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Beyond blood brain barrier breakdown - in vivo detection of occult neuroinflammatory foci by magnetic nanoparticles in high field MRI

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Item Type:Article
Title:Beyond blood brain barrier breakdown - in vivo detection of occult neuroinflammatory foci by magnetic nanoparticles in high field MRI
Creators Name:Tysiak, E. and Asbach, P. and Aktas, O. and Waiczies, H. and Smyth, M. and Schnorr, J. and Taupitz, M. and Wuerfel, J.
Abstract:BACKGROUND: Gadopentate dimeglumine (Gd-DTPA) enhanced magnetic resonance imaging (MRI) is widely applied for the visualization of blood brain barrier (BBB) breakdown in multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). Recently, the potential of magnetic nanoparticles to detect macrophage infiltration by MRI was demonstrated. We here investigated a new class of very small superparamagnetic iron oxide particles (VSOP) as novel contrast medium in murine adoptive-transfer EAE. METHODS: EAE was induced in 17 mice via transfer of proteolipid protein specific T cells. MR images were obtained before and after application of Gd-DTPA and VSOP on a 7 Tesla rodent MR scanner. The enhancement pattern of the two contrast agents was compared, and correlated to histology, including Prussian Blue staining for VSOP detection and immunofluorescent staining against IBA-1 to identify macrophages/microglia. RESULTS: Both contrast media depicted BBB breakdown in 42 lesions, although differing in plaques appearances and shapes. Furthermore, 13 lesions could be exclusively visualized by VSOP. In the subsequent histological analysis, VSOP was localized to microglia/macrophages, and also diffusely dispersed within the extracellular matrix. CONCLUSION: VSOP showed a higher sensitivity in detecting BBB alterations compared to Gd-DTPA enhanced MRI, providing complementary information of macrophage/microglia activity in inflammatory plaques that has not been visualized by conventional means.
Keywords:Adoptive Transfer, Blood-Brain Barrier, Brain, Capillaries, Cultured Cells, Leukocyte Chemotaxis, Contrast Media, Animal Disease Models, Encephalitis, Experimental Autoimmune Encephalomyelitis, Extracellular Matrix, Ferric Compounds, Gliosis, Macrophages, Magnetic Resonance Imaging, Microcirculation, Microglia, Multiple Sclerosis, Nanoparticles, Animals, Mice
Source:Journal of Neuroinflammation
ISSN:1742-2094
Publisher:BioMed Central (U.K.)
Volume:6
Number:1
Page Range:20
Date:6 August 2009
Official Publication:https://doi.org/10.1186/1742-2094-6-20
PubMed:View item in PubMed

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