In vivo real-time vessel imaging and ex vivo 3D reconstruction of atherosclerotic plaque in apolipoprotein E-knockout mice using synchrotron radiation microscopy

Background: To examine the pathophysiology of atherosclerosis, imaging the vascular wall and pathology without tissue damage is required. We used the unmonochromatized synchrotron X-ray to acquire in vivo real-time and ex vivo images of atherosclerotic lesions in apo E-knockout mice without contrast agents or staining. Methods: In the five apo E-knockout mice (apo E-/-, 12, 24, 32, 48, 62-week-old, 3 males) and age/sex matched five wild type mice on cow diets, we acquired in vivo real-time images of thoracic aorta without contrast agents and then, the central arterial trees were dissected intact. Ex vivo synchrotron images with tomographic reconstruction were done and compared with the corresponding pathology. Results: For all living animals, in vivo real-time images of thoracic aorta could be acquired without contrast agents but could not identify the atherosclerotic lesions. Ex vivo images accurately determined aortic wall and atherosclerotic plaque without staining in comparison to histopathology according to the AHA classification (r = 0.84, p < 0.001). The volume rendered 3 D images of plaque showed central cholesterol clefts as matched with optical images. Conclusions: The combination of synchrotron enhanced X-ray microscopy and genetically engineered hyperlipidemic animals would be a useful tool to investigate the changes of advanced atherosclerotic lesions.