Graduation Date

Spring 5-5-2018

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Programs

Cellular & Integrative Physiology

First Advisor

Thomas R. Porter

Abstract

Current treatment of acute myocardial infarction (AMI), which is the main pathophysiological event leading to death in the United States, has advanced considerably with the introduction of emergent percutaneous interventions, but there remains an urgent need for novel techniques to rapidly and accurately detect infarcted or ischemic tissue that results from AMI. Ultrasound contrast agents, also known as microbubbles (MB), have become commonplace in echocardiography. However, MBs are purely intravascular tracers and unable to cross endothelial barriers due to size. The limitations of MBs, namely size and short circulation times within the human body, led to the development of phase-change agents (PCA) or nanodroplets (ND). The size and stability of NDs introduced potential for development of applications that extend into the extravascular space. In this dissertation, we presented a novel method for detection and quantification of the infarct zone after AMI through the delayed contrast enhancement of a PCA. The first study characterized the properties of a ND formed from a MB precursor before in vitro and in vivo experiments were performed to understand the acoustic behavior of the particle. The results from this study demonstrated that a significant population of NDs < 250 nm in size could be formulated, and a commercial ultrasound system could be utilized to activate and visualize the PCA. The NDs also had significantly different acoustic behavior than their precursor.We also investigated the viability of the NDs for diagnostic imaging in the setting of AMI. A rodent and porcine model of AMI were utilized to test the use of the NDs to selectively enhance the infarcted tissue within the myocardium. Through refinement of the ultrasound imaging protocol, selective enhancement of infarction zone was demonstrated. Both the MB precursor and the ultrasound system utilized in the studies are currently used in clinical cardiology, thus this methodology could be brought from the bench to bedside to rapidly diagnose myocardial infarction in the acute setting.

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