Molecular Magnetic Resonance Imaging for the Detection of Vulnerable Plaques

Abstract

Abstract-Recent advances in molecular resonance imaging of atherosclerosis enable to visualize atherosclerotic plaques in vivo using molecular targeted contrast agents. This offers opportunities to study atherosclerosis development and plaque vulnerability noninvasively. In this review, we discuss MRI contrast agents targeted toward atherosclerotic plaques and illustrate how these new imaging platforms could assist in our understanding of atherogenesis and atheroprogression. In particular, we highlight the challenges and limitations of the different contrast agents and hurdles for clinical application. We describe the most promising existing compounds to detect atherosclerosis and plaque vulnerability. Of particular interest are the fibrin-targeted compounds that detect thrombi and, furthermore, the contrast agents targeted to integrins that allow to visualize plaque neovascularization. Moreover, vascular cell adhesion molecule 1-targeted iron oxides seem promising for early detection of atherosclerosis. These targeted MRI contrast agents, however promising and well characterized in (pre)clinical models, lack specificity for plaque vulnerability. or cardiovascular diseases but are also upregulated in other diseases as compared with disease-free conditions. Moreover, these molecular targets are often present at relatively low levels. To overcome sensitivity issues, high-payload contrast agent vehicles have been developed for molecular MRI to generate sufficient signal change. The biological processes described above and their accompanying molecular and cellular events create numerous opportunities for targeting the atherosclerotic plaque. This can be done using nanoparticles carrying an imaging modality and targeting vector. Several novel nanoparticle platforms have emerged in molecular MRI that allows the visualization of atherosclerotic plaques. These contrast agents targeting molecules on different plaque components will be highlighted here in the context of their relevance to plaque vulnerability and summarized in the Table. Intraplaque Targeting R E T R A C T E D A R T I C L Eby Lesional MacrophagesIn the last years, it has become accepted that classically activated macrophages (or M1) and alternatively activated MØ (or M2) are 2 extremes of a spectrum of macrophage phenotypes that both contribute to plaque development progression and vulnerability. 10Macrophages Myeloid-related protein (Mrp)-8/14 is a member of the S100-family of Ca 2+ -modulated proteins with a role for the Mrp-complex in the innate inflammatory response to injury. Mrp-8/14 is detected in nonfoam cell macrophages in human and mouse atherosclerotic plaques with rupture-prone lesions.11 Levels of Mrp also have been shown to be an independently prognostic marker of cardiovascular risk. ) and MDA were developed to deliver Mn into a cell resulting in >20-fold increases in MR efficacy compared with the chelated form. 18 In vivo plaque imaging findings with these Mn-based compounds were comparable with the previous results with iron and Gd; ho...