Danny Bluestein

Fluid Mechanics of Arterial Stenosis: Relationship to the Development of Mural Thrombus

In this study, we analyzed blood flow through a model stenosis with Reynolds numbers ranging from 300 to 3,600 using both experimental and numerical methods. The jet produced at the throat was turbulent, leading to an axisymmetric region of slowly recirculating flow. For higher Reynolds numbers, this region became more disturbed and its length was reduced. The numerical predictions were confirmed by digital particle image velocimetry and used to describe the fluid dynamics mechanisms relevant to prior measurements of platelet deposition in canine blood flow (R.T. Schoephoersteret al., Atherosclerosis and Thrombosis 12:1806–1813, 1993). Actual deposition onto the wall was dependent on the wall shear stress distribution along the stenosis, increasing in areas of flow recirculation and reattachment. Platelet activation potential was analyzed under laminar and turbulent flow conditions in terms of the cumulative effect of the varying shear and elongational stresses, and the duration platelets are exposed to them along individual platelet paths. The cumulative product of shear rate and exposure time along a platelet path reached a value of 500, half the value needed for platelet activation under constant shear (J. M. Ramstacket al., Journal of Biomechanics 12: 113–125, 1979).

Steady Flow in an Aneurysm Model: Correlation Between Fluid Dynamics and Blood Platelet Deposition

Laminar and turbulent numerical simulations of steady flow in an aneurysm model were carried out over Reynolds numbers ranging from 300 to 3600. The numerical simulations are validated with Digital particle Image Velocimetry (DPIV) measurements, and used to study the fluid dynamic mechanisms that characterize aneurysm deterioration, by correlating them to in vitro blood platelet deposition results. It is shown that the recirculation zone formed inside the aneurysm cavity creates conditions that promote thrombus formation and the viability of rupture. Wall shear stress values in the recirculation zone are around one order of magnitude less than in the entrance zone. The point of reattachment at the distal end of the aneurysm is characterized by a pronounced wall shear stress peak. As the Reynolds number increases in laminar flow, the center of the recirculation region migrates toward the distal end of the aneurysm, increasing the pressure at the reattachment point. Under fully turbulent flow conditions (Re = 3600) the recirculation zone inside the aneurysm shrinks considerably. The wall shear stress values are almost one order of magnitude larger than those for the laminar cases. The fluid dynamics mechanisms inferred from the numerical simulation were correlated with measurements of blood platelet deposition, offering useful explanations for the different morphologies of the platelet deposition curves.

Influence of microcalcifications on vulnerable plaque mechanics using FSI modeling

Sudden heart attacks remain one of the primary causes of premature death in the developed world. Asymptomatic vulnerable plaques that rupture are believed to prompt such fatal heart attacks and strokes. The role of microcalcifications in the vulnerable plaque rupture mechanics is still debated. Recent studies suggest the microcalcifications increase the plaque vulnerability. In this manuscript we present a numerical study of the role of microcalcifications in plaque vulnerability in an eccentric stenosis model using a transient fluid-structure interaction (FSI) analysis. Two cases are being compared (i) in the absence of a microcalcification (ii) with a microcalcification spot fully embedded in the fibrous cap. Critical plaque stress/strain conditions were affected considerably by the presence of a calcified spot, and were dependent on the timing (phase) during the flow cycle. The vulnerable plaque with the embedded calcification spot presented higher wall stress concentration region in the fibrous cap a bit upstream to the calcified spot, with stress propagating to the deformable parts of the structure around the calcified spot. Following previous studies, this finding supports the hypothesis that microcalcifications increase the plaque vulnerability. Further studies in which the effect of additional microcalcifications and parametric studies of critical plaque cap thickness based on plaque properties and thickness, will help to establish the mechanism by which microcalcifications weaken the plaque and may lead to its rupture.

Vortex Shedding as a Mechanism for Free Emboli Formation in Mechanical Heart Valves

The high incidence of thromboembolic complications of mechanical heart valves (MHV) limits their success as permanent implants. The thrombogenicity of all MHV is primarily due to platelet activation by contact with foreign surfaces and by nonphysiological flow patterns. The latter include elevated flow stresses and regions of recirculation of blood that are induced by valve design characteristics. A numerical simulation of unsteady turbulent flow through a bileaflet MHV was conducted, using the Wilcox k-omega turbulence model for internal low-Reynolds-number flows, and compared to quantitative flow visualization performed in a pulse duplicator system using Digital Particle Image Velocimetry (DPIV). The wake of the valve leaflet during the deceleration phase revealed an intricate pattern of interacting shed vortices. Particle paths showed that platelets that were exposed to the highest flow stresses around the leaflets were entrapped within the shed vortices. Potentially activated, such platelets may tend to aggregate and form free emboli. Once formed, such free emboli would be convected downstream by the shed vortices, increasing the risk of systemic emboli.

Comparison of the Hemodynamic and Thrombogenic Performance of Two Bileaflet Mechanical Heart Valves Using a CFD/FSI Model

The hemodynamic and the thrombogenic performance of two commercially available bileaflet mechanical heart valves (MHVs)--the ATS Open Pivot Valve (ATS) and the St. Jude Regent Valve (SJM), was compared using a state of the art computational fluid dynamics-fluid structure interaction (CFD-FSI) methodology. A transient simulation of the ATS and SJM valves was conducted in a three-dimensional model geometry of a straight conduit with sudden expansion distal the valves, including the valve housing and detailed hinge geometry. An aortic flow waveform (60 beats/min, cardiac output 4 l/min) was applied at the inlet. The FSI formulation utilized a fully implicit coupling procedure using a separate solver for the fluid problem (FLUENT) and for the structural problem. Valve leaflet excursion and pressure differences were calculated, as well as shear stress on the leaflets and accumulated shear stress on particles released during both forward and backward flow phases through the open and closed valve, respectively. In contrast to the SJM, the ATS valve opened to less than maximal opening angle. Nevertheless, maximal and mean pressure gradients and velocity patterns through the valve orifices were comparable. Platelet stress accumulation during forward flow indicated that no platelets experienced a stress accumulation higher than 35 dyne x s/cm2, the threshold for platelet activation (Hellums criterion). However, during the regurgitation flow phase, 0.81% of the platelets in the SJM valve experienced a stress accumulation higher than 35 dyne x s/cm2, compared with 0.63% for the ATS valve. The numerical results indicate that the designs of the ATS and SJM valves, which differ mostly in their hinge mechanism, lead to different potential for platelet activation, especially during the regurgitation phase. This numerical methodology can be used to assess the effects of design parameters on the flow induced thrombogenic potential of blood recirculating devices.

Platelet Activation Due to Hemodynamic Shear Stresses: Damage Accumulation Model and Comparison to in vitro Measurements

The need to optimize the thrombogenic performance of blood recirculating cardiovascular devices, e.g., prosthetic heart valves (PHV) and ventricular assist devices (VAD), is accentuated by the fact that most of them require lifelong anticoagulation therapy that does not eliminate the risk of thromboembolic complications. The formation of thromboemboli in the flow field of these devices is potentiated by contact with foreign surfaces and regional flow phenomena that stimulate blood clotting, especially platelets. With the lack of appropriate methodology, device manufacturers do not specifically optimize for thrombogenic performance. Such optimization can be facilitated by formulating a robust numerical methodology with predictive capabilities of flow-induced platelet activation. In this study, a phenomenological model for platelet cumulative damage, identified by means of genetic algorithms (GAs), was correlated with in vitro experiments conducted in a Hemodynamic Shearing Device (HSD). Platelets were uniformly exposed to flow shear representing the lower end of the stress levels encountered in devices, and platelet activity state (PAS) was measured in response to six dynamic shear stress waveforms representing repeated passages through a device, and correlated to the predictions of the damage accumulation model. Experimental results demonstrated an increase in PAS with a decrease in “relaxation” time between pulses. The model predictions were in very good agreement with the experimental results.

Abdominal aortic aneurysm risk of rupture: patient-specific FSI simulations using anisotropic model.

Abdominal aortic aneurysm (AAA) rupture represents a major cardiovascular risk, combining complex vascular mechanisms weakening the abdominal artery wall coupled with hemodynamic forces exerted on the arterial wall. At present, a reliable method to predict AAA rupture is not available. Recent studies have introduced fluid structure interaction (FSI) simulations using isotropic wall properties to map regions of stress concentrations developing in the aneurismal wall as a much better alternative to the current clinical criterion, which is based on the AAA diameter alone. A new anisotropic material model of AAA that closely matches observed biomechanical AAA material properties was applied to FSI simulations of patient-specific AAA geometries in order to develop a more reliable predictor for its risk of rupture. Each patient-specific geometry was studied with and without an intraluminal thrombus (ILT) using two material models-the more commonly used isotropic material model and an anisotropic material model-to delineate the ILT contribution and the dependence of stress distribution developing within the aneurismal wall on the material model employed. Our results clearly indicate larger stress values for the anisotropic material model and a broader range of stress values as compared to the isotropic material, indicating that the latter may underestimate the risk of rupture. While the locations of high and low stresses are consistent in both material models, the differences between the anisotropic and isotropic models become pronounced at large values of strain-a range that becomes critical when the AAA risk of rupture is imminent. As the anisotropic model more closely matches the biomechanical behavior of the AAA wall and resolves directional strength ambiguities, we conclude that it offers a more reliable predictor of AAA risk of rupture.

Vortex Shedding in Steady Flow Through a Model of an Arterial Stenosis and Its Relevance to Mural Platelet Deposition

AbstractIn this study, the development of unsteady vortical formations in the separated flow region distal to a stenosis throat is presented and compared with the platelet deposition measurements, to enhance our understanding of the mechanisms involved in platelet kinetics in flowing blood. Qualitative and quantitative flow visualization and numerical simulations were performed in a model of a streamlined axisymmetric stenosis with an area reduction of 84% at the throat of the stenosis. Measurements were performed at Reynolds numbers (Re), based on upstream diameter and average velocity, ranging from 300 to 1800. Both the digital particle image visualization method employed and the numerical simulations were able to capture the motion of the vortices through the separated flow region. Periodic shedding of vortices began at approximately Re=375 and continued for the full range of Re studied. The locales at which these vortices are initiated, their size, and their life span, were a function of Re. The numerical simulations of turbulent flow through the stenosis model entailed a detailed depiction of the process of vortex shedding in the separated flow region downstream of the stenosis. These flow patterns were used to elucidate the mechanisms involved in blood platelet kinetics and deposition in the area in and around an arterial stenosis. The unsteady flow development in the recirculation region is hypothesized as the mechanism for observed changes in the distribution of mural platelet deposition between Re=300, 900, and 1800, despite only a marginal variation in the size and shape of the recirculation zone under these flow conditions.

Flow-Induced Platelet Activation in Bileaflet and Monoleaflet Mechanical Heart Valves

A study was conducted to measure in vitro the procoagulant properties of platelets induced by flow through Carbomedics bileaflet and Bjork–Shiley monoleaflet mechanical heart valves (MHVs). Valves were mounted in a left ventricular assist device, and platelets were circulated through them under pulsatile flow. Platelet activation states (PAS) were measured during circulation using a modified prothrombinase method. Computational fluid dynamics (CFD) simulations of turbulent, transient, and non-Newtonian blood flow patterns generated by the two valve designs were done using the Wilcox k−ω turbulence model, and platelet shear-stress histories (the integral of shear-stress exposure with respect to time) through the two MHVs were calculated. PAS measurements indicated that the bileaflet MHV activated platelets at a rate more than twice that observed with the monoleaflet MHV. Turbulent flow patterns were evident in CFD simulations for both valves, and corroborated the PAS observations, showing that, for particles close to the leaflet(s), shear-stress exposure in the bileaflet MHV can be more than four times that in the monoleaflet valve.

Platelet activation in a circulating flow loop: combined effects of shear stress and exposure time 1

Measurement of small changes in platelet activation state (PAS) in circulating stenotic systems in vitro has been problematic because of a paucity of real-time assay methods and circulation systems of low platelet-activating potential. PAS was measured by a modified prothrombinase assay in which activated platelets provide the essential cofactors in the activation of prothrombin by factor Xa. Chemical modification of the prothrombin ensures that the thrombin produced, while assayable, does not activate platelets. Human platelets were circulated in loops in which exposure to shear stress was adjusted by independently varying flow rate, viscosity, and the time of exposure to shear. Although with some differences in platelet response to different conditions of stress, the PAS directly increased with time of circulation, shear stress, and time of exposure to shear. The results show that low-level platelet activation caused by shear stress in a circulation loop can be quantitatively assessed in near-real time in a system of tube geometry. They confirm previous results obtained in non-circulating systems that exposure of platelets to shear conditions on the same order as found in the vasculature causes significant platelet activation, and that this activation is dependent on both shear stress and time of exposure.