Transcutaneous ARFI Ultrasound for Differentiating Carotid Plaque With High Stroke Risk

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.