In vitro comparison of steady and pulsatile flow characteristics of jellyfish heart valve

In examining the hydrodynamic performance of artificial heart valves in vitro, experiments are carried out under either steady or pulsatile flow conditions. Steady flow experiments are simple to set up and analysis of the data is also simple; however, their validity and accuracy have been questioned. In this study, the flow characteristics of jellyfish valves are evaluated and analyzed for steady and pulsatile flow conditions. The analysis is given in terms of velocity and shear stress distributions for a cardiac flow rate of 4.5l/min, and the corresponding steady flow rate is measured at two locations, 0.5D and 1D downstream of the valve face (D being the diameter of the pipe). At the 0.5D location, the velocity profile results obtained for both flow conditions indicated that jetting flow occurred close to the wall, and flow reversal as well as stagnation zones occurred in the core of the valve chamber. These phenomena were also evident in the shear stress profiles for both pulsatile and steady flow conditions. At this location, the maximum difference between the steady and pulsatile values of peak velocity is about 18%. However, the maximum difference between the peak shear stresses was in the range of 5%–7%. At the 1D location, the flow characteristics observed under both the pulsatile and steady flow conditions were almost identical, with a maximum difference between the peak values of less than 4%. From the data presented here, it can be stated that, at least in the initial optimization of the valve hemodynamic performance, the steady hydrodynamic evaluation of the valve could be an effective tool for analyzing the flow characteristics.     

Quantification of wall shear stress in large blood vessels using Lagrangian interpolation functions with cine phase-contrast magnetic resonance imaging

Arterial wall shear stress is hypothesized to be an important factor in the localization of atherosclerosis. Current methods to compute wall shear stress from magnetic resonance imaging (MRI) data do not account for flow profiles characteristic of pulsatile flow in noncircular vessel lumens. We describe a method to quantify wall shear stress in large blood vessels by differentiating velocity interpolation functions defined using cine phase-contrast MRI data on a band of elements in the neighborhood of the vessel wall. Validation was performed with software phantoms and an in vitro flow phantom. At an image resolution corresponding to in vivo imaging data of the human abdominal aorta, time-averaged, spatially averaged wall shear stress for steady and pulsatile flow were determined to be within 16% and 23% of the analytic solution, respectively. These errors were reduced to 5% and 8% with doubling in image resolution. For the pulsatile software phantom, the oscillation in shear stress was predicted to within 5%. The mean absolute error of circumferentially resolved shear stress for the nonaxisymmetric phantom decreased from 28% to 15% with a doubling in image resolution. The irregularly shaped phantom and in vitro investigation demonstrated convergence of the calculated values with increased image resolution. We quantified the shear stress at the supraceliac and infrarenal regions of a human abdominal aorta to be 3.4 and 2.3 dyn/cm², respectively. © 2002 Biomedical Engineering Society. PAC2002: 8761-c, 8719Uv     

寡聚核苷酸微阵列技术应用于脉动流剪应力作用下人体动脉平滑肌细胞基因差异表达的研究

采用本实验室自行设计和研制的 Flow Cham ber血液流动剪切装置 ,从细胞生物力学的角度 ,采用寡聚核苷酸微阵列技术 ,探讨人体脐动脉平滑肌细胞 (VSMC)在脉动流剪应力作用下的基因差异性表达 ,以及相关基因表达的调控 ;比较脉动流和定常流两种剪应力作用下 VSMC基因表达的差异。通过提取细胞总 RNA ,逆转录合成单链 c DNA,双链 c DNA,体外转录合成生物素标记的 c DNA与基因进行芯片杂交 ,经抗体的检测标记荧光染料Cy3,用基因芯片扫描仪进行基因芯片的图像扫描。结果发现 ,与对照组比较 ,经脉动流剪应力作用后 ,血管平滑肌细胞有 1330个基因出现差异表达 ;经定常流剪应力作用后 ,与对照组比较 ,有 2 6 76个基因出现差异表达 ;比较定常流和脉动流两组的血管平滑肌细胞基因 ,有 2 2 97个基因存在表达差异。实验表明 ,近生理状态的脉动流与定常流两种剪应力 ,对体外培养的人体血管平滑肌细胞的基因表达 ,在数量、范围和调控水平上有着很大的差异。提示在生理或病理情况下 ,血液流体力学的变化 ,可诱导血管平滑肌细胞基因在 m RNA表达水平出现不同的应力响应。     

Factors Influencing Blood Flow Patterns in the Human Right Coronary Artery

Evidence suggests that atherogenesis is linked to local hemodynamic factors such as wall shear stress. We investigated the velocity and wall shear stress patterns within a human right coronary artery (RCA), an important site of atherosclerotic lesion development. Emphasis was placed on evaluating the effect of flow waveform and inlet flow velocity profile on the hemodynamics in the proximal, medial, and distal arterial regions. Using the finite-element method, velocity and wall shear stress patterns in a rigid, anatomically realistic model of a human RCA were computed. Steady flow simulations (Re_D=500) were performed with three different inlet velocity profiles; pulsatile flow simulations utilized two different flow waveforms (both with Womersley parameter=1.82, mean Re_D=233),1 as well as two of the three inlet profiles. Velocity profiles showed Dean-like secondary flow features that were remarkably sensitive to the local curvature of the RCA model. Particularly noteworthy was the rotation of these Dean-like profiles, which produced large local variations in wall shear stress along the sidewalls of the RCA model. Changes in the inlet velocity profiles did not produce significant changes in the arterial velocity and wall shear stress patterns. Pulsatile flow simulations exhibited remarkably similar cycle-average wall shear stress distributions regardless of waveform and inlet velocity profile. The oscillatory shear index was very small and was attributed to flow reversal in the waveform, rather than separation. Cumulatively, these results illustrate that geometric effects (particularly local three-dimensional curvature) dominate RCA hemodynamics, implying that studies attempting to link hemodynamics with atherogenesis should replicate the patient-specific RCA geometry. © 2001 Biomedical Engineering Society. PAC01: 8719Uv, 0270Dh, 8719Xx, 8710+e     

二维脉动流场中内皮细胞表面切应力分布的数值模拟

本文对三种生理相关的正弦入口速度波形的脉动流场内,VEC表面的切应力分布进行了有限差分方法的数值模拟。结果表明：（1）脉动流场与稳态流场中内皮细胞表面的流场分布完全不同,脉动流场中内皮细胞表面的切应力变化幅度远大于稳态流场中的值。（2）同一时刻,每个VEC上的切应力分布是不均匀的,细胞形状影响其表面的切应力分布。（3）在脉动周期的不同时刻,细胞表面的切应力分布也是不均匀的,切应力分布随时间的变化波形与入口波形相类似,但相位有所超前,（4）细胞的伸长主要取决于EC表面的最大平均应力大小。（5）本章的计算结果可以用于Helmilinger实验现象的解释。     

Experimental Investigation of the Steady Flow Downstream of the St. Jude Bileaflet Heart Valve: A Comparison Between Laser Doppler Velocimetry and Particle Image Velocimetry Techniques

This study investigates turbulent flow, based on high Reynolds number, downstream of a prosthetic heart valve using both laser Doppler velocimetry (LDV) and particle image velocimetry (PIV). Until now, LDV has been the more commonly used tool in investigating the flow characteristics associated with mechanical heart valves. The LDV technique allows point by point velocity measurements and provides enough statistical information to quantify turbulent structure. The main drawback of this technique is the time consuming nature of the data acquisition process in order to assess an entire flow field area. Another technique now used in fluid dynamics studies is the PIV measurement technique. This technique allows spatial and temporal measurement of the entire flow field. Using this technique, the instantaneous and average velocity flow fields can be investigated for different positions. This paper presents a comparison of PIV two-dimensional measurements to LDV measurements, performed under steady flow conditions, for a measurement plane parallel to the leaflets of a St. Jude Medical (SJM) bileaflet valve. Comparisons of mean velocity obtained by the two techniques are in good agreement except for where there is instability in the flow. For second moment quantities the comparisons were less agreeable. This suggests that the PIV technique has sufficient temporal and spatial resolution to estimate mean velocity depending on the degree of instability in the flow and also provides sufficient images needed to duplicate mean flow but not for higher moment turbulence quantities such as maximum turbulent shear stress. © 2000 Biomedical Engineering Society. PAC00: 8719Uv, 4262Be, 8780-y     

Development of a custom-designed echo particle image velocimetry system for multi-component hemodynamic measurements: system characterization and initial experimental results

We have recently developed an ultrasound-based velocimetry technique, termed echo particle image velocimetry (Echo PIV), to measure multi-component velocity vectors and local shear rates in arteries and opaque fluid flows by identifying and tracking flow tracers (ultrasound contrast microbubbles) within these flow fields. The original system was implemented on images obtained from a commercial echocardiography scanner. Although promising, this system was limited in spatial resolution and measurable velocity range. In this work, we propose standard rules for characterizing Echo PIV performance and report on a custom-designed Echo PIV system with increased spatial resolution and measurable velocity range. Then we employed this system for initial measurements on tube flows, rotating flows and in vitro carotid artery and abdominal aortic aneurysm (AAA) models to acquire the local velocity and shear rate distributions in these flow fields. The experimental results verified the accuracy of this technique and indicated the promise of the custom Echo PIV system in capturing complex flow fields non-invasively.     

Steady flow velocity field and turbulent stress mappings downstream of a porcine bioprosthetic aortic valveIn Vitro

Velocity profiles and Reynolds stresses downstream of heart valve prostheses are vital parameters in the study of hemolysis and thrombus formation associated with these valves. These parameters have previously been evaluated using single-point measurement techniques such as laser Doppler anemometry (LDA). The purpose of this study is to map the velocity vector fields and Reynolds stresses downstream of a porcine bioprosthetic heart valve in the aortic root region with particle image velocimetry (PIV) techniques in vitro under steady flow conditions. PIV is essentially a multipoint measurement technique that allows full-field measurement of instantaneous velocity vectors in a flow field, thus allowing us to map the entire velocity or stress field over the aortic root (where single-point measurements are difficult). Coupled with flow visualization techniques, the hydrodynamic consequences of introducing a porcine bioprosthetic heart valve into the aortic root was examined, and compared with data obtained from an empty aortic root and an aortic root with the valve mounting ring alone. From our velocity and stress mappings, we found that the valve mounting ring effectively diminishes the central orifice area, giving rise to a higher central axial flow with strong recirculating regions and a corresponding large pressure drop. This in turn produces an intermixing zone between the central jet and recirculating region further downstream from the valve, which contributes to the high-stress zone measured. The development of the flow is further restricted by the valve stents, giving rise to stagnation regions and wakes. High-velocity gradients were also measured at the interface of the jet and recirculating region in the sinus cavity. The overall view of the velocity and stress mappings helps to identify regions of flow disturbances that otherwise may be lost with single-point measuring systems. Although the PIV measurements may lack the accuracy of single-point measuring systems, the overall view of the flow in the aortic root region compensates for the shortcoming.     

On the Characterization of a Non-Newtonian Blood Analog and Its Response to Pulsatile Flow Downstream of a Simplified Stenosis

Particle image velocimetry (PIV) was used to investigate the influence of a non-Newtonian blood analog of aqueous xanthan gum on flow separation in laminar and transitional environments and in both steady and pulsatile flow. Initial steady pressure drop measurements in laminar and transitional flow for a Newtonian analog showed an extension of laminar behavior to Reynolds number (Re) ~ 2900 for the non-Newtonian case. On a macroscale level, this showed good agreement with porcine blood. Subsequently, PIV was used to measure flow patterns and turbulent statistics downstream of an axisymmetric stenosis in the aqueous xanthan gum solution and for a Newtonian analog at Re ~ 520 and Re ~ 1250. The recirculation length for the non-Newtonian case was reduced at Re ~ 520 resultant from increased viscosity at low shear strain rates. At Re ~ 1250, peak turbulent intensities and turbulent shear stresses were dampened by the non-Newtonian fluid in close proximity to the blockage outlet. Although the non-Newtonian case’s recirculation length was increased at peak pulsatile flow, turbulent shear stress was found to be elevated for the Newtonian case downstream from the blockage, suggesting shear layer fragmentation and radial transport. Our findings conclude that the xanthan gum elastic polymer prolongs flow stabilization, which in turn emphasizes the importance of non-Newtonian blood characteristics on the resulting flow patterns in such cardiovascular environments.     

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.     

Numerical and experimental study of blood flow through a patient-specific arteriovenous fistula used for hemodialysis

Arteriovenous fistula (AVF) pathologies related to blood flow necessitate valid calculation tools for local velocity and wall shear stress determination to overcome the clinical diagnostic limits. To illustrate this issue, a reconstructed patient-specific AVF was investigated, using computational fluid dynamics (CFDs) and particle image velocimetry (PIV). The aim of this study was to validate the methodology from medical images to numerical simulations of an AVF by comparing numerical and experimental data. Two numerical grids were presented with a refinement difference of a factor of four. A mold of the same volume was created and mounted on an experimental bench with similar boundary conditions. The patient's acquired echo D006Fppler flow waveform was injected at the arterial inlet. Experimental and numerical velocity vector cartography qualitatively produced similar flow fields. Quantification with a point-to-point approach thoroughly investigated the velocity profiles using the mean difference between both results. The finest mesh generated CFD results with a mean percentage of the difference in velocity magnitude, taking the PIV as reference, did not exceed 10%. At specific zones, the coarse mesh required adaptive meshing to improve fitting with experimental data. Meshing refinement was necessary to improve velocity accuracy at wide diameters and wall shear stress at narrow diameters. Provided that these criteria were properly respected, we show through this difficult example the validity of using CFD to properly describe flow patterns in image-based reconstructed blood vessels.     

PIV validation of blood-heart valve leaflet interaction modelling

The aim of this study was to validate the 2D computational fluid dynamics (CFD) results of a moving heart valve based on a fluid-structure interaction (FSI) algorithm with experimental measurements. Firstly, a pulsatile laminar flow through a monoleaflet valve model with a stiff leaflet was visualized by means of Particle Image Velocimetry (PIV). The inflow data sets were applied to a CFD simulation including blood-leaflet interaction. The measurement section with a fixed leaflet was enclosed into a standard mock loop in series with a Harvard Apparatus Pulsatile Blood Pump, a compliance chamber and a reservoir. Standard 2D PIV measurements were made at a frequency of 60 bpm. Average velocity magnitude results of 36 phase-locked measurements were evaluated at every 10 degrees of the pump cycle. For the CFD flow simulation, a commercially available package from Fluent Inc. was used in combination with inhouse developed FSI code based on the Arbitrary Lagrangian-Eulerian (ALE) method. Then the CFD code was applied to the leaflet to quantify the shear stress on it. Generally, the CFD results are in agreement with the PIV evaluated data in major flow regions, thereby validating the FSI simulation of a monoleaflet valve with a flexible leaflet. The applicability of the new CFD code for quantifying the shear stress on a flexible leaflet is thus demonstrated.     

X-ray velocimetry and haemodynamic forces within a stenosed femoral model at physiological flow rates

High resolution in vivo velocity measurements within the cardiovascular system are essential for accurate calculation of vessel wall shear stress, a highly influential factor for the progression of arterial disease. Unfortunately, currently available techniques for in vivo imaging are unable to provide the temporal resolution required for velocity measurement at physiological flow rates. Advances in technology and improvements in imaging systems are allowing a relatively new technique, X-ray velocimetry, to become a viable tool for such measurements. This study investigates the haemodynamics of pulsatile blood flow in an optically opaque in vitro model at physiological flow rates using X-ray velocimetry. The in vitro model, an asymmetric stenosis, is designed as a 3:1 femoral artery with the diameter and flow rate replicating vasculature of a mouse. Velocity measurements are obtained over multiple cycles of the periodic flow at high temporal and spatial resolution (1 ms and 29 μm, respectively) allowing accurate measurement of the velocity gradients and calculation of the wall shear stress. This study clearly illustrates the capability of in vitro X-ray velocimetry, suggesting it as a possible measurement technique for future in vivo vascular wall shear stress measurement.     

Modelling of flow and wall behaviour in a mildly stenosed tube

In the present computational analysis, pulsatile flow and vessel wall behaviour in a simplified model of a stenosed vessel were investigated. Geometry of a 45% axisymmetrically stenosed (by area) cylindrical tube and a sinusoidal inflow waveform were simulated, with the fluid being assumed to be incompressible and Newtonian. The vessel wall was treated as a thick-walled, incompressible and isotropic material with uniform mechanical properties across the normal as well as the constricted segment. The study of fluid flow and wall motion was initially carried out separately using two commercial codes CFX4.2 and ABAQUS7 respectively. Their combined effects and interactions were later investigated through an iteratively coupled algorithm. Model validations on the rigid-wall fluid and static no-flow solid models were satisfactory, with Root Mean Square deviations of around 7% in centreline axial velocity between the prediction and measurement values for the rigid wall stenosis model, and 5% in circumferential stress for a cylindrical tube model under static loading when compared with the analytical solution. Results on velocity profiles, wall shear stress, intramural strain and stress for the rigid and compliant cases were all presented. Comparison between the rigid and compliant models revealed that, the flow separation layer distal to the stenosis was thicker and longer, and wall shear stress was slightly lower in the compliant model by less than 7.2%. Results obtained from the static wall model (with uniform pressure loading) and coupled fluid/wall interaction modelling of pulsatile flow showed qualitatively similar wall strain and stress patterns but considerable differences in magnitude. The radial and axial stresses were reduced by 31 and 8%, while the circumferential stress was increased by 13% due to the presence of pulsatile flow. Under the flow and structural conditions investigated, the effects of wall compliance were small, and did not change the flow and solid behaviours qualitatively in this case.     

Differential Response of Endothelial Cells to Simvastatin When Conditioned with Steady,Non-Reversing Pulsatile or Oscillating Shear Stress

Few studies have investigated whether fluid mechanics can impair or enhance endothelial cell response to pharmacological agents such as statin drugs. We evaluated and compared Kruppel-like factor 2 (KLF2), endothelial nitric oxide synthase (eNOS), and thrombomodulin (TM) expression in human abdominal aortic endothelial cells (HAAEC) treated with increasing simvastatin concentrations (0.1, 1 or 10 μM) under static culture and shear stress (steady, non-reversing pulsatile, and oscillating). Simvastatin, steady flow, and non-reversing pulsatile flow each separately upregulated KLF2, eNOS, and TM mRNA. At lower simvastatin concentrations (0.1 and 1 μM), the combination of statin and unidirectional steady or pulsatile flow produced an overall additive increase in mRNA levels. At higher simvastatin concentration (10 μM), a synergistic increase in eNOS and TM mRNA expression was observed. In contrast, oscillating flow impaired KLF2 and TM, but not eNOS expression by simvastatin at 1 μM. A higher simvastatin concentration of 10 μM overcame the inhibitory effect of oscillating flow. Our findings suggest that oscillating shear stress renders the endothelial cells less responsive to simvastatin than cells exposed to unidirectional steady or pulsatile flow. Consequently, the pleiotropic effects of statins in vivo may be less effective in endothelial cells exposed to atheroprone hemodynamics.     

In vitro LDA and flow visualization analysis of the spiral vortex pump: effect of inlet valve orientation

The spiral vortex pump (SV), an innovative, penumatically driven ventricular assist device, was tested using the flow visualization technique and laser Doppler anemometry to study the effect of inlet valve orientation under steady and pulsatile flow conditions in a purposely constructed flow circuit aimed at obtaining flow field data. Qualitative information was obtained using the flow visualization technique. The slit-lighting technique and fluorescent bees provided a clear flow field view at the desired location, and a 200 frames/s high-speed video camera was used, capturing the vortex nature of the flow field. Mean velocity and fluctuating velocity profile were obtained using a Kanomax single-channel FLV system. Three diametrically transverse locations and three vertical locations were selected for measurements. The particle-tracking method was also incorporated to obtain velocity vectors. Based on the experimental data, the following general conclusions can be drawn: (1) The SV pump created a vortex flow field under steady and pulsatile flow conditions. (2) The inlet valve orientation sharply influenced the flow inside the SV pump. (3) A relatively strong circulatory flow field was observed when the major orifice was oriented toward the HD junction under steady flow. (4) A relatively weak circulatory flow field was observed when the major orifice was oriented toward the center under steady flow. (5) The directional flow field was more accentuated under pulsatile flow conditions. (6) A relatively stable flow field was observed when the major orifice was oriented upward (pump outlet direction). (7) Directional flow toward the diaphragm was observed when the major orifice was oriented downward. (8) A strong circulatory flow with possible colliding flow toward the peripheral area was observed when the major orifice was oriented outward. (9) A relatively weak circulatory flow was observed when the major orifice was oriented inward. (10) The strength of the circulatory flow during the peak flow phase under pulsatile conditions was not affected by the orientation of the inlet valve.     

Quantitative Assessment of Steady and Pulsatile Flow Fields in a Parallel Plate Flow Chamber

Steady and pulsatile flows were imaged and quantified in a parallel plate flow chamber that was designed to allow constant variation of the volumetric flow rate and to minimize pressure gradients across the width of the flow field. Results indicated that both the steady and pulsatile flow fields were uniform across the width of the flow chamber as shown by linear regression analysis. Further, the dynamic effects of the fluid pulse were transmitted almost instantaneously across the length of the flow field. These findings verify that parallel plate devices designed in this manner are suitable for delivering uniform steady and pulsatile shear stress to adherent cell populations in vitro. © 1999 Biomedical Engineering Society. PAC99: 8780-y, 4780+v, 8718-h     

Boundary Conditions by Schwarz-Christoffel Mapping in Anatomically Accurate Hemodynamics

Appropriate velocity boundary conditions are a prerequisite in computational hemodynamics. A method for mapping analytical or experimental velocity profiles on anatomically realistic boundary cross-sections is presented. Interpolation is required because the computational and experimental domains are seldom aligned. In the absence of velocity information one alternative is the adaptation of analytical profiles based on volumetric flux constraints. The presented algorithms are based on the Schwarz-Christoffel (S-C) mapping of singly or doubly connected polygons to the unit circle or an annulus with unary external radius. S-C transformations are combined to construct a one-to-one invertible map between the target surface and the measurement domain or the support of the source analytical profile. The proposed technique permits us to segment each space separately and map one onto the other in its entirety. Tests are performed with normal velocity boundary conditions for computational simulations of blood flow in the ascending aorta and cerebrospinal fluid flow in the spinal cavity. Mappings of axisymmetric velocity profiles of the Womersley type through a simply connected circular pipe as well as through a doubly connected circular annulus, and interpolations from in-vivo phase-contrast magnetic resonance imaging velocity measurements under instantaneous volumetric flux constraints are considered.     

弯曲颈总动脉内流场的模拟实验研究

目的模拟研究弯曲颈总动脉定常流动速度剖面的不对称性。方法用粒子图像测速技术(PIV)测量并分析曲率分别为1:60和1:20的90°弯管模型在颈总动脉生理平均雷诺数、峰值雷诺数和极限雷诺数条件下,在不同位置的弯曲平面及其垂直方向的轴向速度剖面。结果当颈总动脉的曲率等于1:60时,在人生理平均流动雷诺数条件下,颈总动脉的速度剖面可用偏斜的抛物面来近似;当颈总动脉曲率增大或流动雷诺数增大时,弯曲平面上的速度剖面中部出现下凹趋势,垂直方向上出现M型速度剖面;沿管轴不同位置上的速度剖面形状不同。结论为确定颈动脉分叉定常流动不对称入口速度剖面条件,认识速度剖面的形状如何随流动雷诺数、弯管曲率和截面位置变化提供实验依据。