Murine atherosclerotic plaque imaging with the uspio ferumoxtran-10

Abstract

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 500μmol Fe/kg or 1000μmol 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). Spinecho 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 1000μmolFe/kg. Atheroma iron uptake was not elevated after 24 hours compared to controls. 48 hours after 1000μmol Fe/kg but not 500μmol 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 500μmolFe/ml and 0.59±0.14 in mice injected with 1000μmol 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.