Boiling histotripsy exhibits anti-fibrotic effects in animal models of liver fibrosis.

Liver fibrosis is a hallmark of chronic liver disease which could lead to liver cirrhosis or liver cancer. However, there is currently lack of a direct treatment for liver fibrosis. Boiling histotripsy (BH) is an emerging non-invasive high-intensity focused ultrasound technique that can be employed to mechanically destruct solid tumour at the focus via acoustic cavitation without significant adverse effect on surrounding tissue. Here, we investigated whether BH can mechanically fractionate liver fibrotic tissue thereby exhibiting an anti-fibrotic effect in an animal model of liver fibrosis. BH-treated penumbra and its identical lobe showed reduced liver fibrosis, accompanied by increased hepatocyte specific marker expression, compared to the BH-untreated lobe. Furthermore, BH treatment improved serological liver function markers without notable adverse effects. The ability of BH to reduce fibrosis and promote liver regeneration in liver fibrotic tissue suggests that BH could potentially be an effective and reliable therapeutic approach against liver fibrosis.

High-intensity focused ultrasound ablation combined with immunotherapy for treating liver metastases: A prospective non-randomized trial.

PURPOSE: Given the unique features of the liver, it is necessary to combine immunotherapy with other therapies to improve its efficacy in patients of advanced cancer with liver metastases (LM). High-intensity focused ultrasound (HIFU) ablation is now widely used in clinical practice and can enhanced immune benefits. The study is intended to prospectively evaluate the safety and clinical feasibility of HIFU ablation in combination with systemic immunotherapy for patients with liver metastases. METHODS: The study enrolled 14 patients with LM who received ultrasound-guided HIFU ablation combined with immune checkpoint inhibitors (ICIs) such as anti-programmed cell death protein 1 (anti-PD-1 agents manufactured in China) at Mianyang Central Hospital. Patients were followed up for adverse events (AEs) during the trial, using the CommonTerminology Criteria for Adverse Events v5.0(CTCAE v5.0) as the standard. Tumour response after treatment was assessed using computerized tomography. RESULTS: The 14 patients (age range, 35-84 years) underwent HIFU ablation at 19 metastatic sites and systemic immunotherapy. The mean lesion volume was 179.9 cm3 (maximum: 733.1 cm3). Median follow-up for this trial was 9 months (range: 3-21) months. The study is clinically feasible and acceptable to patients. CONCLUSION: This prospective study confirmed that HIFU combined with immunotherapy is clinically feasible and safe for treating liver metastases.

Feasibility, safety and efficacy of high intensity focused ultrasound ablation as a preoperative treatment for challenging hysteroscopic myomectomy.

PURPOSE: To investigate the feasibility, safety and efficacy of high intensity focused ultrasound ablation (HIFU) as a preoperative treatment for challenging hysteroscopic myomectomies. MATERIALS AND METHODS: A total of 75 patients diagnosed with types 0-III of uterine fibroids were enrolled. Based on the Size, Topography, Extension of the base, Penetration and lateral Wall position (STEPW) classification scoring system, 25 cases with a score ≥ 5 points were treated with HIFU followed by hysteroscopic myomectomy (HIFU + HM group), whereas 50 cases with a score < 5 points were treated with hysteroscopic myomectomy (HM group). RESULTS: The median preoperative STEPW score was 7 in the HIFU + HM group and 2 in the HM group. The average non-perfused volume (NPV) ratio achieved in fibroids after HIFU was 86.87%. Patients in the HIFU + HM group underwent hysteroscopic myomectomy one to four days after HIFU, and downgrading was observed in 81.81% of fibroids. The operation time for patients in the HIFU + HM group was 73 min and the success rate of myomectomy in a single attempt was 60%. The volume of distention medium used during the operation was greater in the HIFU + HM group than in the HM group (15,500 ml vs. 7500 ml). No significant difference was observed between the two groups in terms of intraoperative blood loss, the incidence of intraoperative and postoperative complications, menstrual volume score, or uterine fibroid quality of life score. CONCLUSION: HIFU can be utilized as a preoperative treatment for large submucosal fibroids prior to hysteroscopic myomectomy. HIFU offers a novel approach in the management of this subset of patients.

Risk factors affecting long-term efficacy of ultrasound-guided high-intensity focused ultrasound treatment for multiple uterine fibroids.

OBJECTIVES: To investigate the long-term efficacy of ultrasound-guided high-intensity focused ultrasound (USgHIFU) for multiple uterine fibroids and the factors associated with recurrence. MATERIALS AND METHODS: Five hundred and forty-nine patients with multiple uterine fibroids treated with USgHIFU from June 2017 to June 2019 were retrospectively analyzed. The Pictorial Blood Loss Assessment Chart (PBAC) was used to assess menstrual blood loss. The patients were asked to undergo pre- and post-USgHIFU magnetic resonance imaging (MRI) and complete routine follow-up after USgHIFU. Cox regression analysis was used to investigate the risk factors associated with recurrence. RESULTS: The median number of fibroids per patient was 3 (interquartile range: 3-4), and a total of 1371 fibroids were treated. Among them, 446 patients completed 3 years follow-up. Recurrence, defined as PBAC score above or equal to 100 and/or the residual fibroid volume increased by 10%, was detected in 90 patients within 3 years after USgHIFU, with a cumulative recurrence rate of 20.2% (90/446). The multi-factor Cox analysis showed that age was a protective factor for recurrence. Younger patients have a greater chance of recurrence than older patients. Mixed hyperintensity of fibroids on T2WI and treatment intensity were risk factors for recurrence. Patients with hyperintense uterine fibroids and treated with lower treatment intensity were more likely to experience recurrence than other patients after USgHIFU. No major adverse effects occurred. CONCLUSIONS: USgHIFU can be used to treat multiple uterine fibroids safely and effectively. The age, T2WI signal intensity and treatment intensity are factors related to recurrence.

Mild hyperthermia with magnetic resonance- guided high intensity focused ultrasound combined with salvage chemoradiation for recurrent rectal cancer.

INTRODUCTION: Pelvic recurrences from rectal cancer present a challenging clinical scenario. Hyperthermia represents an innovative treatment option in combination with concurrent chemoradiation to enhance therapeutic effect. We provide the initial results of a prospective single center feasibility study (NCT02528175) for patients undergoing rectal cancer retreatment using concurrent chemoradiation and mild hyperthermia with MR-guided high intensity focused ultrasound (MR-HIFU). METHODS: All patients were deemed ineligible for salvage surgery and were evaluated in a multidisciplinary fashion with a surgical oncologist, radiation oncologist and medical oncologist. Radiation was delivered to a dose of 30.6 Gy in 1.8 Gy per fraction with concurrent capecitabine. MR-HIFU was delivered on days 1, 8 and 15 of concurrent chemoradiation. Our primary objective was feasibility and toxicity. RESULTS: Six patients (total 11 screened) were treated with concurrent chemoradiation and mild hyperthermia with MR-HIFU. Tumor size varied between 3.1-16.6 cm. Patients spent an average of 228 min in the MRI suite and sonication with the external transducer lasted an average of 35 min. There were no complications on the day of the MR-HIFU procedure and all acute toxicities (no grade >/=3 toxicities) resolved after completion of treatment. There were no late grade >/=3 toxicities. CONCLUSION: Mild hyperthermia with MR-HIFU, in combination with concurrent chemoradiation for appropriately selected patients, is safe for localized pelvic recurrences from rectal cancer. The potential for MR-HIFU to be applied in the recurrent setting in rectal cancer treatment requires further technical development and prospective evaluation.

A Case of Hemi-ablation with High-intensity Focused Ultrasound for a Localized Reducted Solitary Lesion in the Prostate.

Recently, effectiveness of local treatment for oncological outcomes for patients with metastatic prostate cancer (PC) has been reported. We performed hemi-ablation with high-intensity focused ultrasound (HIFU) for a patient with a localized reducted solitary lesion in the prostate, which was diagnosed with magnetic resonance imaging (MRI)-transrectal ultrasound fusion image-guided target biopsy with PSA level of 0.24 ng/mL, after androgen receptor signaling inhibitors (ARSIs) and chemotherapy for metastatic PC. Prostate specific antigen levels decreased to 0.01ng/mL at 1 month after the treatment, and cancer suspicious lesion disappeared on MRI. During the follow-up of 24 months, there was no elevation of PSA level with no severe complication related to the treatment. HIFU has possibility to be an effective and minimally invasive treatment as a local treatment for the localized reducted solitary lesion in the prostate after ARSIs and chemotherapy for metastatic PC.

The Impact of High Intensity Focused Ultrasound (HIFU) on Tumor-Specific Immune Responses of Prostate Cancer.

High intensity focused ultrasound (HIFU), also referred to as focused ultrasound surgery (FUS), has garnered recent attention as a non-invasive therapeutic strategy for prostate cancer. It utilizes focused acoustic energy to achieve localized thermal ablation, while also potentially exerting immunomodulatory effects. This review aims to elucidate the mechanisms underlying how HIFU influences tumor-specific immune responses in prostate cancer. These mechanisms include the release of tumor-associated antigens and damage-associated molecular patterns, the activation of innate immune cells, the facilitation of antigen presentation to adaptive immune cells, the enhancement of activation and proliferation of tumor-specific cytotoxic T lymphocytes, and the attenuation of the immunosuppressive tumor microenvironment by reducing the activity of regulatory T cells and myeloid-derived suppressor cells. Both preclinical investigations and emerging clinical data in prostate cancer models highlight HIFU's potential to modulate the immune system, as evidenced by increased infiltration of effector immune cells, elevated levels of pro-inflammatory cytokines, and improved responsiveness to immune checkpoint inhibitors. HIFU induces immunogenic cell death, leading to the release of tumor antigens and danger signals that activate dendritic cells and facilitate cross-presentation to cytotoxic T cells. Additionally, FUS ablation reduces immunosuppressive cells and increases infiltration of CD8+ T cells into the tumor, reshaping the tumor microenvironment. By priming the immune system while overcoming immunosuppression, combining FUS with other immunotherapies like checkpoint inhibitors and cancer vaccines holds promise for synergistic anti-tumor effects. Despite challenges in optimizing parameters and identifying suitable patients, FUS represents a novel frontier by modulating the tumor microenvironment and enhancing anti-tumor immunity through a non-invasive approach.

[Unilateral thalamotomy with high intensity focal ultrasound in patients with refractory essential tremor: a comparative study between patients under and over 70 years of age]. / Talamotomía unilateral con ultrasonidos focales de alta intensidad en pacientes con temblor esencial refractario: un estudio comparativo entre pacientes menores y mayores de 70 años.

INTRODUCTION: High intensity focal ultrasound (HIFU) thalamotomy is a novel treatment for refractory tremor. This study aims to compare the reduction in tremor intensity and adverse effects of treatment between patients younger and older than 70 years of age. PATIENTS AND METHODS: All the patients with refractory essential tremor treated with HIFU between March 2021 and March 2023 were included consecutively. Various demographic and clinical variables were analysed, including age and the items on the Clinical Rating Scale for Tremor (CRST). Cerebral vascular pathology was quantified using the Fazekas scale. Outcomes and adverse effects were compared between the patients aged 70 years or younger, and those older than 70 years. RESULTS: Ninety patients were included, and 50 of them were over 70 years old. Prior to treatment, the CRST A + B score was 20.4 ± 5.7 among those under 70 years of age, and 23.3 ± 5.1 in those older (p = 0.013). At six months after treatment, the mean was 3.8 ± 5.1 and 4.8 ± 4.5, respectively (p = 0.314). We found no significant differences in the CRST C score (2.8 ± 4.1 and 3.5 ± 4.8, p = 0.442). There were also no significant differences between the patients with vascular pathology (Fazekas = 1) and those without (4.6 ± 7.3 and 4.3 ± 4, p = 0.832). There were no differences in the presence of adverse effects between the groups based on age and vascular pathology. CONCLUSIONS: Contrary to traditional opinion, older patients do not have a poorer response or a higher rate of adverse effects after HIFU treatment.

TITLE: Talamotomía unilateral con ultrasonidos focales de alta intensidad en pacientes con temblor esencial refractario: un estudio comparativo entre pacientes menores y mayores de 70 años.Introducción. La talamotomía con ultrasonidos focales de alta intensidad (HIFU) es un tratamiento novedoso para el temblor refractario. El objetivo de este estudio es comparar la reducción en la intensidad del temblor y los efectos adversos del tratamiento entre pacientes menores y mayores de 70 años. Pacientes y métodos. Se incluyó consecutivamente a todos los pacientes con temblor esencial refractario tratados con HIFU entre marzo de 2021 y marzo de 2023. Se analizaron diferentes variables demográficas y clínicas, incluyendo la edad y los apartados de la Clinical Rating Scale for Tremor (CRST). Se cuantificó la patología vascular cerebral mediante la escala de Fazekas. Se compararon los resultados y los efectos adversos entre los grupos de edad de 70 años o menos y de más de 70 años. Resultados. Se incluyó a 90 pacientes, 50 de ellos de más de 70 años. Previamente al tratamiento, la CRST A + B era de 20,4 ± 5,7 en los menores de 70 años y de 23,3 ± 5,1 en los mayores (p = 0,013). A los seis meses tras el tratamiento, la media fue de 3,8 ± 5,1 y 4,8 ± 4,5, respectivamente (p = 0,314). No hallamos diferencias significativas en la CRST C (2,8 ± 4,1 y 3,5 ± 4,8, p = 0,442). Tampoco hubo diferencias significativas entre pacientes con patología vascular (Fazekas = 1) y sin ella (4,6 ± 7,3 y 4,3 ± 4, p = 0,832). No hubo diferencias en la presencia de efectos adversos entre los grupos de edad y de patología vascular. Conclusiones. En contra de lo tradicionalmente concebido, los pacientes de mayor edad no tienen una peor respuesta ni una mayor tasa de efectos adversos tras el tratamiento con HIFU.

Patient Preferences for Benefit and Risk Associated With High Intensity Focused Ultrasound for the Ablation of Prostate Tissue in Men With Localized Prostate Cancer.

INTRODUCTION: Food and Drug Administration must make decisions about emerging high intensity focused ultrasound (HIFU) devices that may lack relevant clinical oncologic data but present with known side effects. This study aims to capture patients' perspective by quantifying their preferences regarding the available benefit and important side effects associated with HIFU for localized prostate cancer. MATERIALS AND METHODS: Preferences for HIFU outcomes were examined using a discrete choice experiment survey. Participants were asked to choose a preferred treatment option in 9 choice questions. Each included a pair of hypothetical treatment profiles that have similar attributes/outcomes with varying levels. Outcomes included prostate biopsy outcome and treatment-related risks of erectile dysfunction (ED) and urinary incontinence (UI). We calculated the maximum risk of side effect patients were willing to tolerate in exchange for increased benefit. Preferences were further explored via clinical and demographic data. RESULTS: About 223 subjects with a mean age of 64.8 years completed the survey. Respondents were willing to accept a 1.51%-point increase in new ED risk for a 1%-point increase in favorable biopsy outcome. They were also willing to accept a 0.93%-point increase in new UI risk for a 1%-point increase in biopsy outcome. Subjects who perceived their cancer to be more aggressive had higher risk tolerance for UI. Younger men were willing to tolerate less ED risk than older men. Respondents with greater than college level of education had a lower risk tolerance for ED or UI. CONCLUSIONS: Results may inform development and regulatory evaluation for future HIFU ablation devices by providing supplemental information from the patient perspective.

Complications and adverse events of high-intensity focused ultrasound in its application to gynecological field - a systematic review and meta-analysis.

OBJECTIVE: To analyze and summarize the types, incidence rates and relevant influencing factors of adverse events (AEs) after high-intensity focused ultrasound ablation of gynecological diseases and provide reference and basis for handling such events in clinical practice. METHOD: We searched PubMed, Cochrane Library, Web of Science and Embase databases to retrieve all literature since its establishment until February 2024. We evaluated the quality of included literature and publication bias and conducted a meta-analysis of single group rates for various AEs using Stata 17.0. RESULTS: This systematic review finally included 41 articles. We summarized 34 kinds of AEs in 7 aspects and conducted a single group rate meta-analysis and sub-group analysis of 16 kinds of AEs. Among the common AEs of High-Intensity Focused Ultrasound (HIFU), the incidence of lower abdominal pain/pelvic pain is 36.1% (95% CI: 24.3%∼48.8%), vaginal bleeding is 20.6% (95% CI: 13.9%∼28.0%), vaginal discharge is 14.0% (95% CI: 9.6%∼19.1%), myoma discharge is 24% (95% CI: 14.6%∼34.8%), buttock pain is 10.8% (95% CI: 6.0%∼16.5%) and sacral pain is 10% (95% CI: 8.8%∼11.2%). Serious complications include uterine rupture, necrotic tissue obstruction requiring surgical intervention, third degree skin burns and persistent lower limb pain or movement disorders. CONCLUSION: The common AEs after HIFU surgery are mostly mild and controllable, and the incidence of serious complications is extremely low. By reasonable prevention and active intervention, these events can be further reduced, making it a safe and effective treatment method. It is a good choice for patients who crave noninvasive treatment or have other surgical contraindications.

Pilot Study on Boiling Histotripsy Treatment of Human Leiomyoma Ex Vivo.

OBJECTIVE: As an alternative to surgical excision and magnetic resonance-guided thermal high-intensity focused ultrasound ablation of uterine leiomyoma, this work was aimed at pilot feasibility demonstration of use of ultrasound-guided boiling histotripsy for non-invasive non-thermal fractionation of human uterine leiomyoma ex vivo. METHODS: A custom-made sector ultrasound transducer of 1.5-MHz operating frequency and nominal f-number F# = 0.75 was used to produce a volumetric lesion (two layers of 5 × 5 foci with a 1 mm step) in surgically resected human leiomyoma ex vivo. A sequence of 10 ms pulses (P+/P-/As = 157/-25/170 MPa in situ) with 1% duty cycle was delivered N = 30 times per focus under B-mode guidance. The treatment outcome was evaluated via B-mode imaging and histologically with hematoxylin and eosin and Masson's trichrome staining. RESULTS: The treatment was successfully performed in less than 30 min and resulted in formation of a rectangular lesion visualized on B-mode images during the sonication as an echogenic region, which sustained for about 10 min post-treatment. Histology revealed loss of cellular structure, necrotic debris and globules of degenerated collagen in the target volume surrounded by injured smooth muscle cells. CONCLUSION: The pilot experiment described here indicates that boiling histotripsy is feasible for non-invasive mechanical disintegration of human uterine leiomyoma ex vivo under B-mode guidance, encouraging further investigation and optimization of this potential clinical application of boiling histotripsy.

Histotripsy and Catheter-Directed Lytic: Efficacy in Highly Retracted Porcine Clots In Vitro.

OBJECTIVE: Standard treatment for deep vein thrombosis (DVT) involves catheter-directed anticoagulants or thrombolytics, but the chronic thrombi present in many DVT cases are often resistant to this therapy. Histotripsy has been found to be a promising adjuvant treatment, using the mechanical action of cavitating bubble clouds to enhance thrombolytic activity. The objective of this study was to determine if histotripsy enhanced recombinant tissue plasminogen activator (rt-PA) thrombolysis in highly retracted porcine clots in vitro in a flow model of occlusive DVT. METHODS: Highly retracted porcine whole blood clots were treated for 1 h with either catheter-directed saline (negative control), rt-PA (lytic control), histotripsy, DEFINITY and histotripsy or the combination of rt-PA and histotripsy with or without DEFINITY. Five-cycle, 1.5 MHz histotripsy pulses with a peak negative pressure of 33.2 MPa and pulse repetition frequency of 40 Hz were applied along the clot. B-Mode and passive cavitation images were acquired during histotripsy insonation to monitor bubble activity. RESULTS: Clots subjected to histotripsy with and without rt-PA exhibited greater thrombolytic efficacy than controls (7.0% flow recovery or lower), and histotripsy with rt-PA was more efficacious than histotripsy with saline (86.1 ± 10.2% compared with 61.7 ± 19.8% flow recovery). The addition of DEFINITY to histotripsy with or without rt-PA did not enhance either thrombolytic efficacy or cavitation dose. Cavitation dose generally did not correlate with thrombolytic efficacy. CONCLUSION: Enhancement of thrombolytic efficacy was achieved using histotripsy, with and without catheter-directed rt-PA, in the presence of physiologic flow. This suggests these treatments may be effective as therapy for DVT.

Neuronavigation-Guided Transcranial Histotripsy (NaviTH) System.

OBJECTIVE: The goal of the work described here was to develop the first neuronavigation-guided transcranial histotripsy (NaviTH) system and associated workflow for transcranial ablation. METHODS: The NaviTH system consists of a 360-element, 700 kHz transmitter-receiver-capable transcranial histotripsy array, a clinical neuronavigation system and associated equipment for patient-to-array co-registration and therapy planning and targeting software systems. A workflow for NaviTH treatments, including pre-treatment aberration correction, was developed. Targeting errors stemming from target registration errors (TREs) during the patient-to-array co-registration process, as well as focal shifts caused by skull-induced aberrations, were investigated and characterized. The NaviTH system was used in treatments of two <96 h post-mortem human cadavers and in experiments in two excised human skullcaps. RESULTS: The NaviTH was successfully used to create ablations in the cadaver brains as confirmed in post-treatment magnetic resonance imaging A total of three ablations were created in the cadaver brains, and targeting errors of 9, 3.4 and 4.4 mm were observed in corpus callosum, septum and thalamus targets, respectively. Errors were found to be caused primarily by TREs resulting from transducer tracking instrument design flaws and imperfections in the treatment workflow. Transducer tracking instrument design and workflow improvements reduced TREs to <2 mm, and skull-induced focal shifts, following pre-treatment aberration correction, were 0.3 mm. Total targeting errors of the NaviTH system following the noted improvements were 2.5 mm. CONCLUSIONS: The feasibility of using the first NaviTH system in a human cadaver model has been determined. Although accuracy still needs to be improved, the proposed system has the potential to allow for transcranial histotripsy therapies without requiring active magnetic resonance treatment guidance.

Nanoparticle-Mediated Histotripsy Using Dual-Frequency Pulsing Methods.

OBJECTIVE: Nanoparticle-mediated histotripsy (NMH) is a novel ablation method that combines nanoparticles as artificial cavitation nuclei with focused ultrasound pulsing to achieve targeted, non-invasive, and cell-selective tumor ablation. The study described here examined the effect of dual-frequency histotripsy pulsing on the cavitation threshold, bubble cloud characteristics, and ablative efficiency in NMH. High-speed optical imaging was used to analyze bubble cloud characteristics and to measure ablation efficiency for NMH inside agarose tissue phantoms containing perfluorohexane-filled nanocone clusters, which were previously developed to reduce the histotripsy cavitation threshold for NMH. METHODS: Dual-frequency histotripsy pulsing was applied at a 1:1 pressure ratio using a modular 500 kHz and 3 MHz dual-frequency array transducer. Optical imaging results revealed predictable, well-defined bubble clouds generated for all tested cases with similar reductions in the cavitation thresholds observed for single-frequency and dual-frequency pulsing. RESULTS: Dual-frequency pulsing was seen to nucleate small, dense clouds in agarose phantoms, intermediate in size of their component frequencies but closer in area to that of the higher component frequency. Red blood cell experiments revealed complete ablations were generated by dual-frequency NMH in all phantoms in <1500 pulses. This result was a significant increase in ablation efficiency compared with the ∼4000 pulses required in prior single-frequency NMH studies. CONCLUSION: Overall, this study indicates the potential for using dual-frequency histotripsy methods to increase the ablation efficacy of NMH.

Biomechanical testing of ex vivo porcine tendons following high intensity focused ultrasound thermal ablation.

INTRODUCTION: Magnetic resonance-guided focused ultrasound (MRgFUS) has been demonstrated to be able to thermally ablate tendons with the aim to non-invasively disrupt tendon contractures in the clinical setting. However, the biomechanical changes of tendons permitting this disrupting is poorly understood. We aim to obtain a dose-dependent biomechanical response of tendons following magnetic resonance-guided focused ultrasound (MRgFUS) thermal ablation. METHODS: Ex vivo porcine tendons (n = 72) were embedded in an agar phantom and randomly assigned to 12 groups based on MRgFUS treatment. The treatment time was 10, 20, or 30s, and the applied acoustic power was 25, 50, 75, or 100W. Following each MRgFUS treatment, tendons underwent biomechanical tensile testing on an Instron machine, which calculated stress-strain curves during tendon elongation. Rupture rate, maximum treatment temperature, Young's modulus and ultimate strength were analyzed for each treatment energy. RESULTS: The study revealed a dose-dependent response, with tendons rupturing in over 50% of cases when energy delivery exceeded 1000J and 100% disruption at energy levels beyond 2000J. The achieved temperatures during MRgFUS were directly proportional to energy delivery. The highest recorded temperature was 56.8°C ± 9.34 (3000J), while the lowest recorded temperate was 18.6°C ± 0.6 (control). The Young's modulus was highest in the control group (47.3 MPa ± 6.5) and lowest in the 3000J group (13.2 MPa ± 5.9). There was no statistically significant difference in ultimate strength between treatment groups. CONCLUSION: This study establishes crucial thresholds for reliable and repeatable disruption of tendons, laying the groundwork for future in vivo optimization. The findings prompt further exploration of MRgFUS as a non-invasive modality for tendon disruption, offering hope for improved outcomes in patients with musculotendinous contractures.

Noninvasive release of tendons using MRI guided focused ultrasound: a hybrid therapy using long-pulse focused ultrasound followed by thermal ablation.

INTRODUCTION: Magnetic Resonance-guided Focused Ultrasound (MRgFUS) thermal ablation is an effective noninvasive ultrasonic therapy to disrupt in vivo porcine tendon but is prone to inducing skin burns. We evaluated the safety profile of a novel hybrid protocol that minimizes thermal spread by combining long-pulse focused ultrasound followed by thermal ablation. METHODS: In-vivo Achilles tendons (hybrid N = 15, thermal ablation alone N = 21) from 15 to 20 kg Yorkshire pigs were randomly assigned to 6 treatment groups in two studies. The first (N = 21) was ablation (600, 900, or 1200 J). The second (N = 15) was hybrid: pulsed FUS (13.5 MPa peak negative pressure) followed by ablation (600, 900, or 1200 J). Measurements of ankle range of motion, tendon temperature, thermal dose (240 CEM43), and assessment of skin burn were performed in both groups. RESULTS: Rupture was comparable between the two protocols: 1/5 (20%), 5/5 (100%) and 5/5 (100%) for hybrid protocol, compared to 2/7 (29%), 6/7 (86%) and 7/7 (100%) for the ablation-only protocol with energies of 600, 900, and 1200 J, respectively. The hybrid protocol produced lower maximum temperatures, smaller areas of thermal dose, fewer thermal injuries to the skin, and fewer full-thickness skin burns. The standard deviation for the area of thermal injury was also smaller for the hybrid protocol, suggesting greater predictability. CONCLUSION: This study demonstrated a hybrid MRgFUS protocol combining long-pulse FUS followed by thermal ablation to be noninferior and safer than an ablation-only protocol for extracorporeal in-vivo tendon rupture for future clinical application for noninvasive release of contracted tendon.

Volumetric hyperthermia delivery using the ExAblate Body MR-guided focused ultrasound system.

OBJECTIVES: To investigate image-guided volumetric hyperthermia strategies using the ExAblate Body MR-guided focused ultrasound ablation system, involving mechanical transducer movement and sector-vortex beamforming. MATERIALS AND METHODS: Acoustic and thermal simulations were performed to investigate volumetric hyperthermia using mechanical transducer movement combined with sector-vortex beamforming, specifically for the ExAblate Body transducer. The system control in the ExAblate Body system was modified to achieve fast transducer movement and MR thermometry-based hyperthermia control, mechanical transducer movements and electronic sector-vortex beamforming were combined to optimize hyperthermia delivery. The experimental validation was performed using a tissue-mimicking phantom. RESULTS: The developed simulation framework allowed for a parametric study with varying numbers of heating spots, sonication durations, and transducer movement times to evaluate the hyperthermia characteristics for mechanical transducer movement and sector-vortex beamforming. Hyperthermic patterns involving 2-4 sequential focal spots were analyzed. To demonstrate the feasibility of volumetric hyperthermia in the system, a tissue-mimicking phantom was sonicated with two distinct spots through mechanical transducer movement and sector-vortex beamforming. During hyperthermia, the average values of Tmax, T10, Tavg, T90, and Tmin over 200 s were measured within a circular ROI with a diameter of 10 pixels. These values were found to be 8.6, 7.9, 6.6, 5.2, and 4.5 °C, respectively, compared to the baseline temperature. CONCLUSIONS: This study demonstrated the volumetric hyperthermia capabilities of the ExAblate Body system. The simulation framework developed in this study allowed for the evaluation of hyperthermia characteristics that could be implemented with the ExAblate MRgFUS system.

Study on the safety and efficacy of HIFU in the treatment of VaIN.

PURPOSE: This study aimed to investigate the safety and efficacy of High-Intensity Focused Ultrasound (HIFU) treatment for vaginal intraepithelial neoplasia(VaIN). METHODS: Retrospective analysis was conducted on clinical, pathological, and follow-up data of 43 patients who underwent HIFU treatment for VaIN at Xiangya Third Hospital of Central South University between January 2018 and December 2022. The preliminary efficacy and safety of HIFU in treating VaIN were discussed. RESULTS: The 36 patients were analyzed, and the average age was 50.09 ± 12.06 years, including 24 patients with VaIN I and 12 patients with VaIN II. Five cases had a history of hysterectomy (4 due to cervical lesions, 1 due to hysteromyoma), and 2 cases had conization of cervical intraepithelial lesions (CIN). All 36 cases were complicated by human papillomavirus (HPV) infection, with 3 cases also having grade I-II CIN and undergoing cervical HIFU treatment. All patients successfully completed the HIFU treatment, with an average treatment time of 5.99 ± 1.25 min, treatment power of 3.5 W, and average total treatment dose of 1118.99 ± 316.20 J. Patients tolerated the treatment well, experiencing only slight pain with VAS score of 3. There was a mild postoperative burning sensation, which resolved within approximately 10-20 min. After 6 follow-up visits, 33 patients (91.66%) achieved cure, 1 patient (2.77%) showed persistence, 2 patients (5.55%) exhibited progression, and 27 patients (75%) tested negative for HPV. At 12 months of follow-up, the results were consistent with those of 6 months. No complications occurred during the procedure and the follow-up period. CONCLUSION: HIFU is a safe and effective treatment for VaIN. However, this study had a small sample size, a relatively short follow-up period, and lacked a control group, requiring further investigation.