Multiscale modeling of blood flow and clotting in cardiovascular devices

心血管设备中血流和凝血的多尺度建模

• 批准号: 8114454
• 负责人: DANNY BLUESTEIN
• 金额: $ 19.07万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-15 至 2013-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8114454
• 关键词: Adhesions; Adopted; Algorithms; Anticoagulants; Biochemical; Biology; Blood; Blood Clot; Blood Platelets; Blood coagulation; Blood flow; Cardiovascular Diseases; Cardiovascular system; Cells; Chronic; Clinical; Coagulation Process; Complex; Computing Methodologies; Couples; Coupling; Devices; Engineering; Event; Goals; Health Care Costs; Heart Valve Prosthesis; Hemorrhage; Hemostatic Agents; High Performance Computing; In Vitro; Kinetics; Knowledge; Length; Life; Life Expectancy; Liquid substance; Measurement; Mechanics; Medicine; Methodology; Modeling; Molecular; Numeric Rating Scale; Patients; Pattern; Platelet Activation; Platelet aggregation; Principal Investigator; Process; Quality of life; Reaction; Recording of previous events; Regimen; Research; Risk; Shapes; Solutions; Stimulus; Stress; Stroke; Surface; Therapeutic Embolization; Thromboembolism; Tissues; Translating; Trauma; advanced simulation; base; blood pump; computing resources; improved; innovation; interdisciplinary approach; molecular scale; mortality; multi-scale modeling; nanoscale; next generation; particle; programs; response; senescence; simulation; spatiotemporal; supercomputer; tool; ventricular assist device

DESCRIPTION (provided by applicant): The advent of implantable blood recirculating devices has provided life saving solutions to patients with severe cardiovascular diseases. Ventricular assist devices (VAD), blood pumps, and prosthetic heart valves (PHV) provide short to long term solutions for such patients. However, blood clots formation and the attendant risk for stroke remains an impediment to these devices. The complex life-long anticoagulant drug regimen they require, which induces vulnerability to hemorrhage and is not a viable therapy for some patients, does not eliminate this risk. Clot formation is potentiated by contact with foreign surfaces and the non-physiologic flow patterns that enhance the hemostatic response by chronically activating platelets. It is now recognized as the salient aspect of blood trauma in devices. We offer to develop state of the art multiscale numerical simulation methodology that will be able to predict and depict flow induced thrombogenicity in devices. Stresses induced by blood flow on platelets can be represented by a continuum mechanics models down to the order of the <m level. However, molecular effects of adhesion- aggregation bonds are on the order of nm. The coupling of such disparate spatiotemporal scales represents a major computational challenge. Our approach couples a macroscopic model that provides information about the flow induced stresses that may activate clotting, transmitted to a micro-to-nanoscale model based on Discrete Particle Dynamics (DPD) approach. This multi-scale model bridges the gap between macroscopic flow and the cellular scales by allowing the platelets to change their shape continuously in response to the mechanical stimuli. The project follows specific aims (1) develop a DPD model of flow induced thrombogenicity; incorporating biochemical and cellular reaction kinetics leading to platelet aggregation, clot formation and embolization. (2)Bridge the gap between macroscopic and molecular scales by incorporating this model into a multiscale model of flow-induced thrombogenicity, translating the stress dynamics to platelet associated biochemical and cellular events. (3) Validate DPD by comparing its predictions to computational fluid dynamics (CFD), and correlating its platelets activation and aggregation predictions to measurements in a blood recirculation loop. (4) Conduct error estimation and parameter sensitivity analysis, and optimize the computational efficiency across the scales in multi-cluster supercomputers. With extended life expectancy, increasing numbers of patients will require CVS devices. The vexing problem of device thrombogenicity calls for innovative approaches that couple biophysical and biochemical transport spanning the spatial and temporal scales. The tools developed in the proposed research are essential for optimizing the next generation of devices in order to reduce mortality rates and the ensuing healthcare costs, and improve patients' quality of life. Recent progress in computational methods and HPC has put such major challenges within our reach. The proposed methodology may stimulate the burgeoning field of multiscale simulations and its application to solving complex clinical problems at the interface of engineering and biology. It represents a paradigm shift in such simulations, advancing our understanding of biotransport processes to a new level that may have a major impact on important problems in biology and medicine. PHS 398/2590 (Rev. 06/09) Page 1 Continuation Format Page PUBLIC HEALTH RELEVANCE: Better understanding of the complex interactions between living tissues and mechanical stimuli, as represented by the vexing problem of flow-induced cardiovascular devices thrombogenicity, calls for innovative multidisciplinary approaches that couple biophysical and biochemical transport phenomena spanning the spatial and temporal scales. In this proposal a multi-scale modeling approach will be developed that will efficiently utilize high performance computing (HPC) resources. The knowledge that will be gained by the proposed research is essential for developing the next generation of devices that will reduce mortality rates, improve patients' quality of life, and reduce the ensuing healthcare costs. The innovative methodology that will be developed may stimulate the burgeoning field of multiscale simulations and its application to solving complex clinical problems at the interface of engineering and biology. It has the potential to advance our understanding of biotransport processes to a new level that will have a major impact on important problems in biology and medicine.

描述（由申请人提供）：植入血液循环装置的出现为严重心血管疾病的患者提供了挽救生命的解决方案。心室辅助装置（VAD），血泵和假肢心脏瓣膜（PHV）为此类患者提供了短期至长期的解决方案。但是，血块形成和中风的危险仍然是这些设备的障碍。他们需要的复杂的终身抗凝药物方案引起了出血的脆弱性，对某些患者而言并不是可行的疗法，并不能消除这种风险。凝块形成通过与外国表面的接触和非生理流动模式增强，从而通过长期激活血小板来增强止血反应。现在，它被认为是设备中血液创伤的显着方面。我们提供了开发最先进的多尺寸数值模拟方法的状态，该方法将能够预测和描述设备中的流动感应诱导的血栓形成性。血小板上血流引起的应力可以由连续力学模型表示，直到<m水平的顺序。但是，粘附聚集键的分子效应对NM的顺序。这种不同的时空尺度的耦合代表了一个主要的计算挑战。我们的方法将宏观模型融合在一起，该模型提供了有关流动应力的信息，这些应力可能会激活凝结，并基于离散的粒子动力学（DPD）方法传输到微观到纳米级模型。该多尺度模型通过允许血小板以响应机械刺激而连续改变其形状，从而弥合了宏观流和细胞尺度之间的差距。该项目遵循特定目的（1）开发出流动诱导的血栓形成的DPD模型；结合生化和细胞反应动力学，导致血小板聚集，凝块形成和栓塞。 （2）通过将该模型纳入流动诱导的血栓形成性的多尺度模型，将应力动力学转化为血小板相关的生化和细胞事件，从而弥合了宏观和分子尺度之间的间隙。 （3）通过将其预测与计算流体动力学（CFD）进行比较，并将其血小板激活和聚集预测与血液再循环环中的测量相关联。 （4）进行误差估计和参数灵敏度分析，并优化多群集超级计算机中范围的计算效率。 随着预期寿命的延长，越来越多的患者需要CVS设备。设备血栓形成的烦恼问题需要创新的方法，这些方法将生物物理和生化运输跨越了空间和时间尺度。拟议研究中开发的工具对于优化下一代设备以降低死亡率和随之而来的医疗保健成本并改善患者的生活质量至关重要。计算方法和HPC的最新进展使我们面临的主要挑战。所提出的方法可能会刺激多尺度模拟的新兴领域及其在解决工程和生物学界面上解决复杂临床问题时的应用。它代表了此类模拟的范式转变，将我们对生物转运过程的理解提高到了一个新的水平，这可能会对生物学和医学的重要问题产生重大影响。 PHS 398/2590（修订06/09）第1页延续格式页面 公共卫生相关性：更好地理解活组织与机械刺激之间的复杂相互作用，这是由流动引起的心血管设备的烦恼问题所代表的，需要采用创新的多学科方法，这些方法将生物物理和生物化学运输现象融入了空间和时间尺度。在此建议中，将开发一种多尺度建模方法，该方法将有效利用高性能计算（HPC）资源。拟议的研究将获得的知识对于开发下一代的设备至关重要，这些设备将降低死亡率，改善患者的生活质量并降低随之而来的医疗保健成本。将要开发的创新方法可能会刺激多尺度模拟的新兴领域及其在工程和生物学界面上解决复杂临床问题的应用。它有可能使我们对生物转运过程的理解达到一个新的水平，这将对生物学和医学的重要问题产生重大影响。