Assessment of neovascularization of carotid artery atherosclerotic plaques using superb microvascular imaging: a comparison with contrast-enhanced ultrasound imaging and histology

Background: This study aimed to investigate the usefulness of superb microvascular imaging (SMI), a novel non-contrast-enhanced ultrasound technique, in characterizing neovessels within carotid atherosclerotic plaques through comparison with contrast-enhanced ultrasound (CEUS) and histology. Methods: Patients with carotid plaque were recruited and underwent SMI and CEUS ultrasound imaging of the carotid arteries. The maximum plaque thickness, length, and stenosis of each plaque were measured. Grade of the neovessels was determined by SMI and CEUS, respectively. Grade 0 was defined as no blood flow signal/microbubbles within plaques; grade 1 was defined as moderate blood flow signals/microbubbles confined to the shoulder and/or adventitial side of the plaque; and grade 2 was defined as extensive intraplaque signals/microbubbles. Patients with symptomatic carotid stenosis (stenosis >= 50%) or asymptomatic carotid stenosis (stenosis >= 70%) underwent endarterectomy, and plaque specimens were subjected to immunohistochemical analysis of CD31 expression. The neovessels were quantified by histology. The agreement of SMI with CEUS and histology in characterizing neovessels was analyzed using weighted Kappa statistic and Spearman's correlation analyses. Results: Seventy-eight patients (mean age: 67.3 +/- 8.9 years old, 63 males) were recruited. Of these patients, 52 (66.7%) had a unilateral plaque and 26 (33.3%) had bilateral plaques in the carotid arteries. For the 104 carotid plaques detected, the mean plaque thickness and length were 4.3 +/- 1.1 and 18.8 +/- 6.6 mm, respectively. The prevalence of <50%, 50-69%, and >= 70% stenosis was 43.3%, 24.0%, and 32.7%, respectively. Excellent agreement was found between SMI and CEUS (kappa=0.825 at the plaque level; kappa=0.820 at the patient level) in evaluating the neovessel grade within the carotid plaques. Of the 25 patients who underwent carotid endarterectomy, a strong correlation (r=0.660, P<0.001) was found between SMI and histology in the evaluation of intraplaque neovessels. SMI had excellent scan-rescan (kappa=0.857), intra-reader (kappa=0.810), and inter-reader (kappa=0.754) agreement in the assessment of intraplaque neovessels. Conclusions: The SMI technique is capable of reliably characterizing neovessels within carotid atherosclerotic plaques and demonstrates good to excellent agreement with histology and CEUS.