Quantitative Monitoring of Tissue Fractionation by Cavitation-Based High-Intensity Focused Ultrasound

Abstract

High-intensity focused ultrasound (HIFU) can non-invasively induce cavitation within tissue, resulting in mechanical tissue damage that ranges from mild disruption with petechial hemorrhage to complete liquefaction at a subcellular scale. This capability positions HIFU as an increasingly promising and valuable tool in various clinical applications, such as enhancing drug delivery through increased tissue permeability, modulating the tumor microenvironment, and ablating tumors. In this dissertation, the quantitative monitoring of residual cavitation bubbles was investigated based on ultrasound Doppler technique. The research focuses on two main HIFU regimes that induce mechanical tissue fractionation: less destructive pulsed HIFU (pHIFU) and boiling histotripsy (BH), each with distinct mechanism of inducing cavitation and varying level of subsequent tissue damage. Doppler-based quantitative metrics for each regime were developed and correlated with tissue damage or liquefaction levels evaluated through histological image analysis. Particularly, a new Doppler technique based on dynamic mode decomposition (DMD) for rapidly dissolving cavitation bubbles following the HIFU pulse was introduced, with demonstrations in silico and ex vivo, where DMD showed superior performance compared to widely used techniques (Chapter 2). This DMD-based Doppler technique was then applied to surgically exposed in vivo tissues, showing a strong correlation between DMD-derived bubble dissolution rate and tissue damage level (Chapter 3). Doppler measurements were also conducted to capture the swiftly moving residual bubbles following BH pulses in ex vivo experiments, displaying gradually increasing and saturating in observed maximum velocity as treatment progressed (Chapter 4). Similar measurements, conducted on in vivo abdominal tissue in pigs, confirmed a strong correlation between maximum velocity and level of tissue liquefactions (Chapter 5).