Mechanical characterization of carotid plaques for stroke risk assessment

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Stroke is the fifth leading cause of death and the primary cause of preventable disability and hospitalization in the U.S according to the most recent statistics by the American Heart Association. Each year, approximately 795,000 people continue to experience a new or recurrent stroke. On average, every 40 seconds, someone in the United States has a stroke, and someone dies of one approximately every 4 minutes. This high fatality rate is partly due to the fact that state-of-the-art methodologies such as CT, MRI and ultrasound are currently failing to inform timely intervention. Identification of patients with high-risk, asymptomatic carotid plaques despite their low stenoses remains thus an elusive but essential step in stroke prevention. In current clinical practice, the risk assessment of carotid plaque rupture is based on the degree of intima- media thickness (IMT) and endoluminal stenosis despite the fact that they do not necessarily correlate with vulnerable plaques or subsequent rupture. Current clinical modalities fall thus short in informing on plaque stability. Reliable information on plaque stability would ensure timely treatment, especially in asymptomatic or low endoluminal stenosis patients whose stroke risk remains severely underdiagnosed. Such information shown to be critical but clinically unavailable lies in the plaque compliance and the associated blood flow. Lipid plaques (which are typically less stable and are associated with ischemic stroke) have been shown to have distinct stiffness from calcified plaques. Increased arterial stiffness has also been reported in stroke patients. The objective of the proposed study is thus to amplify the role of carotid sonography by optimizing the combined PWI and VFI methodologies (PWI+VFI) and quantifying the biomarkers of compliance and flow in order to provide critical biomechanical information on plaque stability. In reported studies, our group has shown that plaque characterization in large animals and stroke patients can be achieved. We have demonstrated that PWI+VFI is capable of characterizing carotid plaques based on their distinct stiffness and flow. In this study, we aim towards the characterization of carotid plaques for the ultimately reliable assessment of ischemic stroke risk based on plaque wall and flow biomarkers. We thus hypothesize that PWI can significantly reinforce the diagnostic capability of a conventional vascular ultrasound. The team assembled is highly multi-disciplinary encompassing expertise in ultrasound imaging, biomechanics, vascular radiology, pathology, neurology, vascular surgery and biostatistics. Following the proposed studies, this highly translational technology could be readily integrated in a standard sonogram to accurately inform carotid plaque stability and thus subsequent timely treatment.