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      Molecular MRI of Inflammation in Atherosclerosis

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          Abstract

          Inflammatory activity in atherosclerotic plaque is a risk factor for plaque rupture and atherothrombosis and may direct interventional therapy. Inflammatory activity can be evaluated at the (sub)cellular level using in vivo molecular MRI. This paper reviews recent progress in contrast-enhanced molecular MRI to visualize atherosclerotic plaque inflammation. Various MRI contrast agents, among others ultra-small particles of iron oxide, low-molecular-weight Gd-chelates, micelles, liposomes, and perfluorocarbon emulsions, have been used for in vivo visualization of various inflammation-related targets, such as macrophages, oxidized LDL, endothelial cell expression, plaque neovasculature, MMPs, apoptosis, and activated platelets/thrombus. An enzyme-activatable magnetic resonance contrast agent has been developed to study myeloperoxidase activity in inflamed plaques. Agents creating contrast based on the chemical exchange saturation transfer mechanism were used for thrombus imaging. Transfer of these molecular MRI techniques to the clinic will critically depend on the safety profiles of these newly developed magnetic resonance contrast agents.

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          Most cited references42

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          A new class of contrast agents for MRI based on proton chemical exchange dependent saturation transfer (CEST).

          It has been previously shown that intrinsic metabolites can be imaged based on their water proton exchange rates using saturation transfer techniques. The goal of this study was to identify an appropriate chemical exchange site that could be developed for use as an exogenous chemical exchange dependent saturation transfer (CEST) contrast agent under physiological conditions. These agents would function by reducing the water proton signal through a chemical exchange site on the agent via saturation transfer. The ideal chemical exchange site would have a large chemical shift from water. This permits a high exchange rate without approaching the fast exchange limit at physiological pH (6.5-7.6) and temperature (37 degrees C), as well as minimizing problems associated with magnetic field susceptibility. Numerous candidate chemicals (amino acids, sugars, nucleotides, heterocyclic ring chemicals) were evaluated in this preliminary study. Of these, barbituric acid and 5, 6-dihydrouracil were more fully characterized with regard to pH, temperature, and concentration CEST effects. The best chemical exchange site found was the 5.33-ppm indole ring -NH site of 5-hydroxytryptophan. These data demonstrate that a CEST-based exogenous contrast agent for MRI is feasible.
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            Atherosclerosis is an inflammatory disease

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              Presence of intraplaque hemorrhage stimulates progression of carotid atherosclerotic plaques: a high-resolution magnetic resonance imaging study.

              Previous studies suggest that erythrocyte membranes from intraplaque hemorrhage into the necrotic core are a source of free cholesterol and may become a driving force in the progression of atherosclerosis. We have shown that MRI can accurately identify carotid intraplaque hemorrhage and precisely measure plaque volume. We tested the hypothesis that hemorrhage into carotid atheroma stimulates plaque progression. Twenty-nine subjects (14 cases with intraplaque hemorrhage and 15 controls with comparably sized plaques without intraplaque hemorrhage at baseline) underwent serial carotid MRI examination with a multicontrast weighted protocol (T1, T2, proton density, and 3D time of flight) over a period of 18 months. The volumes of wall, lumen, lipid-rich necrotic core, calcification, and intraplaque hemorrhage were measured with a custom-designed image analysis tool. The percent change in wall volume (6.8% versus -0.15%; P=0.009) and lipid-rich necrotic core volume (28.4% versus -5.2%; P=0.001) was significantly higher in the hemorrhage group than in controls over the course of the study. Furthermore, those with intraplaque hemorrhage at baseline were much more likely to have new plaque hemorrhages at 18 months compared with controls (43% versus 0%; P=0.006). Hemorrhage into the carotid atherosclerotic plaque accelerated plaque progression in an 18-month period. Repeated bleeding into the plaque may produce a stimulus for the progression of atherosclerosis by increasing lipid core and plaque volume and creating new destabilizing factors.
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                Author and article information

                Contributors
                b.t.boekhorst@tue.nl
                gtilborg@gmail.com
                g.j.strijkers@tue.nl
                k.nicolay@tue.nl
                Journal
                Curr Cardiovasc Imaging Rep
                Current Cardiovascular Imaging Reports
                Current Science Inc. (New York )
                1941-9066
                1941-9074
                5 November 2011
                5 November 2011
                February 2012
                : 5
                : 1
                : 60-68
                Affiliations
                [1 ]Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Den Dolech 2, 5612 AZ Eindhoven, The Netherlands
                [2 ]Biomedical MR Imaging and Spectroscopy Group, Image Sciences Institute, University Medical Center Utrecht, Yalelaan 2, 3584 CM Utrecht, The Netherlands
                Article
                9114
                10.1007/s12410-011-9114-4
                3261392
                22308200
                a5bb0f2b-3f74-4421-b806-119c6698a918
                © The Author(s) 2011
                History
                Categories
                Cardiac Molecular Imaging (F Jaffer, Section Editor)
                Custom metadata
                © Springer Science+Business Media, LLC 2012

                Cardiovascular Medicine
                macrophages,nanoparticles,iron oxide,activated platelets,perfluorocarbon nanoparticle,ox-ldl,uspio,molecular mri,gadolinium,hdl-like nanoparticle,activatable contrast agent,atherosclerosis,liposome,mmps,apoptosis,myeloperoxidase,vascular adhesion molecules,fibrin,micelle,cellular mri,inflammation,integrins

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