH stainless steel and it considers the importance of post-processing and the need for calibration to achieve a high-quality printing at the end. By using this proposed AM modelling and simulation process, optimal process parameters, material properties, and topology can be obtained to ensure a part 3D printed successfully

Analysis and experiments on flow-induced hemolysis.

Hemolysis (red cells lysis) caused by fluid stresses in flows within hypodermic needles, blood pumps, artificial hearts and other cardiovascular devices, is one of the major concerns during the design and use of cardiovascular or blood-processing extracorporeal devices. A non-invasive experimental method which does not interfere directly with red blood cells was designed to investigate the red cells\u27 deformations in response to a range of flow conditions. The designed flow chamber and pump system provided a controlled two-dimensional Poiseuille flow with average velocity of up to 4 m/s and a range of fluid stresses up to 5000 dyn/cm 2 . The dimension of deformed cells and positions was measured to obtain the aspect ratio of red cells under stress from images captured by the microscope-laser-camera system. A strain-based blood damage model from Rand\u27s viscoelastic model was built to predict cell strain. The empirical coefficients in the blood damage model were calibrated by the measurements from the experiments. Flow-induced hemolysis in the blood flow through hypodermic needles was investigated. The flow-induced hemolysis of the needles may be reduced by a modified design of the entrance geometry of the needle. Three groups of 16 gauge needles were compared: one standard group with sharp entrance, another with beveled entrance and a third with rounded entrance. The CFD analysis combined with the strain-based blood damage model, Heuser et al. model and Giersiepen et al. model respectively was used to analyze the flow-induced hemolysis of the three needles. The predicted results were compared to the experimental results, which showed the rounded entrance reduced hemolysis by 34%, but the beveled entrance increased hemolysis by 38%. The strain-based blood damage model predicted the reduced hemolysis by 7.4% in rounded needle and the increased hemolysis by 13% in beveled needle. Both Heuser et al. model and Giersiepen et al. model predicted increased hemolysis in rounded needle

Reports about 8 selected benchmark cases of model hierarchies : Deliverable number: D5.1 - Version 0.1

Based on the multitude of industrial applications, benchmarks for model hierarchies will be created that will form a basis for the interdisciplinary research and for the training programme. These will be equipped with publically available data and will be used for training in modelling, model testing, reduced order modelling, error estimation, efficiency optimization in algorithmic approaches, and testing of the generated MSO/MOR software. The present document includes the description about the selection of (at least) eight benchmark cases of model hierarchies.EC/H2020/765374/EU/Reduced Order Modelling, Simulation and Optimization of Coupled Systems/ROMSO

Development and characterization of the arterial windkessel and its role during left ventricular assist device assistance

Modeling of the cardiovascular system is challenging, but it has the potential to further advance our understanding of normal and pathological conditions. Morphology and function are closely related. The arterial system provides steady blood flow to each organ and damps out wave fluctuations as a consequence of intermittent ventricular ejection. These actions can be approached separately in terms of mathematical relationships between pressure and flow. Lumped parameter models are helpful for the study of the interactions between the heart and the arterial system. The arterial windkessel model still plays a significant role despite its limitations. This review aims to discuss the model and its modifications and derive the fundamental equations by applying electric circuits theory. In addition, its role during left ventricular assist device assistance is explored and discussed in relation to rotary blood pumps

Modified mass-spring system for physically based deformation modeling

Mass-spring systems are considered the simplest and most intuitive of all deformable models. They are computationally efficient, and can handle large deformations with ease. But they suffer several intrinsic limitations. In this book a modified mass-spring system for physically based deformation modeling that addresses the limitations and solves them elegantly is presented. Several implementations in modeling breast mechanics, heart mechanics and for elastic images registration are presented

Modified mass-spring system for physically based deformation modeling

Mass-spring systems are considered the simplest and most intuitive of all deformable models. They are computationally efficient, and can handle large deformations with ease. But they suffer several intrinsic limitations. In this book a modified mass-spring system for physically based deformation modeling that addresses the limitations and solves them elegantly is presented. Several implementations in modeling breast mechanics, heart mechanics and for elastic images registration are presented

A versatile platform for three-dimensional dynamic suspension culture applications

In the last decades, the rapid upgrading in cell biological knowledge has bumped the interest in using cell-based therapeutic approaches as well as cell-based model systems for the treatment of diseases. Given the rapid translation towards cell-based clinical treatments and the consequent increasing demand of cell sources, three-dimensional (3D) suspension cultures have demonstrated to be an advantageous alternative to monolayer techniques for large scale expansion of cells and for the generation of three-dimensional model systems in a scale-up perspective. In this scenario, a versatile bioreactor platform suitable for 3D dynamic suspension cell culture under tuneable shear stress conditions is developed and preliminarily tested in two different biotechnological applications. By adopting simple technological solutions and avoiding rotating components, the bioreactor exploits a laminar hydrodynamics, enabling dynamic cell suspension in an environment favourable to mass transport. Technically, the bioreactor is conceived to produce dynamic suspension cell culture under tuneable shear stress conditions without the use of moving components (from ultralow to moderate shear stress). A multiphysics computational modelling strategy is applied for the development and optimization of the suspension bioreactor platform. The in silico modelling is used to support the design and optimization phase of the bioreactor platform, providing a comprehensive analysis of its operating principles, also supporting the development/optimization of culture protocols directly in silico, and thus minimizing preliminary laboratory tests. After the technical assessment of the functionality of the device and a massive number of in silico simulations for its characterization, the bioreactor platform has been employed for two preliminary experimental applications, in order to determine the suitability of the device for culturing human cells under dynamic suspension. In detail, the bioreactor platform has been used to culture lung cancer cells for spheroid formation (Calu-3 cell line) under ultralow shear stress conditions, and for human induced pluripotent stem cell (hiPSC) dynamic suspension culture. The use of the bioreactor platform for the formation of cancer cell spheroids under low shear stress conditions confirms the suitability of the device for its use as dynamic suspension bioreactor. In fact, compared to static cell suspension, after 5 days of dynamic suspension culture the bioreactor platform preserves morphological features, promotes intercellular connection, increases the number of cycling cells, and reduces double strand DNA damage. Calu-3 cells form functional 3D spheroids characterized by more functional adherence junctions between cells. Moreover, the computational model has been used as a tool for assisting the setup of the experimental framework with the extraction of the fluid dynamic features establishing inside the bioreactor culture chamber. As second proof of concept application, the bioreactor platform has been tested for the dynamic suspension of hiPSCs. Starting from the ‘a priori’ knowledge gained by the development of the in silico culture protocol, the agglomeration of human induced pluripotent stem cells has been modulated by means of the combination of moderate intermittent shear stress and free-fall transport within the bioreactor culture chamber. The inoculation of single cells suspensions inside the bioreactor chamber promotes cell-cell interaction and consequently the formation of human induced pluripotent stem cell aggregates. In conclusion, the impeller-free functioning principle characterizing the proposed bioreactor platform demonstrates to be promising for human cell dynamic suspension culture. In the future, this bioreactor platform will be further optimized for the realization of impeller-free dynamic suspension bioreactors dedicated and optimized to specific applications in stem cell and cancer cell culture

Towards patient-specific modelling as a pre-operative planning strategy and follow up assessment for the treatment of advanced heart failure with rotary blood pumps

Background: Ventricular Assist Devices (VADs) insertion is an established treatment for patients with end-stage heart failure waiting for a heart transplant or in need for long-term circulatory support (destination therapy). Rotary blood pumps (RBP) are the most popular devices in view of their size and performance. Pre-operative planning strategy for the insertion of a left ventricular assist device (LVAD) requires a timely discussion at a Multi-Disciplinary Team Meeting (MDT). Clinical-decision making is based according to the needs of the patient and must be processed without delays. Nevertheless, thrombus formation remains a feared complication which affects outcome. VADs operate in a flow regime which is difficult to simulate: the transitional region at the boundary of laminar and turbulent flow (low Reynolds number). Different methods have been used but the best approach remains debatable. Computational Fluid Dynamics (CFD) is an attractive and invaluable tool for the study of the interactions between VADs and the cardiovascular system. The aim of this thesis is three-fold: a) to investigate the use of pressure-volume analysis in a clinical setting through the review of six heart failure patients previously discussed at a MDT meeting with a view to predict or guide further management; b) to review the theory behind modelling approaches to VADs and their interactions with the cardiovascular system for better understanding of their clinical use. Then, an overview of computational fluid dynamics (CFD) is considered as a prelude to its application to the analysis of VADs performance. Additionally, the development of a simplified model of centrifugal pump will be used in initial simulations as preliminary analysis; c) to examine an example of a proof-of-concept pilot patient-specific model of an axial flow pump (HeartMate II) as pre-operative planning strategy in a patient-specific model with a view to identify potential critical areas that may affect pump function and outcome in a clinical setting. Material and Methods: 3D reconstruction from CT-scan images of patients who underwent the insertion of rotary blood pumps, namely HeartWare HVAD and HeartMate II. Ansys Fluent has been used for CFD analysis based on the fundamental governing equations of motion. Blood has been modelled as incompressible, Newtonian fluid with density = 1060 and viscosity = 0.0035 kg/m-s. The laminar and SST models have been used for comparison purposes. The rotational motion of the impeller has been implemented using the moving reference frame (MRF) approach. The sliding mesh method has also been used to account for unsteady interaction between stationary and moving part. The no-slip condition has been applied to all walls, which were assumed to be rigid. Boundary conditions consisting of velocity inlet and pressure outlet of the pump based on different settings and constant rotational speed for the impeller. Pressure-velocity coupling has been based on the coupled scheme. Spatial discretisation consisted of the “least square cell based” gradient for velocity and “PRESTO” or second order for pressure. Second order upwind has been set for the momentum, turbulent kinetic energy and specific dissipation rate. First order implicit has been set for transient formulation. The pseudo transient algorithm (steady state), the high order relaxation term and the warped-face gradient correction have been used to add an unsteady term to the solution equations with the aim to improve stability and enhance convergence. Specific settings have been considered for comparison purposes. Results: Pressure-volume simulation analysis in six advanced heart failure patients showed that an integrated model of the cardiovascular system based on lumped-parameter representation, modified time-varying elastance and pressure-volume analysis of ventricular function seems a feasible and suitable approach yielding a sufficiently accurate quantitative analysis in real time, therefore applicable within the time-constraints of a clinical setting. Lumped-parameter models consist of simultaneous ordinary differential equations complemented by an algebraic balance equation and are suitable for examination of global distribution of pressure, flow and volume over a range of physiological conditions with inclusion of the interaction between modelled components. Higher level lumped-parameter modelling is needed to address the interaction between the circulation and other systems based on a compromise between complexity and ability to set the required parameters to personalise an integrated lumped-parameter model for a patient-specific approach. CARDIOSIM© fulfils these requirements and does address the systems interaction with its modular approach and assembly of models with varying degree of complexity although 0-D and 1-D coupling may be required for the evaluation of long-term VAD support. The challenge remains the ability to predict outcome over a longer period of time. The preliminary CFD simulations with the HeartWare HVAD centrifugal pump demonstrated that it is possible to obtain an accurate analysis in a timely manner to complement the clinical review process. The simulations with the pilot patient-specific model of the HeartMate II axial flow pump revealed that a complex 3D reconstruction is feasible in a timely manner and can be used to generate sufficiently accurate results to be used in the context of a MDT meeting for the purposes of clinical decision-making. Overall, these three studies demonstrate that the time frame of the simulations was within hours which may fit the time constraints of the clinical environment in the context of a MDT meeting. More specifically, it was shown that the laminar model may be used for an initial evaluation of the flow development within the pump. Nonetheless, the k- model offers higher accuracy if the timeline of the clinical setting allows for a longer simulation. Conclusion: This thesis aimed at the understanding of the use of computational modelling as a pre-operative planning strategy and follow up assessment for the treatment of advanced heart failure with rotary blood pumps. The novelty lays in the use of both pressure-volume simulation analysis and 3D flow dynamics studies in VADs with a view to treatment optimisation and outcome prediction within the time constraints of a clinical setting in the context of a MDT meeting. The clinical significance and the contribution to the field is a more targeted approach for different groups of patients and a more quantitative evaluation in the clinical decision process based on a pro-active co-operation between clinicians and scientists reducing the potential for “guess work”. The results of this thesis are a proof-of-concept as a prelude to a potential future implementation of patient-specific modelling within a clinical setting on a daily basis demonstrating a clear clinical significance and contribution to the field. The proposed approach does not consider modelling and simulation as a substitute for clinical experience but an additional tool to guide therapeutic intervention and complement the clinical decision process in which the clinician remains the ultimate decision-maker. Such an approach may well add a different dimension to the problem of heart failure with potential for high return in terms of patient’s outcome and long-term surveillance. The same principles would be applicable to other cardiovascular problems in line with the current concept of “Team Approach” such as the Heart Team, the Structural Heart Team or the Aortic Team. The present work has taken this concept closer to clinical delivery and has highlighted its potential but further work remains to be done in refining the technique.Background: Ventricular Assist Devices (VADs) insertion is an established treatment for patients with end-stage heart failure waiting for a heart transplant or in need for long-term circulatory support (destination therapy). Rotary blood pumps (RBP) are the most popular devices in view of their size and performance. Pre-operative planning strategy for the insertion of a left ventricular assist device (LVAD) requires a timely discussion at a Multi-Disciplinary Team Meeting (MDT). Clinical-decision making is based according to the needs of the patient and must be processed without delays. Nevertheless, thrombus formation remains a feared complication which affects outcome. VADs operate in a flow regime which is difficult to simulate: the transitional region at the boundary of laminar and turbulent flow (low Reynolds number). Different methods have been used but the best approach remains debatable. Computational Fluid Dynamics (CFD) is an attractive and invaluable tool for the study of the interactions between VADs and the cardiovascular system. The aim of this thesis is three-fold: a) to investigate the use of pressure-volume analysis in a clinical setting through the review of six heart failure patients previously discussed at a MDT meeting with a view to predict or guide further management; b) to review the theory behind modelling approaches to VADs and their interactions with the cardiovascular system for better understanding of their clinical use. Then, an overview of computational fluid dynamics (CFD) is considered as a prelude to its application to the analysis of VADs performance. Additionally, the development of a simplified model of centrifugal pump will be used in initial simulations as preliminary analysis; c) to examine an example of a proof-of-concept pilot patient-specific model of an axial flow pump (HeartMate II) as pre-operative planning strategy in a patient-specific model with a view to identify potential critical areas that may affect pump function and outcome in a clinical setting. Material and Methods: 3D reconstruction from CT-scan images of patients who underwent the insertion of rotary blood pumps, namely HeartWare HVAD and HeartMate II. Ansys Fluent has been used for CFD analysis based on the fundamental governing equations of motion. Blood has been modelled as incompressible, Newtonian fluid with density = 1060 and viscosity = 0.0035 kg/m-s. The laminar and SST models have been used for comparison purposes. The rotational motion of the impeller has been implemented using the moving reference frame (MRF) approach. The sliding mesh method has also been used to account for unsteady interaction between stationary and moving part. The no-slip condition has been applied to all walls, which were assumed to be rigid. Boundary conditions consisting of velocity inlet and pressure outlet of the pump based on different settings and constant rotational speed for the impeller. Pressure-velocity coupling has been based on the coupled scheme. Spatial discretisation consisted of the “least square cell based” gradient for velocity and “PRESTO” or second order for pressure. Second order upwind has been set for the momentum, turbulent kinetic energy and specific dissipation rate. First order implicit has been set for transient formulation. The pseudo transient algorithm (steady state), the high order relaxation term and the warped-face gradient correction have been used to add an unsteady term to the solution equations with the aim to improve stability and enhance convergence. Specific settings have been considered for comparison purposes. Results: Pressure-volume simulation analysis in six advanced heart failure patients showed that an integrated model of the cardiovascular system based on lumped-parameter representation, modified time-varying elastance and pressure-volume analysis of ventricular function seems a feasible and suitable approach yielding a sufficiently accurate quantitative analysis in real time, therefore applicable within the time-constraints of a clinical setting. Lumped-parameter models consist of simultaneous ordinary differential equations complemented by an algebraic balance equation and are suitable for examination of global distribution of pressure, flow and volume over a range of physiological conditions with inclusion of the interaction between modelled components. Higher level lumped-parameter modelling is needed to address the interaction between the circulation and other systems based on a compromise between complexity and ability to set the required parameters to personalise an integrated lumped-parameter model for a patient-specific approach. CARDIOSIM© fulfils these requirements and does address the systems interaction with its modular approach and assembly of models with varying degree of complexity although 0-D and 1-D coupling may be required for the evaluation of long-term VAD support. The challenge remains the ability to predict outcome over a longer period of time. The preliminary CFD simulations with the HeartWare HVAD centrifugal pump demonstrated that it is possible to obtain an accurate analysis in a timely manner to complement the clinical review process. The simulations with the pilot patient-specific model of the HeartMate II axial flow pump revealed that a complex 3D reconstruction is feasible in a timely manner and can be used to generate sufficiently accurate results to be used in the context of a MDT meeting for the purposes of clinical decision-making. Overall, these three studies demonstrate that the time frame of the simulations was within hours which may fit the time constraints of the clinical environment in the context of a MDT meeting. More specifically, it was shown that the laminar model may be used for an initial evaluation of the flow development within the pump. Nonetheless, the k- model offers higher accuracy if the timeline of the clinical setting allows for a longer simulation. Conclusion: This thesis aimed at the understanding of the use of computational modelling as a pre-operative planning strategy and follow up assessment for the treatment of advanced heart failure with rotary blood pumps. The novelty lays in the use of both pressure-volume simulation analysis and 3D flow dynamics studies in VADs with a view to treatment optimisation and outcome prediction within the time constraints of a clinical setting in the context of a MDT meeting. The clinical significance and the contribution to the field is a more targeted approach for different groups of patients and a more quantitative evaluation in the clinical decision process based on a pro-active co-operation between clinicians and scientists reducing the potential for “guess work”. The results of this thesis are a proof-of-concept as a prelude to a potential future implementation of patient-specific modelling within a clinical setting on a daily basis demonstrating a clear clinical significance and contribution to the field. The proposed approach does not consider modelling and simulation as a substitute for clinical experience but an additional tool to guide therapeutic intervention and complement the clinical decision process in which the clinician remains the ultimate decision-maker. Such an approach may well add a different dimension to the problem of heart failure with potential for high return in terms of patient’s outcome and long-term surveillance. The same principles would be applicable to other cardiovascular problems in line with the current concept of “Team Approach” such as the Heart Team, the Structural Heart Team or the Aortic Team. The present work has taken this concept closer to clinical delivery and has highlighted its potential but further work remains to be done in refining the technique