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The combination of different molecular biomarkers may improve the risk stratification of patients. This study aimed to investigate the feasibility of simultaneous visualization and quantification of plaque-burden and inflammatory activity by dual-probe molecular MRI in a mouse-model of progressive atherosclerosis and in response-to-therapy. Homozygous apolipoprotein E knockout mice (ApoE<jats:sup>\u2212\/\u2212<\/jats:sup>) were fed a high-fat-diet (HFD) for up to four-months prior to MRI of the brachiocephalic-artery. To assess response-to-therapy, a statin was administered for the same duration. MR imaging was performed before and after administration of an elastin-specific gadolinium-based and a macrophage-specific iron-oxide-based probe. Following <jats:italic>in-vivo<\/jats:italic> MRI, samples were analyzed using histology, immunohistochemistry, inductively-coupled-mass-spectrometry and laser-inductively-coupled-mass-spectrometry. In atherosclerotic-plaques, intraplaque expression of elastic-fibers and inflammatory activity were not directly linked. While the elastin-specific probe demonstrated the highest accumulation in advanced atherosclerotic-plaques after four-months of HFD, the iron-oxide-based probe showed highest accumulation in early atherosclerotic-plaques after two-months of HFD. <jats:italic>In-vivo<\/jats:italic> measurements for the elastin and iron-oxide-probe were in good agreement with <jats:italic>ex-vivo<\/jats:italic> histopathology (Elastica-van-Giesson stain: y\u2009=\u2009298.2\u2009+\u20095.8, R<jats:sup>2<\/jats:sup>\u2009=\u20090.83, p\u2009&lt;\u20090.05; Perls\u2018 Prussian-blue-stain: y\u2009=\u2009834.1\u2009+\u20090.67, R<jats:sup>2<\/jats:sup>\u2009=\u20090.88, p\u2009&lt;\u20090.05). Contrast-to-noise-ratio (CNR) measurements of the elastin probe were in good agreement with ICP-MS (y\u2009=\u20090.11x-11.3, R\u00b2\u2009=\u20090.73, p\u2009&lt;\u20090.05). Late stage atherosclerotic-plaques displayed the strongest increase in both CNR and gadolinium concentration (p\u2009&lt;\u20090.05). The gadolinium probe did not affect the visualization of the iron-oxide-probe and vice versa. This study demonstrates the feasibility of simultaneous assessment of plaque-burden and inflammatory activity by dual-probe molecular MRI of progressive atherosclerosis. The <jats:italic>in-vivo<\/jats:italic> detection and quantification of different MR biomarkers in a single scan could be useful to improve characterization of atherosclerotic-lesions.<\/jats:p>","DOI":"10.1038\/s41598-019-50100-8","type":"journal-article","created":{"date-parts":[[2019,9,25]],"date-time":"2019-09-25T10:03:27Z","timestamp":1569405807000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Dual-probe molecular MRI for the in vivo characterization of atherosclerosis in a mouse model: Simultaneous assessment of plaque inflammation and extracellular-matrix remodeling"],"prefix":"10.1038","volume":"9","author":[{"given":"Carolin","family":"Reimann","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Brangsch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan O.","family":"Kaufmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5836-4542","authenticated-orcid":false,"given":"Lisa C.","family":"Adams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David C.","family":"Onthank","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0782-2755","authenticated-orcid":false,"given":"Christa","family":"Th\u00f6ne-Reineke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon P.","family":"Robinson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd","family":"Hamm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9447-4367","authenticated-orcid":false,"given":"Rene M.","family":"Botnar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus R.","family":"Makowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,9,25]]},"reference":[{"key":"50100_CR1","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1161\/CIRCULATIONAHA.106.179918","volume":"115","author":"W Rosamond","year":"2007","unstructured":"Rosamond, W. et al. 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