Ultrasound-guided noninvasive pancreas ablation using histotripsy: feasibility study in an in vivo porcine model

Abstract

Pancreatic cancer is a malignant disease associated with poor survival and nearly 80% present with unresectable tumors. Treatments such as chemotherapy and radiation therapy have shown overall improved survival benefits, albeit limited. Histotripsy is a noninvasive, non-ionizing, and non-thermal focused ultrasound ablation modality that has shown efficacy in treating hepatic tumors and other malignancies. In this novel study, we investigate histotripsy for noninvasive pancreas ablation in a pig model. In two studies, histotripsy was applied to the healthy pancreas in 11 pigs using a custom 32-element, 500 kHz histotripsy transducer attached to a clinical histotripsy system, with treatments guided by real-time ultrasound imaging. A pilot study was conducted in 3 fasted pigs with histotripsy applied at a pulse repetition frequency (PRF) of 500 Hz. Results showed no pancreas visualization on coaxial ultrasound imaging due to overlying intestinal gas, resulting in off-target injury and no pancreas damage. To minimize gas, a second group of pigs (n = 8) were fed a custard diet containing simethicone and bisacodyl. Pigs were euthanized immediately (n = 4) or survived for 1 week (n = 4) post-treatment. Damage to the pancreas and surrounding tissue was characterized using gross morphology, histological analysis, and CT imaging. Results showed histotripsy bubble clouds were generated inside pancreases that were visually maintained on coaxial ultrasound (n = 4), with 2 pigs exhibiting off-target damage. For chronic animals, results showed the treatments were well-tolerated with no complication signs or changes in blood markers. This study provides initial evidence suggesting histotripsy’s potential for noninvasive pancreas ablation and warrants further evaluation in more comprehensive studies.

Keywords:

• Pancreas
• pancreatic cancer
• histotripsy
• large animal model
• focused ultrasound

Acknowledgements

The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or any other funding agency. The authors would like to thank HistoSonics, Inc. for providing the clinical histotripsy cart for this study. This article includes research previously included in a thesis entitled “Determining the Oncological and Immunological Effects of Histotripsy for Tumor Ablation” authored by Alissa Hendricks-Wenger.

Disclosure statement

Author Dr. Eli Vlaisavljevich has an ongoing research partnership and financial relationship with HistoSonics, Inc. Author Dr. Joan Vidal-Jove is a consultant for Advanced Microbubbles Inc., for Chongqing Haifu Medical Technology Co. Ltd., and for HistoSonics, Inc. Author Lauren Ruger has an ongoing consulting relationship with Theraclion. No other authors have a conflict of interest to report.

Data availability statement

The data presented in this study are available on request from the corresponding authors.

Additional information

Funding

This work was supported by the Virginia Maryland College of Veterinary Medicine; The Virginia Tech Institute for Critical Technology and Applied Sciences Center for Engineered Health; The National Institutes of Health (EB028429, CA269811); and the Focused Ultrasound Foundation (FUF61057). Author Jessica Gannon was supported by a National Science Foundation Graduate Research Fellowship for the duration of this work.