Division of Applied Mechanics, Office of Science and Engineering Laboratories, Center for Devices and Radiological Health, United States Food and Drug Administration, Silver Spring, MD, USA.
Biomech Model Mechanobiol. 2019 Aug;18(4):1005-1030. doi: 10.1007/s10237-019-01126-4. Epub 2019 Feb 27.
Most stress-based hemolysis models used in computational fluid dynamics (CFD) are based on an empirical power law correlation between hemolysis generation and the flow-induced stress and exposure time. Empirical model coefficients are typically determined by fitting global hemolysis measurements in simplified blood shearing devices under uniform shear conditions and with well-defined exposure times. CFD simulations using these idealized global empirical coefficients are then performed to predict hemolysis in a medical device with complex hemodynamics. The applicability, however, of this traditional approach of using idealized coefficients for a real device with varying exposure times and non-uniform shear is currently unknown. In this study, we propose a new approach for determining device- and species-specific hemolysis power law coefficients (C, a, and b). The approach consists of calculating multiple hemolysis solutions using different sets of coefficients to map the hemolysis response field in three-dimensional (C, a, b) parameter space. The resultant response field is then compared with experimental data in the same device to determine the coefficients that when incorporated into the locally defined power law model yield correct global hemolysis predictions. We first develop the generalized approach by deriving analytical solutions for simple uniform and non-uniform shear flows (planar Couette flow and circular Poiseuille flow, respectively) that allow us to continuously map the hemolysis solution in (C, a, b) parameter space. We then extend our approach to more practical cases relevant to blood-contacting medical devices by replacing the requirement for an analytical solution in our generalized approach with CFD and Kriging surrogate modeling. Finally, we apply our verified CFD-based Kriging surrogate modeling approach to predict the device- and species-specific power law coefficients for developing laminar flow in a small capillary tube. We show that the resultant coefficients are much different than traditional idealized coefficients obtained from simplified uniform shear experiments and that using such idealized coefficients yields a highly inaccurate prediction of hemolysis that is in error by more than 2000% compared to experiments. Our approach and surrogate modeling framework may be applied to more complex medical devices and readily extended to determine empirical coefficients for other continuum-based models of hemolysis and other forms of flow-induced blood damage (e.g., platelet activation and thrombosis).
大多数用于计算流体动力学 (CFD) 的基于压力的溶血模型都是基于溶血生成与流致应力和暴露时间之间的经验幂律关系。经验模型系数通常通过在简化的血液剪切装置中拟合均匀剪切条件下和定义明确的暴露时间的全局溶血测量来确定。然后使用这些理想化的全局经验系数进行 CFD 模拟，以预测具有复杂血液动力学的医疗器械中的溶血。然而，使用具有变化的暴露时间和非均匀剪切的实际设备的这种传统方法的适用性目前尚不清楚。在这项研究中，我们提出了一种确定设备和物种特异性溶血幂律系数 (C、a 和 b) 的新方法。该方法包括使用不同的系数集计算多个溶血解，以在三维 (C、a、b) 参数空间中绘制溶血响应场。然后将得到的响应场与同一设备中的实验数据进行比较，以确定当将系数合并到局部定义的幂律模型中时，哪些系数可以产生正确的全局溶血预测。我们首先通过为简单的均匀和非均匀剪切流（分别为平面库埃特流和圆形泊肃叶流）推导出解析解来开发通用方法，从而允许我们在 (C、a、b) 参数空间中连续绘制溶血解。然后，我们通过用 CFD 和克里金代理建模代替我们的通用方法中的解析解要求，将我们的方法扩展到更实际的与血液接触的医疗器械相关的情况。最后，我们应用我们经过验证的基于 CFD 的克里金代理建模方法来预测在小毛细管中发展层流的设备和物种特异性幂律系数。我们表明，所得系数与从简化的均匀剪切实验获得的传统理想化系数有很大不同，并且使用这种理想化系数会导致溶血的高度不准确预测，与实验相比误差超过 2000%。我们的方法和代理建模框架可以应用于更复杂的医疗器械，并易于扩展以确定其他基于连续体的溶血模型和其他形式的流致血液损伤（例如血小板激活和血栓形成）的经验系数。
