Biomechanical Evaluation of Aortic Valve Stenosis by Means of a Virtual Stress Test: A Fluid-Structure Interaction Study.

The impact of aortic valve stenosis (AS) extends beyond the vicinity of the narrowed leaflets into the left ventricle (LV) and into the systemic vasculature because of highly unpredictable valve behavior and complex blood flow in the ascending aorta that can be attributed to the strong interaction between the narrowed cusps and the ejected blood. These effects can become exacerbated during exercise and may have implications for disease progression, accurate diagnosis, and timing of intervention. In this 3-D patient-specific study, we employ strongly coupled fluid-structure interaction (FSI) modeling to perform a comprehensive biomechanical evaluation of systolic ejection dynamics in a stenosed aortic valve (AV) during increasing LV contraction. Our model predictions reveal that the heterogeneous ∆P vs. Q relationship that was observed in our previous clinical study can be attributed to a non-linear increase (by ~ 1.5-fold) in aortic valve area as LV heart rate increases from 70 to 115 bpm. Furthermore, our results show that even for a moderately stenotic valve, increased LV contraction during exercise can lead to high-velocity flow turbulence (Re = 11,700) in the aorta similar to that encountered with a severely stenotic valve (Re ~ 10,000), with concomitant greater viscous loss (~3-fold increase) and elevated wall stress in the ascending aorta. Our FSI predictions also reveal that individual valve cusps undergo distinct and highly non-linear increases (>100%) in stress during exercise, potentially contributing to progressive calcification. Such quantitative biomechanical evaluations from realistic FSI workflows provide insights into disease progression and can be integrated with current stress testing for AS patients to comprehensively predict hemodynamics and valve function under both baseline and exercise conditions.

Improving transcatheter aortic valve interventional predictability via fluid-structure interaction modelling using patient-specific anatomy.

Transcatheter aortic valve replacement (TAVR) is now a standard treatment for high-surgical-risk patients with severe aortic valve stenosis. TAVR is being explored for broader indications including degenerated bioprosthetic valves, bicuspid valves and for aortic valve (AV) insufficiency. It is, however, challenging to predict whether the chosen valve size, design or its orientation would produce the most-optimal haemodynamics in the patient. Here, we present a novel patient-specific evaluation framework to realistically predict the patient's AV performance with a high-fidelity fluid-structure interaction analysis that included the patient's left ventricle and ascending aorta (AAo). We retrospectively evaluated the pre- and post-TAVR dynamics of a patient who underwent a 23 mm TAVR and evaluated against the patient's virtually de-calcified AV serving as a hypothetical benchmark. Our model predictions were consistent with clinical data. Stenosed AV produced a turbulent flow during peak-systole, while aortic flow with TAVR and de-calcified AV were both in the laminar-to-turbulent transitional regime with an estimated fivefold reduction in viscous dissipation. For TAVR, dissipation was highest during early systole when valve deformation was the greatest, suggesting that an efficient valve opening may reduce energy loss. Our study demonstrates that such patient-specific modelling frameworks can be used to improve predictability and in the planning of AV interventions.

Synergy between Diastolic Mitral Valve Function and Left Ventricular Flow Aids in Valve Closure and Blood Transport during Systole.

Highly resolved three-dimensional (3D) fluid structure interaction (FSI) simulation using patient-specific echocardiographic data can be a powerful tool for accurately and thoroughly elucidating the biomechanics of mitral valve (MV) function and left ventricular (LV) fluid dynamics. We developed and validated a strongly coupled FSI algorithm to fully characterize the LV flow field during diastolic MV opening under physiologic conditions. Our model revealed that distinct MV deformation and LV flow patterns developed during different diastolic stages. A vortex ring that strongly depended on MV deformation formed during early diastole. At peak E wave, the MV fully opened, with a local Reynolds number of ~5500, indicating that the flow was in the laminar-turbulent transitional regime. Our results  showed that during diastasis, the vortex structures caused the MV leaflets to converge, thus increasing mitral jet's velocity. The vortex ring became asymmetrical, with the vortex structures on the anterior side being larger than on the posterior side. During the late diastolic stages, the flow structures advected toward the LV outflow tract, enhancing fluid transport to the aorta. This 3D-FSI study demonstrated the importance of leaflet dynamics, their effect on the vortex ring, and their influence on MV function and fluid transport within the LV during diastole.

Computational mitral valve evaluation and potential clinical applications.

The mitral valve (MV) apparatus consists of the two asymmetric leaflets, the saddle-shaped annulus, the chordae tendineae, and the papillary muscles. MV function over the cardiac cycle involves complex interaction between the MV apparatus components for efficient blood circulation. Common diseases of the MV include valvular stenosis, regurgitation, and prolapse. MV repair is the most popular and most reliable surgical treatment for early MV pathology. One of the unsolved problems in MV repair is to predict the optimal repair strategy for each patient. Although experimental studies have provided valuable information to improve repair techniques, computational simulations are increasingly playing an important role in understanding the complex MV dynamics, particularly with the availability of patient-specific real-time imaging modalities. This work presents a review of computational simulation studies of MV function employing finite element structural analysis and fluid-structure interaction approach reported in the literature to date. More recent studies towards potential applications of computational simulation approaches in the assessment of valvular repair techniques and potential pre-surgical planning of repair strategies are also discussed. It is anticipated that further advancements in computational techniques combined with the next generations of clinical imaging modalities will enable physiologically more realistic simulations. Such advancement in imaging and computation will allow for patient-specific, disease-specific, and case-specific MV evaluation and virtual prediction of MV repair.

The effect of patient-specific annular motion on dynamic simulation of mitral valve function.

Most surgical procedures for patients with mitral regurgitation (MR) focus on optimization of annular dimension and shape utilizing ring annuloplasty to restore normal annular geometry, increase leaflet coaptation, and reduce regurgitation. Computational studies may provide insight on the effect of annular motion on mitral valve (MV) function through the incorporation of patient-specific MV apparatus geometry from clinical imaging modalities such as echocardiography. In the present study, we have developed a novel algorithm for modeling patient-specific annular motion across the cardiac cycle to further improve our virtual MV modeling and simulation strategy. The MV apparatus including the leaflets, annulus, and location of papillary muscle tips was identified using patient 3D echocardiography data at end diastole and peak systole and converted to virtual MV model. Dynamic annular motion was modeled by incorporating the ECG-gated time-varying scaled annular displacement across the cardiac cycle. We performed dynamic finite element (FE) simulation of two sets of patient data with respect to the presence of MR. Annular morphology, stress distribution across the leaflets and annulus, and contact stress distribution were determined to assess the effect of annular motion on MV function and leaflet coaptation. The effect of dynamic annular motion clearly demonstrated reduced regions with large stress values and provided an improved accuracy in determining the location of improper leaflet coaptation. This strategy has the potential to better quantitate the extent of pathologic MV and better evaluate functional restoration following MV repair.

Patient-specific bicuspid valve dynamics: overview of methods and challenges.

About 1-2 % of the babies are born with bicuspid aortic valves instead of the normal aortic valve with three leaflets. A significant portion of the patients with the congenital bicuspid valve morphology suffer from aortic valve stenosis and/or ascending aortic dilatation and dissection thus requiring surgical intervention when they are young adults. Patients with bicuspid aortic valves (BAVs) have also been found to develop valvular stenosis earlier than those with the normal aortic valve. This paper overviews current knowledge of BAVs, where several studies have suggested that the mechanical stresses induced on the valve leaflets and the abnormal flow development in the ascending aorta may be an important factor in the diseases of the valve and the aortic root. The long-term goals of the studies being performed in our laboratory are aimed towards potential stratification of bicuspid valve patients who may be at risk for developing these pathologies based on analyzing the hemodynamic environment of these valves using fluid-structure interaction (FSI) modeling. Patient-specific geometry of the normal tri-cuspid and bicuspid valves are reconstructed from real-time 3D ultrasound images and the dynamic analyses performed in order to determine the potential effects of mechanical stresses on the valve leaflet and aortic root pathology. This paper describes the details of the computational tools and discusses challenges with patient-specific modeling.

Peak wall stress predicts expansion rate in descending thoracic aortic aneurysms.

BACKGROUND: Aortic diseases, including aortic aneurysms, are the 12th leading cause of death in the United States. The incidence of descending thoracic aortic aneurysms is estimated at 10.4 per 100,000 patient-years. Growing evidence suggests that stress measurements derived from structural analysis of aortic geometries predict clinical outcomes better than diameter alone. METHODS: Twenty-five patients undergoing clinical and radiologic surveillance for thoracic aortic aneurysms were retrospectively identified. Custom MATLAB algorithms were employed to extract aortic wall and intraluminal thrombus geometry from computed tomography angiography scans. The resulting reconstructions were loaded with 120 mm Hg of pressure using finite element analysis. Relationships among peak wall stress, aneurysm growth, and clinical outcome were examined. RESULTS: The average patient age was 71.6 ± 10.0 years, and average follow-up time was 17.5 ± 9 months (range, 6 to 43). The mean initial aneurysm diameter was 47.8 ± 8.0 mm, and the final diameter was 52.1 ± 10.0 mm. Mean aneurysm growth rate was 2.9 ± 2.4 mm per year. A stronger correlation (r = 0.894) was found between peak wall stress and aneurysm growth rate than between maximal aortic diameter and growth rate (r = 0.531). Aneurysms undergoing surgical intervention had higher peak wall stresses than aneurysms undergoing continued surveillance (300 ± 75 kPa versus 229 ± 47 kPa, p = 0.01). CONCLUSIONS: Computational peak wall stress in thoracic aortic aneurysms was found to be strongly correlated with aneurysm expansion rate. Aneurysms requiring surgical intervention had significantly higher peak wall stresses. Peak wall stress may better predict clinical outcome than maximal aneurysmal diameter, and therefore may guide clinical decision-making.

Increased wall stress of saccular versus fusiform aneurysms of the descending thoracic aorta.

BACKGROUND: Repair of fusiform descending thoracic aortic aneurysms (DTAs) is indicated when aneurysmal diameter exceeds a certain threshold; however, diameter-related indications for repair of saccular DTA are less well established. METHODS: Human subjects with fusiform (n = 17) and saccular (n = 17) DTAs who underwent computed tomographic angiography were identified. Patients with aneurysms related to connective tissue disease were excluded. The thoracic aorta was segmented, reconstructed, and triangulated to create a mesh. Finite element analysis was performed using a pressure load of 120 mm Hg and a uniform aortic wall thickness of 3.2 mm to compare the pressure-induced wall stress of fusiform and saccular DTAs. RESULTS: The mean maximum diameter of the fusiform DTAs (6.0 ± 1.5 cm) was significantly greater (p = 0.006) than that of the saccular DTAs (4.4 ± 1.8 cm). However, mean peak wall stress of the fusiform DTAs (0.33 ± 0.15 MPa) was equivalent to that of the saccular DTAs (0.30 ± 0.14 MPa), as found by using an equivalence threshold of 0.15 MPa. The mean normalized wall stress (peak wall stress divided by maximum aneurysm radius) of the saccular DTAs was greater than that of the fusiform DTAs (0.16 ± 0.09 MPa/cm vs. 0.11 ± 0.03 MPa/cm, p = 0.035). CONCLUSIONS: The normalized wall stress for saccular DTA is greater than that for fusiform DTA, indicating that geometric factors such as aneurysm shape influence wall stress. These results suggest that saccular aneurysms may be more prone to rupture than fusiform aneurysms of similar diameter, provide a theoretical rationale for the repair of saccular DTAs at a smaller diameter, and suggest investigation of the role of biomechanical modeling in surgical decision making is warranted.

Effect of Geometry on the Leaflet Stresses in Simulated Models of Congenital Bicuspid Aortic Valves.

The aim of the study was to assess the effect of geometric variations on the stresses developed in the leaflets of congenital bicuspid aortic valves (CBAV). We developed a model for the human tri-leaflet aortic valve based on the geometry and dimensions published in the literature. We also developed simulated CBAV geometry based on the most common geometry present in patients with CBAV that is published in the literature. We employed a constitutive relationship for the leaflet material from the previously published experimental data of fresh porcine aortic valve leaflet specimens for the analysis. We performed dynamic finite element (FE) structural analysis of the valves in the aortic position in order to compute the strain and stress distribution on the leaflets of the tri-leaflet valve and the CBAV models. Our results showed that large changes in the computed in-plane leaflet strain and stress occurred with variations in the geometry of the simulated CBAV whereas changes due to alterations in material constants were correspondingly less. The valve orifice area in the fully open position was significantly reduced in CBAV compared to that for the tri-leaflet valve. The changes in geometry of CBAV resulted in large changes in in-plane strain and stress and our results suggest that geometrical variations may be a potential risk factor inducing calcific aortic stenosis frequently present in patients with CBAV.

Increased ascending aortic wall stress in patients with bicuspid aortic valves.

BACKGROUND: Patients with bicuspid aortic valves (BAV) are at increased risk of ascending aortic dilatation, dissection, and rupture. We hypothesized that ascending aortic wall stress may be increased in patients with BAV compared with patients with tricuspid aortic valves (TAV). METHODS: Twenty patients with BAV and 20 patients with TAV underwent electrocardiogram-gated computed tomographic angiography. Patients were matched for diameter. The thoracic aorta was segmented, reconstructed, and triangulated to create a mesh. Utilizing a uniform pressure load of 120 mm Hg, and isotropic, incompressible, and linear elastic shell elements, finite element analysis was performed to predict 99th percentile wall stress. RESULTS: For patients with BAV and TAV, aortic root diameter was 4.0 ± 0.6 cm and 4.0 ± 0.6 cm (p = 0.724), sinotubular junction diameter was 3.6 ± 0.8 cm and 3.6 ± 0.7 cm (p = 0.736), and maximum ascending aortic diameter was 4.0 ± 0.8 cm and 4.1 ± 0.9 cm (p = 0.849), respectively. The mean 99 th percentile wall stress in the BAV group was greater than in the TAV group (0.54 ± 0.06 MPa vs 0.50 ± 0.09 MPa), though this did not reach statistical significance (p = 0.090). When normalized by radius, the 99 th percentile wall stress was greater in the BAV group (0.31 ± 0.06 MPa/cm vs 0.27 ± 0.03 MPa/cm, p = 0.013). CONCLUSIONS: Patients with BAV, regardless of aortic diameter, have increased 99 th percentile wall stress in the ascending aorta. Ascending aortic three-dimensional geometry may account in part for the increased propensity to aortic dilatation, rupture, and dissection in patients with BAV.

Pathogenesis of acute aortic dissection: a finite element stress analysis.

BACKGROUND: Type A and type B aortic dissections typically result from intimal tears above the sinotubular junction and distal to the left subclavian artery (LSA) ostium, respectively. We hypothesized that this pathology results from elevated pressure-induced regional wall stress. METHODS: We identified 47 individuals with normal thoracic aortas by electrocardiogram-gated computed tomography angiography. The thoracic aorta was segmented, reconstructed, and triangulated to create a geometric mesh. Finite element analysis using a systolic pressure load of 120 mm Hg was performed to predict regional thoracic aortic wall stress. RESULTS: There were local maxima of wall stress above the sinotubular junction in the ascending aorta and distal to the ostia of the supraaortic vessels, including the LSA, in the aortic arch. No local maximum of wall stress was found in the descending thoracic aorta. Comparison of the mean peak wall stress above the sinotubular junction (0.43 ± 0.07 MPa), distal to the LSA (0.21 ± 0.07 MPa), and in the descending thoracic aorta (0.06 ± 0.01 MPa) showed a significant effect for wall stress by aortic region (p < 0.001). CONCLUSIONS: In the normal thoracic aorta, there are peaks in wall stress above the sinotubular junction and distal to the LSA ostium. This stress distribution may contribute to the pathogenesis of aortic dissections, given their colocalization. Future investigations to determine the utility of image-derived biomechanical calculations in predicting aortic dissection are warranted, and therapies designed to reduce the pressure load-induced wall stress in the thoracic aorta are rational.

Role of Computational Simulations in Heart Valve Dynamics and Design of Valvular Prostheses.

Computational simulations are playing an increasingly important role in enhancing our understanding of the normal human physiological function, etiology of diseased states, surgical and interventional planning, and in the design and evaluation of artificial implants. Researchers are taking advantage of computational simulations to speed up the initial design of implantable devices before a prototype is developed and hence able to reduce animal experimentation for the functional evaluation of the devices under development. A review of the reported studies to date relevant to the simulation of the native and prosthetic heart valve dynamics is the subject of the present paper. Potential future directions toward multi-scale simulation studies for our further understanding of the physiology and pathophysiology of heart valve dynamics and valvular implants are also discussed.

Flow interactions with cells and tissues: cardiovascular flows and fluid-structure interactions. Sixth International Bio-Fluid Mechanics Symposium and Workshop, March 28-30, 2008, Pasadena, California.

Interactions between flow and biological cells and tissues are intrinsic to the circulatory, respiratory, digestive and genitourinary systems. In the circulatory system, an understanding of the complex interaction between the arterial wall (a living multi-component organ with anisotropic, nonlinear material properties) and blood (a shear-thinning fluid with 45% by volume consisting of red blood cells, platelets, and white blood cells) is vital to our understanding of the physiology of the human circulation and the etiology and development of arterial diseases, and to the design and development of prosthetic implants and tissue-engineered substitutes. Similarly, an understanding of the complex dynamics of flow past native human heart valves and the effect of that flow on the valvular tissue is necessary to elucidate the etiology of valvular diseases and in the design and development of valve replacements. In this paper we address the influence of biomechanical factors on the arterial circulation. The first part presents our current understanding of the impact of blood flow on the arterial wall at the cellular level and the relationship between flow-induced stresses and the etiology of atherosclerosis. The second part describes recent advances in the application of fluid-structure interaction analysis to arterial flows and the dynamics of heart valves.

Impact of design parameters on bileaflet mechanical heart valve flow dynamics.

BACKGROUND AND AIM OF THE STUDY: One significant problem encountered during surgery to implant mechanical heart valve prostheses is the propensity for thrombus formation near the valve leaflet and housing. This may be caused by the high shear stresses present in the leakage jet flows through small gaps between leaflets and the valve housing during the valve closure phase. METHODS: A two-dimensional (2D) study was undertaken to demonstrate that design changes in bileaflet mechanical valves result in notable changes in the flow-induced stresses and prediction of platelet activation. A Cartesian grid technique was used for the 2D simulation of blood flow through two models of bileaflet mechanical valves, and their flow patterns, closure characteristics and platelet activation potential were compared. A local mesh refinement algorithm allowed efficient and fast flow computations with mesh adaptation based on the gradients of the flow field in the gap between the leaflet and housing at the instant of valve closure. Leaflet motion was calculated dynamically, based on the fluid forces acting on it. Platelets were modeled and tracked as point particles by a Lagrangian particle tracking method which incorporated the hemodynamic forces on the particles. RESULTS: A comparison of results showed that the velocity, wall shear stress and simulated platelet activation parameter were lower in the valve model, with a smaller angle of leaflet traverse between the fully open to the fully closed position. The parameters were also affected to a lesser extent by local changes in the leaflet and housing geometry. CONCLUSION: Computational simulations can be used to examine local design changes to help minimize the fluid-induced stresses that may play a key role in thrombus initiation with the implanted mechanical valves.

A novel flex-stretch-flow bioreactor for the study of engineered heart valve tissue mechanobiology.

Tissue engineered heart valves (TEHV) have been observed to respond to mechanical conditioning in vitro by expression of activated myofibroblast phenotypes followed by improvements in tissue maturation. In separate studies, cyclic flexure, stretch, and flow (FSF) have been demonstrated to exhibit both independent and coupled stimulatory effects. Synthesis of these observations into a rational framework for TEHV mechanical conditioning has been limited, however, due to the functional complexity of tri-leaflet valves and the inherent differences of separate bioreactor systems. Toward quantifying the effects of individual mechanical stimuli similar to those that occur during normal valve function, a novel bioreactor was developed in which FSF mechanical stimuli can be applied to engineered heart valve tissues independently or in combination. The FSF bioreactor consists of two identically equipped chambers, each having the capacity to hold up to 12 rectangular tissue specimens (25 x 7.5 x 1 mm) via a novel "spiral-bound" technique. Specimens can be subjected to changes-in-curvature up to 50 mm(-1) and uniaxial tensile strains up to 75%. Steady laminar flow can be applied by a magnetically coupled paddlewheel system. Computational fluid dynamic (CFD) simulations were conducted and experimentally validated by particle image velocimetry (PIV). Tissue specimen wall shear stress profiles were predicted as a function of paddlewheel speed, culture medium viscosity, and the quasi-static state of specimen deformation (i.e., either undeformed or completely flexed). Velocity profiles predicted by 2D CFD simulations of the paddlewheel mechanism compared well with PIV measurements, and were used to determine boundary conditions in localized 3D simulations. For undeformed specimens, predicted inter-specimen variations in wall shear stress were on average +/-7%, with an average wall shear stress of 1.145 dyne/cm(2) predicted at a paddlewheel speed of 2000 rpm and standard culture conditions. In contrast, while the average wall shear stress predicted for specimens in the quasi-static flexed state was approximately 59% higher (1.821 dyne/cm(2)), flexed specimens exhibited a broad intra-specimen wall shear stress distribution between the convex and concave sides that correlated with specimen curvature, with peak wall shear stresses of approximately 10 dyne/cm(2). This result suggests that by utilizing simple flexed geometric configurations, the present system can also be used to study the effects of spatially varying shear stresses. We conclude that the present design provides a robust tool for the study of mechanical stimuli on in vitro engineered heart valve tissue formation.

Dynamic simulation of bioprosthetic heart valves using a stress resultant shell model.

It is a widely accepted axiom that localized concentration of mechanical stress and large flexural deformation is closely related to the calcification and tissue degeneration in bioprosthetic heart valves (BHV). In order to investigate the complex BHV deformations and stress distributions throughout the cardiac cycle, it is necessary to perform an accurate dynamic analysis with a morphologically and physiologically realistic material specification for the leaflets. We have developed a stress resultant shell model for BHV leaflets incorporating a Fung-elastic constitutive model for in-plane and bending responses separately. Validation studies were performed by comparing the finite element predicted displacement and strain measures with the experimentally measured data under physiological pressure loads. Computed regions of stress concentration and large flexural deformation during the opening and closing phases of the cardiac cycle correlated with previously reported regions of calcification and/or mechanical damage on BHV leaflets. It is expected that the developed experimental and computational methodology will aid in the understanding of the complex dynamic behavior of native and bioprosthetic valves and in the development of tissue engineered valve substitutes.

An experimentally derived stress resultant shell model for heart valve dynamic simulations.

In order to achieve a more realistic and accurate computational simulation of native and bioprosthetic heart valve dynamics, a finite shell element model was developed. Experimentally derived and uncoupled in-plane and bending behaviors were implemented into a fully nonlinear stress resultant shell element. Validation studies compared the planar biaxial extension and three-point bending simulations to the experimental data and demonstrated excellent fidelity. Dynamic simulations of a pericardial bioprosthetic heart valve with the developed shell element model showed significant differences in the deformation characteristics compared to the simulation with an assumed isotropic bending model. The new finite shell element model developed in the present study can also incorporate various types of constitutive models and is expected to help us to understand the complex dynamics of native and bioprosthetic heart valve function in physiological and pathological conditions.

Dynamic simulation pericardial bioprosthetic heart valve function.

While providing nearly trouble-free function for 10-12 years, current bioprosthetic heart valves (BHV) continue to suffer from limited long-term durability. This is usually a result of leaflet calcification and/or structural degeneration, which may be related to regions of stress concentration associated with complex leaflet deformations. In the current work, a dynamic three-dimensional finite element analysis of a pericardial BHV was performed with a recently developed FE implementation of the generalized nonlinear anisotropic Fung-type elastic constitutive model for pericardial BHV tissues (W. Sun and M.S. Sacks, 2005, [Biomech. Model. Mechanobiol., 4(2-3), pp. 190-199]). The pericardial BHV was subjected to time-varying physiological pressure loading to compute the deformation and stress distribution during the opening phase of the valve function. A dynamic sequence of the displacements revealed that the free edge of the leaflet reached the fully open position earlier and the belly region followed. Asymmetry was observed in the resulting displacement and stress distribution due to the fiber direction and the anisotropic characteristics of the Fung-type elastic constitutive material model. The computed stress distribution indicated relatively high magnitudes near the free edge of the leaflet with local bending deformation and subsequently at the leaflet attachment boundary. The maximum computed von Mises stress during the opening phase was 33.8 kPa. The dynamic analysis indicated that the free edge regions of the leaflets were subjected to significant flexural deformation that may potentially lead to structural degeneration after millions of cycles of valve function. The regions subjected to time varying flexural deformation and high stresses of the present study also correspond to regions of tissue valve calcification and structural failure reported from explanted valves. In addition, the present simulation also demonstrated the importance of including the bending component together with the in-plane material behavior of the leaflets towards physiologically realistic deformation of the leaflets. Dynamic simulations with experimentally determined leaflet material specification can be potentially used to modify the valve towards an optimal design to minimize regions of stress concentration and structural failure.

Coronary arteries: imaging, reconstruction, and fluid dynamic analysis.

Atherosclerosis is the underlying cause of most cardiovascular-related deaths in industrialized nations. Determining the etiology of atherosclerosis and detecting lesions in the early stages of the disease for possible pharmacological or mechanical intervention have been challenges facing cardiovascular researchers. In addition to genetic and environmental factors, the formation and growth of atheroma have been linked to the complex fluid dynamics and mass transport in these arterial segments. This article reviews the current state of affairs in imaging modalities and image processing techniques that allow the visualization and morphologically realistic reconstruction of coronary arterial geometry to aid in the diagnosis and treatment of coronary artery disease (CAD). In addition, studies pertaining to our current understanding of the complex flow dynamics in the coronary arteries and the relationship between fluid-induced stresses on the initiation and growth of the atherosclerotic lesions are also reviewed. The article concludes with a brief discussion on possible future directions of research that will advance our knowledge of this challenging problem.