Histotripsy methods in mechanical disintegration of tissue: Towards clinical applications

Abstract

In high intensity focused ultrasound (HIFU) therapy, an ultrasound beam is focused within the body to locally affect the targeted site without damaging intervening tissues. The most common HIFU regime is thermal ablation. Recently there has been increasing interest in generating purely mechanical lesions in tissue (histotripsy). This paper provides an overview of several studies on the development of histotripsy methods toward clinical applications. Two histotripsy approaches and examples of their applications are presented. In one approach, sequences of high-amplitude, short (microsecond-long), focused ultrasound pulses periodically produce dense, energetic bubble clouds that mechanically disintegrate tissue. In an alternative approach, longer (millisecond-long) pulses with shock fronts generate boiling bubbles and the interaction of shock fronts with the resulting vapour cavity causes tissue disintegration. Recent preclinical studies on histotripsy are reviewed for treating benign prostatic hyperplasia (BPH), liver and kidney tumours, kidney stone fragmentation, enhancing anti-tumour immune response, and tissue decellularisation for regenerative medicine applications. Potential clinical advantages of the histotripsy methods are discussed. Histotripsy methods can be used to mechanically ablate a wide variety of tissues, whilst selectivity sparing structures such as large vessels. Both ultrasound and MR imaging can be used for targeting and monitoring the treatment in real time. Although the two approaches utilise different mechanisms for tissue disintegration, both have many of the same advantages and offer a promising alternative method of non-invasive surgery.

• High intensity focused ultrasound
• physics
• ultrasound

Acknowledgements

The authors, as a part of large teams at the University of Michigan, the University of Washington, and Moscow State University, would like to acknowledge many students, post-doctoral fellows, researchers, and collaborators who have contributed to the development of histotripsy methods.

Declaration of interest

This work was supported by the US National Institutes of Health (R01 DK091267, EB007643, EB008998, CA134579; P01DK043881, K01EB015745, T32DK007779), the Russian Science Foundation (14-12-00974), the American Cancer Society (RSG-13-101-01-CCE), the Hartwell Foundation, the Focus Ultrasound Foundation, and NSBRI through NASA NCC 9-58. The authors alone are responsible for the content and writing of the paper.