Molecular MRI of Atherosclerosis with USPIO

Abstract

Inflammation in atherosclerosis is a risk factor for plaque rupture and atherothrombosis. USPIO-enhanced MRI is capable of evaluating the inflammatory activity in vivo on a cellular as well as a sub-cellular level. This paper reviews the recent advances in USPIO-enhanced MRI of atherosclerotic plaque inflammation. Imaging strategies for evidentiating the presence of the USPIO label in plaques take advantage of the susceptibility effect induced by the nanoparticles in their surroundings to obtain a negative contrast (T2* weighted imaging) or a positive contrast (the White Maker and Susceptibility Gradient Mapping). Quantitative methods have more recently been adapted to in vivo imaging of USPIO in atherosclerotic plaques, and showed great promise in detecting treatment responses. When they are not taken up rapidly from blood by the reticulo-endothelial system (RES), USPIOs nanoparticles passively target inflammation in atherosclerosis by engulfment in intra-plaque phagocytic cells. This has been demonstrated in both animal models and human patients. However, by modifying the surface of coating materials, nanoparticles can actively target atherosclerosis molecular and cellular actors in animal models. The goal of molecular imaging of atherosclerotic plaques is to identify events in the early onset of the disease, as well as critical evolution to vulnerable plaques. USPIO agents are preferred as basis to develop targeted agents because of the ability to overcome the toxicity issue of long-term body residence of Gd-based agents, and their lower sensitivity based on their relaxivity properties. MRI agents capable of efficiently targeting oxidized LDL, cell adhesion molecules (VCAM-1, P-selectin, E-selection), apoptosis and activated platelets have been demonstrated in animal models. The use of these methodologies at the clinical level will depend on the availability and toxicity profiles of the agents, and will require standardized state of the art imaging techniques.