Targeted contrast agent helps to monitor advanced plaque during progression: a magnetic resonance imaging study in rabbits.
OBJECTIVE
Gadofluorine M has been reported to enhance early atherosclerotic plaque signals in magnetic resonance imaging (MRI). The aim of this study was to examine the use of Gadofluorine M to monitor the progression of advanced plaques in a rabbit model.


METHODS
Focal advanced atherosclerosis was induced in the right femoral arteries of 6 New Zealand white rabbits using a combination of cholesterol-enriched diet, and sequential air-desiccation, and balloon-overstretch injury. MRI with conventional 3 contrasts (T1, T2, and proton density [PD]) was performed to monitor the progression of the atherosclerotic plaques with 2 MRI scans separated by 4 to 8 weeks. Gadofluorine M was given intravenously to the rabbits 24 hours before the first MRI scans, and before (n = 3) or during (n = 3) the second MRI scan. The left femoral arteries were used as a control. Histopathologic images localized individual plaque components.


RESULTS
The advanced plaque displayed multilayered neointima that included foam cells, smooth muscle cells, and extracellular matrix. The separate image contrasts offered similar T1-weighted enhancement patterns, but the combination of all 3 contrasts helped to delineate plaque and lumen boundaries. Gadofluorine M strongly enhanced neointima areas with an image contrast (contrast-to-noise ratio [CNR]) of approximately 15, versus 2 in the control femoral arterial wall. With improved images, significant changes in neointima and total plaque volumes over the 4 to 8 weeks between scans could be identified. Gadofluorine M remained within the plaques with significant image enhancements (contrast-to-noise ratio = 5.8) for 2 months after a single injection.


CONCLUSIONS
This preliminary study in rabbits indicated that Gadofluorine M provides specific enhancements of components associated with advanced atherosclerotic plaques and may help to monitor the progression of the plaque in a rabbit model of atherogenesis.
Zheng
Jie
J
Mallinckrodt Institute of Radiology, Washington University, St. Louis, Missouri 63110, USA. zhengj@mri.wustl.edu
Ochoa
Elizabeth
E
Misselwitz
Bernd
B
Yang
Deshan
D
El Naqa
Issam
I
Woodard
Pamela K
PK
Abendschein
Dana
D
D000465:Algorithms; D000818:Animals; D050197:Atherosclerosis / Q000175:diagnosis*; D003287:Contrast Media; D004195:Disease Models, Animal; D018450:Disease Progression; D016503:Drug Delivery Systems / Q000379:methods*; D005240:Feasibility Studies; D005466:Fluorocarbons; D007089:Image Enhancement / Q000379:methods*; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009942:Organometallic Compounds / Q000008:administration & dosage; D011817:Rabbits; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D003287:Contrast Media; D005466:Fluorocarbons; D009942:Organometallic Compounds; C517961:gadofluorine M