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      Ferumoxytol-enhanced three-dimensional magnetic resonance imaging of carotid atheroma- a feasibility and temporal dependence study

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          Abstract

          Ferumoxytol is an ultrasmall super paramagnetic particles of iron oxide (USPIO) agent recently used for magnetic resonance (MR) vascular imaging. Other USPIOs have been previously used for assessing inflammation within atheroma. We aim to assess feasibility of ferumoxytol in imaging carotid atheroma (with histological assessment); and the optimum MR imaging time to detect maximum quantitative signal change post-ferumoxytol infusion. Ten patients with carotid artery disease underwent high-resolution MR imaging of their carotid arteries on a 1.5 T MR system. MR imaging was performed before and at 24, 48, 72 and 96 hrs post ferumoxytol infusion. Optimal ferumoxytol uptake time was evaluated by quantitative relaxometry maps indicating the difference in T 2* (ΔT 2*) and T 2 (ΔT 2) between baseline and post-Ferumoxytol MR imaging using 3D DANTE MEFGRE qT 2*w and iMSDE black-blood qT 2w sequences respectively. 20 patients in total (10 symptomatic and 10 with asymptomatic carotid artery disease) had ferumoxytol-enhanced MR imaging at the optimal imaging window. 69 carotid MR imaging studies were completed. Ferumoxytol uptake (determined by a decrease in ΔT 2* and ΔT 2) was identified in all carotid plaques (symptomatic and asymptomatic). Maximum quantitative decrease in ΔT 2* (10.4 [3.5–16.2] ms, p < 0.001) and ΔT 2 (13.4 [6. 2–18.9] ms; p = 0.001) was found on carotid MR imaging at 48 hrs following the ferumoxytol infusion. Ferumoxytol uptake by carotid plaques was assessed by histopathological analysis of excised atheroma. Ferumoxytol -enhanced MR imaging using quantitative 3D MR pulse sequences allows assessment of inflammation within carotid atheroma in symptomatic and asymptomatic patients. The optimum MR imaging time for carotid atheroma is 48 hrs after its administration.

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          Macrophage accumulation within the vascular wall is a hallmark of atherosclerosis. In atherosclerotic lesions, macrophages respond to various environmental stimuli, such as modified lipids, cytokines, and senescent erythrocytes, which can modify their functional phenotypes. The results of studies on human atherosclerotic plaques demonstrate that the relative proportions of macrophage subsets within a plaque might be a better indicator of plaque phenotype and stability than the total number of macrophages. Understanding the function of specific macrophage subsets and their contribution to the composition and growth of atherosclerotic plaques would aid the identification of novel strategies to delay or halt the development of the disease and its associated pathophysiological consequences. However, most studies aimed at characterizing the phenotypes of human macrophages are performed in vitro and, therefore, their functional relevance to human pathology remains uncertain. In this Review, the diverse range of macrophage phenotypes in atherosclerotic lesions and their potential roles in both plaque progression and stability are discussed, with an emphasis on human pathology.
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                Author and article information

                Contributors
                us229@cam.ac.uk
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                4 February 2020
                4 February 2020
                2020
                : 10
                : 1808
                Affiliations
                [1 ]ISNI 0000 0004 0622 5016, GRID grid.120073.7, University Department of Radiology, Addenbrooke’s Hospital, ; Cambridge, CB2 0QQ UK
                [2 ]ISNI 0000 0004 0622 5016, GRID grid.120073.7, Department of Pathology, Addenbrooke’s Hospital, ; Cambridge, CB2 0QQ UK
                [3 ]ISNI 0000000121885934, GRID grid.5335.0, Christ’s College, ; Cambridge, CB2 3BU UK
                [4 ]ISNI 0000000121885934, GRID grid.5335.0, University Department of Surgery, Addenbrooke’s Hospital, ; Cambridge, CB2 0QQ UK
                Article
                58708
                10.1038/s41598-020-58708-x
                7000763
                32020031
                60c89184-b4f9-46ab-bba4-bf1b78170451
                © The Author(s) 2020

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 29 August 2019
                : 1 January 2020
                Funding
                Funded by: FundRef https://doi.org/10.13039/501100000590, University of Cambridge | Christ&apos;s College, University of Cambridge (Christ&apos;s College);
                Categories
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                © The Author(s) 2020

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                diagnostic markers
                Uncategorized
                diagnostic markers

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