[Frontiers in Bioscience 14, 2546-2552, January 1, 2009]

Murine atherosclerotic plaque imaging with the USPIO Ferumoxtran-10

Klug, Gert1, Kampf Thomas2, Ziener Christan2, Parczyk Marco 2, Bauer Elisabeth 1, Herold Volker2, Rommel, Eberhard2, Jakob Michael Peter2, Bauer Rudolf Wolfgang1

1Medizinische Klinik und Poliklinik I, Universitaetsklinik Wuerzburg, Germany,2 Experimentelle Physik 5, Universitaet Wuerzburg, Germany

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Materials and methods
2.1. Animals
2.2. ex vivo MRI
2.3. in vivo MRI
2.4. Histological analysis
2.5. MR images analysis
2.6. Statistical analysis
3. Results
3.1. Histology
3.2. ex vivo T2* mapping
3.3. in vivo MRI
4. Discussion
6. Acknowledgement
7. References

1. 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). 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 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.