Ultrasound Imaging Innovations for Visualization and Quantification of Vascular Biomarkers

Abstract

The existence of plaque in the carotid arteries, which provide circulation to the brain, is a known risk for stroke and dementia. Alas, this risk factor is present in 25% of the adult population. Proper assessment of carotid plaque may play a significant role in preventing and managing stroke and dementia. However, current plaque assessment routines have known limitations in assessing individual risk for future cardiovascular events. There is a practical need to derive new vascular biomarkers that are indicative of cardiovascular risk based on hemodynamic information. Nonetheless, the derivation of these biomarkers is not a trivial technical task because none of the existing clinical imaging modalities have adequate time resolution to track the spatiotemporal dynamics of arterial blood flow that is pulsatile in nature. The goal of this dissertation is to devise a new ultrasound imaging framework to measure vascular biomarkers related to turbulent flow, intra-plaque microvasculature, and blood flow rate. Central to the proposed framework is the use of high frame rate ultrasound (HiFRUS) imaging principles to track hemodynamic events at fine temporal resolution (through using frame rates of greater than 1000 frames per second). The existence of turbulent flow and intra-plaque microvessels, as well as anomalous blood flow rate, are all closely related to the formation and progression of carotid plaque. Therefore, quantifying these biomarkers can improve the identification of individuals with carotid plaque who are at risk for future cardiovascular events. To facilitate the testing and the implementation of the proposed imaging algorithms, this dissertation has included the development of new experimental models (in the form of flow phantoms) and a new HiFRUS imaging platform with live scanning and on-demand playback functionalities. Pilot studies were also carried out on rats and human volunteers. Results generally demonstrated the real-time performance and the practical efficacy of the proposed algorithms. The proposed ultrasound imaging framework is expected to improve carotid plaque risk classification and, in turn, facilitate timely identification of at-risk individuals. It may also be used to derive new insights on carotid plaque formation and progression to aid disease management and the development of personalized treatment strategies.