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: 8063023
• 负责人: Alison L Marsden
• 金额: $ 18.27万
• 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 2013-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8063023
• 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; 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（由申请人提供）：川崎病（KD）是一种严重的儿童疾病，如果不及时治疗，可能会对心血管系统造成永久性损害。如果不及时使用高剂量静脉注射丙种球蛋白进行治疗，25% 的儿童会出现潜在的危及生命的冠状动脉瘤。这些动脉瘤可能形成血栓并导致突发的、不可预测的心血管事件。目前，对于这些患者的血运重建时机尚无明确的指南，也没有工具可以预测哪些患者发生血栓和心肌梗死的风险最高。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、健康的年轻人承受与血管成形术、支架置入或冠状动脉搭桥手术相关的风险，要么等待观望，因为他们知道如果发生心肌梗塞，这可能是一场毁灭性的事件。年轻人川崎病的血管病变与动脉粥样硬化性疾病不同且截然不同，因此传统冠状动脉疾病的治疗指南不适用。为了生成模型来帮助临床医生对患有动脉瘤的川崎病患者进行风险评估，我们将开发第一个定量计算工具，使用复杂的血流计算机模拟对川崎病患者进行风险分层。这项研究将建立在我们对患有先天性心脏病的儿童进行特定患者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，我们将使用粒子图像测速实验和快速原型化的患者特定模型来根据体外数据验证模拟数据。第三，我们将检验这样一个假设：根据动脉瘤的形状，KD 患者的流动条件（包括剪切应力、流动停滞和颗粒停留时间）存在很大差异。最后，我们将使用心脏 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，从而根据多种生物力学因素提供血栓风险的初步预测。借助这些工具，我们将为未来的动物和体外细胞实验奠定基础，从而验证我们的发现。拟议的项目汇集了一个独特的团队，包括一名 KD 儿科医生专家、一名成人心脏病专家 MRI 成像专家和一名心血管生物力学专业知识的工程师，目标是让计算工具更接近床边，并优化 KD 冠状动脉瘤患者的临床护理。 公共卫生相关性：川崎病是儿童获得性心脏病的主要原因，每年影响美国 4,000 多名儿童。该项目应用计算机模拟血流，结合 MRI 成像和临床数据，对 KD 引起的冠状动脉瘤的血流动力学进行详细分析。这项工作带来的模拟技术的改进将为血流特征提供以前无法获得的见解，并将为川崎病患者提供第一个定量血栓风险评估工具。

项目成果

Thrombotic risk stratification using computational modeling in patients with coronary artery aneurysms following Kawasaki disease.

• DOI: 10.1007/s10237-014-0570-z
• 发表时间: 2014-11
• 期刊: Biomechanics and modeling in mechanobiology
• 影响因子: 3.5
• 作者: Sengupta D;Kahn AM;Kung E;Esmaily Moghadam M;Shirinsky O;Lyskina GA;Burns JC;Marsden AL
• 通讯作者: Marsden AL

In Vitro Validation of Patient-Specific Hemodynamic Simulations in Coronary Aneurysms Caused by Kawasaki Disease.

• DOI: 10.1007/s13239-014-0184-8
• 发表时间: 2014-06-01
• 期刊: CARDIOVASCULAR ENGINEERING AND TECHNOLOGY
• 影响因子: 1.8
• 作者: Kung, Ethan;Kahn, Andrew M.;Burns, Jane C.;Marsden, Alison
• 通讯作者: Marsden, Alison