Using High Frequency Ultrasound to Investigate Methods for Strengthening Future Murine Abdominal Aortic Aneurysm Therapeutic Studies

Cardiovascular related diseases are the leading cause of mortality in the United States, with abdominal aortic aneurysms (AAAs) contributing as the 13th leading cause of death through sudden, unpredictable rupture. Researchers have developed elastase-induced and angiotensin II-induced (AngII) AAA mouse models to investigate pathophysiology and evaluate the efficacy of potential therapeutics. Medical imaging, particularly ultrasound, has become an extremely useful tool for studying aneurysm development and exploring more localized therapeutic strategies in mice. We first consider an integrated digital vaporizer compared to a traditional vaporizer for use in anesthetizing mice for our procedures. Then, we present the results of a study aimed at using high frequency ultrasound to guide the injection of type I collagen oligomers near the infrarenal abdominal aorta in mice, with the purpose of implanting a therapeutic into the collagen for localized AAA treatment in a future study. Finally, we use ultrasound again to obtain measurements in the angiotensin II-induced aneurysm model, with the intent of developing prediction models of aneurysm formation and growth. Taken together, our main goals were to optimize our methods to deliver localized therapeutics in mice and to develop prediction methods to enhance therapeutic efficacy studies. We found that the integrated digital vaporizer kept mice at a comparable depth of anesthesia while using less isoflurane, waste gas filters, and compressed gas. In the collagen injection study, we proved that ultrasound could not only be used to guide the injections, but also to track the location and size of the collagen implant over 14 days. Further, the collagen implants did not cause an inflammatory response or degrade significantly over two weeks. Lastly, the AAA development study showed that ultrasound can detect small biomechanical differences between mouse aortas at baseline to predict dissecting AAA formation and at diagnosis of a AAA to predict final aneurysm volume/length, providing a way to delineate the variability of the AngII AAA model from the effects treatments in future therapeutic studies. Future studies could focus on utilizing the collagen injection technique in the AngII model and developing growth prediction models for the elastase AAA model to help decrease variability in these mouse models for future therapeutic studies. Overall, this work highlights promising future directions for strengthening therapeutic development studies to increase their clinical translational success.