Non-Invasive Liver Ablation Using Histotripsy: Preclinical Safety Study in an In Vivo Porcine Model.
This study investigates the safety profile for use of histotripsy, a non-invasive ultrasonic ablation method currently being developed for the treatment of liver cancer, for liver ablation in an in vivo porcine model. Histotripsy treatments were applied to the liver and hepatic veins of 22 porcine subjects, with half of the subjects receiving systemic heparinization. Vital signs (heart rate, blood pressure, temperature, electrocardiogram and SpO2) were monitored throughout the procedure and for 1 h post-treatment. Blood was drawn at six points during the experiment to analyze blood gases, liver function and free hemoglobin levels. All treatments were guided and monitored by real-time ultrasound imaging. After treatment, the tissue was harvested for histological analysis. Results indicated that histotripsy generated well-defined lesions inside the liver and around the treated hepatic veins of all subjects in both treatment groups. Vital signs and blood analysis revealed that animals responded well to histotripsy, with all animals surviving the treatment. One animal in the non-heparinized group had a transient increase in pH and decreases in blood pressure, heart rate and PCO2during the 15-min vessel treatment, with these changes returning to baseline levels soon after the treatment. Overall, the results indicate that histotripsy can safely be performed on the liver without the need for systemic heparinization, even in regions containing large hepatic vessels, supporting its future use for the treatment of liver cancer.
Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA; HistoSonics, Inc., Ann Arbor, Michigan, USA. Electronic address: evlaisav@umich.edu.
Eli
E
Vlaisavljevich
Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA; Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, Michigan, USA.
Gabe
G
Owens
Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA.
Jonathan
J
Lundt
HistoSonics, Inc., Ann Arbor, Michigan, USA.
Dejan
D
Teofilovic
Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA.
Kimberly
K
Ives
HistoSonics, Inc., Ann Arbor, Michigan, USA.
Alexander
A
Duryea
HistoSonics, Inc., Ann Arbor, Michigan, USA.
Jim
J
Bertolina
Department of Surgery, University of Michigan, Ann Arbor, Michigan, USA.
Theodore H
TH
Welling
Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA; Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, Michigan, USA.
Zhen
Z
Xu
D000818:Animals; D006498:Hepatectomy / Q000009:adverse effects / Q000379:methods*; D057086:High-Intensity Focused Ultrasound Ablation / Q000009:adverse effects / Q000379:methods*; D008099:Liver / Q000000981:diagnostic imaging / Q000473:pathology / Q000601:surgery*; D023421:Models, Animal; D013552:Swine; D016896:Treatment Outcome
Ablation; Cavitation; Histotripsy; Liver; Non-invasive; Safety; Ultrasound