Keefe B. Manning

Viscoelasticity of pediatric blood and its implications for the testing of a pulsatile pediatric blood pump.

Red blood cell hematocrit, aggregation and deformability, and plasma protein concentration influence the viscosity and elasticity of whole blood. These parameters affect the flow properties, especially at low shear rates (< 50 s–1). In particular, we have previously shown that the viscoelasticity of fluid affects the inlet filling characteristics and regions of flow separation in small pulsatile blood pumps. Although the viscosity of pediatric blood has been thoroughly studied, its elasticity has not been previously measured. Here we present the viscosity and elasticity of pediatric blood against shear rate for hematocrits from 19–56, measured using an oscillatory rheometer. There is little effect of patient age on blood viscoelasticity. A statistical analysis showed that when compared at constant hematocrit, blood from adult and pediatric patients had similar viscoelastic properties. We present blood analog solutions, as a function of hematocrit, constructed on the basis of the pediatric measurements. Flow field results for viscoelastic analogs of 20, 40 and 60% hematocrit and a Newtonian analog will be compared in the initial, in vitro testing of the Penn State pediatric blood pump, to determine the importance of incorporating a viscoelastic analog into the desigh interaction.

Wall Shear-Rate Estimation Within the 50cc Penn State Artificial Heart Using Particle Image Velocimetry

Particle image velocimetry (PIV) has been gaining acceptance as a routine tool to evaluate the flow fields associated with fluid mechanical devices. We have developed algorithms to investigate the wall shear-rates within the 50cc Penn State artificial heart using low magnification, conventional particle image velocimetry (PIV). Wall shear has been implicated in clot formation, a major post-implant problem with artificial hearts. To address the issues of wall scattering and incomplete measurement volumes, associated with near wall measurements, we have introduced a zero masking and a fluid centroid shifting technique. Simulations using different velocity fields were conducted with the techniques to assess their viability. Subsequently, the techniques were applied to the experimental data collected. The results indicate that the size of the interrogation region should be chosen to be as small as possible to maximize resolution while large enough to ensure an adequate number of particles per region. In the current study, a 16 x 16 interrogation window performed well with good spatial resolution and particle density for the estimation of wall shear rate. The techniques developed with PIV allow wall shear-rate estimates to be obtained from a large number of sites at one time. Because a planar image of a flow field can be determined relatively rapidly, PIV may prove useful in any preliminary design procedure.

Towards Non-thrombogenic Performance of Blood Recirculating Devices

Implantable blood recirculating devices have provided life saving solutions to patients with severe cardiovascular diseases. However, common problems of hemolysis and thromboembolism remain an impediment to these devices. In this article, we present a brief review of the work by several groups in the field that has led to the development of new methodologies that may facilitate achieving the daunting goal of optimizing the thrombogenic performance of blood recirculating devices. The aim is to describe work which pertains to the interaction between flow-induced stresses and the blood constituents, and that supports the hypothesis that thromboembolism in prosthetic blood recirculating devices is initiated and maintained primarily by the non-physiological flow patterns and stresses that activate and enhance the aggregation of blood platelets, increasing the risk of thromboembolism and cardioembolic stroke. Such work includes state-of-the-art numerical and experimental tools used to elucidate flow-induced mechanisms leading to thromboembolism in prosthetic devices. Following the review, the paper describes several efforts conducted by some of the groups active in the field, and points to several directions that should be pursued in the future in order to achieve the goal for blood recirculating prosthetic devices becoming more effective as destination therapy in the future.

Multilaboratory Particle Image Velocimetry Analysis of the FDA Benchmark Nozzle Model to Support Validation of Computational Fluid Dynamics Simulations

This study is part of a FDA-sponsored project to evaluate the use and limitations of computational fluid dynamics (CFD) in assessing blood flow parameters related to medical device safety. In an interlaboratory study, fluid velocities and pressures were measured in a nozzle model to provide experimental validation for a companion round-robin CFD study. The simple benchmark nozzle model, which mimicked the flow fields in several medical devices, consisted of a gradual flow constriction, a narrow throat region, and a sudden expansion region where a fluid jet exited the center of the nozzle with recirculation zones near the model walls. Measurements of mean velocity and turbulent flow quantities were made in the benchmark device at three independent laboratories using particle image velocimetry (PIV). Flow measurements were performed over a range of nozzle throat Reynolds numbers (Re(throat)) from 500 to 6500, covering the laminar, transitional, and turbulent flow regimes. A standard operating procedure was developed for performing experiments under controlled temperature and flow conditions and for minimizing systematic errors during PIV image acquisition and processing. For laminar (Re(throat)=500) and turbulent flow conditions (Re(throat)≥3500), the velocities measured by the three laboratories were similar with an interlaboratory uncertainty of ∼10% at most of the locations. However, for the transitional flow case (Re(throat)=2000), the uncertainty in the size and the velocity of the jet at the nozzle exit increased to ∼60% and was very sensitive to the flow conditions. An error analysis showed that by minimizing the variability in the experimental parameters such as flow rate and fluid viscosity to less than 5% and by matching the inlet turbulence level between the laboratories, the uncertainties in the velocities of the transitional flow case could be reduced to ∼15%. The experimental procedure and flow results from this interlaboratory study (available at http://fdacfd.nci.nih.gov) will be useful in validating CFD simulations of the benchmark nozzle model and in performing PIV studies on other medical device models.

Electrospun PGS:PCL microfibers align human valvular interstitial cells and provide tunable scaffold anisotropy.

Tissue engineered heart valves (TEHV) can be useful in the repair of congenital or acquired valvular diseases due to their potential for growth and remodeling. The development of biomimetic scaffolds is a major challenge in heart valve tissue engineering. One of the most important structural characteristics of mature heart valve leaflets is their intrinsic anisotropy, which is derived from the microstructure of aligned collagen fibers in the extracellular matrix (ECM). In the present study, a directional electrospinning technique is used to fabricate fibrous poly(glycerol sebacate):poly(caprolactone) (PGS:PCL) scaffolds containing aligned fibers, which resemble native heart valve leaflet ECM networks. In addition, the anisotropic mechanical characteristics of fabricated scaffolds are tuned by changing the ratio of PGS:PCL to mimic the native heart valves mechanical properties. Primary human valvular interstitial cells (VICs) attach and align along the anisotropic axes of all PGS:PCL scaffolds with various mechanical properties. The cells are also biochemically active in producing heart-valve-associated collagen, vimentin, and smooth muscle actin as determined by gene expression. The fibrous PGS:PCL scaffolds seeded with human VICs mimick the structure and mechanical properties of native valve leaflet tissues and would potentially be suitable for the replacement of heart valves in diverse patient populations.

Correlation of In Vivo Clot Deposition With the Flow Characteristics in the 50 cc Penn State Artificial Heart: A Preliminary Study

Flow stasis in an artificial heart may provide a situation where thrombus develops. Should part, or all, of the clot dislodge, a thromboembolism may lead to stroke(s), neurologic deficits, or even death. In an effort to determine if the regime of low shear or stasis exists, a two-dimensional particle image velocimetry (PIV) system was implemented to measure the velocity field within the 50 cc Penn State Artificial Heart. The velocity measurements were decomposed nearest the wall to obtain wall shear rates along the bottom of the chamber. The PIV measurements were made in three image planes across the depth of the chamber to reconstruct a surface distribution of the wall shear rates at the bottom over the entire heart cycle. The wall shear rate is shown to be spatially nonuniform, with persistently low wall shear rates. An area near the front edge of the chamber at the bottom showed wall shear rates not exceeding 250 s−1. This was an area of clot formation seen in vivo, suggesting a link may exist between the low wall shear rate zone and thrombus formation.

Development and validation of a computational fluid dynamics methodology for simulation of pulsatile left ventricular assist devices.

An unsteady computational fluid dynamic methodology was developed so that design analyses could be undertaken for devices such as the 50cc Penn State positive-displacement left ventricular assist device (LVAD). The piston motion observed in vitro was modeled, yielding the physiologic flow waveform observed during pulsatile experiments. Valve closure was modeled numerically by locally increasing fluid viscosity during the closed phase. Computational geometry contained Bjork-Shiley Monostrut mechanical heart valves in mitral and aortic positions. Cases for computational analysis included LVAD operation under steady-flow and pulsatile-flow conditions. Computations were validated by comparing simulation results with previously obtained in vitro particle image velocimetry (PIV) measurements. The steady portion of the analysis studied effects of mitral valve orientation, comparing the computational results with in vitro data obtained from mock circulatory loop experiments. The velocity field showed good qualitative agreement with the in vitro PIV data. The pulsatile flow simulations modeled the unsteady flow phenomena associated with a positive-displacement LVAD operating through several beat cycles. Flow velocity gradients allowed computation of the scalar wall strain rate, an important factor for determining hemodynamics of the device. Velocity magnitude contours compared well with PIV data throughout the cycle. Computational wall shear rates over the pulsatile cycle were found to be in the same range as wall shear rates observed in vitro.

Fluid Dynamic Analysis of the 50 cc Penn State Artificial Heart Under Physiological Operating Conditions Using Particle Image Velocimetry

In order to bridge the gap of existing artificial heart technology to the diverse needs of the patient population, we have been investigating the viability of a scaled-down design of the current 70 cc Penn State artificial heart. The issues of clot formation and hemolysis may become magnified within a 50 cc chamber compared to the existing 70 cc one. Particle image velocimetry (PIV) was employed to map the entire 50 cc Penn State artificial heart chamber. Flow fields constructed from PIV data indicate a rotational flow pattern that provides washout during diastole. In addition, shear rate maps were constructed for the inner walls of the heart chamber The lateral walls of the mitral and aortic ports experience high shear rates while the upper and bottom walls undergo low shear rates, with sufficiently long exposure times to potentially induce platelet activation or thrombus formation. In this study, we have demonstrated that PIV may adequately map the flow fields accurately in a reasonable amount of time. Therefore, the potential exists of employing PIV as a design tool.

The 12cc Penn State Pulsatile Pediatric Ventricular Assist Device: Fluid Dynamics Associated With Valve Selection

The mortality rate for infants awaiting a heart transplant is 40% because of the extremely limited number of donor organs. Ventricular assist devices (VADs), a common bridge-to-transplant solution in adults, are becoming a viable option for pediatric patients. A major obstacle faced by VAD designers is thromboembolism. Previous studies have shown that the interrelated flow characteristics necessary for the prevention of thrombosis in a pulsatile VAD are a strong inlet jet, a late diastolic recirculating flow, and a wall shear rate greater than 500 s(-1). Particle image velocimetry was used to compare the flow fields in the chamber of the 12 cc Penn State pediatric pulsatile VAD using two mechanical heart valves: Bjork-Shiley monostrut (BSM) tilting disk valves and CarboMedics (CM) bileaflet valves. In conjunction with the flow evaluation, wall shear data were calculated and analyzed to help quantify wall washing. The major orifice inlet jet of the device containing BSM valves was more intense, which led to better recirculation and wall washing than the three jets produced by the CM valves. Regurgitation through the CM valve served as a significant hindrance to the development of the rotational flow.

Validation of a CFD Methodology for Positive Displacement LVAD Analysis Using PIV Data

Computational fluid dynamics (CFD) is used to asses the hydrodynamic performance of a positive displacement left ventricular assist device. The computational model uses implicit large eddy simulation direct resolution of the chamber compression and modeled valve closure to reproduce the in vitro results. The computations are validated through comparisons with experimental particle image velocimetry (PIV) data. Qualitative comparisons of flow patterns, velocity fields, and wall-shear rates demonstrate a high level of agreement between the computations and experiments. Quantitatively, the PIV and CFD show similar probed velocity histories, closely matching jet velocities and comparable wall-strain rates. Overall, it has been shown that CFD can provide detailed flow field and wall-strain rate data, which is important in evaluating blood pump performance.