# Heterogeneity of Ex Vivo and In Vivo Properties along the Length of the Abdominal Aortic Aneurysm
## 1 Introduction  
An abdominal aortic aneurysm (AAA) is a slowly progressing disease that affects the wall of the abdominal aorta and results in the asymptomatic enlargement of the artery until rupture, which is associated with high mortality. The clinical management of aortic aneurysms is challenging and mostly based on an assessment aimed at weighing the risk of surgery-related complication versus the risk of catastrophic rupture. The maximum aortic diameter (greater than 5 cm) is considered the indicator for elective aortic repair; however, this approach has been proved to lead to suboptimal patient prioritization resulting in many cases of critical aneurysms left untreated or, in contrast, unnecessary interventions on stable aneurysms. In recent years, different studies highlighted the inadequacy of the diameter criterion by pointing out the high level of heterogeneity in the aneurysm tissue and its impact on the risk of rupture of individual aortas [1, 2, 3, 4, 5]. Aneurysm initiation and progression are multifactorial processes linked to the tissue's heterogeneous remodeling and structuraldegradation in response to the local environment, including both mechanical (altered hemodynamics) and biological factors (inflammation, presence of intraluminal thrombus) [6; 7; 8]. Considering only the diameter as a metric for rupture risk fails to capture the localized structural weakening and decrease in wall strength that drive aneurysm growth and rupture in individual aortas. In this context, the aortic diameter provides clinicians with limited information and ultimately does not account for inter- and intra-patient heterogeneity. It is therefore essential to fully characterize the local structural and mechanical changes in the aneurys tissue with respect to disease progression and rupture potential. This will assist in improving the aortic assessment for clinical purposes through correlation of the heterogeneity at the tissue level with non-invasive measurements. Uniaxial tensile tests have been used to study the mechanical behaviour of aortic tissue ex vivo [9; 10; 11]. However, planar biaxial tests better represent the in vivo loading conditions of the artery and allow for a more appropriate characterization of the three-dimensional mechanical response of the aorta given tissue anisotropy and coupling of fibers in two orthogonal directions. Due to the specifics of AAA-related interventions resulting in minimal tissue being excised, as well as the overall AAA tissue fragility, there is a limited number of biaxial studies in the area [12; 13; 14; 15]. Even less studies are concerned with heterogeneity of the AAA wall, with the focus being towards the heterogeneity along the circumference of the aorta [16]. Axial heterogeneity (along the length of the aorta) of ex vivo mechanical properties is absent in the literature. Therefore, a comprehensive assessment of the heterogeneity in both circumferential and axial directions is necessary to fully understand the localized changes in the aneurys wall. As the mechanical behavior of the aorta depends heavily on its microstructure, the assessment of microstructural components in the aortic wall--in terms of content as well as architecture and organization--is essential to fully understand the pathological remodeling associated to disease progression and material properties change. While a reported increase in the collagen-to-elastin ratio is thought to alter the wall structure and thus alter its mechanical response, there is no literature data investigating the heterogeneity of the aortic wall composition along the length and circumference of the aorta [2; 17; 18]. Immunohistochemical (IHC) analysis provides important information on cellular mechanisms of AAA development and progression. Inflammation and macrophage infiltration are thought to have a significant role in the progressive degradation and remodeling of the extracellular matrix [19]. The primary cells involved in AAA inflammatory response are T-cells and macrophages [20].