Iron-oxide labeling of hematogenous macrophages in a model of experimental autoimmune encephalomyelitis and the contribution to signal loss in fast imaging employing steady state acquisition (FIESTA) images.
OBJECTIVE
To determine the contribution of blood-derived macrophages to the signal loss observed in MR images of inflammatory lesions in experimental autoimmune encephalomyelitis (EAE).


METHODS
A relapsing-remitting form of EAE was induced in transgenic mice that express enhanced green fluorescent protein (EGFP) specifically in hematopoietic cells of the myelomonocytic lineage. Animals were injected with Feridex, a superparamagnetic iron oxide (SPIO) nanoparticle, 24 hours prior to in vivo MRI. MRI was performed using a 1.5T whole-body scanner; a high-performance, custom-built gradient coil insert; and a 3D steady-state free precession (SSFP) imaging pulse sequence. Comparisons were made between MR images and corresponding anti-GFP and Perl's Prussian blue (PPB)-stained brain sections.


RESULTS
MR images revealed the presence of discrete regions of signal loss throughout the brains of EAE animals that were administered Feridex. Histological staining showed that regions of signal loss on MR images corresponded anatomically with regions of PPB- and GFP-positive cells.


CONCLUSIONS
This experiment provides the first direct evidence that macrophages of hematogenous origin are labeled with SPIO after intravenous administration of Feridex, and contribute to the regions of signal loss detected in MR images of EAE brain.
Oweida
Ayman J
AJ
Imaging Research Laboratories, Robarts Research Institute, London, Ontario, Canada. aoweida@imaging.robarts.ca
Dunn
Elizabeth A
EA
Karlik
Stephen J
SJ
Dekaban
Gregory A
GA
Foster
Paula J
PJ
D000818:Animals; D003287:Contrast Media / Q000493:pharmacokinetics*; D003911:Dextrans; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000473:pathology*; D005260:Female; D052203:Ferrosoferric Oxide; D007090:Image Interpretation, Computer-Assisted; D007501:Iron / Q000493:pharmacokinetics*; D008264:Macrophages / Q000166:cytology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles; D051379:Mice; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D010087:Oxides / Q000493:pharmacokinetics*; D015203:Reproducibility of Results
D003287:Contrast Media; D003911:Dextrans; D058185:Magnetite Nanoparticles; D010087:Oxides; D007501:Iron; C065507:ferumoxides; D052203:Ferrosoferric Oxide