Tomographic studies in atherosclerosis mouse models
Animal models of atherosclerosis and response to vascular injury rely predominantly on time-consuming and labor-intensive histological analysis for assessment of disease progression and therapeutic response. Quantitative Tomography, together with a variety of biocompatible fluorescence agents, provides:
- A histology-independent, non-invasive technique that enables serial analysis
- Specific detection of multiple biological activities quantitative in vivo data
Non-invasive Quantitative Tomography highlights areas of inflammation (AngioSPARK)
2D reflectance. FMT System. AngioSPARK shows area of carotid inflammation
3D reconstruction. FMT System. AngioSPARK shows area of cardiovascular inflammation
FRI with AngioSPARK highlights areas of inflammation, but requires invasive surgery
Image: FRI image of exposed torso. AngioSPARK shows areas of inflammationBackground information
Atherosclerosis carotid ligation mouse model: The use of flow cessation (carotid ligation) to induce the development of plaque formation in ApoE-/- mice kept on a high fat diet is a well-established model in atherosclerosis research.
Imaging: AminoSPARK and AngioSPARK are superbright fluorescence agents with an approximate half-life in plasma of 20 h, making them well suited for prolonged monitoring of blood vessels and observing phenomena such as blood leakage in tumors, inflammation and angiogenesis. At later timepoints, as in carotid artery ligation, these agents are phagocytosed by inflammatory macrophages.
Experimental procedure:
Confirming the presence of disease-related cathepsin B activity and phagocytic macrophages in aortic root and arch (ex vivo FRI, ProSense and AngioSPARK)
 |  | Image: Ex vivo FRI image of aorta, ApoE KO mouse (left) and BALB/c mouse control (right). Investigation: ApoE KO mouse c. 7 months old, fed Cholesterol Diet for 24 weeks. Imaging performed 24 h after i.v. injection of ProSense (4 nmol/mouse). Aortas perfused, isolated and harvested. |
 |  | Image: Ex vivo FRI image of aorta, ApoE KO mouse (left) and BALB/c mouse control (right). Investigation: Normal BALB/C mouse c. 7 months old. Imaging performed 24 h after i.v. injection of AngioSPARK (4 nmol/mouse). Aortas perfused, isolated and harvested. |
Background information
Detecting cathepsin activity: ProSense is a fluorescence agent activated predominantly by cathepsin B in vivo (with some ability to activate by K, L and S, plasmin, plasma kallikrein, uPA and CD10 in vitro).