Ascending aortic aneurysm growth in the Fbln4<sup>SMKO</sup> mouse is consistent with uniform growth laws.

Abstract

Arterial growth and remodeling (G&R), in response to biomechanical stimuli, plays a pivotal role in vascular health. Disruptions in G&R, often seen in conditions such as aneurysms and atherosclerosis, can lead to pathological changes and pose significant health risks. Assessing risk should not only consider the current state of the aneurysm but also how it develops over the subsequent months. Herein, we make a controlled, subject-specific assessment of maladaptive aortic tissue growth using data previously obtained for the Fbln4^SMKO mouse model. The computational model uses a locally applied continuum G&R approach coupled with fluid-structure interaction (FSI) simulations. Ten mice were studied, exhibiting varying degrees of aneurysm formation over time. This investigation focused on the ascending aorta, where aneurysms develop in the Fbln4^SMKO mouse. A continuous G&R model was tuned and evaluated using information from 2, 4, and 6 months obtained from CT scans. A G&R model with uniform growth laws showed variable accuracy in predicting circumferential growth across different mice, exhibiting both under- and over-estimations compared to in vivo measurements. Modeling prediction showed to be improved by multiple-domain modeling. There is correlation between (1) the fitted circumferential growth time constants and the observed ascending aorta Young's modulus and (2) the fitted axial growth time constant and the tortuosity index. Furthermore, the ratio of the circumferential growth time constant to the circumferential stress correlated with mouse lifespan more strongly than diameter change, suggesting that analysis of a G&R model may be valuable in predicting risk of aneurysm rupture.