학술논문

Mechanical High-Intensity Focused Ultrasound (Histotripsy) in Dogs With Spontaneously Occurring Soft Tissue Sarcomas
Document Type
Periodical
Source
IEEE Transactions on Biomedical Engineering IEEE Trans. Biomed. Eng. Biomedical Engineering, IEEE Transactions on. 70(3):768-779 Mar, 2023
Subject
Bioengineering
Computing and Processing
Components, Circuits, Devices and Systems
Communication, Networking and Broadcast Technologies
Tumors
Immune system
Dogs
Surgery
Ultrasonic imaging
Transducers
Cancer
Ablation
cancer
canine
focused ultrasound
histotripsy
immuno-oncology
soft tissue sarcoma
Language
ISSN
0018-9294
1558-2531
Abstract
Introduction: Histotripsy is a non-invasive focused ultrasound therapy that uses controlled acoustic cavitation to mechanically disintegrate tissue. To date, there are no reports investigating histotripsy for the treatment of soft tissue sarcoma (STS). Objective: This study aimed to investigate the in vivo feasibility of ablating STS with histotripsy and to characterize the impact of partial histotripsy ablation on the acute immunologic response in canine patients with spontaneous STS. Methods: A custom 500 kHz histotripsy system was used to treat ten dogs with naturally occurring STS. Four to six days after histotripsy, tumors were surgically resected. Safety was determined by monitoring vital signs during treatment and post-treatment physical examinations, routine lab work, and owners’ reports. Ablation was characterized using radiologic and histopathologic analyses. Systemic immunological impact was evaluated by measuring changes in cytokine concentrations, and tumor microenvironment changes were evaluated by characterizing changes in infiltration with tumor-associated macrophages (TAMs) and tumor-infiltrating lymphocytes (TILs) using multiplex immunohistochemistry and differential gene expression. Results: Results showed histotripsy ablation was achievable and well-tolerated in all ten dogs. Immunological results showed histotripsy induced pro-inflammatory changes in the tumor microenvironment. Conclusion & Significance: Overall, this study demonstrates histotripsy's potential as a precise, non-invasive treatment for STS.