Christian Wenning1, Christopher Kloth2, Michael T Kuhlmann2, Andreas H Jacobs2, Otmar Schober3, Sven Hermann2, Michael A Schäfers4. 1. 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. 2. European Institute for Molecular Imaging - EIMI, University of Münster, Münster, Germany. 3. Department of Nuclear Medicine, University Hospital Münster, Münster, Germany. 4. 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.
Abstract
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.
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.
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