https://orcid.org/0000-0002-7033-1062
Histotripsy is the first noninvasive, nonthermal, nonionizing focused ultrasound treatment modality which could impact many patients as its full potential is realized. The term histotripsy stems from Greek root words ‘histo,’ meaning soft tissue and ‘tripsy,’ meaning breakdown, and originally appeared in print from the founding University of Michigan group in 2004 [Citation1]. Histotripsy falls within the broader group of focused ultrasound therapies, commonly referred to as high-intensity focused ultrasound (HIFU). Before histotripsy, regulatory approvals for a variety of clinical diseases have utilized a form of thermal HIFU ablation to destroy tissue. Histotripsy is differentiated by using short, high-amplitude pulses that lead to mechanical breakdown of tissue. This unique method for a noninvasive therapy confers benefits for nontarget tissue sparing and positive immunologic effects when treating tumors [Citation2,Citation3]. In October 2023, the first FDA approval for histotripsy was granted for the treatment of liver tumors based on data from the #HOPE4LIVER trials (NCT04572633 and NCT04573881) [Citation4].
This special collection follows the first-in-human trial of hepatic histotripsy (THERESA) and two previous excellent reviews on histotripsy published in the journal and brings together many of the researchers pushing the field forward [Citation2,Citation3,Citation5]. The authors discuss a wide variety of applications currently being studied for translation to humans, while also describing existing challenges to ensure histotripsy can realize its potential for patients.
The issue begins with a review of the spectrum of histotripsy techniques by Williams, et al. outlining the various mechanisms and their potential clinical applications [Citation6]. This provides an excellent baseline of knowledge for those beginning clinical adoption. With the recent FDA approval for liver tumor treatment and upcoming trials in the space focusing on the abdomen, articles describing preclinical development of abdominal histotripsy by Falk, et al. and challenges and solutions for aberration of the ultrasound field when delivering ultrasound energy to the abdomen by Yeats, et al. follow [Citation7,Citation8]. Gannon, et al. subsequently describe the feasibility of pancreas ablation in a swine model in an original research article [Citation9].
While the abdomen has been an early focus for histotripsy development, there is significant potential in extra-abdominal applications. Veterinary patients provide both the ability to treat treasured companion animals and help to inform human translation. Two articles in this issue explore musculoskeletal applications in veterinary patients. Hay, et al. provide a review of histotripsy use in canine veterinary patients and how this informs human treatments [Citation10]. This is followed by a first-in-cat report of the feasibility of histotripsy for the treatment of injection site sarcomas by Ruger, et al. [Citation11].
In addition, histotripsy has the potential to treat a variety of lesions in the brain. Duclos, et al. provide a report on transcranial histotripsy parameters in murine brain tumor models [Citation12].
Due to its mechanism of tissue destruction, histotripsy shows potential in the treatment of cancer that differs from other available focal therapies. Worlikar, et al. summarize insights from preclinical cancer studies with histotripsy [Citation13]. Two original research studies provide insights into the mechanism of cell death following histotripsy, a critical step forward in the field. The first by Iwanicki, et al. utilizes neuroblastoma xenografts and the second by Hay, et al. utilizes a canine osteosarcoma model [Citation14,Citation15].
Finally, one of the areas of greatest excitement in the development of histotripsy is local and systemic immunologic responses. To provide further understanding, two groups describe the existing knowledge and potential in this area. Osada, et al. outline the rationale for exploring the immune effects of histotripsy [Citation16]. Finally, Imran, et al. describe how histotripsy modulates the tumor microenvironment and improves systemic anti-tumor immune responses [Citation17].
This collection of articles provides an understanding of the current state of the field, while also outlaying potential future applications. We hope that you find it both informational and inspiring as the technology pushes into clinical adoption.
Disclosures
SL: Hold shares and ordinary options in FUSMobile, Clinical consultant FUSMobile.
TZ: Shareholder and research support, Histosonics; Consultant and research support, Ethicon; Consultant, Elephas.
Additional information
Funding
References
- Xu Z, Ludomirsky A, Eun LY, et al. Controlled ultrasound tissue erosion. IEEE Trans Ultrason Ferroelectr Freq Control. 2004;51(6):726–736. doi: 10.1109/tuffc.2004.1308731.
- Khokhlova VA, Fowlkes JB, Roberts WW, et al. Histotripsy methods in mechanical disintegration of tissue: towards clinical applications. Int J Hyperthermia. 2015;31(2):145–162. doi: 10.3109/02656736.2015.1007538.
- Xu Z, Hall TL, Vlaisavljevich E, et al. Histotripsy: the first noninvasive, non-ionizing, non-thermal ablation technique based on ultrasound. Int J Hyperthermia. 2021;38(1):561–575. doi: 10.1080/02656736.2021.1905189.
- Wah TM, Pech M, Thormann M, et al. A multi-Centre, single arm, non-randomized, prospective european trial to evaluate the safety and efficacy of the HistoSonics system in the treatment of primary and metastatic liver cancers (#HOPE4LIVER). Cardiovasc Intervent Radiol. 2023;46(2):259–267. doi: 10.1007/s00270-022-03309-6.
- Vidal-Jove J, Serres X, Vlaisavljevich E, et al. First-in-man histotripsy of hepatic tumors: the THERESA trial, a feasibility study. Int J Hyperthermia. 2022;39(1):1115–1123. doi: 10.1080/02656736.2022.2112309.
- Williams RP, Simon JC, Khokhlova VA, et al. The histotripsy spectrum: differences and similarities in techniques and instrumentation. Int J Hyperthermia. 2023;40(1):2233720. doi: 10.1080/02656736.2023.2233720.
- Falk KL, Laeseke PF, Kisting MA, et al. Clinical translation of abdominal histotripsy: a review of preclinical studies in large animal models. Int J Hyperthermia. 2023;40(1):2272065.
- Yeats E, Hall TL. Aberration correction in abdominal histotripsy. Int J Hyperthermia. 2023;40(1):2266594. doi: 10.1080/02656736.2023.2266594.
- Gannon J, Imran KM, Hendricks-Wenger A, et al. Ultrasound-guided noninvasive pancreas ablation using histotripsy: feasibility study in an in vivo porcine model. Int J Hyperthermia. 2023;40(1):2247187.
- Hay AN, Ruger L, Hsueh A, et al. A review of the development of histotripsy for extremity tumor ablation with a canine comparative oncology model to inform human treatments. Int J Hyperthermia. 2023;40(1):2274802.
- Ruger L, Yang E, Coutermarsh-Ott S, et al. Histotripsy ablation for the treatment of feline injection site sarcomas: a first-in-cat in vivo feasibility study. Int J Hyperthermia. 2023;40(1):2210272.
- Duclos S, Golin A, Fox A, et al. Transcranial histotripsy parameter study in primary and metastatic murine brain tumor models. Int J Hyperthermia. 2023;40(1):2237218.
- Worlikar T, Hall T, Zhang M, et al. Insights from in vivo preclinical cancer studies with histotripsy. Int J Hyperthermia. 2024;41(1):2297650.
- Iwanicki I, Wu LL, Flores-Guzman F, et al. Histotripsy induces apoptosis and reduces hypoxia in a neuroblastoma xenograft model. Int J Hyperthermia. 2023;40(1):2222941.
- Hay AN, Vickers ER, Patwardhan M, et al. Investigating cell death responses associated with histotripsy ablation of canine osteosarcoma. Int J Hyperthermia. 2023;40(1):2279027.
- Osada T, Jiang X, Zhao Y, et al. The use of histotripsy as intratumoral immunotherapy beyond tissue ablation-the rationale for exploring the immune effects of histotripsy. Int J Hyperthermia. 2023;40(1):2263672.
- Imran KM, Ganguly A, Paul T, et al. Magic bubbles: utilizing histotripsy to modulate the tumor microenvironment and improve systemic anti-tumor immune responses. Int J Hyperthermia. 2023;40(1):2244206.