Beyond blood brain barrier breakdown - in vivo detection of occult neuroinflammatory foci by magnetic nanoparticles in high field MRI.
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.
Tysiak
Eva
E
Cecilie Vogt Clinic for Neurology, Charité - University Medicine Berlin, Germany. etysiak@med.uni-goettingen.de
Asbach
Patrick
P
Aktas
Orhan
O
Waiczies
Helmar
H
Smyth
Maureen
M
Schnorr
Joerg
J
Taupitz
Matthias
M
Wuerfel
Jens
J
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
D003287:Contrast Media; D005290:Ferric Compounds; C000499:ferric oxide