Abstract 308: Cardiac Cycle Affects Ultrasound Measurements of Ascending Aortic Diameter in a Marfan Mouse Model

Abstract

Objective: Ultrasound measurements of aortic diameter are a common endpoint in preclinical studies. However, there is a lack of standardization in both image capture and analysis. For our study, we developed a standardized protocol for measuring ascending aortic diameter and examined effects of cardiac cycle in wild type and fibrillin-1 hypomorphic (FBN mgR/mgR ) mice. Methods and Results: Twelve week old male and female FBN mgR/mgR mice were anesthetized and maintained at a heart rate of 450-550 beats per minute. Ultrasound images were captured using a Vevo 2100 system with a 40MHz tranducer. Images captured were standardized according to two anatomical landmarks: the innominate artery branchpoint and aortic valves. The largest luminal ascending aortic diameter between the sinotubular junction and the innominate artery were measured in mid-systole and end-diastole by two blinded, independent observers. Aortic diameters were significantly different (p<0.05) when comparing systole and diastole within gender and genotype. Interestingly, wild-type male (n=4) and female (n=3) mice exhibited a 19% and 15% expansion of the ascending aorta respectively during systole compared to diastole. This difference was not recapitulated in either male (n=6) or female (n=5) FBN mgR/mgR mice (4% expansion in both; p<0.05 vs wild-type). Agreement between observers was excellent (R^2 = 0.99) but interobserver variability was a mean of .09 mm (%CV = 5%) Conclusion: As expected, there is a difference in aortic diameters between wild-type and FBN mgR/mgR mice. Luminal aortic diameters in FBN mgR/mgR vs wild-type mice of both genders are affected by cardiac cycle. Mid-systolic aortic expansion in wild-type vs FBN mgR/mgR mice were different. Error introduced by interobserver variability impacts ascending aortic measurements. Altogether, these phenomena may confound analyses of aortic dilation in FBN mgR/mgR mice, especially when studying interventions with modest effect sizes.