Progression Assessment of Carotid Artery Stenosis by Ultrafast Ultrasound Flow Imaging (CAS-PRO)

Rationale: Approximately 15-20% of strokes originates from an atherosclerotic plaque rupture in the carotid artery. To reduce the risk of stroke, patients should be evaluated for possible carotid endarterectomy (CEA), which is based on simple geometrical and clinical measures. Multiple studies have shown that the current risk stratification may lead to both over- and under-treatment for patients with carotid artery stenosis. This implicates that the current guidelines are lacking patient-specific parameters and have limited sensitivity. There is a wealth of evidence implicating the important role of local (disturbed) blood flow throughout the onset and progression of atherosclerosis. Novel flow-related measures, that go beyond simple geometrical indications, are required to improve diagnosis and treatment in patients with carotid artery stenosis. Nowadays, ultrasound (US) is one of the main techniques to assess for the presence and extent of carotid artery stenosis. However, current clinically-used US systems are unable to acquire and visualize the complex flow phenomena that play such a crucial role in the atherosclerotic disease process. With the advent of ultrafast ultrasound imaging, acquiring thousands of images per second, continuous tracking of flow in all directions became feasible, which enables us to image two-dimensional blood flow and possible disturbances with high accuracy and precision.

In this project, we aim to assess whether flow (related) parameters are associated with disease progression (and if so, which), in order to map the progression of atherosclerotic plaques using non-invasive, US-based blood flow imaging. In the future, this could improve risk stratification for individual patients for surgery, decrease patient mortality and morbidity, and therefore reduce healthcare costs.

Objective: To longitudinally assess the association between spatio-temporal blood flow velocities (peak systole and end-diastole at common carotid artery, maximum stenosis and internal carotid artery) and the progression of carotid atherosclerosis defined by duplex measurements.

Secondary objectives are to investigate the association between blood flow-derived parameters, including wall shear stress (WSS), vector complexity and vorticity, and the progression of atherosclerosis defined by duplex measurements. Furthermore, to assess the association between spatio-temporal blood flow velocities and blood flow-derived parameters (WSS, vector complexity and vorticity) and the progression of atherosclerosis as measured using ultrasound-based strain imaging.

Study Overview

• Status: Recruiting
• Conditions: Carotid Artery Stenosis
• Intervention / Treatment: Diagnostic test: Ultrasound-based flow imaging; Diagnostic test: Ultrasound-based strain imaging; Diagnostic test: Conventional duplex

• Study Type: Observational
• Enrollment (Anticipated): 85

Contacts and Locations

Study Locations

• Netherlands
  • Arnhem, Netherlands
    • Recruiting
    • Rijnstate Hospital
    • Contact: Michel M.P.J. Reijnen, MD, PhD; Phone Number: 088 005 7282; Email: mreijnen@rijnstate.nl
  • Nijmegen, Netherlands
    • Recruiting
    • Radboud University Medical Center
    • Contact: Chris L. de Korte, PhD; Phone Number: +31 24 3617694; Email: c.l.dekorte@radboudumc.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients with an asymptomatic carotid artery stenosis, defined by 30% to 69% narrowing of the carotid artery according to conventional duplex measurements in the absence of ipsilateral retinal or cerebral ischemia in the preceding 6 months.

Description

Inclusion Criteria:

• Adult male or female (≥18 years old);
• Informed consent form understood and signed, and patient agrees to follow-up visits;
• Presence of carotid artery stenosis (between 30%-69%) according to conventional duplex measurements (peak-systolic velocity of 125-230 cm/s [5] in combination with visible lumen reduction >30% according to North American Symptomatic Carotid Endarterectomy Trial [NASCET] method);
• Defined asymptomatic with respect to the ipsilateral carotid artery stenosis.

Exclusion Criteria:

• A planned carotid revascularisation for the ipsilateral carotid artery stenosis at date of inclusion;
• History of carotid revascularisation at artery under investigation;
• Visible near occlusion at asymptomatic stenosis side according to conventional duplex measurements;
• Life expectancy < 2 years;
• Participating in another clinical study, interfering on outcomes

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Asymptomatic carotid artery stenosis; Patients with an asymptomatic carotid artery stenosis, defined by 30% to 69% narrowing of the carotid artery according to conventional duplex measurements in the absence of ipsilateral retinal or cerebral ischemia in the preceding 6 months.

Diagnostic test: Ultrasound-based flow imaging; Ultrasound-based flow imaging of the carotid artery stenosis will be acquired at baseline and two annual follow-up appointments.; Diagnostic test: Ultrasound-based strain imaging; Ultrasound-based strain imaging of the carotid artery stenosis will be acquired at baseline and two annual follow-up appointments.; Diagnostic test: Conventional duplex; Conventional duplex measurements of the carotid artery stenosis will be acquired at baseline and two annual follow-up appointments.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Two-dimensional spatio-temporal blood flow velocities	Two-dimensional vector velocity fields derived from the US-based flow imaging will be used to calculate the spatio-temporal blood flow velocities.	2 year follow-up
Plaque progression (stenosis degree)	Plaque progression, defined by increase in stenosis degree. Stenosis degree will be quantified by conventional ultrasound imaging.	2 year follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Wall shear stress	Multiple blood flow-related parameters will be derived from the spatio-temporal blood flow velocity data. One parameter is the wall shear stress.	2 year follow-up
Vorticity	Multiple blood flow-related parameters will be derived from the spatio-temporal blood flow velocity data. One parameter is vorticity.	2 year follow-up
Vector complexity	Multiple blood flow-related parameters will be derived from the spatio-temporal blood flow velocity data. One parameter is vector complexity.	2 year follow-up
Plaque progression (deformation)	Plaque progression, defined by change in plaque deformation. Plaque deformation will be quantified by strain imaging.	2 year follow-up
Symptomatic carotid stenosis		2 year follow-up

Collaborators and Investigators

• Sponsor: Rijnstate Hospital
• Collaborators: Radboud University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): April 7, 2022
• Primary Completion (Anticipated): February 1, 2025
• Study Completion (Anticipated): April 1, 2025

Study Registration Dates

• First Submitted: February 2, 2022
• First Submitted That Met QC Criteria: February 25, 2022
• First Posted (Actual): March 8, 2022

Study Record Updates

• Last Update Posted (Actual): November 28, 2022
• Last Update Submitted That Met QC Criteria: November 21, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: Atherosclerotic plaque; Disease progression; Ultrafast ultrasound flow imaging; Velocity vector imaging
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Arterial Occlusive Diseases; Disease Attributes; Pathological Conditions, Anatomical; Carotid Artery Diseases; Disease Progression; Carotid Stenosis; Constriction, Pathologic
• Other Study ID Numbers: 2021-1915

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No