CDI Type II/Collaborative Research: A New Approach to the Modeling of Clot Formation and Lysis in Arteries

动脉血栓形成引起的急性心脏综合征(ACS)在美国是主要的死亡原因。显然有必要制定定量风险评估和分析的方法。然而，由于对控制动脉血栓形成的各种参数的了解不充分、不完善和不确定，这样的方法还不存在。鉴于目前的不完全知识，建议的方法寻求开发有效的模拟技术来洞察血栓形成并对结果进行概率预测，例如在特定时间间隔内形成血栓的概率。将连续介质力学与估计理论和统计信号处理的思想相结合，PI将开发其参数为随机变量的模型，从而允许将参数的可变性纳入建模阶段本身。通过确保连续介质模型具有隐马尔可夫模型(HMM)的结构，可以利用估计理论的强大工具从实验测量中寻找隐藏变量的概率分布。为了模拟凝血的生物化学及其与血流和动脉变形的复杂相互作用，并进行风险分析，PI将使用可并行的计算算法进行模拟。PI计划用高度可并行化的随机或概率流取代传统力学平衡定律的通常离散近似。基于仿真技术。凝血和出血的障碍具有重要的临床意义。包括急性冠脉综合征、心肌梗死、肺血栓、深静脉血栓形成和出血性疾病在内的这些疾病是西方世界死亡的主要原因。这项拟议的研究将提供对凝血和出血过程的了解，并有可能对各种血液疾病产生巨大影响。这项拟议的工作具有变革性，因为它将融合来自生物医学和生物力学、数学、统计学和概率论、估计理论和信号处理的各种科学界的想法，并有可能对许多科学界产生重大影响。由于研究人员在教育创新方面有着丰富的记录，拟议的研究也将对教育方面产生有益的影响。

Acute cardiac syndrome (ACS) due to arterial thrombosis is a leading cause of death in the US. There is a clear need to develop methods for quantitative risk assessment and analysis of ACS. However, due to inadequate, imperfect and uncertain knowledge regarding the various parameters that control arterial thrombosis, such methods do not exist. Given current incomplete knowledge, the proposed approach seeks to develop efficient simulation techniques to gain insight into thrombogenesis and to make probabilistic predictions of outcomes such as the probability of clot formation over specific time intervals. Coupling continuum mechanics to ideas from estimation theory and statistical signal processing the PIs will develop models whose parameters are random variables that allows for the incorporation of variability of parameters in the modeling stage itself. By ensuring that the continuum models have the structure of Hidden Markov Models (HMMs) it is possible to use the powerful tools of estimation theory to find probability distributions for the hidden variables from experimental measurements. In order to simulate the biochemistry of clotting and its complex interaction with blood flow and artery deformation, and to carry out risk analysis, the PIs will use parallelizable computational algorithms for the simulations. The PIs plan to replace the usual discrete approximation of the traditional balance laws of mechanics with highly parallelizable stochastic or ?probability flow? based simulation techniques. Disorders of coagulation and bleeding are of substantial clinical importance. Such conditions including ACS, myocardial infarction, pulmonary embolus, deep vein thrombosis and hemorrhagic disorders, amongst others are major contributors to mortality in the western world. The proposed research will provide an understanding of the processes of coagulation and bleeding and has the potential to have a tremendous impact on a variety of blood disorders. The proposed work is transformative in that it will meld together ideas from various scientific communities from biomedicine and biomechanics, mathematics, statistics and probability theory, estimation theory and signal processing, and has the potential to have significant impact on numerous scientific communities. As the researchers have a substantial track record in educational innovations the proposed research will also have salutary effect on educational aspects.