Biomechanical Evaluation of Abdominal Aortic Aneurysm

描述（由申请人提供）：腹主动脉瘤（AAA）是肾下主动脉的局灶性扩大。如果不及时治疗，AAA将逐渐扩大，直到破裂，这一事件的死亡率为90%。每年有1.5万美国人死于AAA破裂，使其成为美国第13大常见死因。与AAA修复相关的费用和风险对患者来说是巨大的。因此，重要的是确定什么时候破裂的风险证明了与手术相关的风险。由于目前还没有可靠的评估标准，可靠地评估特定AAA破裂的易感性的能力可以极大地改善这些患者的临床管理。当局部作用在动脉瘤壁上的机械应力超过其破坏强度时，发生AAA破裂。特定AAA的壁应力-壁强度比越大，破裂的可能性越大。因此，我们认为，仔细考虑破裂电位指数（RPI）将导致在患者特异性基础上改进AAA破裂倾向的评估。RPI定义为局部作用壁应力除以局部壁强度。随着RPI的增加，AAA破裂的可能性也随之增加。我们最初的拨款，目前的提案作为一个竞争性的续期申请，使我们能够开发出基于特定患者的非侵入性确定AAA RPI分布的方法。该建议的工作假设是，RPI（即局部壁应力与局部壁强度的峰值比）比最大动脉瘤直径或峰值壁应力单独更好地预测AAA破裂。为了解决这一假设，我们将执行以下三个具体目标：1)使用患者特异性AAA的物理（即定制聚合物）模型对我们的RPI技术进行“体外验证”；2)通过分析AAA破裂（或修复前有症状）患者的现有数据，并与AAA未破裂患者的数据进行比较，对我们的RPI技术进行“回顾性临床验证”；3)通过收集和分析长期随访AAA患者的数据，对我们的RPI技术进行“前瞻性临床验证”，以评估RPI的时间过程及其与不良临床结果的相关性。这种新颖的、创新的、基于计算的、无创的方法的成功验证，将通过定义一个新的、更可靠的标准来决定AAA的修复，从而使AAA患者的管理和护理发生重要的范式转变。这将极大地改善患有这种疾病的人的临床管理。

DESCRIPTION (provided by applicant): Abdominal aortic aneurysm (AAA) is a focal enlargement of the infrarenal aorta. If left untreated, AAA will gradually expand until rupture, an event that carries a mortality rate of 90%. 15,000 Americans die each year from AAA rupture, making it the 13th most common cause of death in the US. Associated with repair of AAA are significant costs and risks to the patient. Thus, it is important to determine when the risk of rupture justifies the risks associated with surgery. The ability to reliably evaluate the susceptibility of a particular AAA to rupture could vastly improve the clinical management of these patients, as there presently exists no such reliable evaluation criterion. AAA rupture occurs when the mechanical stress acting on the aneurysm wall locally exceeds its failure strength. The greater the wall stress-to-wall strength ratio for a particular AAA, the greater the likelihood of rupture. We therefore believe that careful consideration of the Rupture Potential Index (RPI) would lead to an improved assessment of the propensity for rupture of AAA on a patient-specific basis. The RPI is defined as the locally acting wall stress divided by the local wall strength. As the RPI increases, so too does the possibility of AAA rupture. Our original grant, for which the current proposal serves as a competing renewal application, allowed us to develop methods to noninvasively determine the RPI distribution for AAA on a patient-specific basis. The working hypothesis of this proposal is that the RPI - i.e., the peak ratio of local wall stress to local wall strength - is a better predictor of AAA rupture than either the maximum aneurysm diameter or peak wall stress alone. To address this hypothesis, we will execute the following three specific aims: 1) Perform an "in-vitro validation" of our RPI technique using physical (i.e., custom-fabricated polymer) models of patient-specific AAA; 2) Perform a "retrospective clinical validation" of our RPI technique by analyzing existing data from patients who underwent AAA rupture (or were symptomatic prior to repair) and comparing to that from patients who's AAA did not rupture; and 3) Perform a "prospective clinical validation" of our RPI technique by collecting and analyzing data from patients with AAA followed over time in order to evaluate the time-course of RPI and its correlation with unfavorable clinical outcome. Successful validation of this novel, innovative, computationally-based, noninvasive method would allow an important paradigm shift to occur in AAA patient management and care by defining a new, more reliable criterion on which decisions to repair AAA will be based. This would greatly improve the clinical management for those afflicted with this disease.