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It is well accepted that major acute events in cardiovascular diseases are the consequences of the rupture of a vulnerable atherosclerotic plaque. The main issue for medical imaging is thus to diagnose vulnerable lesions before rupture and sudden vessel occlusion. The pathogenesis of atherosclerosis contains an important inflammatory component, which has been recognized as a key process in the malignant evolution of the disease. Magnetic Resonance Imaging (MRI) has recently evolved from a powerful non invasive morphological diagnostic technique to a more functional one, and is rapidly moving to molecular imaging thanks to the conception of new MRI contrast agents. Progress in molecular MRI of atherosclerosis is performed using animal models, where it is necessary to develop adequate methodology to enable in-vivo plaque imaging both in rabbits and mice. The next step is to synthesize an MR contrast agent targeted to inflammation in the plaque. For this, various targeting strategies are under evaluation. In our example, a gadolinium contrast agent was designed to target adhesion molecules highly expressed in active atherosclerotic plaques. Then, the arterial wall contrast enhancement was evaluated in vivo in ApoE-/mice after the intravenous injection of the new macromolecular gadolinium agent, functionalized to target inflammation. To enable dual detection by MRI and fluorescence imaging, a fluorochrome was grafted on the gadolinium platform.

Quantitative and bi-modal (optical-MRI) imaging of the vulnerable atherosclerosis plaque in the mouse with specific functional markers