title: Beyond blood brain barrier breakdown - in vivo detection of occult neuroinflammatory foci by magnetic nanoparticles in high field MRI.
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.
  
  
  CONCLUSIONS
  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.
authors: Cecilie Vogt Clinic for Neurology, Charité - University Medicine Berlin, Germany. etysiak@med.uni-goettingen.de
authors: Eva
authors: E
authors: Tysiak
authors: Patrick
authors: P
authors: Asbach
authors: Orhan
authors: O
authors: Aktas
authors: Helmar
authors: H
authors: Waiczies
authors: Maureen
authors: M
authors: Smyth
authors: Joerg
authors: J
authors: Schnorr
authors: Matthias
authors: M
authors: Taupitz
authors: Jens
authors: J
authors: Wuerfel
mesh_terms: D019264:Adoptive Transfer / Q000379:methods; D000818:Animals; D001812:Blood-Brain Barrier / Q000473:pathology* / Q000503:physiopathology; D001921:Brain / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology; D002196:Capillaries / Q000473:pathology / Q000503:physiopathology; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D003287:Contrast Media / Q000737:chemistry; D004195:Disease Models, Animal; D004660:Encephalitis / Q000473:pathology* / Q000503:physiopathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000473:pathology* / Q000503:physiopathology; D005109:Extracellular Matrix / Q000473:pathology; D005260:Female; D005290:Ferric Compounds / Q000737:chemistry; D005911:Gliosis / Q000473:pathology / Q000503:physiopathology; D008264:Macrophages / Q000473:pathology; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008833:Microcirculation / Q000276:immunology; D017628:Microglia / Q000473:pathology; D009103:Multiple Sclerosis / Q000473:pathology / Q000503:physiopathology; D053758:Nanoparticles / Q000737:chemistry
chemical_list: D003287:Contrast Media; D005290:Ferric Compounds; C000499:ferric oxide