Detection of synovial macrophages in an experimental rabbit model of antigen-induced arthritis: ultrasmall superparamagnetic iron oxide-enhanced MR imaging.
OBJECTIVE
To evaluate intravenously administered ultrasmall superparamagnetic iron oxide (USPIO) as a marker of macrophage activity in an experimental rabbit model of antigen-induced arthritis.


METHODS
Unilateral arthritis was induced by means of intraarticular injection of methylated bovine serum albumin in 10 knees of 10 rabbits that had been presensitized to the same antigen. The contralateral knees in these rabbits, as well as six knees in three other rabbits, served as controls. After onset of arthritis, all knees were imaged prior to and 24 hours after administration of USPIO. The magnetic resonance (MR) imaging protocol included T1-weighted spin-echo, T2-weighted fast spin-echo, T2*-weighted gradient-echo, and short inversion time inversion-recovery sequences. Images were analyzed quantitatively and qualitatively with regard to signal characteristics and pattern. MR findings were correlated with histopathologic findings. Wilcoxon signed rank test was used to compare results of signal-to-noise ratio calculations before and after USPIO administration.


RESULTS
All knees with intraarticular injection of antigen suspension developed unilateral arthritis, whereas no signs of arthritis occurred in the control knees. On USPIO-enhanced images obtained 24 hours after contrast agent administration, significant T1 (P =.03) and more predominantly T2* (P =.02) and T2 effects (P =.01) were evident in the synovium of all 10 arthritic knees, which reflected USPIO uptake by macrophages in the synovial tissue. To a lesser extent, T2* effects were present also within the joint effusion (P =.01). No significant changes in signal characteristics were detected in the 10 nonarthritic knees in the antigen-injected group or the six knees in the control group (P =.06-.91). Histologic examination confirmed uptake of iron in the macrophages of arthritic knees. Changes in MR signal characteristics within the arthritic synovium and synovial effusion were visually detectable after intravenous administration of USPIO.


CONCLUSIONS
MR imaging at 1.5 T can depict USPIO uptake in phagocytic-active macrophages in an antigen-induced arthritis animal model.
Lutz
Amelie M
AM
Institute of Diagnostic Radiology and Center for Experimental Rheumatology, Department of Rheumatology, University Hospital Zurich, Rämistrasse 100, 8091 Zurich, Switzerland.
Seemayer
Christian
C
Corot
Claire
C
Gay
Renate E
RE
Goepfert
Kerstin
K
Michel
Beat A
BA
Marincek
Borut
B
Gay
Steffen
S
Weishaupt
Dominik
D
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology / Q000473:pathology*; D002417:Cattle; D003287:Contrast Media / Q000008:administration & dosage; D003911:Dextrans; D004195:Disease Models, Animal; D005260:Female; D052203:Ferrosoferric Oxide; D007089:Image Enhancement / Q000379:methods*; D007270:Injections, Intra-Articular; D007275:Injections, Intravenous; D007501:Iron / Q000008:administration & dosage; D008264:Macrophages / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles; D010087:Oxides / Q000008:administration & dosage; D010587:Phagocytosis / Q000502:physiology; D011817:Rabbits; D012709:Serum Albumin / Q000008:administration & dosage / Q000276:immunology; D018709:Statistics, Nonparametric; D013582:Synovial Fluid; D013583:Synovial Membrane / Q000473:pathology*
D000276:Adjuvants, Immunologic; D003287:Contrast Media; D003911:Dextrans; D058185:Magnetite Nanoparticles; D010087:Oxides; D012709:Serum Albumin; C097921:ferumoxtran-10; D007501:Iron; D052203:Ferrosoferric Oxide