Abstract

In vivo imaging of vascular disease models has been largely underutilized, but it can greatly benefit cardiovascular research. An improved understanding of the development of the angiotensin II (AngII) apolipoprotein E knockout model of abdominal aortic aneurysms (AAAs) could help patients with this life-threatening disease. The objective of this study was to investigate the early hemodynamic, biomechanical, and volumetric changes in AngII AAAs using high-frequency ultrasound. Five male apolipoprotein E-deficient C57BL/6J mice were subcutaneously implanted with AngII-loaded miniosmotic pumps (1000 ng/kg/min) and screened for appearance of AAAs. We acquired imaging data of the morphology, pulsatility, and blood flow profiles in newly formed AAAs over 7 days. We found that biomechanical and hemodynamic changes occurred during initial AAA formation alongside an increase in AAA volume. Average AAA volume increased by 140±24% between baseline and AAA diagnosis, while true lumen volume decreased by 46±12% due to formation of a focal dissection. The resulting intramural thrombus evolved in shape and volume but with variability between animals. Regional differences in blood flow velocity were apparent down the length of the largest AAAs and mean blood flow velocity significantly increased by 150±42% upon initial aortic expansion and true lumen narrowing. Mean velocity decreased over 7 days as the total AAA volume increased. Circumferential cyclic strain also significantly decreased upon initial aortic expansion and remained reduced, indicating the AAAs had stiffened vessel walls with initial aortic expansion. We are also exploring the heterogeneity of this AAA development using computational pulsatile flow models built from these ultrasound datasets. These models can provide information on site-specific changes in wall shear stress and oscillatory shear index, which are potentially predictive metrics for intramural thrombus formation and AAA growth.

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