O16 - Development of High Frequency Histotripsy for the Ablation of Oral Tumors

Introduction: : Oral tumors are one of the most commonly diagnosed tumors worldwide in human and canine patients. Standard of care for oral tumors is surgical resection and adjuvant radiation, often leading to facial disfigurement and has shown to be a negatively impacting factor associated with quality of life. Surgical resection involves high risk of infection and damage to critical structures in the oral cavity. Certain oral tumors are unresectable due to critical structures and are associated with poor prognosis, emphasizing the need for less invasive treatments that preserve oral function.

Histotripsy is a non-invasive, non-thermal, non-ionizing, and image-guided focused ultrasound (FUS) ablation method that uses acoustic cavitation to ablate tissue into acellular debris. High pressure ultrasound pulses converge at the transducer focus at a targeted region within tissue to generate a cavitation bubble cloud capable of mechanically ablating tissue. Current clinical histotripsy transducers are large, cart-based systems typically ranging from 500kHz to 1MHz. These systems are optimized for large, deep targets like the liver. In this study, we investigate the development of miniaturized histotripsy systems that enables high precision histotripsy treatments for smaller, more shallow targets such as oral tumors.

Materials and

Methods: : Excised canine oral tumors were embedded in tissue phantom gels and treated with either a 6.3 MHz (Fig.1A) or a 2MHz (Fig.1B) histotripsy transducer at 1000 Hz pulse repetition frequency (PRF), 10 cycles, and a dose of 2,000 pulses per point (PPP). Treatment planning and monitoring was performed using a coaxially aligned 30 MHz ultrasound (US) imaging probe. Posttreatment histological analysis was conducted with hematoxylin and eosin (H&E) staining.

Results, Conclusions, and Discussions:: A well confined bubble cloud was visualized in the oral tumor with US imaging during treatment (Fig.1C). A hypoechoic region was observed after the treatment, suggesting the liquifying and ablation of the tumor. Histology of the tumor with H&E staining showed precise, delineated ablations that similarly resembled the applied treatment volume (Fig.1D). There were no viable cells remaining within the ablation volume. The 2 MHz and 6.3 MHz transducer were both able to ablate the oral tumor at an approximate rate of 2.67 mm^3/minute 0.36 mm^3/minute respectively. Both transducers successfully ablated excised canine oral tumors. The 2 MHz transducer had a faster ablation rate while the 6.3 MHz was able to ablate more precisely. Ongoing studies are underway to analyze the acoustic windows in human and canine patients with oral tumors to determine the optimal frequency for a clinical system. Additionally, ongoing studies are looking into different approaches to improve ablation efficiency, such as the development of steerable array histotripsy transducers. Overall, this study shows the feasibility of ablating oral tumors with histotripsy for the first time and provides insight on optimizing histotripsy devices for oral tumor ablation

Acknowledgements and/or References (Optional):: The authors thank the Focused Ultrasound Foundation, the Virginia-Maryland College of Veterinary Medicine, and all the patients who have supported this study.