Serial F-18-FDG PET/CT distinguishes inflamed from stable plaque phenotypes in shear-stress induced murine atherosclerosis.
BACKGROUND
Detection of inflamed atherosclerotic plaques is of crucial importance. The carotid artery cuff-model in ApoE(-/-) mice results in shear-stress induced atherosclerosis with inflamed plaques upstream (US) and 'stable' plaques downstream (DS) of the cuff. We evaluated the potential of F-18-FDG PET/CT to differentiate these plaque phenotypes.


METHODS
A predefined cuff was implanted round the left (n = 23) or right (n = 12) common carotid artery (CCA) of 35 ApoE(-/-) mice on a cholesterol-rich diet. Small animal F-18-FDG PET/CT was performed after 4, 6 and 8 weeks. F-18-FDG uptake was quantified US and DS of the cuff and on the contralateral CCA. Subsequently, regional F-18-FDG uptake was normalized by the contralateral CCA uptake to obtain plaque-to-background (P/B)-ratios. Thereafter, CCA were explanted and investigated by immunohistology.


RESULTS
P/B-ratio in the US-plaques increased from 1.22 ± 0.23 at 4 weeks over 1.23 ± 0.32 at 6 weeks to 1.37 ± 0.56 (p = ns) at 8 weeks after cuff implantation (left and right side of cuff implantation considered together). Uptake in the DS-plaques remained stable (1.14 ± 0.23, 1.10 ± 0.26 and 1.11 ± 0.25; p = ns). Uptake in the US-plaques was significantly higher than in the DS-plaques (all p < 0.05). P/B-ratios correlated with plaque size, degree of stenosis and macrophage density in the plaques. Moreover, there was a correlation between plaque size and macrophage density in the plaque.


CONCLUSIONS
F-18-FDG-PET/CT distinguishes atherosclerotic plaques with an inflamed from those with a 'stable' phenotype in a mouse model of shear-stress induced atherosclerosis in vivo.
European Institute for Molecular Imaging - EIMI, University of Münster, Münster, Germany; Department of Nuclear Medicine, University Hospital Münster, Münster, Germany. Electronic address: cwenning@uni-muenster.de.
Christian
C
Wenning
European Institute for Molecular Imaging - EIMI, University of Münster, Münster, Germany.
Christopher
C
Kloth
European Institute for Molecular Imaging - EIMI, University of Münster, Münster, Germany.
Michael T
MT
Kuhlmann
European Institute for Molecular Imaging - EIMI, University of Münster, Münster, Germany.
Andreas H
AH
Jacobs
Department of Nuclear Medicine, University Hospital Münster, Münster, Germany.
Otmar
O
Schober
European Institute for Molecular Imaging - EIMI, University of Münster, Münster, Germany.
Sven
S
Hermann
European Institute for Molecular Imaging - EIMI, University of Münster, Münster, Germany; Department of Nuclear Medicine, University Hospital Münster, Münster, Germany; DFG Cluster of Excellence EXC 1003 'CiM - Cells in Motion', Münster, Germany.
Michael A
MA
Schäfers
D000818:Animals; D001057:Apolipoproteins E; D002340:Carotid Artery Diseases / Q000000981:diagnostic imaging* / Q000473:pathology; D002791:Cholesterol, Dietary; D003937:Diagnosis, Differential; D004195:Disease Models, Animal; D019788:Fluorodeoxyglucose F18; D006801:Humans; D007249:Inflammation / Q000473:pathology; D010641:Phenotype; D058226:Plaque, Atherosclerotic / Q000000981:diagnostic imaging* / Q000473:pathology; D049268:Positron-Emission Tomography / Q000379:methods
D001057:Apolipoproteins E; D002791:Cholesterol, Dietary; D019788:Fluorodeoxyglucose F18
Atherosclerosis; Plaque inflammation; Positron emission tomography; Shear-stress