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

  • Tysiak E
  • Asbach P
  • Aktas O
 et al. 
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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.

Author-supplied keywords

  • Adoptive Transfer
  • Animal; Encephalitis
  • Autoimmune
  • Cultured; Chemotaxis
  • Experimental
  • Leukocyte
  • blood supply/pathology/physiopathology; Capillari
  • chemistry/diagnostic use
  • chemistry/diagnostic use; Disease Models
  • chemistry/diagnostic use; Gliosis
  • immunology; Contrast Media
  • immunology; Microglia
  • methods; Animals; Blood-Brain Barrier
  • methods; Mice; Microcirculation
  • pathology/physiopathology; Brain
  • pathology/physiopathology; Cells
  • pathology/physiopathology; Encephalomyelitis
  • pathology/physiopathology; Extracellular Matrix
  • pathology/physiopathology; Macrophages
  • pathology/physiopathology; Nanoparticles
  • pathology; Female; Ferric Compounds
  • pathology; Magnetic Resonance Imaging
  • pathology; Multiple Sclerosis

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  • Eva Tysiak

  • Patrick Asbach

  • Orhan Aktas

  • Helmar Waiczies

  • Maureen Smyth

  • Joerg Schnorr

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