Serial F-18-FDG PET/CT distinguishes inflamed from stable plaque phenotypes in shear-stress induced murine atherosclerosis

Wenning C, Kloth C, Kuhlmann MT, Jacobs AH, Schober O, Hermann S, Schafers MA

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 {\textquoteright}stable{\textquoteright} 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 {\textquoteright}stable{\textquoteright} phenotype in a mouse model of shear-stress induced atherosclerosis in vivo.