Functional mechanical behavior of the murine pulmonary heart valve.

Genetically modified mouse models provide a versatile and efficient platform to extend our understanding of the underlying disease processes and evaluate potential treatments for congenital heart valve diseases. However, applications have been limited to the gene and molecular levels due to the small size of murine heart valves, which prohibits the use of standard mechanical evaluation and in vivo imaging methods. We have developed an integrated imaging/computational mechanics approach to evaluate, for the first time, the functional mechanical behavior of the murine pulmonary heart valve (mPV). We utilized extant mPV high resolution µCT images of 1-year-old healthy C57BL/6J mice, with mPVs loaded to 0, 10, 20 or 30 mmHg then chemically fixed to preserve their shape. Individual mPV leaflets and annular boundaries were segmented and key geometric quantities of interest defined and quantified. The resulting observed inter-valve variations were small and consistent at each TVP level. This allowed us to develop a high fidelity NURBS-based geometric model. From the resultant individual mPV geometries, we developed a mPV shape-evolving geometric model (SEGM) that accurately represented mPV shape changes as a continuous function of transvalvular pressure. The SEGM was then integrated into an isogeometric finite element based inverse model that estimated the individual leaflet and regional mPV mechanical behaviors. We demonstrated that the mPV leaflet mechanical behaviors were highly anisotropic and nonlinear, with substantial leaflet and regional variations. We also observed the presence of strong axial mechanical coupling, suggesting the important role of the underlying collagen fiber architecture in the mPV. When compared to larger mammalian species, the mPV exhibited substantially different mechanical behaviors. Thus, while qualitatively similar, the mPV exhibited important functional differences that will need to accounted for in murine heart valve studies. The results of this novel study will allow detailed murine tissue and organ level investigations of semi-lunar heart valve diseases.

Isogeometric finite element-based simulation of the aortic heart valve: Integration of neural network structural material model and structural tensor fiber architecture representations.

The functional complexity of native and replacement aortic heart valves (AVs) is well known, incorporating such physical phenomenons as time-varying non-linear anisotropic soft tissue mechanical behavior, geometric non-linearity, complex multi-surface time varying contact, and fluid-structure interactions to name a few. It is thus clear that computational simulations are critical in understanding AV function and for the rational basis for design of their replacements. However, such approaches continued to be limited by ad-hoc approaches for incorporating tissue fibrous structure, high-fidelity material models, and valve geometry. To this end, we developed an integrated tri-leaflet valve pipeline built upon an isogeometric analysis framework. A high-order structural tensor (HOST)-based method was developed for efficient storage and mapping the two-dimensional fiber structural data onto the valvular 3D geometry. We then developed a neural network (NN) material model that learned the responses of a detailed meso-structural model for exogenously cross-linked planar soft tissues. The NN material model not only reproduced the full anisotropic mechanical responses but also demonstrated a considerable efficiency improvement, as it was trained over a range of realizable fibrous structures. Results of parametric simulations were then performed, as well as population-based bicuspid AV fiber structure, that demonstrated the efficiency and robustness of the present approach. In summary, the present approach that integrates HOST and NN material model provides an efficient computational analysis framework with increased physical and functional realism for the simulation of native and replacement tri-leaflet heart valves.

A contact formulation based on a volumetric potential: Application to isogeometric simulations of atrioventricular valves.

This work formulates frictionless contact between solid bodies in terms of a repulsive potential energy term and illustrates how numerical integration of the resulting forces is computationally similar to the "pinball algorithm" proposed and studied by Belytschko and collaborators in the 1990s. We thereby arrive at a numerical approach that has both the theoretical advantages of a potential-based formulation and the algorithmic simplicity, computational efficiency, and geometrical versatility of pinball contact. The singular nature of the contact potential requires a specialized nonlinear solver and an adaptive time stepping scheme to ensure reliable convergence of implicit dynamic calculations. We illustrate the effectiveness of this numerical method by simulating several benchmark problems and the structural mechanics of the right atrioventricular (tricuspid) heart valve. Atrioventricular valve closure involves contact between every combination of shell surfaces, edges of shells, and cables, but our formulation handles all contact scenarios in a unified manner. We take advantage of this versatility to demonstrate the effects of chordal rupture on tricuspid valve coaptation behavior.

An anisotropic constitutive model for immersogeometric fluid-structure interaction analysis of bioprosthetic heart valves.

This paper considers an anisotropic hyperelastic soft tissue model, originally proposed for native valve tissue and referred to herein as the Lee-Sacks model, in an isogeometric thin shell analysis framework that can be readily combined with immersogeometric fluid-structure interaction (FSI) analysis for high-fidelity simulations of bioprosthetic heart valves (BHVs) interacting with blood flow. We find that the Lee-Sacks model is well-suited to reproduce the anisotropic stress-strain behavior of the cross-linked bovine pericardial tissues that are commonly used in BHVs. An automated procedure for parameter selection leads to an instance of the Lee-Sacks model that matches biaxial stress-strain data from the literature more closely, over a wider range of strains, than other soft tissue models. The relative simplicity of the Lee-Sacks model is attractive for computationally-demanding applications such as FSI analysis and we use the model to demonstrate how the presence and direction of material anisotropy affect the FSI dynamics of BHV leaflets.

A framework for designing patient-specific bioprosthetic heart valves using immersogeometric fluid-structure interaction analysis.

Numerous studies have suggested that medical image derived computational mechanics models could be developed to reduce mortality and morbidity due to cardiovascular diseases by allowing for patient-specific surgical planning and customized medical device design. In this work, we present a novel framework for designing prosthetic heart valves using a parametric design platform and immersogeometric fluid-structure interaction (FSI) analysis. We parameterize the leaflet geometry using several key design parameters. This allows for generating various perturbations of the leaflet design for the patient-specific aortic root reconstructed from the medical image data. Each design is analyzed using our hybrid arbitrary Lagrangian-Eulerian/immersogeometric FSI methodology, which allows us to efficiently simulate the coupling of the deforming aortic root, the parametrically designed prosthetic valves, and the surrounding blood flow under physiological conditions. A parametric study is performed to investigate the influence of the geometry on heart valve performance, indicated by the effective orifice area and the coaptation area. Finally, the FSI simulation result of a design that balances effective orifice area and coaptation area reasonably well is compared with patient-specific phase contrast magnetic resonance imaging data to demonstrate the qualitative similarity of the flow patterns in the ascending aorta.

Projection-based stabilization of interface Lagrange multipliers in immersogeometric fluid-thin structure interaction analysis, with application to heart valve modeling.

This paper discusses a method of stabilizing Lagrange multiplier fields used to couple thin immersed shell structures and surrounding fluids. The method retains essential conservation properties by stabilizing only the portion of the constraint orthogonal to a coarse multiplier space. This stabilization can easily be applied within iterative methods or semi-implicit time integrators that avoid directly solving a saddle point problem for the Lagrange multiplier field. Heart valve simulations demonstrate applicability of the proposed method to 3D unsteady simulations. An appendix sketches the relation between the proposed method and a high-order-accurate approach for simpler model problems.

Immersogeometric cardiovascular fluid-structure interaction analysis with divergence-conforming B-splines.

This paper uses a divergence-conforming B-spline fluid discretization to address the long-standing issue of poor mass conservation in immersed methods for computational fluid-structure interaction (FSI) that represent the influence of the structure as a forcing term in the fluid subproblem. We focus, in particular, on the immersogeometric method developed in our earlier work, analyze its convergence for linear model problems, then apply it to FSI analysis of heart valves, using divergence-conforming B-splines to discretize the fluid subproblem. Poor mass conservation can manifest as effective leakage of fluid through thin solid barriers. This leakage disrupts the qualitative behavior of FSI systems such as heart valves, which exist specifically to block flow. Divergence-conforming discretizations can enforce mass conservation exactly, avoiding this problem. To demonstrate the practical utility of immersogeometric FSI analysis with divergence-conforming B-splines, we use the methods described in this paper to construct and evaluate a computational model of an in vitro experiment that pumps water through an artificial valve.

Biomechanical Behavior of Bioprosthetic Heart Valve Heterograft Tissues: Characterization, Simulation, and Performance.

The use of replacement heart valves continues to grow due to the increased prevalence of valvular heart disease resulting from an ageing population. Since bioprosthetic heart valves (BHVs) continue to be the preferred replacement valve, there continues to be a strong need to develop better and more reliable BHVs through and improved the general understanding of BHV failure mechanisms. The major technological hurdle for the lifespan of the BHV implant continues to be the durability of the constituent leaflet biomaterials, which if improved can lead to substantial clinical impact. In order to develop improved solutions for BHV biomaterials, it is critical to have a better understanding of the inherent biomechanical behaviors of the leaflet biomaterials, including chemical treatment technologies, the impact of repetitive mechanical loading, and the inherent failure modes. This review seeks to provide a comprehensive overview of these issues, with a focus on developing insight on the mechanisms of BHV function and failure. Additionally, this review provides a detailed summary of the computational biomechanical simulations that have been used to inform and develop a higher level of understanding of BHV tissues and their failure modes. Collectively, this information should serve as a tool not only to infer reliable and dependable prosthesis function, but also to instigate and facilitate the design of future bioprosthetic valves and clinically impact cardiology.

Dynamic and fluid-structure interaction simulations of bioprosthetic heart valves using parametric design with T-splines and Fung-type material models.

This paper builds on a recently developed immersogeometric fluid-structure interaction (FSI) methodology for bioprosthetic heart valve (BHV) modeling and simulation. It enhances the proposed framework in the areas of geometry design and constitutive modeling. With these enhancements, BHV FSI simulations may be performed with greater levels of automation, robustness and physical realism. In addition, the paper presents a comparison between FSI analysis and standalone structural dynamics simulation driven by prescribed transvalvular pressure, the latter being a more common modeling choice for this class of problems. The FSI computation achieved better physiological realism in predicting the valve leaflet deformation than its standalone structural dynamics counterpart.

An immersogeometric variational framework for fluid-structure interaction: application to bioprosthetic heart valves.

In this paper, we develop a geometrically flexible technique for computational fluid-structure interaction (FSI). The motivating application is the simulation of tri-leaflet bioprosthetic heart valve function over the complete cardiac cycle. Due to the complex motion of the heart valve leaflets, the fluid domain undergoes large deformations, including changes of topology. The proposed method directly analyzes a spline-based surface representation of the structure by immersing it into a non-boundary-fitted discretization of the surrounding fluid domain. This places our method within an emerging class of computational techniques that aim to capture geometry on non-boundary-fitted analysis meshes. We introduce the term "immersogeometric analysis" to identify this paradigm. The framework starts with an augmented Lagrangian formulation for FSI that enforces kinematic constraints with a combination of Lagrange multipliers and penalty forces. For immersed volumetric objects, we formally eliminate the multiplier field by substituting a fluid-structure interface traction, arriving at Nitsche's method for enforcing Dirichlet boundary conditions on object surfaces. For immersed thin shell structures modeled geometrically as surfaces, the tractions from opposite sides cancel due to the continuity of the background fluid solution space, leaving a penalty method. Application to a bioprosthetic heart valve, where there is a large pressure jump across the leaflets, reveals shortcomings of the penalty approach. To counteract steep pressure gradients through the structure without the conditioning problems that accompany strong penalty forces, we resurrect the Lagrange multiplier field. Further, since the fluid discretization is not tailored to the structure geometry, there is a significant error in the approximation of pressure discontinuities across the shell. This error becomes especially troublesome in residual-based stabilized methods for incompressible flow, leading to problematic compressibility at practical levels of refinement. We modify existing stabilized methods to improve performance. To evaluate the accuracy of the proposed methods, we test them on benchmark problems and compare the results with those of established boundary-fitted techniques. Finally, we simulate the coupling of the bioprosthetic heart valve and the surrounding blood flow under physiological conditions, demonstrating the effectiveness of the proposed techniques in practical computations.

Fluid-structure interaction analysis of bioprosthetic heart valves: Significance of arterial wall deformation.

We propose a framework that combines variational immersed-boundary and arbitrary Lagrangian-Eulerian (ALE) methods for fluid-structure interaction (FSI) simulation of a bioprosthetic heart valve implanted in an artery that is allowed to deform in the model. We find that the variational immersed-boundary method for FSI remains robust and effective for heart valve analysis when the background fluid mesh undergoes deformations corresponding to the expansion and contraction of the elastic artery. Furthermore, the computations presented in this work show that the arterial wall deformation contributes significantly to the realism of the simulation results, leading to flow rates and valve motions that more closely resemble those observed in practice.