Boiling Histotripsy Using Dual-Frequency Protocol on Murine Breast Tumor Model and Promotes Immune Activation

免疫系统 烧蚀 超声波 生物医学工程 乳腺癌 医学 材料科学 癌症研究 癌症 放射科 免疫学 内科学
作者
Tingting Qi,Yanshu Jing,Jie Deng,Juntao Chang,Weihao Sun,Rongzheng Yang,Xiaoning Liu,Quan Zhang,Mingxi Wan,Mingzhu Lu
出处
期刊:IEEE Transactions on Ultrasonics Ferroelectrics and Frequency Control [Institute of Electrical and Electronics Engineers]
卷期号:70 (12): 1773-1785 被引量:2
标识
DOI:10.1109/tuffc.2023.3326561
摘要

Histotripsy is an ultrasound-guided, noninvasive, nonthermal ablation therapy that can mechanically lyse target tissues. There have been no reports of enhanced histotripsy for large-volume triple-negative breast cancer (TNBC). This study aims to verify the ability of a novel approach of dual-frequency mode combined with two-stage millisecond-length ultrasound pulses (DF-TS) to accelerate the treatment of murine subcutaneous 4T1 tumors and determine immune changes after treatment. A custom-designed 1.1-/2.2-MHz two-element confocal-annular array was used to treat approximately 6-mm tumors under ultrasound guidance and real-time monitoring. Two-stage millisecond-length ultrasound pulses were used to generate approximate cuboid ablation volumes (diagonal 5-6 mm) within each tumor, with a dose of 100 pulses/point. Immune effects were characterized by changes of pro-inflammatory cytokine levels and infiltration levels of immune cells. In all targeted treatment areas, bubble cloud activity was visualized by ultrasound monitoring. The novel protocol resulted in elliptical and controllable sized lesions, reducing the number of scanning points, and was generally well tolerated. After treatment, tumor growth experienced a seven-day stagnation period, the survival period of mice was prolonged, and the levels of pro-inflammatory cytokines and immune cell infiltration increased. This study demonstrates that DF-TS boiling histotripsy (BH) has a noninvasive, efficient, and precise ablation ability for TNBC and potentially enhances immune responses.
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