Head-to-Head Comparison of Inflammation and Neovascularization in Human Carotid Plaques

Abstract

Background: Inflammation and neovascularization are two recognized features of plaque vulnerability. However, the inflammatory state as well as the intraplaque neoangiogenesis can vary overtime and little is known about their potential for predicting clinical events. Accordingly, we systematically assessed inflammation and neovascularization in carotid plaque of symptomatic and asymptomatic patients scheduled for carotid surgery. Method(s): Twenty-five patients (20 men; 9 symptomatic) with severe carotid stenosis underwent PET/CT imaging 151+/-24 min after injection of 309+/-19 MBq of 18F-fluorodeoxyglucose (FDG). Plaque FDG-uptake was measured by calculating the target to background ratio (TBR) representing the ratio of the plaque FDG-uptake to the blood pool activity. The same day, all patients underwent a contrast enhanced ultrasound (US) examination to assess intraplaque neovascularization. For this purpose, a contrast-specific US imaging was performed after a bolus injection of Sonovue (2 mL). The plaque contrast enhancement (CE) was then visually graded (low CE suggesting the absence and high CE suggesting the presence of neovascularization). Carotid surgery was performed 24 hours later in all patients and the presence of macrophages and neovessels were quantified by immunohistology on surgical samples. Result(s): As expected, we found a high correlation between TBR and the number of macrophages (R = 0.82, p < 0.001). The number of vessels was also significantly higher in carotid plaque with high CE (p=0.021). More surprisingly, high CE and the number of vessels were not associated with higher TBR (p= 0.34 and p= 0.4 respectively) or with macrophage infiltration on histology (p = 0.57 and p = 0.10 respectively). Finally, macrophage infiltration as well as TBR were higher in carotid plaque of symptomatic patients (p = 0.023 and p = 0.043 respectively) while the CE and the presence of neovessels were not. Conclusion(s): Inflammation and neovascularization are not systematically associated in carotid plaques and inflammation is more pronounced when symptoms are present. Thus, the prediction of clinical events should be based on inflammation rather than on neovascularization.