Biomechanical Understanding of Ascending Thoracic Aortic Aneurysms

 描述（由申请人提供）：胸升主动脉瘤（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%。临床指南建议主要根据aTAA大小以及生长、症状和二尖瓣或结缔组织病理进行择期手术修复。然而，相当比例的A型夹层患者在规定的修复尺寸限制下出现动脉瘤。我们的长期目标是使用患者特定的生物力学、流体动力学和临床特征来预测破裂/夹层，并对患者进行风险分层，以进行早期手术修复，从而实现临床aTAA决策的现代化。基本原理是，aTA破裂/夹层是当壁应力超过壁强度时发生的机械失效。根据拉普拉斯定律，指南使用直径作为壁应力的替代物。我们假设aTAA壁应力的流体结构相互作用（FSI）分析是真实壁应力的更好预测因子，因此比直径更好地预测不良临床事件。不幸的是，真实的壁应力不能在体内直接测量，而是需要离体aTAA样本，其中可以以非常高的分辨率测量患者特异性3D零压力几何形状、壁厚度、残余应力和材料特性。之前的aTAA计算模型已经使用广义壁厚、基于文献的材料特性做出了许多假设，并且经常忽略零应力几何形状-所有这些都大大改变了模拟结果。迄今为止，aTAA模型的致命弱点是，没有一个模型经过验证，从而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，以比较FSI与基于直径的方法在预测外科aTAA患者的真实壁应力方面的有效性。目标是：1）使用金标准（来自手术样本对照的离体患者特异性aTAA），在接受修复的aTAA患者中开发并验证体内患者特异性FSI; 2）证明体内FSI在预测真实壁应力方面优于直径; 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。建立无创预测体内壁强度的经验模型; 4）比较正常受试者和外科aTAA患者的主动脉壁应力和材料特性。使用壁应力、流体剪切应力和湍流以及临床风险因素定义高风险特征。我们建议首先使用4-D血流心脏磁共振成像（CMR）和模拟回波电影位移编码（DENSE）提高体内aTAA FSI的准确性，以确定壁材料特性、壁厚度和零应力几何形状。我们将使用外科aTAA样本验证体内模型，并将aTAA失效强度与应力相关联。我们使用先进的CMR技术来确定壁应力和流体剪切应力以及临床风险因素，从而开发了高风险特征，未来可用于前瞻性随访和预测所有aTAA患者的生长和并发症

 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