title: In vivo MR imaging of intercellular adhesion molecule-1 expression in an animal model of multiple sclerosis.
abstract: Upregulation of intercellular adhesion molecule 1 (ICAM-1) is an early event in lesion formation in multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Monitoring its expression may provide a biomarker for early disease activity and allow validation of anti-inflammatory interventions. Our objective was therefore to explore whether ICAM-1 expression can be visualized in vivo during EAE with magnetic resonance imaging (MRI) using micron-sized particles of iron oxide (MPIO), and to compare accumulation profiles of targeted and untargeted MPIO, and a gadolinium-containing agent. Targeted αICAM-1-MPIO/untargeted IgG-MPIO were injected at two model-characteristic phases of EAE (in myelin oligodendrocyte glycoprotein35-55 -immunized C57BL/6 J mice), that is, at the peak of the acute phase (14 ± 1 days post-immunization) and during the chronic phase (26 ± 1 days post-immunization), followed by T2 *-weighted MRI. Blood-brain barrier (BBB) permeability was measured using gadobutrol-enhanced MRI. Cerebellar microvessels were analyzed for ICAM-1 mRNA expression using quantitative PCR (qPCR). ICAM-1 and iron oxide presence was examined with immunohistochemistry (IHC). During EAE, ICAM-1 was expressed by brain endothelial cells, macrophages and T-cells as shown with qPCR and (fluorescent) IHC. EAE animals injected with αICAM-1-MPIO showed MRI hypointensities, particularly in the subarachnoid space. αICAM-1-MPIO presence did not differ between the phases of EAE and was not associated with BBB dysfunction. αICAM-1-MPIO were associated with endothelial cells or cells located at the luminal side of blood vessels. In conclusion, ICAM-1 expression can be visualized with in vivo molecular MRI during EAE, and provides an early tracer of disease activity.
authors.affiliation: Biomedical MR Imaging and Spectroscopy Group, Image Sciences Institute, University Medical Center Utrecht, Yalelaan 2, 3584 CM, Utrecht, The Netherlands.
authors.forename: Erwin L A
authors.initials: EL
authors.lastname: Blezer
authors.forename: Lisette H
authors.initials: LH
authors.lastname: Deddens
authors.forename: Gijs
authors.initials: G
authors.lastname: Kooij
authors.forename: Joost
authors.initials: J
authors.lastname: Drexhage
authors.forename: Susanne M A
authors.initials: SM
authors.lastname: van der Pol
authors.forename: Arie
authors.initials: A
authors.lastname: Reijerkerk
authors.forename: Rick M
authors.initials: RM
authors.lastname: Dijkhuizen
authors.forename: Helga E
authors.initials: HE
authors.lastname: de Vries
mesh_terms: D000818:Animals; D002531:Cerebellum / Q000098:blood supply / Q000000981:diagnostic imaging / Q000378:metabolism; D002560:Cerebrovascular Circulation; D003287:Contrast Media / Q000494:pharmacology; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000000981:diagnostic imaging / Q000378:metabolism; D042783:Endothelial Cells / Q000000981:diagnostic imaging / Q000378:metabolism; D005290:Ferric Compounds / Q000494:pharmacology; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D018810:Magnetic Resonance Angiography / Q000379:methods*; D051379:Mice; D009103:Multiple Sclerosis / Q000000981:diagnostic imaging / Q000378:metabolism; D011859:Radiography
chemical_list: D003287:Contrast Media; D005290:Ferric Compounds; C090509:Icam1 protein, mouse; D018799:Intercellular Adhesion Molecule-1; C000499:ferric oxide
keywords: MPIO; MS model; experimental autoimmune encephalomyelitis; intercellular adhesion molecule; micron-sized particles of iron oxide; molecular MRI; multiple sclerosis