Histotripsy is a non-invasive and non-thermal focused ultrasound therapy that can be used to ablate tissue within the body while overcoming many of the limitations of thermal ablation. Histotripsy utilizes short-duration, high pressure ultrasound pulses to create a cavitation bubble cloud of numerous rapidly expanding and collapsing bubbles, which cause mechanical stress on the targeted region. Histotripsy contains multiple subtypes including intrinsic threshold, shock scattering, and boiling histotripsy, where intrinsic threshold histotripsy utilizes single cycle pulses focused to a single point to create a bubble cloud from the peak negative pressure (p- ≥ 25 MPa for water-based tissues). Nanoparticle-mediated histotripsy (NMH) uses perfluorocarbon-filled nanoparticles to create bubble clouds at lower pressures than that of the intrinsic threshold of histotripsy. Prior studies have shown that nanodroplets (NDs) and nanocone clusters (NCCs) both reduce the cavitation threshold, but further investigation on different parameters to optimize treatments have not fully been studied. Additional research is needed for the characterization of these nanoparticles with different pulsing parameters such as cycle number and frequency in order to better predict and understand the mechanisms underlying NMH. In this thesis, I investigate the ability of new nanodroplets and nanocone clusters to reduce histotripsy cavitation threshold with NMH. I also investigate the effect that multi-cycle pulsing parameters have on NMH and stable bubble formation from acoustic droplet vaporization (ADV) for nancone clusters. The culmination of this thesis will advance our understanding of the behavior of acoustically-active nanoparticles when exposed to varied pulsing schemes and frequencies. This knowledge will allow for the further investigation of more efficient, effective, and safe methods for clinical focused ultrasound therapies. / Master of Science / Histotripsy is a non-invasive and non-thermal focused ultrasound therapy that can be used to destroy targeted tissue within the body. Histotripsy is currently being developed for non-invasive and non-thermal cancerous tissue destruction with the first-in-man trial having been conducted within the last year for the treatment of liver tumors. Histotripsy utilizes high-pressure, short-duration pulses focused to a single region to create a cloud of bubbles that are rapidly expanding and collapsing which causes mechanical damage to the targeted cells. Nanoparticle-mediated histotripsy (NMH) has been developed to utilize nanoparticles to reduce the pressure needed to induce cavitation. Despite many studies and advances in histotripsy, there are many areas within the topic that need additional research to better understand the capabilities of the treatment method. This additional research is crucial in allowing for the development of new nanoparticles, faster treatment times, and new parameters that could allow for more precision near critical structures. In this thesis, I investigate the ability of new nanoparticles to reduce histotripsy cavitation threshold with NMH. I also investigate the effect that multi-cycle pulsing parameters have on NMH and stable bubble formation for nanoparticles. The culmination of this thesis will advance our understanding of the behavior of acoustically-active nanoparticles when exposed to varied pulsing schemes and frequencies. This knowledge will allow for the further investigation of more efficient, effective, and safe methods for clinical focused ultrasound therapies.