In Vivo Quantitative Microcomputed Tomographic Analysis of Vasculature and Organs in a Normal and Diseased Mouse Model.

Abstract

Non-bone in vivo micro-CT imaging has many potential applications for preclinical evaluation. Specifically, the in vivo quantification of changes in the vascular network and organ morphology in small animals, associated with the emergence and progression of diseases like bone fracture, inflammation and cancer, would be critical to the development and evaluation of new therapies for the same. However, there are few published papers describing the in vivo vascular imaging in small animals, due to technical challenges, such as low image quality and low vessel contrast in surrounding tissues. These studies have primarily focused on lung, cardiovascular and brain imaging. In vivo vascular imaging of mouse hind limbs has not been reported. We have developed an in vivo CT imaging technique to visualize and quantify vasculature and organ structure in disease models, with the goal of improved quality images. With 1-2 minutes scanning by a high speed in vivo micro-CT scanner (Quantum CT), and injection of a highly efficient contrast agent (Exitron nano 12000), vasculature and organ structure were semi-automatically segmented and quantified via image analysis software (Analyze). Vessels of the head and hind limbs, and organs like the heart, liver, kidneys and spleen were visualized and segmented from density maps. In a mouse model of bone metastasis, neoangiogenesis was observed, and associated changes to vessel morphology were computed, along with associated enlargement of the spleen. The in vivo CT image quality, voxel size down to 20 μm, is sufficient to visualize and quantify mouse vascular morphology. With this technique, in vivo vascular monitoring becomes feasible for the preclinical evaluation of small animal disease models.