Multiscale modeling for vein graft failure risk stratification in CABG patients

描述（由申请人提供）：冠状动脉旁路移植术（CABG）手术是晚期冠状动脉疾病患者的金标准治疗方法，在美国每年进行超过40万例。虽然动脉移植物比静脉移植物具有更大的长期通畅，但其使用受到可用性的限制，大多数患者使用隐静脉移植物（SVGs）。在CABG手术后，SVG的失败率高得惊人，5- 10%的SVG在手术后第一个月内闭塞，40-50%的SVG在10年内失效。已知SVG疾病的风险和移植物失败的复杂力学生物学与机械刺激有关，包括血液动力学和血管壁力学。然而，标准的计算机断层扫描（CT）成像没有提供表征这些刺激的直接手段。多尺度建模的最新进展现在允许具有真实材料特性的生理闭环模拟，避免了理想化解剖，刚性壁和不完整冠状动脉模型的先前限制。我们提出了一个新的冠状动脉模拟框架，可以全面表征搭桥血流动力学和壁力学仅使用非侵入性临床数据。我们建议，经过验证的模拟真实的血流动力学和壁运动，与现代成像技术相结合，将使冠脉搭桥后的风险分层和早期识别高危患者的隐静脉移植物

DESCRIPTION (provided by applicant): 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 f 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 revers 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.