Head-to-Head Comparison of Inflammation and Neovascularization in Human Carotid Plaques: Implications for the Imaging of Vulnerable Plaques

Background: Inflammation and intraplaque neovascularization are acknowledged to be 2 features of plaque vulnerability, although their temporal expression and their respective value in predicting clinical events are poorly understood. To determine their respective temporal associations, we conducted a comprehensive assessment of inflammation and intraplaque neovascularization in the carotid plaque of symptomatic and asymptomatic patients.

Methods and results: Thirty patients with severe carotid stenosis underwent ¹⁸F-fluorodeoxyglucose-positron emission tomography/computed tomographic imaging. Plaque ¹⁸F-fluorodeoxyglucose-uptake, indicative of inflammation, was measured by calculating the target:background ratio. The presence of intraplaque neovascularization during contrast-enhanced ultrasound was judged semiquantitatively; low-grade contrast enhancement (CE) suggested its absence, and high-grade CE, the presence of neovascularization. Carotid surgery was performed 1.6±1.8 days after completing both imaging modalities in all patients, and the presence of macrophages and neovessels was quantified by immunohistochemistry. We identified a significant correlation between the target:background ratio and macrophage quantification (R=0.78; P<0.001). The number of vessels was also significantly higher in carotid plaque with high-CE (P<0.001). Surprisingly, immunohistochemistry showed that high-CE and vessel number were neither associated with an elevated target:background ratio (P=0.28 and P=0.60, respectively) nor macrophage infiltration (P=0.59 and P=0.40, respectively). Finally, macrophage infiltration and target:background ratio were higher in the carotid plaque of symptomatic patients (P=0.021 and P=0.05, respectively), whereas CE grade and the presence of neovessels were not.

Conclusions: Inflammation and intraplaque neovascularization are not systematically associated in carotid plaques, suggesting a temporal separation between the 2 processes. Inflammation seems more pronounced when symptoms are present. These data highlight the challenges that face any imaging strategy designed to assess plaque vulnerability.