Biomechanical Evaluation of Abdominal Aortic Aneurysm

描述(申请人提供)：腹主动脉瘤(AAA)是肾下动脉的局灶性增大。如果不治疗，AAA将逐渐扩大，直到破裂，这一事件的死亡率为90%。每年有15,000名美国人死于腹主动脉破裂，在美国最常见的死亡原因中排名第13位。与修复AAA相关的是给患者带来巨大的成本和风险。因此，重要的是确定何时破裂的风险与手术相关的风险是合理的。能够可靠地评估特定AAA破裂的易感性可以极大地改善这些患者的临床管理，因为目前还没有这样可靠的评估标准。当作用于局部动脉瘤壁上的机械应力超过其破坏强度时，就会发生AAA破裂。对于特定的AAA，壁应力与壁强比越大，破裂的可能性就越大。因此，我们认为，仔细考虑破裂潜力指数(RPI)将有助于根据患者的具体情况更好地评估AAA破裂的倾向。RPI定义为局部作用的墙体应力除以局部墙体强度。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，目前的提案作为竞争续签申请，允许我们开发方法，在患者特定的基础上非侵入性地确定AAA的RPI分布。这一建议的工作假设是，RPI--即局部壁应力与局部壁应力峰值的比率--是AAA破裂的更好的预测指标，而不是仅用最大动脉瘤直径或峰值壁应力来预测。为了解决这一假设，我们将执行以下三个具体目标：1)使用患者特定AAA的物理模型(即定制的聚合物)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未破裂的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)通过收集和分析随时间推移的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的时间进程及其与不良临床结果的相关性。这种新颖的、创新的、基于计算的非侵入性方法的成功验证，将通过定义一个新的、更可靠的标准来决定修复AAA，从而使AAA患者管理和护理发生重要的范式转变。这将极大地改善对患有这种疾病的患者的临床管理。

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.