MULTI-SCALE MODEL OF THORMBOSIS IN ARTIFICIAL CIRCULATION

人工循环中血栓形成的多尺度模型

• 批准号: 8029501
• 负责人: JAMES F. ANTAKI
• 金额: $ 50.68万
• 依托单位: CARNEGIE-MELLON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-02-01 至 2014-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8029501
• 关键词: Address; Adhesions; Adopted; Agonist; Animals; Anisotropy; Anticoagulation; Benchmarking; Biochemical; Biocompatible Materials; Biological Assay; Biological Process; Biomedical Engineering; Blood; Blood Cells; Blood Circulation; Blood Clot; Blood Platelets; Blood coagulation; Blood flow; Cardiovascular system; Cell Aging; Cell model; Cells; Chemicals; Child; Childhood; Clinical; Coagulation Process; Computer Simulation; Computers; Convection; Coupled; Coupling; Custom; Development; Device Designs; Devices; Diagnosis; Diffusion; Elements; Equation; Erythrocytes; Event; Exclusion; Feedback; Health; Hemodilution; Hemoglobin; Hemorheology; Human; Imagery; Implant; Injury; Lateral; Lifting; Liquid substance; Lytic; Mechanics; Mediating; Medical Device; Methods; Microfluidics; Microscopic; Modeling; Pathway interactions; Patients; Phase; Physics; Plasma; Platelet Activation; Platelet Inhibitors; Process; Radial; Reaction; Recording of previous events; Recruitment Activity; Research; Rest; Risk; Safety; Simulate; Speed; Stretching; Stroke; Surface; Suspension substance; Suspensions; Thrombosis; Time; Trauma; Uncertainty; Whole Blood; blood pump; blood rheology; cell age; design; experience; hazard; hemodynamics; high end computer; implantable device; improved; inhibitor/antagonist; innovation; insight; mathematical model; multi-scale modeling; neglect; physical process; practical application; predictive modeling; programs; research study; shear stress; simulation; theories; tool; viscoelasticity

DESCRIPTION (provided by applicant): The physical and biological processes governing the flow of blood are intimately responsible for safety and efficacy of all blood-wetted medical devices. The quest to design improved cardiovascular devices is however stifled by the inadequacies of current understanding of blood trauma and thrombosis. In spite of decades of experience with device design, hemotrauma research, and computational fluid dynamics modeling, it is virtually impossible to avoid deleterious hematological effects without experimental trail-and-error. Contemporary design relies upon venerable mathematical formula for blood that is more descriptive than predictive. Furthermore, we now understand that that these three phenomena are more closely coupled that previously appreciated. Indeed, previous models virtually neglected the existence of any coupling between these three processes. The objective of proposed project is to advance the accuracy and utility of a predictive model for thrombosis in blood-wetted cardiovascular devices. The research is built upon a combination of a previous model developed by the PI and colleagues for shear- mediated thrombosis and recent progress in modeling cellular-scale hemodynamics. Further incorporation of a model for synergy of platelet agonists is intended to yield a comprehensive design tool that is practical for design optimization of cardiovascular devices. Computer simulations will predict the dynamic interaction of red blood cells (RBCs) with platelets (Plts) in blood flow, and will rely upon a sophisticated theory of interacting continua that can predict the distribution of cells in any arbitrary flow path. The model will be validated and calibrated by both micro-scale computer simulations and microscopic visualization of blood cells in micro-channels. The predictive capacity of model will be demonstrated in three benchmark applications motivated by the development of cardiovascular devices for children: (1) parallel plate study incorporating various microscopic steps and crevices, (2) flow within blade tip of rotary blood pump, and (3) hydrodynamic bearing for pediatric rotary blood pump. Successful completion of these aims will produce a comprehensive computational model for blood trauma in cardiovascular devices, which we believe will contribute to the paradigm shift in the way these devices are developed: replacing trial-and-error with prescriptive bioengineering methods. Combined with computer optimization, the use of this model will greatly accelerate development of innovative new devices, and will reduce the occurrence of adverse complications. We also envision that the models will also be informative for diagnosing various clinical events, and help guide management of anticoagulation therapy. PUBLIC HEALTH RELEVANCE: Cardiovascular devices that are implanted today carry a risk of un-intended blood clotting, which may cause serious injury including stroke. The purpose of this project is to create a computer simulation program that will predict when this might occur, and thereby guide developers of these devices to produce more safe and effective devices.

描述（由申请人提供）：控制血液流动的物理和生物过程与所有血液润湿的医疗器械的安全性和有效性密切相关。然而，由于目前对血液创伤和血栓形成的理解不足，设计改进的心血管装置的追求受到抑制。尽管在设备设计、血伤研究和计算流体动力学建模方面拥有数十年的经验，但如果不进行实验反复试验，几乎不可能避免有害的血液学效应。当代设计依赖于古老的血液数学公式，该公式更具描述性而非预测性。此外，我们现在了解到，这三种现象比以前认识到的联系更加紧密。事实上，以前的模型实际上忽略了这三个过程之间任何耦合的存在。拟议项目的目标是提高血液润湿心血管装置中血栓形成预测模型的准确性和实用性。该研究结合了 PI 及其同事之前开发的剪切介导血栓形成模型和细胞尺度血流动力学建模的最新进展。进一步纳入血小板激动剂协同作用模型旨在产生可用于心血管装置设计优化的综合设计工具。计算机模拟将预测血流中红细胞 (RBC) 与血小板 (Plts) 的动态相互作用，并将依赖于复杂的相互作用连续体理论，该理论可以预测细胞在任意流动路径中的分布。该模型将通过微型计算机模拟和微通道中血细胞的微观可视化进行验证和校准。该模型的预测能力将在由儿童心血管设备开发推动的三个基准应用中得到证明：(1) 结合各种微观台阶和缝隙的平行板研究，(2) 旋转式血泵叶尖内的流动，以及 (3) 儿科旋转式血泵的流体动力轴承。成功完成这些目标将为心血管设备中的血液创伤产生一个全面的计算模型，我们相信这将有助于这些设备开发方式的范式转变：用规定的生物工程方法取代试错法。结合计算机优化，该模型的使用将大大加速创新新设备的开发，并减少不良并发症的发生。我们还预计这些模型还将为诊断各种临床事件提供信息，并有助于指导抗凝治疗的管理。公众健康相关性：当今植入的心血管装置存在意外血液凝固的风险，这可能会导致包括中风在内的严重伤害。该项目的目的是创建一个计算机模拟程序，预测这种情况何时可能发生，从而指导这些设备的开发人员生产更安全、更有效的设备。