Histotripsy: A Method for Mechanical Tissue Ablation with Ultrasound

Annual Review of Biomedical Engineering, Год журнала: 2024, Номер 26(1), С. 141 - 167

Опубликована: Фев. 12, 2024

Histotripsy is a relatively new therapeutic ultrasound technology to mechanically liquefy tissue into subcellular debris using high-amplitude focused pulses. In contrast conventional high-intensity thermal therapy, histotripsy has specific clinical advantages: the capacity for real-time monitoring imaging, diminished heat sink effects resulting in lesions with sharp margins, effective removal of treated tissue, tissue-selective feature preserve crucial structures, and immunostimulation. The being evaluated small large animal models treating cancer, thrombosis, hematomas, abscesses, biofilms; enhancing tumor-specific immune response; neurological applications. been recently approved by US Food Drug Administration treat liver tumors, trials undertaken benign prostatic hyperplasia renal tumors. This review outlines physical principles various types histotripsy; presents major parameters corresponding hardware software, imaging methods, bioeffects; discusses most promising preclinical

Язык: Английский

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The #HOPE4LIVER Single-Arm Pivotal Trial for Histotripsy of Primary and Metastatic Liver Tumors

Radiology, Год журнала: 2024, Номер 312(3)

Опубликована: Сен. 1, 2024

Background Histotripsy is a nonthermal, nonionizing, noninvasive, focused US technique that relies on cavitation for mechanical tissue breakdown at the focal point. Preclinical data have shown its safety and technical success in ablation of liver tumors. Purpose To evaluate histotripsy destroying primary or metastatic Materials Methods The parallel United States European Union England #HOPE4LIVER trials were prospective, multicenter, single-arm studies. Eligible patients recruited 14 sites Europe from January 2021 to July 2022. Up three tumors smaller than 3 cm size could be treated. CT MRI clinic visits performed 1 week less preprocedure, index-procedure, 36 hours postprocedure, 30 days postprocedure. There co-primary end points tumor treatment absence procedure-related major complications within days, with performance goals greater 70% 25%, respectively. A two-sided 95% Wilson score CI was derived each Results Forty-four participants (21 States, 23 England; 22 female participants, male participants; mean age, 64 years ± 12 [SD]) 49 enrolled Eighteen (41%) had hepatocellular carcinoma 26 (59%) non-hepatocellular metastases. maximum pretreatment diameter 1.5 0.6 post-histotripsy zone 3.6 1.4. Technical observed 42 44 treated (95%; CI: 84, 100) reported (7%; 2, 18), both meeting goal. Conclusion met end-point complications, supporting early clinical adoption. Clinical trial registration nos. NCT04572633, NCT04573881 Published under CC BY 4.0 license.

Язык: Английский

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Exploiting the mechanical effects of ultrasound for noninvasive therapy

Science, Год журнала: 2024, Номер 385(6714)

Опубликована: Сен. 12, 2024

Focused ultrasound is a platform technology capable of eliciting wide range biological responses with high spatial precision deep within the body. Although focused already in clinical use for focal thermal ablation tissue, there has been recent growth development and translation ultrasound-mediated nonthermal therapies. These approaches exploit physical forces to produce dependent on exposure conditions. This review discusses advances four application areas that have seen particular immense potential: brain drug delivery, neuromodulation, tissue destruction, endogenous immune system activation. Owing maturation transcranial technology, major target organ; however, indications outside are also discussed.

Язык: Английский

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Insights from in vivo preclinical cancer studies with histotripsy

International Journal of Hyperthermia, Год журнала: 2024, Номер 41(1)

Опубликована: Янв. 12, 2024

Histotripsy is the first noninvasive, non-ionizing, and non-thermal ablation technique that mechanically fractionates target tissue into acellular homogenate via controlled acoustic cavitation. has been evaluated for various preclinical applications requiring noninvasive removal including cancer, brain surgery, blood clot hematoma liquefaction, correction of neonatal congenital heart defects. Promising results local tumor suppression, improved survival outcomes, systemic anti-tumor immune responses, histotripsy-induced abscopal effects have reported in animal models. also being investigated veterinary patients with spontaneously arising tumors. Research underway to combine histotripsy immunotherapy chemotherapy improve therapeutic outcomes. In addition cancer research, human clinical trials are ongoing treatment liver tumors renal recently approved by FDA This review highlights key learnings from vivo shock-scattering histotripsy, intrinsic threshold boiling studies treating cancers different anatomic locations discusses major considerations planning regarding instrumentation, model, study design, dose, post-treatment monitoring.

Язык: Английский

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Magic bubbles: utilizing histotripsy to modulate the tumor microenvironment and improve systemic anti-tumor immune responses

International Journal of Hyperthermia, Год журнала: 2023, Номер 40(1)

Опубликована: Авг. 14, 2023

Focused Ultrasound (FUS) is emerging as a promising primary and adjunct therapy for the treatment of cancer. This includes histotripsy, which noninvasive, non-ionizing, non-thermal ultrasound guided ablation modality. As histotripsy has progressed from bench-to-bedside, it become evident that this benefits beyond local tumor ablation. Specifically, potential to shift microenvironment immunologically 'cold' 'hot'. associated with production damage molecular patterns, release selection proinflammatory mediators, induction inflammatory forms cell death in cells just outside zone. In addition innate immune response, can also improve engagement adaptive system promote systemic anti-tumor immunity targeting distal tumors metastatic lesions. These tantalizing observations suggest that, settings widely disease burden, selective limited number accessible could be means maximizing responsiveness immunotherapy. More work certainly needed optimize strategies best synergize parameters responses. Likewise, rigorous clinical studies are still necessary verify presence repeatability these phenomena human patients. technology nears regulatory approval use, our expectation insights immunomodulatory mechanisms summarized review will serve directional guides rational validate immunotherapeutic role

Язык: Английский

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Ultrasound-Guided Histotripsy Triggers the Release of Tumor-Associated Antigens from Breast Cancers

Cancers, Год журнала: 2025, Номер 17(2), С. 183 - 183

Опубликована: Янв. 8, 2025

Background/Objectives: There is increasing evidence to indicate that histotripsy treatment can enhance the host anti-tumor immune responses both locally at targeting tumor site as well systemically from abscopal effects. Histotripsy a non-invasive ultrasound ablation technology mechanically disrupts target tissue via cavitation. A key factor contributing histotripsy-induced effects believed be release of tumor-specific antigens (TSAs) or tumor-associated (TAAs) induce systemic response. In this study, we studied effect on HER2, well-defined TAA for cancer immunotherapy. Methods: range doses administered HER2-postive mammary cells in an vitro cell culture system and ex vivo were applied. addition, single dose was used murine model. The released proteins, specifically cell-free supernatants pellets analyzed by BCA protein assay, ultra-performance liquid chromatography (UPLC) Western blot. Results: Our results showed could significantly trigger HER2 proteins current study. level actually higher than pellets, suggesting intracellular domain into extracellular compartment. Furthermore, proportionally more doses, indicating free histotripsy-dose-dependent. Conclusions: conclusion, have qualitatively quantitatively demonstrated triggers histotripsy-mediated provides important insights mechanism underlying its immunostimulation suggests potential TSA/TAA-based immunotherapies numerous types.

Язык: Английский

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Perfluorohexane Nanodroplet-Assisted Mechanical High Intensity Focused Ultrasound Cavitation: A Strategy for Hepatocellular Carcinoma Treatment

Acta Biomaterialia, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

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Ethanol inhibits the growth and metastasis of hepatocellular carcinoma by inducing immunogenic cell death

Journal for ImmunoTherapy of Cancer, Год журнала: 2025, Номер 13(2), С. e010472 - e010472

Опубликована: Фев. 1, 2025

Immunogenic cell death (ICD) can elicit an adaptive immune response with significant antitumor effects. Percutaneous ethanol injection therapy has been applied as tumor ablation for small hepatocellular carcinoma (HCC). However, it was not clear whether ICD. The aim of this study is to investigate the role ICD inducer. HCC lines were treated low-concentration and markers, such calreticulin, high-mobility group box 1, ATP assayed. mouse vaccination-rechallenge assay used further confirm Western blot real-time PCR ICD-related endoplasmic reticulum (ER) stress signaling pathways. genes differential expression levels between primary distant tumors analyzed by nCounter gene expression. Intratumoral done abscopal effect. could induce in through unfolded protein responses initiated ER multiple cell-death injections had significantly direct effects models both subcutaneous orthotopic HCC. analysis revealed activation various immune-response pathways, notably those mediated CD8 T cells interferon pathway. Vaccinating mice ethanol-treated successfully inhibited metastasis intravenous intrasplenic models. Our results suggest that serve inducer Low-concentration potentially improve therapeutic immunity inducing substantial

Язык: Английский

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Acoustic Cavitation Emissions Predict Near-complete/complete Histotripsy Treatment in Soft Tissues

Ultrasound in Medicine & Biology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 1, 2025

Histotripsy is a non-invasive acoustic ablation technique that leverages cavitation to impart mechanical damage viscoelastic medium, such as tissue. Although histotripsy bubbles and lesions can be imaged with variety of modalities, reliable methods predict tissue disruption across different tissue-types remain determined. Several ex-vivo bovine tissues were ablated by intrinsic threshold over range pulse-per-location doses. Acoustic Cavitation Emission (ACE) signals captured following every other therapeutic pulse using transmit-receive capable arrays. Final bubble lifespan, lifespan-slope, percent-reduction calculated correlated against histologic necrosis score (0-5: 0=0% necrosis, 5=>95% necrosis) residual structure (0-4: 0=none present, 4=intact) evaluate the ability features from ACE-signals histotripsy-induced damage. Further, optimal ACE-feature thresholds determined for binary evaluation whether equal or greater than 4 had been reached. Measured lifespans increased lifespan-slopes decreased pulses per location (ppl) eventually plateaued in all types, similar trends those previously observed phantoms. Necrosis increasing dose. Bubble lifespan-slope well score. Thresholds able brain, liver, kidney high sensitivity/specificity (>80%). The 5 expected correspond near-complete/complete histological evaluation. Features measured ACE-signals, particularly percent reduction, used large-volume treatments ex vivo kidney, brain good accuracy. Tissue heterogeneities impact corresponding thus predication

Язык: Английский

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The Emerging Role of Histotripsy in Liver Cancer Treatment: A Scoping Review

Cancers, Год журнала: 2025, Номер 17(6), С. 915 - 915

Опубликована: Март 7, 2025

Background/Objective: Hepatocellular carcinoma (HCC) is an aggressive disease that known to be resistant conventional chemotherapy and radiotherapy. While surgical resection transarterial therapy can improve overall survival, the biological aspects of HCC contribute complexity its management limit effectiveness current treatment options. The purpose this scoping review identify limitations currently available therapies for explore emerging role histotripsy could play in addressing these limitations, with intent informing direction future research clinical management. Methods: PRISMA checklist reviews was followed structure review, a systematic search conducted following online databases: PubMed/MEDLINE (National Library Medicine), Embase (Elsevier), Scopus (Elsevier). Results: evidence supports offers several key advantages address strategies HCC. Clinical trials have highlighted ability technology destroy solid tumors induce remission minimal side effects. In addition, preclinical studies point potent immunostimulatory effects histotripsy, including induction abscopal This poses significant promise treating tumor metastasis as well improving regimens by combining immunotherapy. Future should aim overcome enhance outcomes patients. examines existing treatments HCC, emphasizing promising potential immunotherapy target metastatic advanced stages disease.

Язык: Английский

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