Multiscale Modeling and Parallel Simulations of Blood Flow in Cerebral Malaria an

脑疟疾血流的多尺度建模和并行模拟

• 批准号: 7901006
• 负责人: George Karniadakis
• 金额: $ 59.33万
• 依托单位: BROWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7901006
• 关键词: Adhesions; Adhesives; Affect; Algorithms; Anemia; Animal Model; Binding; Biochemical; Biological Models; Biomechanics; Biophysics; Blood capillaries; Blood flow; Brain; Capsid Proteins; Cell Adhesion Process; Cell Aggregation; Cell membrane; Cell model; Cell surface; Cells; Cephalic; Cereals; Cerebral Malaria; Clinical; Code; Complex; Computer Systems; Computer software; Coupled; Cytoskeleton; Data; Development; Diabetes Mellitus; Diffusion; Disease; Documentation; Elliptocytosis found; Endothelial Cells; Equation; Erythrocytes; Falciparum Malaria; Future; Generations; Glycocalyx; Goals; Hematocrit procedure; Hematological Disease; Hemoglobin; High Performance Computing; Human; In Vitro; Individual; Intercellular adhesion molecule 1; Laboratories; Lasers; Lead; Length; Ligands; Link; Liquid substance; Malaria; Measurement; Measures; Mechanics; Mediating; Methodology; Methods; Metric; Microcirculation; Microfluidic Microchips; Microfluidics; Microscopy; Mining; Minor; Modeling; Molecular; Monitor; Motion; Nanotechnology; Nutrient; Obstruction; Online Systems; Optics; Organ; Oxygen; Pharmaceutical Preparations; Phase; Physiological; Preparation; Procedures; Process; Property; Proteins; Reaction; Recording of previous events; Recovery; Resources; Rheology; Schools; Severity of illness; Shapes; Sickle Cell; Signal Pathway; Simulate; Site; Software Tools; Spectrin; Staging; Symptoms; System; Techniques; Testing; Time; Tissues; Transport Reaction; Trees; Uncertainty; Validation; Width; Work; abstracting; adhesion process; arteriole; base; cancer cell; capillary; computer code; computing resources; design; flexibility; laser tweezer; molecular dynamics; multi-scale modeling; nanoscale; oxygen transport; parallel computing; particle; polymerization; pressure; programs; public health relevance; receptor; repository; research study; response; sensor; sickling; simulation; theories; three-dimensional modeling; tool; venule; working group

DESCRIPTION (provided by applicant): Project Summary/Abstract The objective of this project is to develop a unified and validated multiscale modeling methodology for two diseases with serious hematological disorders: celebral malaria (CM) and sickle-cell (SS) anemia. The common clinical symptom of both diseases is obstruction in the microcirculation caused primarily by loss of deformability of red blood cells (RBCs) and increased cytoadhesion. Both diseases are characterized by multiscale phenomena, spanning at least four orders of magnitude in length scale with corresponding disparity in the temporal scale. Moreover, the local vaso-oclusions occurring in CM and SS strongly affect blood flow and oxygen transport at the global organ scale as well. Building on recent progress in modeling RBCs at the spectrin level and cell-aggregation processes and taking advantage of available petaflop-level computing resources, we propose a parallel multiscale methodology to model CM and SS and use it as a predictive tool for quantitatively assessing the severity of these diseases. This will form a general simulation platform for adding further complexity in future studies, e.g., incorporating more biochemical details or studying other hemolytic disorders. Predictability of multiscale models requires quantifying uncertainty, and, to this end, we will incorporate polynomial chaos methods to model and propagate parametric uncertainties through the multiscale system. In addition, to validate the new methodology, microfluidic experiments, optical tweezers measurements and 3D phase microscopy will be used to test different aspects of the conceptual and numerical modeling under different conditions. The specific contributions of this project include: (1) Development of fine- and coarse-grained RBC models in CM (cytoskeleton dynamics) and SS (oxygen transport and polymerization) using molecular dynamics (MD), partial differential equations (PDEs), and mean-field theory. (2) Characterization of infected RBCs and sickle cells at different developmental stages using optical non-invasive means. (3) Modeling of flow and rheology in small vessels. Flow modeling will be based on the "triple-decker"1 - a new algorithm that we have developed for interfacing seamlessly MD, mesoscopic dynamics, and the Navier-Stokes equations. For mesoscopic dynamics we will employ the dissipative particle dynamics (DPD) method, a particularly effective simulation approach for complex fluids. We plan to disseminate our models and software tools, including the general-purpose triple-decker algorithm, via web-based repositories, existing public openware sites, summer schools, and through the MSM consortium. 1 http://www.cfm.brown.edu/crunch/IMAG/FedosovK08.pdf PUBLIC HEALTH RELEVANCE: We propose to develop a unified multiscale modeling methodology for two diseases with serious hematological disorders: celebral malaria (CM) and sickle-cell (SS) anemia. We will model the increase in stiffness of the deformable red blood cells and the adhesion processes involved and correspondingly blood flow in capillaries and arterioles, modeling multiscale phenomena across more than four orders of magnitude in spatio-temporal scales.

描述（由申请人提供）：项目摘要/摘要本项目的目标是开发一个统一的和验证的多尺度建模方法，两种疾病与严重的血液系统疾病：脑疟疾（CM）和镰状细胞（SS）贫血。这两种疾病的共同临床症状是主要由红细胞（RBC）的变形能力丧失和细胞粘附增加引起的微循环障碍。这两种疾病的特点是多尺度现象，跨越至少四个数量级的长度尺度与相应的差距在时间尺度。此外，在CM和SS中发生的局部血管闭塞也强烈影响全局器官尺度的血流和氧运输。基于红细胞血影蛋白水平和细胞聚集过程建模的最新进展，并利用可用的petaflop级计算资源，我们提出了一种并行多尺度方法来建模CM和SS，并将其用作定量评估这些疾病严重程度的预测工具。这将形成一个通用的模拟平台，用于在未来的研究中增加进一步的复杂性，例如，整合更多的生化细节或研究其他溶血性疾病。多尺度模型的可预测性需要量化的不确定性，为此，我们将采用多项式混沌方法来建模和传播参数的不确定性通过多尺度系统。此外，为了验证新方法，微流控实验，光镊测量和3D相位显微镜将用于测试不同条件下的概念和数值建模的不同方面。本项目的具体贡献包括：（1）利用分子动力学（MD）、偏微分方程（PDE）和平均场理论，开发了CM（细胞骨架动力学）和SS（氧运输和聚合）中的细粒度和粗粒度RBC模型。(2)使用光学非侵入性手段表征不同发育阶段的受感染RBC和镰状细胞。(3)小容器中流动和流变学的模拟。流动建模将基于“三层“1 -一种新的算法，我们已经开发了无缝接口MD，介观动力学和Navier-Stokes方程。对于介观动力学，我们将采用耗散粒子动力学（DPD）方法，一个特别有效的模拟复杂流体的方法。我们计划传播我们的模型和软件工具，包括通用的三层算法，通过基于网络的存储库，现有的公共开放软件网站，暑期学校，并通过MSM财团。第1页http://www.cfm.brown.edu/crunch/IMAG/FedosovK08.pdf 公共卫生相关性：我们建议开发一个统一的多尺度建模方法，为两种严重的血液系统疾病：脑型疟疾（CM）和镰状细胞（SS）贫血。我们将对可变形红细胞的刚度增加和所涉及的粘附过程以及相应的毛细血管和小动脉中的血流进行建模，在时空尺度上对超过四个数量级的多尺度现象进行建模。