Biomechanical Understanding of Ascending Thoracic Aortic Aneurysms

胸主动脉瘤的生物力学理解

基本信息

批准号：
8888208
负责人：
Liang Ge
金额：
$ 38.33万
依托单位：
NORTHERN CALIFORNIA INSTITUTE/RES/EDU
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-04-01 至 2019-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8888208
关键词：
Age Aneurysm Aorta Aortic Aneurysm Bicuspid Biomechanics Caliber Cardiac Cardiovascular system Cause of Death Clinical Clinical Trials Computer Simulation Conduct Clinical Trials Connective Tissue Coupled Data Decision Making Development Dissection Emergency Situation Event Failure Foundations Future Geometry Goals Gold Growth Guidelines Health Hospital Mortality Hospitals Imaging Techniques Knowledge Liquid substance Literature Magnetic Resonance Imaging Measures Mechanics Methodology Modeling Morphology Motivation Operative Surgical Procedures Outcome Pathology Patients Phase Property Prospective Studies Residual state Resolution Risk Risk Factors Rupture Specific qualifier value Specimen Stress Structure Swelling Symptoms Testing Thick Thoracic Aortic Aneurysm Thoracic aorta Time Uncertainty base clinical application clinical decision-making clinical risk compare effectiveness high risk improved in vivo in vivo Model innovation mechanical behavior mortality non-invasive imaging pressure prospective regional difference repaired shear stress simulation

项目摘要

DESCRIPTION (provided by applicant): Dissection and/or rupture of ascending thoracic aortic aneurysms (aTAA) are catastrophic emergencies with 40% pre-hospital mortality, and operative mortality as high as 25%. Clinical guidelines recommend elective surgical repair based primarily on aTAA size, as well as growth, symptoms, and bicuspid or connective tissue pathologies. However, significant proportion of type A dissection patients presented with aortas under specified size limits for repair. Our long-term goal is to modernize clinical aTAA decision-making using patient-specific biomechanics, fluid dynamics, and clinical profiles to predict rupture/dissection and risk-stratify patients for earlier surgical repair. The rationale is that aTA rupture/dissection is a mechanical failure occurring when wall stress exceeds wall strength. Guidelines use diameter as a surrogate for wall stress based on LaPlace's Law. We hypothesize that fluid structure interaction (FSI) analyses of aTAA wall stress is a better predictor of true wall stress and therefore better predict adverse clinical events than diameter. True wall stress, unfortunately, cannot be measured directly in vivo but requires ex vivo aTAA specimens, where patient-specific 3D zero- pressure geometry, wall thickness, residual stress, and material properties can be measured with very high resolution. Prior aTAA computational models have made numerous assumptions using generalized wall thickness, literature-based material properties, and often ignored zero-stress geometry-all of which substantially change simulation results. The Achilles heel of aTAA models to date is that none have been validated casting doubts on their accuracy and clinical utility. We propose a prospective study to compare the effectiveness of FSI vs. diameter-based approaches in predicting true wall stress in surgical aTAA patients. Aims are: 1) Develop and validate in vivo patient-specific FSI in aTAA patients undergoing repair with the gold standard, ex vivo patient-specific aTAA from surgical specimen controls; 2) Demonstrate superiority of in vivo FSI over diameter in predicting true wall stress; 3 Quantify aTAA wall material strength from aTAA specimens and elucidate its relationship to regional aTAA wall stress. Develop empirical model to noninvasively predict in vivo wall strength; 4) Compare aortic wall stress and material properties between normal subjects and surgical aTAA patients. Define high-risk profiles using wall stress, fluid shear stress and turbulence, and clinical risk factors. We propose to first improve accuracy of in vivo aTAA FSI using 4-D flow cardiac magnetic resonance imaging (CMR) with Cine Displacement Encoding with Simulated Echos (DENSE) to determine wall material properties, wall thickness, and zero-stress geometry. We will validate in vivo models with surgical aTAA specimens and correlate aTAA failure strength with stress. Our development of high risk profiles using advanced CMR techniques to determine wall stress and fluid shear stress coupled with clinical risk factors may be used in the future to prospectively follow and predict growth and complications in all aTAA patients

描述（由申请人提供）：升胸主动脉瘤 (aTAA) 的夹层和/或破裂是灾难性的紧急情况，院前死亡率为 40%，手术死亡率高达 25%。临床指南建议主要基于 aTAA 进行择期手术修复。然而，A 型夹层患者的比例相当大。我们的长期目标是利用患者特定的生物力学、流体动力学和临床特征来实现 aTAA 临床决策的现代化，以预测破裂/夹层并对患者进行风险分层，以便进行早期手术修复。是，aTA 破裂/剥离是当壁应力超过壁强度时发生的机械故障。根据拉普拉斯定律，指南使用直径作为壁应力的替代。我们捕获了流体结构相互作用。不幸的是，aTAA 壁应力的 (FSI) 分析可以更好地预测真实壁应力，因此比直径更好地预测不良临床事件。真实壁应力无法在体内直接测量，而是需要离体 aTAA 样本，其中患者特定的 3D 样本。零压力几何形状、壁厚、残余应力和材料属性可以以非常高的分辨率进行测量，之前的 aTAA 计算模型使用广义壁厚、基于文献的材料属性做出了许多假设，并且经常忽略零应力几何形状。其中实质性改变模拟迄今为止，aTAA 模型的致命弱点是尚未对其准确性和临床实用性产生怀疑，我们提出了一项前瞻性研究来比较 FSI 与基于直径的方法在预测手术 aTAA 中真实壁应力方面的有效性。目标是： 1) 在接受手术标本对照的金标准、离体患者特异性 aTAA 修复的 aTAA 患者中开发和验证体内患者特异性 FSI；2) 证明体内方法的优越性；通过 FSI 预测真实的壁应力；3 量化 aTAA 样本的 aTAA 壁材料强度，并阐明其与局部 aTAA 壁应力的关系；开发经验模型以无创地预测体内壁强度；4) 比较正常情况下的主动脉壁应力和材料特性。我们建议首先提高体内 aTAA 的准确性。 FSI 使用 4-D 血流心脏磁共振成像 (CMR) 和模拟回波电影位移编码 (DENSE) 来确定壁材料特性、壁厚度和零应力几何形状。我们将使用手术 aTAA 标本验证体内模型并进行关联。 aTAA 应力失效强度。我们使用先进的 CMR 技术开发高风险概况，以确定壁应力和流体剪切应力以及临床风险因素，将来可用于前瞻性跟踪和预测所有疾病的生长和并发症。 aTAA 患者