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Background and Aims: The advantage of combining molecular and morphological imaging, e.g. positron emission tomography and magnetic resonance imaging (PET/MRI), is reflected in the increased use of these modalities as surrogate end-points in clinical trials. This study aimed at evaluating plaque inflammation using 18 F-fluorodeoxyglucose ( 18 F-FDG)-PET/MRI, and gene expression in a minipig model of atherosclerosis., Methods: Göttingen Minipigs were fed for 60 weeks with fat/fructose/cholesterol-rich diet (FFC), chow (Control) or FFC-diet changed to chow midway (diet normalization group; DNO). In all groups, 18 F-FDG-PET/MRI of the abdominal aorta was assessed midway and at study-end. The aorta was analyzed using histology and gene expression., Results: At study-end, FFC had significantly higher FDG-uptake compared to Control (target-to-background maximal uptake, TBR Max (95% confidence interval) CI TBRMax : 0.092; 7.32) and DNO showed significantly decreased uptake compared to FFC (CI TBRMax : -5.94;-0.07). No difference was observed between DNO and Control (CI TBRMax : -2.71; 4.11). FFC displayed increased atherosclerosis and gene expression of inflammatory markers, including vascular cell adhesion molecule 1 (VCAM-1), cluster of differentiation 68 (CD68), matrix metalloproteinase 9 (MMP9), cathepsin K (CTSK) and secreted phosphoprotein 1 (SPP1) compared to Control and DNO (all, p < 0.05). FDG-uptake correlated with gene expression of inflammatory markers, including CD68, ρ s  = 0.58; MMP9, ρ s  = 0.46; SPP1, ρ s  = 0.44 and CTSK, ρ s  = 0.49; (p ≤ 0.01 for all)., Conclusions: In a model of atherosclerosis, 18 F-FDG-PET/MRI technology allows for detection of inflammation in atherosclerotic plaques, consistent with increased inflammatory gene expression. Our findings corroborate clinical data and are important in pre-clinical drug development targeting plaque inflammation., (Copyright © 2019. Published by Elsevier B.V.)