During the study, conducted from 2018 to 2020, 73 patients with duplex ultrasound detected unstable plaque were enrolled. All patients examined with Duplex US, CEUS, CTA and in 50 cases the histology of the atherosclerotic plaque was acquired after endarterectomy.

Fig 1: Histology specimen. Image of carotid aterosclerotic plaque with fibrosis and...

Fig 2: CEUS/B mode side by side US image. Calcified atherosclerotic plaque at internal...

Fig 3: CEUS/B mode side by side US image. Grade 0 neovascularization within carotid...

Fig 4: CEUS/B mode side by side US image with maximum intensity pixel projection mode....

Fig 5: CEUS image. Atherosclerotic carotid plaque with ulceration and Grade 1...

Project study selection criteria:

The criteria for inclusion in the study are as follows:

1. Carotid artery moderate and severe stenosis detected by ultrasound (by NASCET).
2. In CTA or ultrasound B mode there are following plaque features:
   • B mode ultrasound structural marked hypoechogenicity/heterogeneity
   • CTA Hypodense/heterogenic plaque;
   • Irregularity of the surface of the plaque, but no indication of ulceration^;
   • Plaque with ulceration;
3. Neovascularization in the plaque in vasa vasorum level suspected by other imaging methods (US microvascular imaging (SMI), magnetic resonance angiography).
4. The site of plaque is accessible and visible by B mode, Duplex Doppler and CEUS
5. Available peripheral vein access for intravenous contrast media injection

The exclusion criteria are as follows:

1. • Mild plaque-related stenosis <50%;
   • Carotid artery stent
   • Atrial fibrillation or any other arrhythmia;
   • Hypotension (TA<120 mmHg);
   • Heart failure III, IV NYHA stage;
   • Person has disability (mental disorders, physical disability by modified Rankin Scale >3)
   • Impossible to provide peripheral venous access for the contrast agent administration;
   • Allergy to iodine-containing contrast agent and/or absence of CTA data;

Allergy to ultrasound contrast agent SonoVue (Bracco, Milan);

CEUS examination:

1. CEUS examination was performed after B mode and Color doppler and Spectral doppler multiparametric ultrasound evaluation by the ultrasound equipment with specific contrast software using contrast agent SonoVue (Bracco, Milan) 1,0-2,0 ml with intravenous administration of contrast bolus followed by saline flush (10 ml).
2. CEUS scanning is performed continuously for first 90 seconds and continued intermittently for up to 3-5 minutes. The dynamic process of scanning is stored as cine loops and still images with information about timing. Stored clips are used for later review or specified postprocessing as the examination is dynamic and subtle uptake requires additional analysis [4, 7.].

One group consisted of patients with extensive calcified plaque component, second group - soft plaques. For every group CEUS sensitivity, specificity was calculated in comparison with histology results. Neovascularization in CEUS examination was defined in 3 grades – no neovascularization (Grade 0), poorly (Grade1), well visible (Grade2) [10]. Contrast uptake onset time was analyzed below and above 30 seconds (early and late).