Novel Evaluation of Preclinical Models of Peripheral Arterial Disease Using Contrast Enhanced Ultrasound

Peripheral arterial disease (PAD) is a vascular disease resulting from poor perfusion of the extremities, particularly the legs, which affects over 200 million people worldwide. One pharmacologic treatment option is cilostazol, which is the only drug approved in the US that has been shown to modestly increase pain-free walking time. Despite decades of research and numerous clinical trials, the efficacy of available therapies is still limited. This may suggest shortcomings in current animal models and/or methods of assessment.

In this dissertation, we focus on optimizing contrast enhanced ultrasound (CEUS) to measure perfusion in preclinical mouse models of PAD. We then assess three different surgical models using CEUS and laser Doppler perfusion imaging (LDPI, most common technique). We show CEUS is well suited for perfusion measurements, and is contradictory to the findings of LDPI. We then validate these findings using several independent techniques, which show agreement with CEUS. Finally, CEUS data is used to assess previously unknown muscle-specific perfusion patterns resulting from surgery. These studies provide a novel framework for assessing perfusion in animal models of PAD; enabling the field to advance and develop greatly needed therapies.