New Technologies to Determine Carotid Plaque Vulnerability: A Pilot Study to Assess Contrast-Enhanced Ultrasound (CEUS) and Shear Wave Elastography (SWE) in Patients With Significant Carotid Plaques
Phase: PHASE2
Conditions: Carotid Artery Plaque
Sponsor: Mayo Clinic

New Technologies to determine Carotid 
Plaque Vulnerability: A Pilot Study to 
Assess Contrast-Enhanced Ultrasound 
(CEUS) and Shear Wave Elastography 
(SWE) in Patients with Significant Carotid 
Plaques 
 
NCT03335033 
 
 
8/24/2018 

 
 
 
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Patient selection: We will prospectively recruit 80 patients for this study from patients being seen in the Gonda 
Vascular Center. Patients with known plaques will be screened before a scheduled appointment. Alternatively, 
patients undergoing an ultrasound examination in the Gonda Vascular Center may also be identified for 
recruitment.  Patients who are will be undergoing a carotid endarterectomy will be approached for recruitment. 
Additionally, patients are going to be scanned and have a known moderate (50-69%) stenosis or a newly 
discovered moderate stenosis will be approached for recruitment. We will prospectively enroll 20 patients that 
are undergoing carotid endarterectomy and 60 cardiovascular high-risk patients with moderate or severe (50%-
99% diameter) stenosis carotid plaques from the Gonda Vascular Center practice for evaluation with SWE and 
CEUS. The main indications of high-risk patients are multiple cardiovascular risk factors, carotid bruit, known 
atherosclerotic disease in coronary (>50% stenosis confirmed by angiography), or peripheral artery disease 
(according to medical history). 
Ultrasound protocol: A standard carotid US examination using Duplex imaging will performed using a 9 MHz 
linear array transducer to obtain longitudinal and transverse images. All ultrasound measurements will be made 
by a trained registered vascular technologist. Severity of stenosis of the plaque will be measured based on 
established protocol and guidelines outlined in [44]. SWE will be performed with the GE Logiq E9 scanner 
acquiring images of each plaque in the longitudinal and transverse imaging planes. In each plane 10 
measurements will be made and the in-phase/quadrature (IQ) data will be saved for further analysis. The plaque 
area in the imaging plane will be user-defined to extract the wave velocity values for a ROI analysis. A mean 
and median of repeated measurements will be calculated. Additionally, the calculated wave motion will be 
analyzed further for characterization of the plaque.  
CEUS will be performed using low mechanical index (0.17-0.20) imaging during ultrasound contrast agent 
intravenous infusion. The ultrasound contrast agent that will be used is Lumason (Bracco Diagnostics, Inc). Real-
time cine-loop including longitudinal and transverse images obtained at least 3 seconds before and 5 minutes 
after the appearance of the contrast effect in the lumen of the carotid artery will be acquired and digitally stored 
for offline analysis. IPN will be visually graded according to microbubble location and kinetics: G0: no visible 
microbubbles within the plaque; G1: moderate microbubbles confined to the shoulder and/or adventitial side of 
the plaque; or G2: extensive microbubbles throughout the plaque, with clear visible appearance of bubble 
moving into the plaque core. We will also use a 3D ultrasound transducer to evaluate the feasibility of using US 
images with contrast to assess the residual diameter of the diseased vessel. Specifically, two 3D acquisitions of 
each lesion would be obtained after contrast has been injected. These will be acquired with the RSP6-16-D 
mechanical 3D probe. One acquisition would be done with the vessel longitudinally oriented in the acquired 
image plane, and the other would orient the vessel trans-axially. 
 
Endarterectomy Sample Analysis: If the surgeon sends the endarterectomy sample for pathological 
examination, we will analyze slides in the Tissue Registry. If the endarterectomy sample is not sent for 
pathological examination, fresh tissue from endarterectomy would be collected during the patient’s surgery. If 
possible, the whole atherosclerotic plaque would be collected, but half the available specimen would also be 
suitable. The sample will be fixed in 10% neutral buffered formalin and subsequently embedded in paraffin 
(FFPE). Slides will be processed identically, whether processed clinically or for the purposes of research. 
Several slides (up to 6) with various stains will be processed for each block. These stains include hematoxylin 
and eosin (H & E), Verhoeff-van Gieson (VVG), Masson’s trichrome, and CD31 antibody. The slides will be 5 
microns thick for each stain. Slides will be stored in Dr. Urban’s laboratory. Dr. 
 (a 
cardiovascular pathologist) will review the slides for this study. 
 

 
 
 
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