Carotid Artery Plaque Vulnerability Assessment Using Ultrafast Ultrasound Techniques

Study Overview
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Brief Summary
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Objective: To explore the association between spatio-temporal blood flow velocities (peak systole and end-diastole at prior-stenosis, at maximum stenosis, and post-stenosis) and carotid plaque vulnerability defined by histology staining. Secondary, to assess the association between ultrasound elastography and carotid plaque vulnerability defined by histology staining. Furthermore, to assess the association between blood flow-derived parameters, including wall shear stress (WSS), vector complexity and vorticity, and plaque vulnerability. To evaluate the hemodynamic consequences of a CEA. Last, to explore whether the presence of circulating biomarkers is related to the degree of plaque vulnerability (as reflected by histology and/or ultrasound). Study design: A multicentre, prospective, observational, cohort study in a total of 70 patients. Study population: Patients with a carotid artery stenosis ≥50% according to clinically performed imaging (i.e. duplex, computed tomography angiography (CTA), or magnetic resonance angiography (MRA)) that are scheduled for a CEA. Intervention (observational): A carotid ultrasound with flow and elastography (strain and shear wave) measurements will be performed maximally 2 weeks prior to the CEA. In the first 20 included patients in the Radboudumc, a 10 mL blood sample will be collected during surgery via the arterial line that is applied for regular care. The plaque excised during CEA will be histologically examined to assess the plaque composition, and therefore plaque vulnerability. Ultrasound-based flow imaging will be repeated six weeks after the CEA to assess the hemodynamic consequences of the CEA procedure. Besides, clinical parameters will be subtracted from electronic health record or, if missing, anamnestically collected from the patient. Main study parameters/endpoints: Association between 2D spatio-temporal blood flow velocities (peak systole and end-diastole at prior-stenosis, maximum stenosis and post-stenosis), measured by ultrafast ultrasound measurements, and plaque vulnerability (stable versus unstable), defined by histology staining.

Official Title
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Carotid Artery Plaque Vulnerability Assessment Using Ultrafast Ultrasound Techniques

Conditions
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Carotid Artery Plaque

Intervention / Treatment
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* Diagnostic Test: Carotid ultrasound
* Other: Biospecimen collection and examination
* Other: Blood sample collection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Presence of carotid artery stenosis (≥50%) according to conventional clinically performed imaging (duplex/CT(A)/MR(A)) and scheduled for a CEA; Possibility to perform carotid ultrasound ≤2 weeks before the CEA ≥18 years old; Able to provide signed or oral informed consent. Exclusion Criteria: Hampered carotid blood flow imaging during clinically performed duplex/doppler measurements due to near to total carotid occlusion at the side of interest or a calcified plaque; Restenosis after carotid revascularisation at side of interest; Participating in another clinical study, interfering on outcomes;

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Participants<br>Patients with a carotid artery stenosis ≥50% according to clinically performed imaging (i.e. duplex, computed tomography angiography (CTA), or magnetic resonance angiography (MRA)) that are scheduled for a CEA. | Diagnostic Test: Carotid ultrasound<br>* Carotid ultrasound with flow and elastography (strain and shear wave) measurements will be performed maximally 2 weeks prior to the CEA. Ultrasound-based flow imaging will be repeated six weeks after the CEA to assess the hemodynamic consequences of the CEA procedure.<br>Other: Biospecimen collection and examination<br>* The plaque excised during CEA will be histologically examined to assess the plaque composition, and therefore plaque vulnerability.<br>Other: Blood sample collection<br>* In the first 20 included patients in the Radboudumc, a 10 mL blood sample will be collected during surgery via the arterial line that is applied for regular care.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assocation between 2D blood flow velocities and plaque vulnerability | Explore the association between 2D spatio-temporal blood flow velocities (peak systole and end-diastole prior-stenosis, at maximum stenosis and post-stenosis) and atherosclerotic carotid plaque vulnerability (stable versus unstable), defined by histology staining. | Time Frame: max 2 weeks prior to CEA | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Association strain and plaque vulnerability | Association between strain parameters and plaque vulnerability (stable versus unstable) quantified by histology staining. | Time Frame: max 2 weeks prior to CEA | 
| Association shear wave elastography measures and plaque vulnerability | Association between shear wave parameters and plaque vulnerability (stable versus unstable) quantified by histology staining. (only Radboudumc) | Time Frame: max 2 weeks prior to CEA | 
| Association blood flow-related parameters and plaque vulnerability | Association between blood flow-related parameters, including WSS, vector complexity and vorticity and carotid plaque vulnerability (stable versus unstable) quantified by histology staining. | Time Frame: max 2 weeks prior to CEA | 
| Comparison predictive value for plaque vulnerability ultrafast imaging techniques vs clinically-used measurements | Comparison between the predictive value for plaque vulnerability (stable versus unstable) of ultrafast imaging techniques (i.e. flow, strain and shear wave elastography) with that of clinically-used duplex measurements. | Time Frame: max 2 weeks prior to CEA | 
| Status 2D blood flow velocity profiles and flow-related parameters prior- and post-CEA | Status of 2D blood flow velocity profiles and flow-related parameters (WSS, vector complexity and vorticity) prior- and post-CEA. | Time Frame: max 2 weeks prior to CEA and 6 weeks after CEA | 
| Association circulating inflammatory cytokines and plaque vulnerability | Association between the presence of circulating inflammatory cytokines and the degree of plaque vulnerability (as reflected by histology and/or ultrasound) | Time Frame: During CEA | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ultrasound, Shear wave elastography, Atherosclerotic plaques, Strain elastography, Ultrafast ultrasound flow imaging, Histological plaque characterization