Contrast-Enhanced Ultrasound Imaging of Intraplaque Neovascularization in Carotid ArteriesCorrelation With Histology and Plaque Echogenicity
Stefano Coli, MD*,*,
Marco Magnoni, MD*,
Giuseppe Sangiorgi, MD, FESC ,
Massimiliano M. Marrocco-Trischitta, MD*,
Giulio Melisurgo, MD*,
Alessandro Mauriello, MD ,
Luigi Spagnoli, MD ,
Roberto Chiesa, MD*,
Domenico Cianflone, MD, FESC* and
Attilio Maseri, MD, FACC*
* Department of Cardiothoracic and Vascular Diseases, University Vita-Salute, San Raffaele Scientific Institute, Milan, Italy
Department of Cardiovascular Diseases, University of Rome Tor Vergata, Rome, Italy
Department of Pathology, University of Rome Tor Vergata, Rome, Italy.

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Figure 1 Vessel Density at Histology According to Plaque Contrast-Agent Enhancement
The density of vasa vasorum at histology (number per square millimeter) is greater in plaques with grade 2 contrast-agent enhancement at ultrasound imaging compared with those with grade 1.
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Figure 2 Plaque Without Contrast-Agent Enhancement Showing Scant Neovascularization at Histology
Panel A shows a large, predominantly hypoechoic plaque, at the origin of the internal carotid artery. No plaque enhancement can be detected by contrast-enhanced ultrasound imaging (B). Panel C shows the micrograph of 1 of the sections studied of the corresponding plaque (Movat's pentachrome staining, x0.5). Panel D represents the inset in panel C. In the region nearby the fibrous cap, only a few newly formed small vessels CD31/34 positive are present (arrow, x10).
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Figure 3 Plaque With Grade 2 Contrast-Agent Enhancement Showing Abundant Neovascularization at Histology
Panel A shows 3 consecutive frames of contrast-enhanced ultrasound imaging of an atherosclerotic lesion in the carotid bulb, showing contrast microbubbles within the plaque (grade 2 contrast-agent enhancement). Micrograph in panel B shows a carotid hemorrhagic fibrocalcific plaque with an eccentric large necrotic core occupying approximately 60% of the plaque area (Movat's pentachrome staining, x0.5). In the area of a thin fibrous cap (C, which represents the inset in B) nearby the atheroma, numerous CD31/CD34 positive neovessels are present. It is worth noting the presence of a large first-order vasa vasorum (*) with a thin vessel wall surrounded by small second-order vasa (arrows, x10).
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Figure 4 Grade of Contrast-Agent Enhancement According to Plaque Echogenicity
The proportion of plaques with grade 2 contrast-agent enhancement (red) is greater in more echolucent plaques.
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Figure 5 Hypoechoic Carotid Plaque With Extensive (Grade 2) Contrast-Agent Enhancement
Panel A shows a hypoechoic plaque at the origin of internal carotid artery. After injection of Optison (panels B to D) an extensive contrast-agent enhancement can be observed, represented by several bright spots within the plaque itself (also see Online Video 1).
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