In vivo MR imaging of intercellular adhesion molecule‐1 expression in an animal model of multiple sclerosis. (22nd April 2014)

• Record Type: Journal Article
• Authors: Blezer, Erwin L. A.; Deddens, Lisette H.; Kooij, Gijs; Drexhage, Joost; van der Pol, Susanne M. A.; Reijerkerk, Arie; Dijkhuizen, Rick M.; de Vries, Helga E.
• Is Part Of: Contrast media & molecular imaging. Volume 10:Number 2(2015:Mar./Apr.)
• Page Start: 111
• Page End: 121
• Publication Date: 2014-04-22
• Subjects: Diagnostic imaging -- Periodicals; Magnetic resonance imaging -- Periodicals; Contrast media (Diagnostic imaging) -- Periodicals; Contrast Media -- Periodicals; Diagnostic Imaging -- Periodicals; Substances de contraste -- Périodiques; Diagnostics moléculaires -- Périodiques; Imagerie médicale; Substance de contraste; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.0754
• DOI: 10.1002/cmmi.1602
• Languages: English
• ISSNs: 1555-4309

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>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 <italic>in vivo</italic> 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 <italic>α</italic>ICAM‐1‐MPIO/untargeted IgG‐MPIO were injected at two model‐characteristic phases of EAE (in myelin oligodendrocyte glycoprotein<sub>35–55</sub>‐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 <italic>T</italic><sub>2</sub>*‐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 <italic>α</italic>ICAM‐1‐MPIO showed MRI hypointensities, particularly in the subarachnoid space. <italic>α</italic>ICAM‐1‐MPIO presence did not differ between the phases of EAE and was not associated with BBB dysfunction. <italic>α</italic>ICAM‐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 <italic>in vivo</italic> molecular MRI during EAE, and provides an early tracer of disease activity. Copyright © 2014 John Wiley & Sons, Ltd.</p> </abstract>