Experimental and Computational Mechanics of Arteries in Health and Disease: An Exploration of Complex Structures and Simple Mathematical Models

Abstract

Aortic aneurysm, or dilatation of the aorta, is a clinically significant pathology as the risk of potentially fatal rupture (through-thickness failure) or dissection (delamination of the layers) is the fifteenth leading cause of death in the U.S. [1], with just under 10,000 deaths occurring in 2017 [2]. Current diagnostics for assessing aneurysm risk are aortic size and growth rate [1, 3]. These criteria correlate with aneurysm risk but are not direct measures of tissue strength. These criteria are especially inadequate for rare disorders involving genetic anomalies, where population sizes are relatively small and disease severity can vary widely between individuals. Therefore, it is important that we recognize and understand the underlying pathology that makes one aneurysm different from another, especially in terms of mechanics as this is what dictates aneurysm rupture risk. In this thesis I explore several testing methods for assessing aortic properties in animal models of health and disease. I evaluate the simple ring pull test as a high-throughput mechanical testbed for circumferential mechanics and explore the use of ultrasound for the assessment of complex aortic structures including vessel bifurcations and the aortic arch. These techniques offer unique insights as screening tools for understanding mechanics and for evaluating therapeutics. In order to further understand how the different mechanics in healthy and diseased tissues arise, I created a novel micromechanical model of pathophysiologic remodeling. Using this model, I was able to show pathological differences in mechanical properties despite similar clinical growth parameters. I further developed a technique to model more complex geometries using a multiscale coupling to finite element models. These methods create a unique and useful tool for evaluating remodeling with complex geometries utilizing complex microstructural remodeling scenarios leading to improved understanding of the mechanics of healthy and diseased tissues, as well as being a convenient way to assess tissue-engineered therapies.