Enhancing Histotripsy Focused Ultrasound Therapy for Treatment of Fibrous Tissues

Abstract

Histotripsy is a pulsed focused ultrasound therapy that ablates tissue through the rapid expansion and collapse of nanoscale endogenous bubbles due to cavitation, imparting strain that leads to mechanical disintegration. While histotripsy has been highly effective in treating various kinds of tissues, its efficacy in ablating tough, fibrous tissues—such as those found in benign prostatic hyperplasia and uterine fibroids—is limited. Treating these tissues often requires an impractically high dose, making clinical application challenging.One reason for inefficacy is inappropriate parameters used in treating fibrous tissue leading to greater memory effects than anticipated. This leads to the repeated growth of bubbles in a single location rather than their formation across multiple locations. This results in inefficient tissue disruption instead of a continuous liquefied lesion. Furthermore, many optimization studies have been conducted in viscoelastic phantom models, such as agarose, which do not adequately mimic the properties of fibrous tissue. Histotripsy has several modalities, including intrinsic threshold histotripsy, shock scattering histotripsy, and boiling histotripsy, each with distinct ablation mechanisms, making the parameter space for optimization extensive. To address the challenges of treating fibrous tissue, this dissertation focuses on hardware development to enhance histotripsy treatment, creating phantom models that closely mimic fibrous tissue properties, and the identification of alternative parameters that improve the liquefaction of tough fibrous tissue. Additionally, it aims to study bubble mechanics in fibrous tissue-mimicking phantoms to explain the treatment outcomes better and establish quantitative metrics for determining effective doses across different parameters. By optimizing histotripsy for fibrous tissue ablation, this research seeks to expand its clinical applicability and improve treatment efficacy for conditions involving tough, fibrous tissues.