In Vivo Detection and Measurement of Aortic Aneurysm and Dissection in Mouse Models Using Microcomputed Tomography with Contrast Agent

Abstract

Objectives. The aim of this study was to evaluate the potential of microcomputed tomography (micro-CT) using the intravascular contrast agent ExiTron nano 12000 for aorta imaging and monitoring the dynamic changing process of the aorta in mouse models with aortic aneurysm and dissection. Materials and Methods. Experiments were performed on healthy mice and mice with aortic dissection. Mice that were developing aortic dissection and healthy mice underwent micro-CT imaging after injection of ExiTron nano 12000. Time-dependent signal enhancement (at 1, 2, 3, 6, and 12 hours after intravenous injection of the contrast agent, respectively) in the aorta of healthy mice was measured to confirm the optimal imaging time of aorta. Various contrast agent doses (70, 100, and 150 μl per 25 g mouse, respectively) were investigated to determine the optimal required dose for imaging of the aorta. The mice were scanned with micro-CT at 1, 14, and 28 days after onset of aneurysm and dissection to monitor the dynamic changing process of the aorta. Mouse aortas were stained with hematoxylin and eosin staining, and the diameter of the aorta was measured and compared with those obtained by micro-CT. Results. Time-dependent signal enhancement in the aorta shows that the contrast agent has a long blood half-life of 6 hours, with a peak enhancement at 2 hours after injection. Injection of 100 μl ExiTron nano 12000 per 25 g mouse allows for effective visualization of the aorta. Micro-CT combined with contrast agent can monitor the changing process of the aorta in the mouse model of aortic aneurysm and dissection dynamically. The values of the diameter of the aortas obtained from the in vivo micro-CT imaging were compared with those obtained from histology and showed a significant correlation (R2 = 0.96). Conclusions. These data demonstrate that in vivo micro-CT is an accurate and feasible technique to detect aortic aneurysm or dissection in a mouse model, and the micro-CT technique using the innovative contrast agent ExiTron nano 12000 allows for monitoring various processes dynamically such as aortic remodeling in longitudinal studies.