Biomechanical Understanding of Ascending Thoracic Aortic Aneurysms

 描述(申请人提供)：胸升主动脉瘤(ATAA)的夹层和/或破裂是灾难性的急症，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、生长、症状和双尖瓣或结缔组织病理情况进行选择性手术修复。然而，相当大比例的A型夹层患者在规定的修复大小限制下出现了主动脉。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预测破裂/夹层和对患者进行早期手术修复的风险分层，从而使临床Ataa决策现代化。其基本原理是，ATA破裂/夹层是当壁应力超过壁强度时发生的机械故障。根据拉普拉斯定律，导则使用直径作为墙体应力的替代。我们假设Ataa壁应力的流体结构相互作用(FSI)分析是预测真实壁应力的更好的指标，因此比直径更能预测不良临床事件。不幸的是，真正的壁应力不能直接在体内测量，但需要体外Ataa样本，其中患者特定的3D零压几何图形、壁厚、残余应力和材料特性可以以非常高的分辨率测量。以前的Ataa计算模型使用概化的壁厚、基于文献的材料特性以及经常忽略的零应力几何形状进行了大量的假设--所有这些都极大地改变了模拟结果。到目前为止，Ataa模型的致命弱点是没有一个模型得到验证，这让人对其准确性和临床实用性产生了怀疑。我们提出了一项前瞻性研究，以比较FSI和基于直径的方法在预测外科Ataa患者真实壁应力方面的有效性。目的是：1)建立和验证以金标准进行修复的Ataa患者的体内特异性FSI，以及手术标本对照的体外患者特异性Ataa；2)证明体内FSI在预测真实壁应力方面的优越性；3)从Ataa标本中量化Ataa壁材强度，并阐明其与局部Ataa壁应力的关系。建立无创性预测活体主动脉壁强度的经验模型；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、流体剪切力和湍流以及临床风险因素定义高危配置文件。我们建议首先提高体内Ataa FSI的准确性，使用4-D流动心脏磁共振成像(CMR)和Cine位移编码与模拟回声(Density)来确定壁材属性、壁厚和零应力几何形状。我们将用手术的Ataa标本验证体内模型，并将Ataa的破坏强度与应力联系起来。我们使用先进的CMR技术来确定壁应力和流体剪切力，并结合临床危险因素建立的高风险图谱，未来可能用于前瞻性跟踪和预测所有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