Ultrasound and Microbubbles: Modulating and Quantifying Blood Flow in Liver Cancers

Abstract

Contrast-enhanced ultrasound (CEUS) is an ever-developing field, uniquely branching between both diagnostic and therapeutic applications. In this body of work, we present several investigations on how ultrasound and microbubbles can be leveraged as a theranostic tool for the improved treatment of primary liver cancer, or hepatocellular carcinomas. These works emphasize clinical translation through the use of clinically approved technologies and agents, aiming for the rapid adoption of these approaches to combat the ever-evolving challenge of liver cancer. We begin with a brief introduction of the current clinical state of liver cancer, existing diagnostic and therapeutic strategies, and role of CEUS in these areas as explored in this thesis (Chapter 1). We then investigate the clinical use of CEUS to develop much needed repeatable metrics of tumor blood flow that enable accurate longitudinal evaluations (Chapter 2). We then describe quantitative diagnostic tools for the early detection of hepatocellular carcinoma and evaluate them in a clinical patient study (Chapter 3). Using these important tumor blood flow quantification methods, we then investigate use of clinical ultrasound scanners image-guided for tumor blood flow alteration for enhanced drug penetration in a murine model of hepatocellular carcinoma (Chapter 4). We then describe the temporal and spatial dynamics of cavitation-induced tumor perfusion loss for a greater understanding of how acoustic conditions influence this phenomenon to design more effective therapeutic ultrasound-mediated cavitation strategies (Chapter 5). We discuss ongoing work investigating the role of ultrasound cavitation treatments in augmenting immunotherapy-based approaches in an orthotopic murine model of liver cancer (Chapter 6). We conclude with a summary of the accomplishments and future directions of this work (Chapter 7).