Multiscale modeling for vein graft failure risk stratification in CABG patients

CABG 患者静脉移植失败风险分层的多尺度建模

• 批准号: 8751621
• 负责人: ANDREW KAHN
• 金额: $ 37.3万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-22 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8751621
• 关键词: Address; Adult; Anatomy; Angiography; Biomechanics; Blood Vessels; Blood flow; Bypass; Cardiology; Cardiovascular system; Catheterization; Clinical; Clinical Data; Collaborations; Complex; Confidence Intervals; Coronary; Coronary Arteriosclerosis; Coronary Artery Bypass; Coronary Circulation; Coronary artery; Data; Data Reporting; Disease; Early identification; Engineering; Excision; Failure; Future; Goals; Gold; Growth; High Resolution Computed Tomography; Image; Imaging Techniques; Implant; Knowledge; Lead; Link; Liquid substance; Mechanics; Medical; Methods; Modeling; Monitor; Morbidity - disease rate; Motion; Obstruction; Operative Surgical Procedures; Outcome; Patients; Performance; Physics; Physiological; Post Technic; Process; Property; Publications; Recording of previous events; Research; Resolution; Risk; Saphenous Vein; Solid; Specialist; Stenosis; Stimulus; Stratification; Stress; Surgical Management; System; Translations; Transplanted tissue; Uncertainty; Validation; Veins; Work; X-Ray Computed Tomography; base; design; experience; graft failure; hemodynamics; high risk; improved; innovation; internal thoracic artery; multi-scale modeling; novel; public health relevance; response; simulation; standard care; success; tool; treatment strategy; virtual

Coronary artery bypass graft (CABG) surgery is a gold standard treatment for patients with advanced coronary artery disease, with over 400,000 cases performed each year in the US. While arterial grafts have greater long- term patency compared to vein grafts, their use is limited by availability, and saphenous vein grafts (SVGs) are used in the majority of patients. Following CABG surgery, SVG failure occurs at alarmingly high rates, with 5- 10% of SVGs occluding within the first month after surgery, and 40-50% of SVGs failing within 10 years. The risk of SVG disease and the complex mechanobiology of graft failure are known to be associated with mechanical stimuli, including hemodynamics and vessel wall mechanics. However, standard computed tomography (CT) imaging provides no direct means to characterize these stimuli. Recent advances in multiscale modeling now permit physiologic closed-loop simulations with realistic material properties, avoiding prior limitations of idealized anatomy, rigid walls, and incomplete coronary models. We propose a novel coronary simulation framework that can comprehensively characterize bypass graft hemodynamics and wall mechanics using only non-invasive clinical data. We propose that validated simulations with realistic hemodynamics and wall motion, in concert with modern imaging techniques will enable post-CABG risk stratification and early identification of patients at high risk for saphenous graft failure. To accomplish these goals, we propose three specific aims: 1) design and validate a novel closed-loop multiscale CABG simulation framework that can predict local hemodynamics and wall mechanics using only non-invasive clinical data, 2) quantify and compare the mechanical stimuli acting on arterial and vein grafts in patient- specific models, and 3) develop a pilot risk stratification scoring system for post-CABG patients by correlating mechanical stimuli with clinical outcomes in vessels with and without SVG disease. The proposed work is significant and innovative because it will (1) use patient-specific simulations to virtually reverse SVG disease thus using patients as their own control (2) enable early identification of patients at increased risk of SVG obstruction whose outcomes may be improved by more intensive treatment and monitoring, (3) enable future vessel wall growth and remodeling simulations which rely on mechanical stimuli data, (4) combine high resolution imaging with sophisticated multiscale modeling of the complete coronary circulation, and (5) directly validate model predictions against clinical data and report confidence intervals on simulation results. This project assembles a unique team including an adult cardiologist and imaging specialist with a background in physics, and an engineering team with established expertise in cardiovascular biomechanics. We will build upon our extensive experience with patient-specific blood flow simulations, and a successful track record of clinical translation and multi-disciplinary collaboration. Our translational goal is to provide clinicians with new tools to improve management decisions for CABG patients at risk for graft failure and improve outcomes.

冠状动脉旁路移植术（CABG）手术是晚期冠心病患者的金标准治疗方法 动脉疾病，美国每年执行的病例超过 400,000 例。虽然动脉移植物具有更大的长 与静脉移植物相比，其长期通畅性受到可用性的限制，并且大隐静脉移植物 (SVG) 用于大多数患者。 CABG 手术后，SVG 失败的发生率高得惊人，其中 5- 10% 的 SVG 在术后第一个月内闭塞，40-50% 的 SVG 在 10 年内失败。这 已知 SVG 疾病的风险和移植失败的复杂机械生物学与 机械刺激，包括血流动力学和血管壁力学。然而，标准计算 断层扫描 (CT) 成像没有提供表征这些刺激的直接方法。最近的进展 多尺度建模现在允许具有真实材料特性的生理闭环模拟，避免 理想化解剖结构、刚性壁和不完整冠状动脉模型的先前限制。我们提议写一本小说 冠状动脉模拟框架，可以全面表征旁路移植血流动力学和壁 仅使用非侵入性临床数据的力学。我们建议通过现实的验证模拟 血流动力学和室壁运动与现代成像技术相结合将使冠状动脉搭桥术后成为可能 风险分层和早期识别隐静脉移植失败高风险患者。到 为了实现这些目标，我们提出了三个具体目标：1）设计和验证一种新颖的闭环多尺度 CABG 模拟框架仅使用非侵入性即可预测局部血流动力学和壁力学 临床数据，2) 量化和比较作用于患者动脉和静脉移植物的机械刺激 特定模型，以及 3) 通过关联 机械刺激对患有和不患有 SVG 疾病的血管具有临床结果。拟议的工作是 意义重大且具有创新性，因为它将 (1) 使用患者特定的模拟来几乎逆转 SVG 疾病 因此，使用患者作为自己的对照 (2) 能够及早识别 SVG 风险增加的患者 梗阻的结果可以通过更强化的治疗和监测来改善，(3) 使未来成为可能 依赖于机械刺激数据的血管壁生长和重塑模拟，（4）结合了高 通过完整冠状循环的复杂多尺度建模进行分辨率成像，以及（5）直接 根据临床数据验证模型预测并报告模拟结果的置信区间。这 该项目组建了一个独特的团队，包括一名具有以下背景的成人心脏病专家和影像专家 物理学，以及一支在心血管生物力学方面拥有丰富专业知识的工程团队。我们将建设 基于我们在患者特定血流模拟方面的丰富经验以及成功的跟踪记录 临床翻译和多学科合作。我们的转化目标是为临床医生提供新的 改善有移植失败风险的 CABG 患者的管理决策并改善结果的工具。