Murine atherosclerotic plaque imaging with the USPIO Ferumoxtran-10.
In this study we intended to image plaque inflammation in a murine model of atherosclerosis with MRI and Ferumoxtran-10 (Sinerem, Guerbet, France). 8 apoE-/- mice were injected 500 micromol Fe/kg or 1000 micromol Fe/kg Ferumoxtran-10. 2 apoE-/- mice were injected NaCl. After a post-contrast time of 24 to 336 hours the mice were scarificed and the aortas were imaged ex vivo. All measurements were performed on a 17.6 Tesla Bruker AVANCE 750WB MR scanner (Bruker, Germany). Spin-echo sequences and gradient-echo sequences with variable TE were performed and T2* maps were generated. Prussian-blue and hematoxilin-eosin histology were obtained afterwards and iron-uptake was quantified by counting iron positive areas. 2 apoE-/- mice were imaged in vivo before and 48 hours after 1000 micromol Fe/kg. Atheroma iron uptake was not elevated after 24 hours compared to controls. 48 hours after 1000 micromol Fe/kg but not 500 micromol Fe/kg histology revealed a 1.3- fold increase in plaque iron content compared to NaCl injected mice. Normalized T2*-times decreased from 0.86+/-0.02 in controls to 0.66+/-0.15 after a dose of 500 micromol Fe/ml and 0.59+/-0.14 in mice injected with 1000 micromol Fe/Kg (p=0.038). These results translated into a mean of 122% increase in CNR, as measured by in vivo MRI. We have demonstrated that Ferumoxtran-10 is taken up by atherosclerotic plaques in untreated apoE-/- mice and this alters plaque signal properties.
Klug
Gert
G
Medizinische Klinik und Poliklinik I, Universitaetsklinik Wuerzburg, Germany,2 Experimentelle Physik 5, Universitaet Wuerzburg, Germany.
Kampf
Thomas
T
Ziener
Christan
C
Parczyk
Marco
M
Bauer
Elizabeth
E
Herold
Volker
V
Rommel
Eberhard
E
Jakob
Peter Michael
PM
Bauer
Wolfgang Rudolf
WR
D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D050197:Atherosclerosis / Q000175:diagnosis / Q000473:pathology*; D003911:Dextrans; D052203:Ferrosoferric Oxide; D007501:Iron; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles; D051379:Mice; D018345:Mice, Knockout; D010087:Oxides
D001057:Apolipoproteins E; D003911:Dextrans; D058185:Magnetite Nanoparticles; D010087:Oxides; C097921:ferumoxtran-10; D007501:Iron; D052203:Ferrosoferric Oxide