Date of Award

5-2018

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Biomedical Engineering

Committee Chair

Michael Sturek

Committee Co-Chair

Ji-Xin Cheng

Committee Member 1

Craig Goergen

Committee Member 2

Nan Kong

Committee Member 3

Islam Bolad

Abstract

Coronary heart disease is the leading cause of death in the United States and the incidence is projected to increase by 18% by 2030. Yet, there remains a pressing clinical need for tools to detect vulnerable atherosclerotic plaques that can rupture and lead to major adverse cardiac events. Plaques that are considered most vulnerable for rupture are thin-capped fibroatheromas, which are grossly defined by hallmarks of a thin fibrous cap, a large lipid-rich necrotic core, inflammatory infiltrate, and positive remodeling. These plaques are often structurally non-obstructive to moderately obstructive, thus asymptomatic and clinically unidentifiable with routine angiography and stress testing. Rather, their vulnerability is a product of their chemical composition. We have developed a dual-mode intravascular catheter which is capable of producing co-registered cross-sectional images of arterial wall morphology and lipid content, via ultrasound and photoacoustic modes, respectively. Validation of this capability will rely on interrogation of atherosclerotic coronary arteries from humans and peripheral arteries from swine, with comparison to gold-standard histopathology and competing technologies. Here, we present ex vivo validation of a novel intravascular photoacoustic-ultrasound (IVPA-US) imaging catheter and the first systematic in vivo IVPA-US imaging study in a preclinical swine model with native disease, necessary benchmarks before proceeding with translation to clinic. We aim to ultimately demonstrate predictive utility to detect plaques that are vulnerable to rupture and trigger adverse cardiac events. In addition, this will be instrumental in elucidating the mechanism of plaque rupture, the development of preventive and therapeutic interventions, and reducing coronary heart disease-related mortality.

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