High-frequency murine ultrasound provides enhanced metrics of BAPN-induced AAA growth

Abstract

An abdominal aortic aneurysm (AAA), defined as a pathological expansion of the largest artery in the abdomen, is a common vascular disease that frequently leads to death if rupture occurs. Once diagnosed, clinicians typically evaluate the rupture risk based on maximum diameter of the aneurysm, a limited metric that is not accurate for all patients. In this study, we worked to evaluate additional distinguishing factors between growing and stable murine aneurysms toward the aim of eventually improving clinical rupture risk assessment. With the use of a relatively new mouse model that combines surgical application of topical elastase to cause initial aortic expansion and a lysyl oxidase inhibitor, β-aminopropionitrile (BAPN), in the drinking water, we were able to create large AAAs that expanded over 28 days. We further sought to develop and demonstrate applications of advanced imaging approaches, including four-dimensional ultrasound (4DUS), to evaluate alternative geometric and biomechanical parameters between 1) growing AAAs, 2) stable AAAs, and 3) nonaneurysmal control mice. Our study confirmed the reproducibility of this murine model and found reduced circumferential strain values, greater tortuosity, and increased elastin degradation in mice with aneurysms. We also found that expanding murine AAAs had increased peak wall stress and surface area per length compared with stable aneurysms. The results from this work provide clear growth patterns associated with BAPN-elastase murine aneurysms and demonstrate the capabilities of high-frequency ultrasound. These data could help lay the groundwork for improving insight into clinical prediction of AAA expansion. NEW & NOTEWORTHY This work characterizes a relatively new murine model of abdominal aortic aneurysms (AAAs) by quantifying vascular strain, stress, and geometry. Furthermore, Green-Lagrange strain was calculated with a novel mapping approach using four-dimensional ultrasound. We also compared growing and stable AAAs, finding peak wall stress and surface area per length to be most indicative of growth. In all AAAs, strain and elastin health declined, whereas tortuosity increased.