Patient-specific simulations for thrombotic risk assessment in Kawasaki disease

描述(申请人提供)：川崎病(KD)是一种严重的儿童疾病，如果不治疗，可能会导致心血管系统的永久性损害。如果不及时使用大剂量静脉注射丙种球蛋白治疗，25%的儿童会患上潜在的危及生命的冠状动脉动脉瘤。这些动脉瘤可能导致血栓形成，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没有明确的指导方针，也没有工具来预测哪些患者可能是血栓形成和心肌梗死的最高风险者。因此，临床医生面临着一个艰难的选择，要么让原本正常、健康的年轻人承受与血管成形术、支架置入或冠状动脉旁路手术相关的风险，要么静观其变，因为他们知道，如果发生心肌梗死，可能会是毁灭性的事件。青壮年KD的血管病变不同于动脉粥样硬化性疾病，因此传统的冠状动脉疾病治疗指南不适用。为了生成帮助临床医生对KD患者进行动脉瘤风险评估的模型，我们将开发第一个量化计算工具，使用复杂的计算机血流模拟对KD患者进行风险分层。这项研究将建立在我们在先天性心脏病儿童特定患者血流模拟方面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，包括关于三维、时变壁切应力和颗粒滞留时间的详细信息。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。有了这些工具，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患者特定模型来验证模拟数据与体外数据。第三，我们将检验这一假设，即KD患者之间的血流条件有很大的差异，包括切应力、血流停滞和颗粒滞留时间，这取决于动脉瘤的形状。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，该风险分层将提供基于多种生物力学因素的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，从而验证我们的发现。拟议的项目汇集了一支独特的团队，其中包括一名KD儿科专家、一名成年心脏病专家、一名MRI成像专家和一名具有心血管生物力学专业知识的工程师，目标是使计算工具更接近床边，并优化患有冠状动脉动脉瘤的KD患者的临床护理。 与公共卫生相关：川崎病是儿童获得性心脏病的主要原因，每年影响美国4000多名儿童。本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提供以前无法获得的对血流特征的洞察，并将导致第一个用于KD患者的定量血栓风险评估工具。

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.