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Öğe Bubble cloud behavior and ablation capacity for histotripsy generated from intrinsic or artificial cavitation nuclei(Elsevier Science Inc, 2021) Edsall, Connor; Khan, Zerin Mahzabin; Mancia, Lauren; Hall, Sarah; Mustafa, Waleed; Johnsen, Eric; Klibanov, Alexander L.; Yüksel Durmaz, Yasemin; Vlaisavljevich, EliThe study described here examined the effects of cavitation nuclei characteristics on histotripsy. Highspeed optical imaging was used to compare bubble cloud behavior and ablation capacity for histotripsy generated from intrinsic and artificial cavitation nuclei (gas-filled microbubbles, fluid-filled nanocones). Results showed a significant decrease in the cavitation threshold for microbubbles and nanocones compared with intrinsic-nuclei controls, with predictable and well-defined bubble clouds generated in all cases. Red blood cell experiments showed complete ablations for intrinsic and nanocone phantoms, but only partial ablation in microbubble phantoms. Results also revealed a lower rate of ablation in artificial-nuclei phantoms because of reduced bubble expansion (and corresponding decreases in stress and strain). Overall, this study demonstrates the potential of using artificial nuclei to reduce the histotripsy cavitation threshold while highlighting differences in the bubble cloud behavior and ablation capacity that need to be considered in the future development of these approaches.Öğe Nanoparticle-mediated histotripsy using dual-frequency pulsing methods(2024) Edsall, Connor; Huynh, Laura; Mustafa, Waleed; Hall, Timothy L.; Yüksel Durmaz, Yasemin; Vlaisavljevich, EliObjective: Nanoparticle-mediated histotripsy (NMH) is a novel ablation method that combines nanoparticles as artificial cavitation nuclei with focused ultrasound pulsing to achieve targeted, non-invasive, and cell-selective tumor ablation. The study described here examined the effect of dual-frequency histotripsy pulsing on the cavitation threshold, bubble cloud characteristics, and ablative efficiency in NMH. High-speed optical imaging was used to analyze bubble cloud characteristics and to measure ablation efficiency for NMH inside agarose tissue phantoms containing perfluorohexane-filled nanocone clusters, which were previously developed to reduce the histotripsy cavitation threshold for NMH. Methods: Dual-frequency histotripsy pulsing was applied at a 1:1 pressure ratio using a modular 500 kHz and 3 MHz dual-frequency array transducer. Optical imaging results revealed predictable, well-defined bubble clouds generated for all tested cases with similar reductions in the cavitation thresholds observed for single-frequency and dual-frequency pulsing. Results: Dual-frequency pulsing was seen to nucleate small, dense clouds in agarose phantoms, intermediate in size of their component frequencies but closer in area to that of the higher component frequency. Red blood cell experiments revealed complete ablations were generated by dual-frequency NMH in all phantoms in <1500 pulses. This result was a significant increase in ablation efficiency compared with the ?4000 pulses required in prior single-frequency NMH studies. Conclusion: Overall, this study indicates the potential for using dual-frequency histotripsy methods to increase the ablation efficacy of NMH.











