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; 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.

冠状动脉搭桥移植（CABG）手术是高级冠状动脉患者的金标准治疗 在美国，动脉疾病，每年有超过40万例病例。而动脉移植具有更大的长期 与静脉移植物相比，术语通畅性，其使用受到可用性的限制，而隐性静脉移植物（SVG）为 用于大多数患者。手术后，SVG失败的发生率令人震惊，5-- 10％的SVG在手术后的第一个月内阻塞，而在10年内失败的SVG中有40％。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。但是，计算出标准 层析成像（CT）成像没有直接表征这些刺激的直接手段。最近的进步 现在，多尺度建模允许具有逼真的材料特性的生理闭环模拟，避免 理想化的解剖学，刚性壁和不完整的冠状动脉模型的先前局限性。我们提出了一本小说 冠状动脉模拟框架可以全面地表征旁路移植血流动力学和墙壁 力学仅使用非侵入性临床数据。我们建议用现实的验证模拟 血液动力学和墙运动与现代成像技术一致 风险分层和早期鉴定患有大隐性移植物风险的患者。到 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仿真框架可以仅使用非侵入性预测局部血液动力学和墙壁力学 临床数据，2）量化和比较作用于患者的动脉和静脉移植的机械刺激 特定模型，以及3）通过关联CABG后患者的飞行员风险分层评分系统 机械刺激具有有或没有SVG疾病的血管中的临床结局。拟议的工作是 重要而创新的，因为它将（1）使用特定于患者的模拟几乎逆转SVG疾病 因此，将患者作为自己的对照（2）使患者以SVG风险增加的早期鉴定 通过更深入的治疗和监测可以改善其结果的阻塞，（3）实现未来 依赖机械刺激数据的容器壁生长和重塑模拟，（4）结合高 通过完整冠状动脉循环的复杂多尺度建模的分辨率成像，（5）直接 验证模型预测针对临床数据，并报告模拟结果的置信区间。这 项目组装了一个独特的团队，包括具有背景的成人心脏病专家和成像专家 物理学和具有心血管生物力学专业知识的工程团队。我们将建造 根据我们对患者特定血流模拟的丰富经验，并成功地记录了 临床翻译和多学科合作。我们的翻译目标是为临床医生提供新的 改善具有移植失败风险并改善结果的CABG患者的管理决策工具。