Introduction: Recent studies indicated that plaque rupture may be associated with: a) extreme mechanical stress/strain conditions; b) large lipid-rich necrotic core; c) thin and weakening fibrous cap; d) cap inflammation; e) intraplaque hemorrhage. Fayad et al and others have been developing multi-modality imaging technology using PET/CT (Positron Emission Tomography/ Computed Tomography) and MRI (magnetic resonance imaging) to identify inflammation in arteries. The goal of this paper is to investigate possible impact of cap inflammation on plaque stress/strain and flow shear stress conditions. Method: An MRI-PET/CT-based modeling approach is proposed to develop fluid-structure interaction (FSI) models for human carotid plaque assessment and quantify the effect of inflammation on plaque stress/strain conditions. The combined PET/CT and MRI data was acquired from a 74 year old male patient (with informed consent) to assess arterial inflammation. The patient was imaged with dark blood multi-contrast MRI and 18F-fluorodeoxyglucose (18F-FDG) PET/CT in separate imaging sessions 12 days apart. For the 15-slice MRI/PET/CT data set, inflammation was identified for S4-S11. The 3D FSI model was built following established procedures. Material stiffness for the fibrous cap was adjusted lower to reflect the cap weakening causing by cap inflammation. Setting stiffness ratio (SR) to be 1.0 for baseline, results for SR=0.5, 0.25, and 0.1 (smaller SR value indicates softer cap stiffness) were obtained. Results: Mean plaque cap stress (PC-Stress), strain (PC-Strain) and flow shear stress (PC-FSS) are reported in Table 1. Roughly, 30-50% decrease in PC-Stress and 50-100% increase in PC-Strain were observed. Greater changes were observed for SR=0.1. Conclusion: Since cap inflammation and extreme stress/strain conditions are of great interest, further investigations are warranted to validate our findings.