Plaque Neovascularization Is Increased in Human Carotid Atherosclerosis Related to Prior Neck Radiotherapy: A Contrast-Enhanced Ultrasound Study

Abstract Objectives The aim of this study was to determine the effect of radiotherapy (RT) on intraplaque neovascularization (IPN) in human carotid arteries. Background Exposure of the carotid arteries to RT during treatment for head and neck cancer is associated with increased risk for stroke. However, the effect of RT on IPN, a precursor to intraplaque hemorrhage and thus associated with plaque vulnerability, is unknown. Methods In this cross-sectional study, patients who had undergone unilateral RT for head and neck cancer ≥2 years previously underwent B-mode and contrast-enhanced ultrasound of both RT-side and non–RT-side carotid arteries. Presence of IPN during contrast-enhanced ultrasound was judged semiquantitatively as grade 0 (absent), grade 1 (present but limited to plaque base), or grade 2 (extensive and noted within plaque body). Results Of 49 patients studied, 38 (78%) had plaques. The number of plaques was significantly greater in the RT than the non-RT arteries. Overall, 48 of 64 RT-side plaques (75%) had IPN compared with 9 of 23 non-RT-side (39%) plaques (p = 0.002). Among patients with plaques, IPN was present in 81% of patients with RT-side plaques and 41% of patients with non-RT-side plaques (p = 0.004). Grade 0 IPN was significantly more common in patients with non-RT-side plaques (25% vs. 61%; p = 0.002), whereas grade 2 plaques were more common on the RT side (31% vs. 9%; p = 0.03). The only clinical variable that predicted the presence or absence of IPN was RT laterality. Conclusions This is the first study in humans to reveal a significant association between RT and the presence and extent of IPN. This may provide insights into the mechanisms underlying the increased stroke risk among survivors of head and neck cancer treated by RT.