{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T12:08:05Z","timestamp":1791461285982,"version":"4.3.4"},"reference-count":124,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Histotripsy is a novel, noninvasive, non-thermal technology invented in 2004 for the precise destruction of biologic tissue. It offers a powerful alternative to more conventional thermal or surgical interventions. Using short-pulse, low-duty cycle ultrasonic waves, histotripsy creates cavitation bubble clouds that selectively and precisely destroy targeted tissue in a predefined volume while sparing critical structures like bile ducts, ureters, and blood vessels. Such precision is of value when treating tumors near vital structures. The FDA has cleared histotripsy for the treatment of all liver tumors. Major medical centers are currently spearheading clinical trials, and some institutions have already integrated the technology into patient care. Histotripsy is now being studied for a host of other cancers, including primary kidney and pancreatic tumors. Preclinical murine and porcine models have already revealed promising outcomes. One of histotripsy\u2019s primary advantages is its non-thermal mechanical actuation. This feature allows it to circumvent the limitations of heat-based techniques, including the heat sink effect and unpredictable treatment margins near sensitive tissues. In addition to its non-invasive ablative capacities, it is being preliminarily explored for its potential to induce immunomodulation and promote abscopal inhibition of distant, untreated tumors through CD8+ T cell responses. Thus, it may provide a multilayered therapeutic effect in the treatment of cancer. Histotripsy has the potential to improve precision and outcomes across a multitude of specialties, from oncology to cardiovascular medicine. Continued trials are crucial to further expand its applications and validate its long-term efficacy. Due to the speed of recent developments, the goal of this review is to provide a comprehensive and updated overview of histotripsy. It will explore its physics-based mechanisms, differentiating it from similar technologies, discuss its clinical applications, and examine its advantages, limitations, and future.<\/jats:p>","DOI":"10.3390\/cancers17152548","type":"journal-article","created":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T11:54:51Z","timestamp":1754308491000},"page":"2548","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Breaking Barriers with Sound: The Implementation of Histotripsy in Cancer"],"prefix":"10.3390","volume":"17","author":[{"given":"Ashutosh P.","family":"Raman","sequence":"first","affiliation":[{"name":"Harvard Medical School, Boston, MA 02115, USA"},{"name":"Harvard-MIT Division of Health Sciences and Technology, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3667-8908","authenticated-orcid":false,"given":"Parker L.","family":"Kotlarz","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, MA 02115, USA"},{"name":"Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA 02129, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9301-9928","authenticated-orcid":false,"given":"Alexis E.","family":"Giff","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine A.","family":"Goundry","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, MA 02115, USA"},{"name":"Harvard-MIT Division of Health Sciences and Technology, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Laeseke","sequence":"additional","affiliation":[{"name":"Department of Radiology, University of Wisconsin, Madison, WI 53705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica M. Knavel","family":"Koepsel","sequence":"additional","affiliation":[{"name":"Department of Radiology, University of Wisconsin, Madison, WI 53705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2459-5591","authenticated-orcid":false,"given":"Mosa","family":"Alhamami","sequence":"additional","affiliation":[{"name":"Department of Radiology, University of Wisconsin, Madison, WI 53705, USA"},{"name":"Department of Medical Physics, University of Wisconsin, Madison, WI 53705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2230-7199","authenticated-orcid":false,"given":"Dania","family":"Daye","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, MA 02115, USA"},{"name":"Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA 02129, USA"},{"name":"Department of Radiology, University of Wisconsin, Madison, WI 53705, USA"},{"name":"Department of Medical Physics, University of Wisconsin, Madison, WI 53705, USA"},{"name":"Department of Radiology, Massachusetts General Hospital, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,1]]},"reference":[{"key":"ref_1","first-page":"394","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"200","DOI":"10.14740\/jocmr4902","article-title":"Prognostic Scores and Survival Rates by Etiology of Hepatocellular Carcinoma: A Review","volume":"15","author":"Vilchez","year":"2023","journal-title":"J. Clin. Med. Res."},{"key":"ref_3","first-page":"230","article-title":"Pancreatic Adenocarcinoma","volume":"115","author":"Vareedayah","year":"2018","journal-title":"Mo. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1186\/s40425-017-0283-9","article-title":"The immune system in cancer metastasis: Friend or foe?","volume":"5","author":"Janssen","year":"2017","journal-title":"J. Immunother. Cancer"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"597","DOI":"10.2217\/bmm.12.69","article-title":"Early diagnosis of pancreatic cancer: Challenges and new developments","volume":"6","author":"Kaur","year":"2012","journal-title":"Biomark. Med."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Li, S., Zhang, G., Lu, Y., Zhao, T., Gao, C., Liu, W., Piao, Y., Chen, Y., Huang, C., and Chang, A. (2022). Perioperative Serum Scoring Systems Predict Early Recurrence and Poor Prognosis of Resectable Pancreatic Cancer. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.841819"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e7018","DOI":"10.1002\/cam4.7018","article-title":"Impact of inflammation and the immune system on hepatocellular carcinoma recurrence after hepatectomy","volume":"13","author":"She","year":"2024","journal-title":"Cancer Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1604","DOI":"10.4251\/wjgo.v14.i9.1604","article-title":"Advances in postoperative adjuvant therapy for primary liver cancer","volume":"14","author":"Zeng","year":"2022","journal-title":"World J. Gastrointest. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e2203699","DOI":"10.1002\/advs.202203699","article-title":"The Single-Cell Landscape of Intratumoral Heterogeneity and The Immunosuppressive Microenvironment in Liver and Brain Metastases of Breast Cancer","volume":"10","author":"Zou","year":"2023","journal-title":"Adv. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1186\/s40425-018-0398-7","article-title":"Combining surgery and immunotherapy: Turning an immunosuppressive effect into a therapeutic opportunity","volume":"6","author":"Bakos","year":"2018","journal-title":"J. Immunother. Cancer"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"20211360","DOI":"10.1259\/bjr.20211360","article-title":"Interventional oncology: New techniques and new devices","volume":"95","author":"Breuer","year":"2022","journal-title":"Br. J. Radiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"302","DOI":"10.6004\/jnccn.2019.0019","article-title":"Guidelines Insights: Hepatobiliary Cancers, Version 2.2019","volume":"17","author":"Benson","year":"2019","journal-title":"J. Natl. Compr. Cancer Netw."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1111\/1754-9485.13613","article-title":"Thermal ablation of hepatocellular carcinoma","volume":"67","author":"Crocetti","year":"2023","journal-title":"J. Med. Imaging Radiat. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1055\/s-2006-941442","article-title":"Complications of hepatic chemoembolization","volume":"23","author":"Clark","year":"2006","journal-title":"Semin. Interv. Radiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1148\/radiol.2262012198","article-title":"Treatment of focal liver tumors with percutaneous radio-frequency ablation: Complications encountered in a multicenter study","volume":"226","author":"Livraghi","year":"2003","journal-title":"Radiology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.jhep.2017.02.022","article-title":"Stereotactic body radiotherapy vs. TACE or RFA as a bridge to transplant in patients with hepatocellular carcinoma. An intention-to-treat analysis","volume":"67","author":"Sapisochin","year":"2017","journal-title":"J. Hepatol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"46","DOI":"10.4293\/108680812X13517013317716","article-title":"Complications of liver resection: Laparoscopic versus open procedures","volume":"17","author":"Slakey","year":"2013","journal-title":"JSLS"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e580","DOI":"10.1097\/MD.0000000000000580","article-title":"Heat sink effect on tumor ablation characteristics as observed in monopolar radiofrequency, bipolar radiofrequency, and microwave, using ex vivo calf liver model","volume":"94","author":"Pillai","year":"2015","journal-title":"Medicine"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1109\/TUFFC.2009.1131","article-title":"Quantitative ultrasound backscatter for pulsed cavitational ultrasound therapy- histotripsy","volume":"56","author":"Wang","year":"2009","journal-title":"IEEE Trans. Ultrason. Ferroelectr. Freq. Control"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1088\/0031-9155\/59\/2\/253","article-title":"Effects of tissue mechanical properties on susceptibility to histotripsy-induced tissue damage","volume":"59","author":"Vlaisavljevich","year":"2014","journal-title":"Phys. Med. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1080\/02656736.2021.1905189","article-title":"Histotripsy: The first noninvasive, non-ionizing, non-thermal ablation technique based on ultrasound","volume":"38","author":"Xu","year":"2021","journal-title":"Int. J. Hyperth."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2244206","DOI":"10.1080\/02656736.2023.2244206","article-title":"Magic bubbles: Utilizing histotripsy to modulate the tumor microenvironment and improve systemic anti-tumor immune responses","volume":"40","author":"Imran","year":"2023","journal-title":"Int. J. Hyperth."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1109\/TUFFC.2004.1308731","article-title":"Controlled ultrasound tissue erosion","volume":"51","author":"Xu","year":"2004","journal-title":"IEEE Trans. Ultrason. Ferroelectr. Freq. Control"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e233051","DOI":"10.1148\/radiol.233051","article-title":"The #HOPE4LIVER Single-Arm Pivotal Trial for Histotripsy of Primary and Metastatic Liver Tumors","volume":"312","author":"Wiggermann","year":"2024","journal-title":"Radiology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"102000","DOI":"10.1016\/j.gassur.2025.102000","article-title":"The first international experience with histotripsy: A safety analysis of 230 cases","volume":"29","author":"Wehrle","year":"2025","journal-title":"J. Gastrointest. Surg."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/j.ultrasmedbio.2012.09.004","article-title":"Probability of cavitation for single ultrasound pulses applied to tissues and tissue-mimicking materials","volume":"39","author":"Maxwell","year":"2013","journal-title":"Ultrasound Med. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Mancia, L., Vlaisavljevich, E., Yousefi, N., Rodriguez, M., Ziemlewicz, T.J., Lee, F.T., Henann, D., Franck, C., Xu, Z., and Johnsen, E. (2019). Modeling tissue-selective cavitation damage. Phys. Med. Biol., 64.","DOI":"10.1088\/1361-6560\/ab5010"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1016\/j.ultrasmedbio.2017.02.020","article-title":"Predicting Tissue Susceptibility to Mechanical Cavitation Damage in Therapeutic Ultrasound","volume":"43","author":"Mancia","year":"2017","journal-title":"Ultrasound Med. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1651","DOI":"10.1016\/j.ultrasmedbio.2015.01.028","article-title":"Effects of ultrasound frequency and tissue stiffness on the histotripsy intrinsic threshold for cavitation","volume":"41","author":"Vlaisavljevich","year":"2015","journal-title":"Ultrasound Med. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1888","DOI":"10.1121\/1.3625239","article-title":"Cavitation clouds created by shock scattering from bubbles during histotripsy","volume":"130","author":"Maxwell","year":"2011","journal-title":"J. Acoust. Soc. Am."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/j.ultras.2017.11.012","article-title":"Effect of pulse duration and pulse repetition frequency of cavitation histotripsy on erosion at the surface of soft material","volume":"84","author":"Zhou","year":"2018","journal-title":"Ultrasonics"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.ultrasmedbio.2010.10.002","article-title":"Examining and analyzing subcellular morphology of renal tissue treated by histotripsy","volume":"37","author":"Winterroth","year":"2011","journal-title":"Ultrasound Med. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3498","DOI":"10.1121\/1.3626152","article-title":"Controlled tissue emulsification produced by high intensity focused ultrasound shock waves and millisecond boiling","volume":"130","author":"Khokhlova","year":"2011","journal-title":"J. Acoust. Soc. Am."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1542","DOI":"10.1109\/TUFFC.2017.2739649","article-title":"A prototype therapy system for transcutaneous application of boiling histotripsy","volume":"64","author":"Maxwell","year":"2017","journal-title":"IEEE Trans. Ultrason. Ferroelectr. Freq. Control"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Heo, J., Joung, C., Pahk, K., and Pahk, K.J. (2022). Investigation of the long-term healing response of the liver to boiling histotripsy treatment in vivo. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-18544-7"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1088\/0031-9155\/61\/2\/663","article-title":"The role of positive and negative pressure on cavitation nucleation in nanodroplet-mediated histotripsy","volume":"61","author":"Vlaisavljevich","year":"2016","journal-title":"Phys. Med. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2466","DOI":"10.1016\/j.ultrasmedbio.2016.05.018","article-title":"Visualizing the Histotripsy Process: Bubble Cloud-Cancer Cell Interactions in a Tissue-Mimicking Environment","volume":"42","author":"Vlaisavljevich","year":"2016","journal-title":"Ultrasound Med. Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1374","DOI":"10.1121\/1.4961364","article-title":"Cavitation-induced damage of soft materials by focused ultrasound bursts: A fracture-based bubble dynamics model","volume":"140","author":"Movahed","year":"2016","journal-title":"J. Acoust. Soc. Am."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Mancia, L., Rodriguez, M., Sukovich, J., Xu, Z., and Johnsen, E. (2020). Single\u2013bubble dynamics in histotripsy and high\u2013amplitude ultrasound: Modeling and validation. Phys. Med. Biol., 65.","DOI":"10.1088\/1361-6560\/abb02b"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1016\/j.ultrasmedbio.2017.11.012","article-title":"Bubble-induced color Doppler feedback correlates with histotripsy-induced destruction of structural components in liver tissue","volume":"44","author":"Macoskey","year":"2018","journal-title":"Ultrasound Med. Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1975","DOI":"10.1007\/s10439-021-02833-9","article-title":"High-intensity focused ultrasound: A review of mechanisms and clinical applications","volume":"49","author":"Bachu","year":"2021","journal-title":"Ann. Biomed. Eng."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1986","DOI":"10.1016\/j.jvir.2023.07.014","article-title":"A Comparison of Histotripsy and Percutaneous Cryoablation in a Chronic Healthy Swine Kidney Model","volume":"34","author":"Couillard","year":"2023","journal-title":"J. Vasc. Interv. Radiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1016\/j.jvir.2019.01.023","article-title":"Robotically-Assisted Sonic Therapy for Renal Ablation in a Live Porcine Model: Initial Preclinical Results","volume":"30","author":"Knott","year":"2019","journal-title":"J. Vasc. Interv. Radiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1016\/j.tibs.2019.04.008","article-title":"Cryo-electron microscopy methodology: Current aspects and future directions","volume":"44","author":"Danev","year":"2019","journal-title":"Trends Biochem. Sci."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Fan, Y., Xu, L., Liu, S., Li, J., Xia, J., Qin, X., Li, Y., Gao, T., and Tang, X. (2024). The state-of-the-art and perspectives of laser ablation for tumor treatment. Cyborg Bionic Syst., 5.","DOI":"10.34133\/cbsystems.0062"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1109\/TUFFC.2021.3110083","article-title":"Histotripsy Ablation in Preclinical Animal Models of Cancer and Spontaneous Tumors in Veterinary Patients: A Review","volume":"69","author":"Arnold","year":"2022","journal-title":"IEEE Trans. Ultrason. Ferroelectr. Freq. Control"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2272065","DOI":"10.1080\/02656736.2023.2272065","article-title":"Clinical translation of abdominal histotripsy: A review of preclinical studies in large animal models","volume":"40","author":"Falk","year":"2023","journal-title":"Int. J. Hyperth."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2297650","DOI":"10.1080\/02656736.2023.2297650","article-title":"Insights from in vivo preclinical cancer studies with histotripsy","volume":"41","author":"Worlikar","year":"2024","journal-title":"Int. J. Hyperth."},{"key":"ref_49","first-page":"6064","article-title":"Histotripsy for Non-Invasive Ablation of Hepatocellular Carcinoma (HCC) Tumor in a Subcutaneous Xenograft Murine Model","volume":"2018","author":"Worlikar","year":"2018","journal-title":"Annu. Int. Conf. IEEE Eng. Med. Biol. Soc."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e000200","DOI":"10.1136\/jitc-2019-000200","article-title":"Non-thermal histotripsy tumor ablation promotes abscopal immune responses that enhance cancer immunotherapy","volume":"8","author":"Qu","year":"2020","journal-title":"J. Immunother. Cancer"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"9830304","DOI":"10.34133\/2020\/9830304","article-title":"Effects of Histotripsy on Local Tumor Progression in an in vivo Orthotopic Rodent Liver Tumor Model","volume":"2020","author":"Worlikar","year":"2020","journal-title":"BME Front."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Worlikar, T., Zhang, M., Ganguly, A., Hall, T.L., Shi, J., Zhao, L., Lee, F.T., Mendiratta-Lala, M., Cho, C.S., and Xu, Z. (2022). Impact of Histotripsy on Development of Intrahepatic Metastases in a Rodent Liver Tumor Model. Cancers, 14.","DOI":"10.3390\/cancers14071612"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Pepple, A.L., Guy, J.L., McGinnis, R., Felsted, A.E., Song, B., Hubbard, R., Worlikar, T., Garavaglia, H., Dib, J., and Chao, H. (2023). Spatiotemporal local and abscopal cell death and immune responses to histotripsy focused ultrasound tumor ablation. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1012799"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2987","DOI":"10.1109\/TUFFC.2021.3078094","article-title":"Histotripsy Ablation Alters the Tumor Microenvironment and Promotes Immune System Activation in a Subcutaneous Model of Pancreatic Cancer","volume":"68","author":"Sereno","year":"2021","journal-title":"IEEE Trans. Ultrason. Ferroelectr. Freq. Control"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2361","DOI":"10.1016\/j.ultrasmedbio.2023.07.013","article-title":"Successful In Situ Targeting of Pancreatic Tumors in a Novel Orthotopic Porcine Model Using Histotripsy","volume":"49","author":"Imran","year":"2023","journal-title":"Ultrasound Med. Biol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2953","DOI":"10.1109\/TUFFC.2021.3073563","article-title":"Histotripsy for the Treatment of Cholangiocarcinoma Liver Tumors: In Vivo Feasibility and Ex Vivo Dosimetry Study","volume":"68","author":"Weber","year":"2021","journal-title":"IEEE Trans. Ultrason. Ferroelectr. Freq. Control"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.ultrasmedbio.2021.10.002","article-title":"Histotripsy for the Treatment of Cholangiocarcinoma in a Patient-Derived Xenograft Mouse Model","volume":"48","author":"Saunier","year":"2022","journal-title":"Ultrasound Med. Biol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1900214","DOI":"10.1002\/adtp.201900214","article-title":"Investigation of the Potential Immunological Effects of Boiling Histotripsy for Cancer Treatment","volume":"3","author":"Nam","year":"2020","journal-title":"Adv. Ther."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Tang, S., McGinnis, R., Cao, Z., Baker, J.R., Xu, Z., and Wang, S. (2025). Ultrasound-Guided Histotripsy Triggers the Release of Tumor-Associated Antigens from Breast Cancers. Cancers, 17.","DOI":"10.3390\/cancers17020183"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1859","DOI":"10.1007\/s10439-023-03194-1","article-title":"Enabling Chemo-Immunotherapy with HIFU in Canine Cancer Patients","volume":"52","author":"Ashar","year":"2024","journal-title":"Ann. Biomed. Eng."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1773","DOI":"10.1109\/TUFFC.2023.3326561","article-title":"Boiling Histotripsy Using Dual-Frequency Protocol on Murine Breast Tumor Model and Promotes Immune Activation","volume":"70","author":"Qi","year":"2023","journal-title":"IEEE Trans. Ultrason. Ferroelectr. Freq. Control"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1016\/j.jvir.2024.03.012","article-title":"Histoplasty Modification of the Tumor Microenvironment in a Murine Preclinical Model of Breast Cancer","volume":"35","author":"Pieper","year":"2024","journal-title":"J. Vasc. Interv. Radiol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1109\/TUFFC.2020.3012303","article-title":"Stereotactic Transcranial Focused Ultrasound Targeting System for Murine Brain Models","volume":"68","author":"Choi","year":"2021","journal-title":"IEEE Trans. Ultrason. Ferroelectr. Freq. Control"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1882","DOI":"10.1016\/j.ultrasmedbio.2023.05.002","article-title":"Histotripsy Treatment of Murine Brain and Glioma: Temporal Profile of Magnetic Resonance Imaging and Histological Characteristics Post-treatment","volume":"49","author":"Choi","year":"2023","journal-title":"Ultrasound Med. Biol."},{"key":"ref_65","unstructured":"Gerhardson, T., Pal, A., Sheetz, L., Sukovich, J., Lundt, J., Hall, T., Chertok, B., Rehemtulla, A., Cain, C., and Xu, Z. (2018, January 14\u201317). Histotripsy mediated immunomodulation in a mouse GL261 intracranial glioma model. Proceedings of the Proc. Int. Symp. Therapeutic Ultrasound, Nashville, TN, USA."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2237218","DOI":"10.1080\/02656736.2023.2237218","article-title":"Transcranial histotripsy parameter study in primary and metastatic murine brain tumor models","volume":"40","author":"Duclos","year":"2023","journal-title":"Int. J. Hyperth."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"15330338241285158","DOI":"10.1177\/15330338241285158","article-title":"First-In-DOg HISTotripsy for Intracranial Tumors Trial: The FIDOHIST Study","volume":"23","author":"Vezza","year":"2024","journal-title":"Technol. Cancer Res. Treat."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2222941","DOI":"10.1080\/02656736.2023.2222941","article-title":"Histotripsy induces apoptosis and reduces hypoxia in a neuroblastoma xenograft model","volume":"40","author":"Iwanicki","year":"2023","journal-title":"Int. J. Hyperth."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1158\/1078-0432.CCR-19-1604","article-title":"High-Intensity Focused Ultrasound (HIFU) Triggers Immune Sensitization of Refractory Murine Neuroblastoma to Checkpoint Inhibitor Therapy","volume":"26","author":"Eranki","year":"2020","journal-title":"Clin. Cancer Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ultsonch.2017.02.035","article-title":"Impact of MR-guided boiling histotripsy in distinct murine tumor models","volume":"38","author":"Hoogenboom","year":"2017","journal-title":"Ultrason. Sonochem."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"540","DOI":"10.7150\/thno.49517","article-title":"Boiling histotripsy and in-situ CD40 stimulation improve the checkpoint blockade therapy of poorly immunogenic tumors","volume":"11","author":"Singh","year":"2021","journal-title":"Theranostics"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1647","DOI":"10.7150\/thno.92089","article-title":"Focused ultrasound ablation of melanoma with boiling histotripsy yields abscopal tumor control and antigen-dependent dendritic cell activation","volume":"14","author":"Thim","year":"2024","journal-title":"Theranostics"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1158\/1535-7163.MCT-24-0715","article-title":"Histotripsy-focused ultrasound treatment abrogates tumor hypoxia responses and stimulates anti-tumor immune responses in melanoma","volume":"24","author":"Song","year":"2025","journal-title":"Mol. Cancer Ther."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1002\/nbm.3520","article-title":"In vivo MR guided boiling histotripsy in a mouse tumor model evaluated by MRI and histopathology","volume":"29","author":"Hoogenboom","year":"2016","journal-title":"NMR Biomed."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Ruger, L.N., Hay, A.N., Vickers, E.R., Coutermarsh-Ott, S.L., Gannon, J.M., Covell, H.S., Daniel, G.B., Laeseke, P.F., Ziemlewicz, T.J., and Kierski, K.R. (2023). Characterizing the Ablative Effects of Histotripsy for Osteosarcoma: In Vivo Study in Dogs. Cancers, 15.","DOI":"10.3390\/cancers15030741"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1109\/TBME.2022.3201709","article-title":"Mechanical High-Intensity Focused Ultrasound (Histotripsy) in Dogs with Spontaneously Occurring Soft Tissue Sarcomas","volume":"70","author":"Ruger","year":"2023","journal-title":"IEEE Trans. Biomed. Eng."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1109\/TBME.2022.3191069","article-title":"Histotripsy Ablation of Spontaneously Occurring Canine Bone Tumors In Vivo","volume":"70","author":"Ruger","year":"2022","journal-title":"IEEE Trans. Biomed. Eng."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2210272","DOI":"10.1080\/02656736.2023.2210272","article-title":"Histotripsy ablation for the treatment of feline injection site sarcomas: A first-in-cat in vivo feasibility study","volume":"40","author":"Ruger","year":"2023","journal-title":"Int. J. Hyperth."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"3435","DOI":"10.1016\/j.ultrasmedbio.2021.08.004","article-title":"Histotripsy Ablation of Bone Tumors: Feasibility Study in Excised Canine Osteosarcoma Tumors","volume":"47","author":"Arnold","year":"2021","journal-title":"Ultrasound Med. Biol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2279027","DOI":"10.1080\/02656736.2023.2279027","article-title":"Investigating cell death responses associated with histotripsy ablation of canine osteosarcoma","volume":"40","author":"Hay","year":"2023","journal-title":"Int. J. Hyperth."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1957","DOI":"10.1016\/j.juro.2012.07.006","article-title":"Histotripsy focal ablation of implanted prostate tumor in an ACE-1 canine cancer model","volume":"188","author":"Schade","year":"2012","journal-title":"J. Urol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1148\/radiol.2016160024","article-title":"Release of Cell-free MicroRNA Tumor Biomarkers into the Blood Circulation with Pulsed Focused Ultrasound: A Noninvasive, Anatomically Localized, Molecular Liquid Biopsy","volume":"283","author":"Chevillet","year":"2017","journal-title":"Radiology"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1089\/end.2010.0123","article-title":"Histotripsy of VX-2 tumor implanted in a renal rabbit model","volume":"24","author":"Styn","year":"2010","journal-title":"J. Endourol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.ultrasmedbio.2018.09.006","article-title":"Boiling Histotripsy Ablation of Renal Cell Carcinoma in the Eker Rat Promotes a Systemic Inflammatory Response","volume":"45","author":"Schade","year":"2019","journal-title":"Ultrasound Med. Biol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1007\/s10143-024-02353-9","article-title":"Revolutionizing brain interventions: The multifaceted potential of histotripsy","volume":"47","author":"Verma","year":"2024","journal-title":"Neurosurg. Rev."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"2455138","DOI":"10.1080\/02656736.2025.2455138","article-title":"Evaluation of targeting accuracy of cone beam CT guided histotripsy in an in vivo porcine model","volume":"42","author":"Wagner","year":"2025","journal-title":"Int. J. Hyperth."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1109\/TUFFC.2025.3553083","article-title":"MRI Co-registered Rodent Histotripsy Array for Orthotopic Liver Models","volume":"72","author":"Hubbard","year":"2025","journal-title":"IEEE Trans. Ultrason. Ferroelectr. Freq. Control"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1080\/02656736.2022.2112309","article-title":"First-in-man histotripsy of hepatic tumors: The THERESA trial, a feasibility study","volume":"39","author":"Serres","year":"2022","journal-title":"Int. J. Hyperth."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1007\/s00270-022-03309-6","article-title":"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)","volume":"46","author":"Wah","year":"2023","journal-title":"Cardiovasc. Interv. Radiol."},{"key":"ref_90","unstructured":"HistoSonics (2025, February 22). (2024, December 18). World\u2019s First Patients Treated with Novel Edison\u00ae Histotripsy System. Available online: https:\/\/histosonics.com\/news\/worlds-first-patients-treated-with-novel-edison-histotripsy-system\/."},{"key":"ref_91","unstructured":"(2025, April 21). Histotripsy\u2014Clinical Trials Search Results, Available online: https:\/\/clinicaltrials.gov\/search?intr=Histotripsy."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1007\/s40477-023-00848-7","article-title":"Revolutionizing cardiovascular care: The power of histotripsy","volume":"27","author":"Verma","year":"2024","journal-title":"J. Ultrasound"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.urology.2017.12.033","article-title":"Histotripsy Treatment of Benign Prostatic Enlargement Using the Vortx R(x) System: Initial Human Safety and Efficacy Outcomes","volume":"114","author":"Schuster","year":"2018","journal-title":"Urology"},{"key":"ref_94","unstructured":"U.S. Food and Drug Administration (2023). De Novo Classification Request for Edison System."},{"key":"ref_95","unstructured":"Rogel Cancer Center (2025, March 10). Histotripsy FAQ. Available online: https:\/\/www.rogelcancercenter.org\/liver-cancer\/histotripsy-faq."},{"key":"ref_96","unstructured":"Comprehensive Cancer Center (2025, March 10). Histotripsy-Liver Cancer Ultrasound. Available online: https:\/\/www.uchicagomedicine.org\/cancer\/types-treatments\/histotripsy."},{"key":"ref_97","unstructured":"UW Health (2025, March 10). Game-Changing Liver Cancer Treatment. Available online: https:\/\/www.uwhealth.org\/treatments\/histotripsy."},{"key":"ref_98","unstructured":"Histosonics (2025, February 20). Patient Education-Histotripsy Procedure in Liver. Available online: https:\/\/myhistotripsy.com\/wp-content\/uploads\/2024\/08\/PatientInformation.pdf."},{"key":"ref_99","unstructured":"Gastroenterology and GI Surgery (2025, March 12). Histotripsy Makes Its Clinical Debut in NYC. Available online: https:\/\/physicianfocus.nyulangone.org\/histotripsy-makes-its-clinical-debut-in-nyc\/."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Kumar, Y.N., Singh, Z., Wang, Y.N., Kanabolo, D., Chen, L., Bruce, M., Vlaisavljevich, E., True, L., Maxwell, A.D., and Schade, G.R. (2024). A comparative study of histotripsy parameters for the treatment of fibrotic ex-vivo human benign prostatic hyperplasia tissue. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-71163-2"},{"key":"ref_101","first-page":"15","article-title":"Imaging for targeting, monitoring, and assessment after histotripsy: A non-invasive, non-thermal therapy for cancer","volume":"10","author":"Kisting","year":"2023","journal-title":"EMJ Radiol."},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Mouratidis, P.X.E., and Ter Haar, G. (2022). Latest Advances in the Use of Therapeutic Focused Ultrasound in the Treatment of Pancreatic Cancer. Cancers, 14.","DOI":"10.3390\/cancers14030638"},{"key":"ref_103","unstructured":"Johns Hopkins Medicine (2025, March 10). Histotripsy for Liver Tumors. Available online: https:\/\/www.hopkinsmedicine.org\/health\/treatment-tests-and-therapies\/histotripsy-for-liver-tumors."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Bader, K.B., Hendley, S.A., Anthony, G.J., and Bollen, V. (2019). Observation and modulation of the dissolution of histotripsy-induced bubble clouds with high-frame rate plane wave imaging. Phys. Med. Biol., 64.","DOI":"10.1088\/1361-6560\/ab1a64"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1109\/TUFFC.2012.2307","article-title":"Imaging feedback of histotripsy treatments using ultrasound shear wave elastography","volume":"59","author":"Wang","year":"2012","journal-title":"IEEE Trans. Ultrason. Ferroelectr. Freq. Control"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1109\/TUFFC.2023.3289918","article-title":"Contrast-Enhanced Imaging of Histotripsy Bubble Clouds Using Chirp-Coded Excitation and Volterra Filtering","volume":"70","author":"Trivedi","year":"2023","journal-title":"IEEE Trans. Ultrason. Ferroelectr. Freq. Control"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1486","DOI":"10.1002\/mrm.26062","article-title":"MR-based detection of individual histotripsy bubble clouds formed in tissues and phantoms","volume":"76","author":"Allen","year":"2016","journal-title":"Magn. Reson. Med."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"7167","DOI":"10.1088\/1361-6560\/aa81ed","article-title":"The response of MRI contrast parameters in in vitro tissues and tissue mimicking phantoms to fractionation by histotripsy","volume":"62","author":"Allen","year":"2017","journal-title":"Phys. Med. Biol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1016\/j.ultrasmedbio.2024.10.010","article-title":"Transcranial MRI-guided Histotripsy Targeting Using MR-thermometry and MR-ARFI","volume":"51","author":"Gupta","year":"2025","journal-title":"Ultrasound Med. Biol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1007\/s00270-019-02215-8","article-title":"Robotically Assisted Sonic Therapy (RAST) for Noninvasive Hepatic Ablation in a Porcine Model: Mitigation of Body Wall Damage with a Modified Pulse Sequence","volume":"42","author":"Longo","year":"2019","journal-title":"Cardiovasc. Interv. Radiol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1016\/j.ultrasmedbio.2023.01.019","article-title":"A Multimodal Phantom for Visualization and Assessment of Histotripsy Treatments on Ultrasound and X-Ray Imaging","volume":"49","author":"Kutlu","year":"2023","journal-title":"Ultrasound Med. Biol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1016\/j.jvir.2022.11.034","article-title":"Hepatic and Renal Histotripsy in an Anticoagulated Porcine Model","volume":"34","author":"Mauch","year":"2023","journal-title":"J. Vasc. Interv. Radiol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1109\/TBME.2022.3198600","article-title":"An X-Ray C-Arm Guided Automatic Targeting System for Histotripsy","volume":"70","author":"Wagner","year":"2023","journal-title":"IEEE Trans. Biomed. Eng."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"2853","DOI":"10.1109\/TUFFC.2021.3073540","article-title":"Contrast-Enhanced Ultrasound: A Useful Tool to Study and Monitor Hepatic Tumors Treated with Histotripsy\u2014PubMed","volume":"68","author":"Ziemlewicz","year":"2021","journal-title":"IEEE Trans. Ultrason. Ferroelectr. Freq. Control"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1109\/TUFFC.2025.3556030","article-title":"Chirp-Coded Subharmonic Imaging with Volterra Filtering: Histotripsy Bubble Cloud Assessment In Vitro and Ex Vivo\u2013PubMed","volume":"72","author":"Trivedi","year":"2025","journal-title":"IEEE Trans. Ultrason. Ferroelectr. Freq. Control"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"3001","DOI":"10.1109\/TUFFC.2021.3100267","article-title":"Liver Histotripsy Mediated Abscopal Effect-Case Report","volume":"68","author":"Ziemlewicz","year":"2021","journal-title":"IEEE Trans. Ultrason. Ferroelectr. Freq. Control"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1016\/j.urology.2012.06.020","article-title":"Histotripsy of renal implanted VX-2 tumor in a rabbit model: Investigation of metastases","volume":"80","author":"Styn","year":"2012","journal-title":"Urology"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/s40164-025-00604-z","article-title":"Bridging therapy with histotripsy prior to liver transplantation for hepatocellular carcinoma: A first case report","volume":"14","author":"Uysal","year":"2025","journal-title":"Exp. Hematol. Oncol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/1750743X.2024.2442899","article-title":"How could histotripsy change cancer immunotherapy?","volume":"17","author":"Queen","year":"2025","journal-title":"Immunotherapy"},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Mungur, R., Zheng, J., Wang, B., Chen, X., Zhan, R., and Tong, Y. (2022). Low-Intensity Focused Ultrasound Technique in Glioblastoma Multiforme Treatment. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.903059"},{"key":"ref_121","first-page":"20190692","article-title":"A dynamical model of oncotripsy by mechanical cell fatigue: Selective cancer cell ablation by low-intensity pulsed ultrasound","volume":"476","author":"Schibber","year":"2020","journal-title":"Proc. Math. Phys. Eng. Sci."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"2344","DOI":"10.1016\/j.ultrasmedbio.2022.06.017","article-title":"Low-Intensity Focused Ultrasound Produces Immune Response in Pancreatic Cancer","volume":"48","author":"Joiner","year":"2022","journal-title":"Ultrasound Med. Biol."},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Amarante-Mendes, G.P., Adjemian, S., Branco, L.M., Zanetti, L.C., Weinlich, R., and Bortoluci, K.R. (2018). Pattern Recognition Receptors and the Host Cell Death Molecular Machinery. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.02379"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1038\/s41586-019-1170-y","article-title":"CD8(+) T cells regulate tumour ferroptosis during cancer immunotherapy","volume":"569","author":"Wang","year":"2019","journal-title":"Nature"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/15\/2548\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:21:09Z","timestamp":1760034069000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/15\/2548"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,1]]},"references-count":124,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["cancers17152548"],"URL":"https:\/\/doi.org\/10.3390\/cancers17152548","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,1]]}}}