Patient-specific simulations for thrombotic risk assessment in Kawasaki disease

川崎病血栓形成风险评估的患者特异性模拟

基本信息

批准号：
7876583
负责人：
Alison L Marsden
金额：
$ 22.2万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-04-15 至 2012-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7876583
关键词：
3-Dimensional Abdomen Abdominal Aortic Aneurysm Ablation Acute Address Adolescence Adult Adverse event Affect Anatomy Aneurysm Angiography Angioplasty Animal Experiments Animal Model Animals Anticoagulation Area Arts Biological Biomechanics Blood Vessels Blood flow Bypass Cardiac Cardiovascular Diseases Cardiovascular system Catheterization Cells Cerebrum Characteristics Child Childhood Clinic Clinical Clinical Data Clinical Management Clinical Treatment Cohort Studies Collaborations Common Ventricle Complex Computer Simulation Computer software Computers Congenital Heart Defects Coronary Coronary Aneurysm Coronary Arteriosclerosis Coronary Artery Bypass Coronary artery Custom Data Diagnosis Diagnostic tests Disease Disease model Dose Elements Engineering Event Exercise Fever Foundations Functional disorder Future Gamma globulin Goals Guidelines Heart Diseases Image Imaging Techniques In Vitro Incidence Intervention Intravenous Intravenous Immunoglobulins Lasers Lead Left Lesion Life Link Liquid substance Longitudinal Studies Magnetic Resonance Imaging Medical Methods Modeling Morbidity - disease rate Morphology Mucocutaneous Lymph Node Syndrome Myocardial Infarction Natural History One-Step dentin bonding system Operative Surgical Procedures Outcome Output Patients Phase Physical therapy exercises Physicians Physiological Process Property Publications Relative Risks Research Research Personnel Resources Risk Risk Assessment Risk Factors Shapes Specialist Stents Stratification Stress Structure Techniques Testing Thick Thrombosis Thrombus Time Ultrasonography Uncertainty Validation Vascular Diseases Velocimetries Viscosity Warfarin Work advanced simulation base clinical care clinical decision-making cohort computerized tools congenital heart disorder experience hemodynamics high risk innovation insight interest left coronary artery method development mortality mouse model novel particle pediatrician pressure public health relevance research study residence shear stress simulation tool young adult

项目摘要

DESCRIPTION (provided by applicant): Kawasaki disease (KD) is a serious childhood disease that can result in permanent damage to the cardiovascular system if left untreated. Without prompt treatment with high dose intravenous gamma globulin, 25% of children develop potential life-threatening coronary artery aneurysms. These aneurysms can thrombose and cause sudden, unpredictable cardiovascular events. Currently, there are no clear guidelines for the timing of revascularization for these patients, and no tools to predict which patients may be at the highest risk for thrombosis and myocardial infarction. As a result, clinicians are left with a difficult choice to either subject an otherwise normal, healthy young adult to the risks associated with angioplasty, stent placement, or coronary bypass surgery, or to wait and watch, knowing that if a myocardial infarction occurs, it will likely be a devastating event. The vasculopathy of KD in young adults is different and distinct from atherosclerotic disease, so management guidelines for traditional coronary artery disease do not apply. To generate models that will assist clinicians in performing risk assessment in KD patients with aneurysms, we will develop the first quantitative computational tools for risk stratification in KD patients using sophisticated computer simulations of blood flow. This research will build upon on our extensive experience with patient- specific blood flow simulations for children with congenital heart disease. These tools will allow us to quantitatively assess hemodynamics in aneurysms resulting from KD, including detailed information about three-dimensional, time-varying wall shear stress and particle residence time. The project will consist of the following aims. First, we will enhance current simulation capabilities to include uncertainty analysis, fluid structure interaction, and physiologic data. With these tools we will demonstrate the potential for simulations to produce detailed hemodynamic data. Second, we will validate simulation data against in vitro data using particle image velocimetry experiments and rapid prototyped patient-specific models. Third, we will test the hypothesis that there are large differences in flow conditions, including shear stress, flow stasis, and particle residence time, among KD patients depending on the shape of the aneurysm. Lastly, we will use data from cardiac MRI studies to create simulations from multiple KD patients to develop a risk stratification that will offer initial predictions of the risk of thrombus based on multiple biomechanical factors. With these tools, we will lay a foundation for future animal and in vitro cell experiments that will validate our findings. The proposed project brings together a unique team including a pediatrician expert in KD, an adult cardiologist MRI imaging specialist, and an engineer with expertise in cardiovascular biomechanics, with the goal of bringing computational tools one step closer to the bedside and optimizing the clinical care of KD patients with coronary aneurysms. PUBLIC HEALTH RELEVANCE: Kawasaki disease is the leading cause of acquired heart disease in children, affecting more than 4,000 children annually in the US. This project applies computer simulations of blood flow incorporating MRI imaging and clinical data to perform detailed analysis of the hemodynamics in coronary artery aneurysms caused by KD. Improvements in simulation techniques resulting from this work will provide previously unavailable insights into flow characteristics and will result in the first quantitative thrombotic risk assessment tool for KD patients.

描述（由申请人提供）：川崎疾病（KD）是一种严重的儿童疾病，如果未治疗，可能会对心血管系统造成永久损害。如果没有高剂量静脉γ球蛋白的迅速治疗，则有25％的儿童会发展潜在的威胁生命的冠状动脉瘤。这些动脉瘤可能会导致突然的，不可预测的心血管事件。目前，对于这些患者的血运重建时间尚无明确的准则，也没有预测哪些患者可能处于血栓形成和心肌梗塞的风险最高的工具。结果，临床医生遇到了一个困难的选择，要么将原本正常的，健康的年轻成年人带到与血管成形术，支架放置或冠状动脉搭桥手术相关的风险，或者等待和观察，因此知道，如果发生心肌梗死，这可能是毁灭性的事件。 KD在年轻人中的血管病变不同，与动脉粥样硬化疾病不同，因此不适用传统冠状动脉疾病的管理指南。为了生成模型，可以帮助临床医生对具有动脉瘤的KD患者进行风险评估，我们将使用复杂的血液流动计算机模拟开发首先的KD患者风险分层的定量计算工具。这项研究将基于我们对先天性心脏病儿童的患者特异性血流模拟的丰富经验。这些工具将使我们能够定量评估由KD引起的动脉瘤中的血液动力学，包括有关三维，时间变化的壁剪应力和粒子停留时间的详细信息。该项目将包括以下目标。首先，我们将增强当前的模拟功能，包括不确定性分析，流体结构相互作用和生理数据。使用这些工具，我们将证明模拟产生详细的血液动力学数据的潜力。其次，我们将使用粒子图像速度测定实验和快速原型患者特异性模型来验证模拟数据针对体外数据。第三，我们将检验以下假设：在流动条件下，KD患者之间的流动条件有很大差异，包括剪切应力，流动性停滞和粒子停留时间，具体取决于动脉瘤的形状。最后，我们将使用来自心脏MRI研究的数据来创建来自多个KD患者的模拟，以开发风险分层，该风险分层将根据多种生物力学因素提供对血栓风险的初步预测。借助这些工具，我们将为将来的动物和体外细胞实验奠定基础，以验证我们的发现。拟议的项目汇集了一个独特的团队，其中包括KD的儿科专家，成人心脏病专家MRI成像专家，以及具有心血管生物力学专业知识的工程师，目的是使计算工具更靠近床边并优化冠状动脉Aneurysms KD患者的临床护理。公共卫生相关性：川崎疾病是儿童心脏病的主要原因，每年在美国影响4,000多名儿童。该项目应用了融合MRI成像和临床数据的血流的计算机模拟，以详细分析由KD引起的冠状动脉动脉瘤中的血液动力学。这项工作产生的仿真技术的改进将提供以前无法获得的对流动特征的见解，并将为KD患者提供首次定量的血栓性风险评估工具。