Comparison of Four Mouse Models for Abdominal Aortic Aneurysm by 3D Ultrasound

Background: Established mouse models for abdominal aortic aneurysms (AAAs) differ in the applied triggers, associated pathomechanisms and rate of vessel expansion. The dilatation of the aorta is commonly monitored by 2D ultrasound analysis of maximum aortic diameter or by measurement of excised aneurysms. In this study, we applied and compared a recently developed, semi-automated 3D ultrasound method for the assessment of aorta expansion in four frequently used mouse models of AAA.

Methods: The models included angiotensin-II infusion in ApoE deficient mice, topical elastase application on aortas in C57BL/6J mice (with or without oral administration of β-aminopropionitrile) and intraluminal elastase perfusion in C57BL/6J mice. AAA development was monitored using semi-automated 3D ultrasound for aortic volume calculation over 12 mm length and 2D assessment of maximum aortic diameter.

Results: While the models differed substantially in the time course of aneurysm development, 3D ultrasound measurements proved highly reproducible with concordance correlation coefficients >0.95 and variations below 10% between two independent observers. Except for the intraluminal elastase perfusion model where aorta expansion was lowest and best detected by diameter increase, all other models showed high sensitivity of absolute volume in monitoring AAA formation and progression by 3D ultrasound. Furthermore, the reconstructed 3D images of abdominal mouse aortas offered morphological information on intramural thrombi, focal bulging versus uniform aneurysm expansion in the distinct models.

Conclusion: In addition to the low interobserver variability and easy application, the strength of 3D ultrasound lies within the high sensitivity in monitoring aorta expansion. A high standardized effect size is achieved to detect significant AAA growth at early time points which may serve to stratify mice into treatment arms and possibly reduce the number of experimental animals. Moreover, 3D volume reconstruction reveals morphological differences among the shaping aneurysms corresponding to the distinct pathological triggers of the four investigated mouse models.

 

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Publikationsverlauf

Artikel online veröffentlicht:
10. Juni 2022