Can the in-vivo aortic strain field explain the initiation of dissecting abdominal aneurysms in mice?

Dissecting abdominal aortic aneurysms in Angiotensin-II mice start with a medial tear near the ostia of celiac and mesenteric arteries. Given the location-specific nature of the disease, we recently hypothesized that the local mechanical equilibrium may drive disease initiation [1]. In addition we presented a novel computational methodology to evaluate the in-vivo strain field in the abdominal aorta. We incorporated model features such as non-uniform aortic wall thickness, non-uniform stretch field and the inclusion of small aortic side branches and showed how these often overlooked features impact the location of hotspots in the computed strain field [2]. In our current work we present a combined experimental-computational approach in order to infer a potential link between predicted regions of maximal strain and sites of precursory vascular damage. N=10 ApoE-/- mice were infused with Angiotensin-II for 3 days and underwent a contrast-enhanced micro-CT scan prior to euthanasia. The aorta was imaged ex-vivo using high-resolution Phase-contrast X-Ray Microscopy (PCXTM) at 6.5 um isotropic resolution. The same protocol was followed for n=6 saline-infused controls. We implemented an in-house automated framework to morph the non-pressurized non-stretched ex-vivo PCXTM geometry onto the pressurized stretched in-vivo micro-CT geometry [2]. For each animal the output was a mouse-specific structural FEM simulation under pressurization and local axial stretch. Contrast agent infiltration in the aortic wall was used as a proxy to detect the location of micro-ruptures in the tunica media [1] and histological H&E sections were obtained in the corresponding locations. Preliminary results show good agreement between hotspots of early vascular damage and hotspots of computed maximal strain. The highest strain values occurred invariably in the vicinity of the celiac and mesenteric arteries and collocated with histologically-identified intramural hematomas and leukocyte infiltration. Moreover, the inter-subject variability of the maximal strain locations (cranial/caudal or right/left of the ostium) corresponded to the inter-subject variability of PCXTM-detected contrast agent leakage. We conclude that strain concentrations near side branches may play an important role in the initiation of cardiovascular disease