Original ArticleM1-Activated Macrophages Migration, A Marker of Aortic Atheroma Progression A Preclinical MRI Study in MiceBessaad, Amine PhD*; Sigovan, Monica PhD*; Alsaid, Hasan PhD*; De Souza, Geneviève MSc*; Provost, Nicolas PhD†; Majd, Zouher PhD†; Menager, Christine PhD‡; Honnorat, Jèrôme MD, PhD§¶; Lagarde, Florence PhD∥; Nighoghossian, Norbert MD, PhD*¶; Nataf, Serge MD, PhD§¶; Canet-Soulas, Emmanuelle DVM, PhD* Author Information From the *CREATIS-LRMN, UMR CNRS 5220, U630 INSERM, University Lyon 1, Villeurbanne, France; †GENFIT, Parc Eurasanté, Lille, France; ‡Laboratoire PECSA, UMR 7195-UPMC-CNRS–ESPCI, University Pierre et Marie Curie, Paris, France; §INSERM U842, University Lyon 1, Lyon, France; ¶Lyon Stroke Unit, Department of Neurology, Hospices Civils de Lyon, Lyon, France; and ∥UMR CNRS 5180, Laboratoire des Sciences Analytiques, University Lyon1, Villeurbanne, France. Received October 13, 2009; and accepted for publication (after revision) January 16, 2010. This study was supported by ANR grant #ANR-07-TECSAN-0009-08. Reprints: Emmanuelle Canet-Soulas, DVM, PhD, University Lyon1, CREATIS-LRMN, UMR CNRS 5220, U630 INSERM, CPE, La Doua, 43 Boulevard du 11 Novembre 1918, 69622 Villeurbanne Cedex, France. E-mail: [email protected]. Investigative Radiology: May 2010 - Volume 45 - Issue 5 - p 262-269 doi: 10.1097/RLI.0b013e3181d78030 Buy Metrics Abstract Background: M1-activated Macrophages (M1M) play a major role in atherosclerotic lesions of aortic arch, promoting proinflammatory response. In vivo trafficking of M1M in aortic plaques is therefore critical. Methods: M1M from bone marrow cell culture were magnetically labeled, using iron nanoparticles, intravenously injected and followed up with 3 day magnetic resonance imaging (MRI) in mice developing macrophage-laden atheroma (ApoE2 knock-in mice). M1M recruitment in aortic arch lesions was assessed both by MRI and histology. Results: In all ApoE2 knock-in mice injected with labeled cells, high resolution MRI showed localized signal loss regions in the thickened aortic wall, with a maximal effect at day 2 (−34% ± 7.3% P < 0.001 compared with baseline). This was confirmed with Prussian blue (iron) staining and corresponded to M1M (Major Histo-compatibility Complex II positive). Clear different intraplaque and adventitial dynamic distribution profiles of labeled cells were observed during the 3 days. Conclusion: M1M dynamic MRI is a promising marker to noninvasively assess the macrophage trafficking underlying aortic arch plaque progression. © 2010 Lippincott Williams & Wilkins, Inc.