Transcutaneous ARFI Ultrasound for Differentiating Carotid Plaque With High Stroke Risk

University of North Carolina, Chapel Hill1 site in 1 country80 target enrollmentJuly 17, 2019

ConditionsPlaque, Atherosclerotic Carotid Artery Plaque Carotid Stenosis

Overview

Phase: N/A
Intervention: Not specified
Conditions: Plaque, Atherosclerotic
Sponsor: University of North Carolina, Chapel Hill
Enrollment: 80
Locations: 1
Primary Endpoint: Acoustic Radiation Force Impulse (ARFI) imaging
Status: Active, Not Recruiting
Last Updated: last year

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

Stroke is a leading cause of death and disability in the United States and around the world. The goal of this work is to develop and test a noninvasive ultrasound-based imaging technology to better identify patients at high risk of stroke so that appropriate and timely intervention may be administered to prevent it.

Detailed Description

Although stroke remains a leading cause of death in the United States, incidence and mortality rates have declined over the past two decades in association with advanced pharmaceutical therapies and revascularization, primarily by carotid endarterectomy (CEA). While CEA's efficacy for preventing stroke in patients with severe (≥70%) carotid artery stenosis and neurological symptoms is well documented, the surgical intervention's usefulness decreases as stroke risk falls in patients with less severe stenosis and patients without symptoms. It is estimated that as many as 13 out of 14 symptomatic patients with 50-69% stenosis and 21 out of 22 asymptomatic patients with 70-99% stenosis undergo CEA surgery unnecessarily. These data demonstrate the inadequacy of degree of stenosis as the primary indication of stroke risk and underscore the urgent yet unmet need for improved biomarkers that differentiate patients at low risk of embolic stroke from those in need of CEA to prevent it. This urgent need for improving CEA indication could be met by assessing the structure and composition of carotid plaques. Plaques composed of thin or ruptured fibrous caps (TRFC), large lipid rich necrotic cores (LRNC), and intraplaque hemorrhage (IPH) are associated with thrombosis in morphological studies from autopsy. Further, plaque hemorrhage and increased intraplaque vessel formation in CEA specimens are independently related to future cardio- and cerebrovascular events or interventions. Finally, previous stroke or transient ischemic attack (TIA) is associated with TRFC and IPH - while increased risk of future stroke or TIA is conferred by TRFC, LRNC, and IPH - in human carotid plaques as determined by in vivo magnetic resonance imaging (MRI). The goal of this work is to develop a low-cost, noninvasive imaging method that reliably delineates carotid plaque structure and composition and is suitable for widespread diagnostic application. Previous research has demonstrated that Acoustic Radiation Force Impulse (ARFI) ultrasound delineates LRNC/IPH, collagen/calcium deposits, and TRFC in human carotid plaque, in vivo, with TRFC thickness measurement as low as 0.49 mm - the mean thickness associated with rupture. This project will exploit ARFI Variance of Acceleration (VoA) imaging, higher center frequencies, and harmonic imaging to newly enable separate discrimination of TRFC, LRNC, and IPH and accurate feature size measurement. The investigators will determine the association between advanced ARFI's plaque characterization and recent history of ipsilateral stroke or TIA.

Registry

clinicaltrials.gov

Start Date

July 17, 2019

End Date

November 2025

Last Updated

last year

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

University of North Carolina, Chapel Hill

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•aged 18 years or older
•having 50-99% stenotic symptomatic carotid plaque with clinical indication for endarterectomy
•having 50-69% stenotic asymptomatic carotid plaque without clinical indication for endarterectomy

Exclusion Criteria

•prior CEA or carotid stenting
•carotid occlusion
•inability to provide informed consent
•prior radiation therapy to the neck
•treatment with immunomodulating drugs
•oncological disease.

Outcomes

Primary Outcomes

Acoustic Radiation Force Impulse (ARFI) imaging

Time Frame: Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years

Ability of ARFI imaging to detect carotid plaque features and measure their size

Secondary Outcomes

VoA AUC for thin or ruptured fibrous caps (TRFC) at 8 MHz fundamental(Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years)
PD AUC for TRFC at 8 MHz fundamental(Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years)
VoA AUC for TRFC at 12 MHz fundamental(Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years)
PD AUC for TRFC at 12 MHz fundamental(Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years)
VoA AUC for TRFC at 12 MHz harmonic(Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years)
PD AUC for TRFC at 12 MHz harmonic(Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years)
VoA AUC for LRNC at 8 MHz fundamental(Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years)
PD AUC for LRNC at 8 MHz fundamental(Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years)
VoA AUC for LRNC at 12 MHz fundamental(Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years)
PD AUC for LRNC at 12 MHz fundamental(Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years)
VoA AUC for LRNC at 12 MHz harmonic(Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years)
PD AUC for LRNC at 12 MHz harmonic(Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years)
VoA AUC for IPH at 8 MHz fundamental(Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years)
PD AUC for IPH at 8 MHz fundamental(Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years)
VoA AUC for IPH at 12 MHz fundamental(Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years)
PD AUC for IPH at 12 MHz fundamental(Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years)
VoA AUC for IPH at 12 MHz harmonic(Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years)
VoA bias for TRFC thickness at 8 MHz fundamental(Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years)
PD AUC for IPH at 12 MHz harmonic(Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years)
PD bias for TRFC thickness at 8 MHz fundamental(Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years)
VoA bias for TRFC thickness at 12 MHz fundamental(Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years)
VoA bias for LRNC size at 8 MHz fundamental(Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years)
PD bias for TRFC thickness at 12 MHz fundamental(Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years)
VoA bias for TRFC thickness at 12 MHz harmonic(Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years)
PD bias for TRFC thickness at 12 MHz harmonic(Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years)
PD bias for LRNC size at 8 MHz fundamental(Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years)
VoA bias for LRNC size at 12 MHz fundamental(Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years)
PD bias for LRNC size at 12 MHz fundamental(Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years)
VoA bias for LRNC size at 12 MHz harmonic(Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years)
PD bias for LRNC size at 12 MHz harmonic(Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years)
VoA bias for IPH size at 8 MHz fundamental(Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years)
PD bias for IPH size at 8 MHz fundamental(Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years)
VoA bias for IPH size at 12 MHz fundamental(Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years)
VoA bias for IPH size at 12 MHz harmonic(Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years)
PD bias for IPH size at 12 MHz harmonic(Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years)
PD bias for IPH size at 12 MHz fundamental(Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years)
VoA prevalence of TRFC detection at 8 MHz fundamental(Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years)
PD prevalence of TRFC detection at 8 MHz fundamental(Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years)
VoA prevalence of TRFC detection at 12 MHz fundamental(Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years)
PD prevalence of TRFC detection at 12 MHz fundamental(Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years)
VoA prevalence of TRFC detection at 12 MHz harmonic(Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years)
PD prevalence of TRFC detection at 12 MHz harmonic(Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years)
VoA prevalence of LRNC detection at 8 MHz fundamental(Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years)
PD prevalence of LRNC detection at 8 MHz fundamental(Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years)
VoA prevalence of LRNC detection at 12 MHz fundamental(Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years)
PD prevalence of LRNC detection at 12 MHz fundamental(Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years)
VoA prevalence of LRNC detection at 12 MHz harmonic(Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years)
PD prevalence of LRNC detection at 12 MHz harmonic(Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years)
VoA prevalence of IPH detection at 8 MHz fundamental(Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years)
PD prevalence of IPH detection at 8 MHz fundamental(Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years)
VoA prevalence of IPH detection at 12 MHz fundamental(Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years)
PD prevalence of IPH detection at 12 MHz fundamental(Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years)
VoA prevalence of IPH detection at 12 MHz harmonic(Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years)
PD prevalence of IPH detection at 12 MHz harmonic(Upon completion of the development of all novel ARFI data processing algorithms, their application to all acquired ARFI data, and the interpretation of the results for all participants, an average of two years)