Richard T. Schoephoerster

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.

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.

Effects of local geometry and fluid dynamics on regional platelet deposition on artificial surfaces.

An important aspect of blood-material interactions is the activation, adhesion, and subsequent aggregation of blood platelets on the artificial surface, all of which are directly affected by local fluid dynamics. The objective of this work was to directly correlate changing local fluid dynamic conditions produced by various vessel geometries, including stenosis, aneurysm, and separate contraction and expansion geometries, with quantitative in vitro measurements of regional platelet deposition. We directly measured platelet deposition as a function of axial position along four Lexan flow chambers with axisymmetric models of these geometries using 111In-labeled platelets. Platelet deposition was maximum in observed areas of flow recirculation and reattachment and minimum in locations of high shear and separation. For the stenosis geometry, two distinct regions of increased platelet deposition were apparent, one proximal to and one distal to the stenosis throat. An approximately linear increase in platelet densities was produced in the aneurysm region, increasing in the direction of flow. Through a comparison of platelet deposition with local fluid streamline orientation, we have shown that platelet deposition is increased in certain areas due to the enhanced convective transport of platelets and blood cells to the vessel wall along locally curved streamlines with velocity components perpendicular to the vessel wall.

Velocity and turbulence measurements past mitrial valve prostheses in a model left ventricle

Thrombogenesis and hemolysis have both been linked to the flow dynamics past heart valve prostheses. To learn more about the particular flow dynamics past mitral valve prostheses in the left ventricle under controlled experimental conditions, an in vitro study was performed. The experimental methods included velocity and turbulent shear stress measurements past caged-ball, tilting disc, bileaflet, and polyurethane trileaflet mitral valves in an acrylic rigid model of the left ventricle using laser Doppler anemometry. The results indicate that all four prosthetic heart valves studied create at least mildly disturbed flow fields. The effect of the left ventricular geometry on the flow development is to produce a stabilizing vortex which engulfs the entire left ventricular cavity, depending on the orientation of the valve. The measured turbulent shear stress magnitudes for all four valves did not exceed the reported value for hemolytic damage. However, the measured turbulent shear stresses were near or exceeded the critical shear stress reported in the literature for platelet lysis, a known precursor to thrombus formation.

Effects of stent geometry on local flow dynamics and resulting platelet deposition in an in vitro model

Platelet deposition has been shown previously to depend on convective transport patterns, visualized by the instantaneous streamlines. Previous attempts to quantify hemodynamic studies of platelet deposition have been limited to 2D geometries. This study provides a physiologic assessment of the effects of stent geometry on platelet deposition by using actual 3D stents. Human blood with fluorescently labeled platelets was circulated through an in vitro system producing physiologic pulsatile flow in a compliant tube in which Bx Velocity, Wallstent and Aurora stents were implanted. Computational fluid dynamic models of the stents provided flow data to aid in explaining localized platelet deposition. Regions of constant flow separation proximal and distal to the strut exhibited very low platelet deposition. Platelet deposition was highest just downstream of flow stagnation regions due to convection towards the wall, then decreased with axial distance from the strut as flow streamlines became locally parallel to the wall. The nearly helically recirculating regions near the Bx Velocity stent connectors exhibited complex fluid dynamics with more platelet deposition, than the smaller separation regions. Localized platelet deposition was heavily dependent on flow convection, suggesting that arterial reaction to stents can be modulated in part by altering the hemodynamics associated with stent design.

Comparison of near-wall hemodynamic parameters in stented artery models.

Four commercially available stent designs (two balloon expandable-Bx Velocity and NIR, and two self-expanding-Wallstent and Aurora) were modeled to compare the near-wall flow characteristics of stented arteries using computational fluid dynamics simulations under pulsatile flow conditions. A flat rectangular stented vessel model was constructed and simulations were carried out using rigid walls and sinusoidal velocity input (nominal wall shear stress of 10+/-5 dyn/cm2). Mesh independence was determined from convergence (<10%) of the axial wall shear stress (WSS) along the length of the stented model. The flow disturbance was characterized and quantified by the distributions of axial and transverse WSS, WSS gradients, and flow separation parameters. Normalized time-averaged effective WSS during the flow cycle was the smallest for the Wallstent (2.9 dyn/cm2) compared with the others (5.8 dyn/cm2 for the Bx Velocity stent, 5.0 dyn/cm2 for the Aurora stent, and 5.3 dyn/cm2 for the NIR stent). Regions of low mean WSS (<5 dyn/cm2) and elevated WSS gradients (>20 dyn/cm3) were also the largest for the Wallstent compared with the others. WSS gradients were the largest near the struts and remained distinctly nonzero for most of the region between the struts for all stent designs. Fully recirculating regions (as determined by separation parameter) were the largest for the Bx Velocity stent compared with the others. The most hemodynamically favorable stents from our computational analysis were the Bx Velocity and NIR stents, which were slotted-tube balloon-expandable designs. Since clinical data indicate lower restenosis rates for the Bx Velocity and NIR stents compared with the Wallstent, our data suggest that near-wall hemodynamics may predict some aspects of in vivo performance. Further consideration of biomechanics, including solid mechanics, in stent design is warranted.

Spatial Distribution of Platelet Deposition in Stented Arterial Models Under Physiologic Flow

This paper presents dynamic flow experiments with fluorescently labeled platelets to allow for spatial observation of wall attachment in inter-strut spacings, to investigate their relationship to flow patterns. Human blood with fluorescently labeled platelets was circulated through an in vitro system that produced physiologic pulsatile flow in a parallel plate flow chamber that contained three different stent designs that feature completely recirculating flow, partially recirculating flow (intermediate strut spacing), and completely reattached flow. Highly resolved spatial distribution of platelets was obtained by imaging fluorescently labeled platelets between the struts. Platelet deposition was higher in areas where flow is directed towards the wall, and lower in areas where flow is directed away from the wall. Flow detachment and reattachment points exhibited very low platelet deposition. Platelet deposition within intermediate strut spacing continued to increase throughout the experimental period, indicating that the deposition rate had not plateaued unlike other strut spacings. The spatial uniformity and temporal increase in platelet deposition for the intermediate strut spacing confirms and helps explain our previous finding that platelet deposition was highest with this strut spacing. Further experimental investigations will include more complex three-dimensional geometries.

EVALUATION OF LEFT VENTRICULAR FUNCTION BASED ON SIMULATED SYSTOLIC FLOW DYNAMICS COMPUTED FROM REGIONAL WALL MOTION

Left ventricular (LV) chamber flow is undoubtedly influenced by the time-dependent regional motion of the LV wall. In an attempt to obtain diagnostic parameters based on LV chamber flow, we computed the LV chamber, two-dimensional systolic velocity and pressure distribution for two right anterior oblique (RAO) ventriculograms: one normal, one with ischemic coronary artery disease, and several simulations with prescribed abnormal wall motion. The flow fields are obtained by solving the discretized two-dimensional Navier-Stokes equations for viscous, incompressible unsteady flow using the finite analytic method. These solutions were used as a basis for two LV assessment parameters: (1) local pressure gradient near the LV wall, and (2) the central ejection region (CER), defined as the region of flow domain in which the obtained velocity field vectors are aligned +/- 5 degrees from the LV long axis. A CER coefficient, R, derived from the location and orientation of the CER within the LV cavity, is defined such that R = 0 for a heart which produces no CER, and R = 1 for a heart whose contraction is perfectly even along the entire RAO LV outline. The computed local pressure gradients in the ischemic heart near the apical wall region were reduced compared with those computed in the normal heart. An observable decrease in magnitude of the pressure gradients in the apical region for increasing severity of abnormal wall motion was also indicated. However, the prescribed abnormal wall motion simulations generated reduced pressure gradients in regions of abnormal wall motion and normal regions as well. Therefore, the local wall pressure gradient may not be suitable for localization of coronary occlusion but for presence of disease only. The time-averaged CER coefficient was 0.709 for the normal heart and 0.453 for the diseased heart. The CER shifted toward the region of LV wall which exhibits the abnormal motion, and the CER coefficient decreased with increasing severity of abnormal wall motion. The CER coefficient provides a qualitative and quantitative measure of global function that regional wall motion analysis cannot provide, and is a parameter which is sensitive to regional and temporal abnormalities and the resulting compensatory actions which cannot be detected by global parameters.

Thrombogenic Potential of Innovia Polymer Valves versus Carpentier-Edwards Perimount Magna Aortic Bioprosthetic Valves

Trileaflet polymeric prosthetic aortic valves (AVs) produce hemodynamic characteristics akin to the natural AV and may be most suitable for applications such as transcatheter implantation and mechanical circulatory support (MCS) devices. Their success has not yet been realized due to problems of calcification, durability, and thrombosis. We address the latter by comparing the platelet activation rates (PARs) of an improved polymer valve design (Innovia LLC) made from poly(styrene-block-isobutylene-block-styrene) (SIBS) with the commercially available Carpentier-Edwards Perimount Magna Aortic Bioprosthetic Valve. We used our modified prothrombinase platelet activity state (PAS) assay and flow cytometry methods to measure platelet activation of a pair of 19 mm valves mounted inside a pulsatile Berlin left ventricular assist device (LVAD). The PAR of the polymer valve measured with the PAS assay was fivefold lower than that of the tissue valve (p = 0.005) and fourfold lower with flow cytometry measurements (p = 0.007). In vitro hydrodynamic tests showed clinically similar performance of the Innovia and Magna valves. These results demonstrate a significant improvement in thrombogenic performance of the polymer valve compared with our previous study of the former valve design and encourage further development of SIBS for use in heart valve prostheses.