• H L Walter, M Walberer, M A Rueger, H Backes, D Wiedermann, M Hoehn, B Neumaier, R Graf, G R Fink, and M Schroeter.
• Department of Neurology, University Hospital Cologne, Kerpener Straße 62, 50937 Cologne, Germany; Max-Planck-Institute for Neurological Research, Gleueler Straße 50, 50931 Cologne, Germany. Electronic address: helene.walter@uk-koeln.de.
• Neuroscience. 2015 Apr 30;292:71-80.

Background And PurposeIn vivo imaging of inflammatory processes is a valuable tool in stroke research. We here investigated the combination of two imaging modalities in the chronic phase after cerebral ischemia: magnetic resonance imaging (MRI) using intravenously applied ultra small supraparamagnetic iron oxide particles (USPIO), and positron emission tomography (PET) with the tracer [(11)C]PK11195.MethodsRats were subjected to permanent middle cerebral artery occlusion (pMCAO) by the macrosphere model and monitored by MRI and PET for 28 or 56 days, followed by immunohistochemical endpoint analysis. To our knowledge, this is the first study providing USPIO-MRI data in the chronic phase up to 8 weeks after stroke.ResultsPhagocytes with internalized USPIOs induced MRI-T2(∗) signal alterations in the brain. Combined analysis with [(11)C]PK11195-PET allowed quantification of phagocytic activity and other neuroinflammatory processes. From 4 weeks after induction of ischemia, inflammation was dominated by phagocytes. Immunohistochemistry revealed colocalization of Iba1+ microglia with [(11)C]PK11195 and ED1/CD68 with USPIOs. USPIO-related iron was distinguished from alternatively deposited iron by assessing MRI before and after USPIO application. Tissue affected by non-phagocytic inflammation during the first week mostly remained in a viably vital but remodeled state after 4 or 8 weeks, while phagocytic activity was associated with severe injury and necrosis accordingly.ConclusionsWe conclude that the combined approach of USPIO-MRI and [(11)C]PK11195-PET allows to observe post-stroke inflammatory processes in the living animal in an intraindividual and longitudinal fashion, predicting long-term tissue fate. The non-invasive imaging methods do not affect the immune system and have been applied to human subjects before. Translation into clinical applications is therefore feasible.Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

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