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

• 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
• 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

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（由申请方提供）：川崎病（KD）是一种严重的儿童疾病，如果不及时治疗，可能导致心血管系统永久性损伤。如果不及时给予大剂量静脉注射丙种球蛋白治疗，25%的儿童会发展成潜在的危及生命的冠状动脉瘤。这些动脉瘤可形成血栓并引起突发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没有明确的指南，也没有工具来预测哪些患者可能处于血栓形成和心肌梗死的最高风险。因此，临床医生面临着一个艰难的选择，要么让一个原本正常、健康的年轻人接受血管成形术、支架置入术或冠状动脉搭桥手术的相关风险，要么等待和观察，因为他们知道如果发生心肌梗死，这可能是一个毁灭性的事件。年轻人KD的血管病变与动脉粥样硬化性疾病不同，因此传统冠状动脉疾病的管理指南不适用。为了生成有助于临床医生对患有动脉瘤的KD患者进行风险评估的模型，我们将使用复杂的血流计算机模拟开发KD患者风险分层的第一个定量计算工具。这项研究将建立在我们对先天性心脏病儿童患者特定血流模拟的丰富经验的基础上。这些工具将使我们能够定量评估KD引起的动脉瘤的血流动力学，包括有关三维、随时间变化的壁面剪切应力和颗粒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能力，包括不确定性分析，流体结构相互作用和生理数据。通过这些工具，我们将展示模拟产生详细血流动力学数据的潜力。其次，我们将验证模拟数据对体外数据，使用粒子图像测速实验和快速原型患者特定模型。第三，我们将检验这一假设，即根据动脉瘤的形状，KD患者之间的血流条件（包括剪切应力、血流停滞和颗粒停留时间）存在很大差异。最后，我们将使用来自心脏MRI研究的数据来创建多个KD患者的模拟，以开发风险分层，该风险分层将基于多种生物力学因素提供血栓风险的初步预测。有了这些工具，我们将为未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，包括KD的儿科专家，成人心脏病专家MRI成像专家和具有心血管生物力学专业知识的工程师，其目标是将计算工具更接近床边并优化KD患者的临床护理。 公共卫生相关性：川崎是儿童获得性心脏病的主要原因，在美国每年影响4,000多名儿童。本计画应用电脑模拟血流，结合核磁共振影像及临床资料，对川崎病所造成的冠状动脉瘤进行详细的血流动力学分析。这项工作所带来的模拟技术的改进将提供以前无法获得的对血流特征的了解，并将为KD患者提供第一个定量血栓形成风险评估工具。