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Abstract 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.

Barsha Shrestha,1 Sheetal Maria Rajan,1 Sultan Aati,1,2 Emielda Yusiharni,3 Omar Kujan,1 Martin Saunders,4 Amr Fawzy1 1UWA Dental School, The University of Western Australia, Perth, WA, Australia; 2Dental Health Department, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia; 3UWA XRD Facility, Material & Environmental Analysis Platform, The University of Western Australia, Perth, WA, Australia; 4Centre for Microscopy, Characterisation and Analysis, The University of Western Australia, Perth, WA, AustraliaCorrespondence: Amr Fawzy, UWA Dental School, The University of Western Australia, 17 Monash Avenue, Nedlands, WA, 6009, Australia, Tel +61894572434, Email amr.fawzy@uwa.edu.auBackground: Remineralization of dental enamel is an important intervention strategy for the treatment of demineralized lesions. Existing approaches have limitations such as failure to adequately reproduce both the ideal structural and mechanical properties of the native tooth. The ability of ultrasound to control and accelerate the crystallization processes has been widely reported. Therefore, a new approach was explored for in-vitro enamel remineralization involving the synergistic effect of high-intensity focused ultrasound (HIFU) coupled with calcium phosphate ion clusters (CPICs).Methods: The demineralized enamel was treated with CPICs, with or without subsequent HIFU exposure for different periods (2.5, 5, and 10 min). The specimens were characterized by scanning electron microscopy (SEM), atomic force microscopy (AFM), and Raman spectroscopy. The surface hardness and crystallographic properties of the treated specimens were evaluated using Vickers microhardness testing and X-ray diffraction (XRD), respectively.Results: SEM revealed distinct, organized, and well-defined prismatic structures, showing clear evidence of remineralization in the combined CPIC/HIFU treatment groups. AFM further revealed a decrease in the surface roughness values with increasing HIFU exposure time up to 5 min, reflecting the obliteration of interprismatic spaces created during demineralization. The characteristic Raman band at 960 cm− 1 associated with the inorganic phase of enamel dominated well in the HIFU-treated specimens. Importantly, microhardness testing further demonstrated that new mineral growth also recovered the mechanical properties of the enamel in the HIFU-exposed groups. Critical to our aspirations for developing this into a clinical process, these results were achieved in only 5 min.Conclusion: HIFU exposure can synergise and significantly accelerate in-vitro enamel remineralization process via calcium phosphate ion clusters. Therefore, this synergistic approach has the potential for use in future clinical interventions. Keywords: enamel remineralization, high intensity focused ultrasound, calcium phosphate ion cluster

Abstract Introduction In dermatology, inflammatory skin conditions impose a substantial burden worldwide, with existing therapies showing limited efficacy and side effects. This report aims to compare a novel immunological activation induced by hyperthermic 20 MHz high intensity focused ultrasound (HIFU) with conventional cryotherapy. The bioeffects from the two methods are initially investigated by numerical models, and subsequently compared to clinical observations after treatment of a patient with the inflammatory disease granuloma annulare (GA). Methods Clinical responses to moderate energy HIFU and cryotherapy were analysed using numerical models. HIFU-induced pressure and heat transfer were calculated, and a three-layer finite element model simulated temperature distribution and necrotic volume in the skin. Model output was compared to 22 lesions treated with HIFU and 10 with cryotherapy in a patient with GA. Results Cryotherapy produced a necrotic volume of 138.5 mm3 at − 92.7 °C. HIFU at 0.3–0.6 J/exposure and focal depths of 0.8 or 1.3 mm generated necrotic volumes up to only 15.99 mm3 at temperatures of 68.3–81.2 °C. HIFU achieved full or partial resolution in all treated areas, confirming its hyperthermic immunological activation effect, while cryotherapy also resolved lesions but led to scarring and dyspigmentation. Conclusion Hyperthermic immunological activation of 20 MHz HIFU shows promise for treating inflammatory skin conditions as exemplified by GA. Numerical models demonstrate minimal skin necrosis compared to cryotherapy. Suggested optimal HIFU parameters are 1.3 mm focal depth, 0.4–0.5 J/exposure, 1 mm spacing, and 1 mm margin. Further studies on GA and other inflammatory diseases are recommended.

Background High intensity focused ultrasound (HIFU) ablation treatment for uterine fibroids and adenomyosis has been long developed. The aim of this study is to investigate miRNA profile changes in vaginal secretions after HIFU treatment and their clinical relevance.Methods We prospectively collected vaginal secretions samples from 8 patients (1 with adenomyosis and 7 with fibroids) before and after HIFU treatment. RNA was isolated and miRNA profiles were analyzed using next-generation sequencing (NGS) sequencing.Results Our study showed miRNA profile change in vaginal secretion samples after HIFU treatment for uterine fibroids/adenomyosis, with 33 miRNAs upregulated and 6 downregulated overall. In fibroid cases, 31 miRNAs were upregulated and 7 downregulated, while in adenomyosis case, 41 miRNAs were upregulated and 71 downregulated. Four miRNAs (hsa-miR-7977, hsa-miR-155-5p, hsa-miR-191-5p, hsa-miR-223-3p) showed significant differences after HIFU treatment in fibroid cases, except in case 5 with the lowest treatment sonications (425 sonications) and energy input (170000 J). hsa-miR-7977 consistently showed downregulation after HIFU treatment. hsa-miR-155-5p were downregulated in case 4 with lowest treatment efficiency (2439.64 J/cm3), while they were upregulated in other cases. hsa-miR-191-5p and hsa-miR-223-3p were downregulated in cases 4 and 7, with case 7 influenced by high sonication and energy due to multiple fibroids.Conclusions HIFU treatment altered miRNA profiles in fibroids/adenomyosis patients. Notably, hsa-miR-7977, hsa-miR-155-5p, hsa-miR-191-5p, and hsa-miR-223-3p showed significant changes in fibroid cases, except in low-energy treatments. hsa-miR-7977 consistently decreased post-treatment, while hsa-miR-155-5p decreased in the least efficient cases. Further research is needed for validation.

Objective This study aims to assess the clinical efficacy and safety of combining high-intensity focused ultrasound (HIFU) with ultrasound-guided suction curettage for the treatment of cesarean scar pregnancy (CSP) at different time intervals.Methods A total of 115 CSP patients were enrolled and divided into two groups based on the time between HIFU ablation and suction curettage. Group A (n = 50) underwent suction curettage 24-48 h after HIFU ablation, while Group B (n = 65) had suction curettage within 6 h of HIFU ablation. The study compared and analyzed the clinical characteristics, treatment success rates, and intraoperative hemorrhage during ultrasound-guided suction curettage.Results The demographic characteristics of the two groups were similar, with no statistically significant differences observed in HIFU parameters, treatment success rates, blood loss, the use of Foley catheter balloons, or hospital expenses (p > 0.05). Importantly, suction curettage performed within 6 h after HIFU ablation resulted in shorter hospitalization times compared to suction curettage performed 24-48 h after the ablation (p

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.

AbstractIntroduction 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.

Abstract The heterogeneity of triple‐negative breast cancers (TNBC) remains challenging for various treatments. Ferroptosis, a recently identified form of cell death resulting from the unrestrained peroxidation of phospholipids, represents a potential vulnerability in TNBC. In this study, a high intensity focused ultrasound (HIFU)‐driven nanomotor is developed for effective therapy of TNBC through induction of ferroptosis. Through bioinformatics analysis of typical ferroptosis‐associated genes in the FUSCCTNBC dataset, gambogic acid is identified as a promising ferroptosis drug and loaded it into the nanomotor. It is found that the rapid motion of nanomotors propelled by HIFU significantly enhanced tumor accumulation and penetration. More importantly, HIFU not only actuated nanomotors to trigger effective ferroptosis of TNBC cells, but also drove nanomotors to activate ferroptosis‐mediated antitumor immunity in primary and metastatic TNBC models, resulting in effective tumor regression and prevention of metastases. Overall, HIFU‐driven nanomotors show great potential for ferroptosis‐immunotherapy of TNBC.

Prostate cancer is the second most common malignant tumor in men worldwide, and its incidence is increasing in China. Treatment methods of prostate cancer include surgery, radiotherapy, chemotherapy, endocrine therapy, and local therapy. Compared to all treatment options for prostate cancer, local treatment has the advantage of less trauma and fewer complications. With the wide application of PSA screening, improvement and enhancement of transperineal puncture technology under template positioning and the development of multi-parameter MRI, more and more low-grade and localized prostate cancer are detected. Most prostate cancer patients receive total gland therapy after diagnosis, but patients with localized prostate cancer may not benefit from treatment because of the side effects of total gland therapy. With the development of imaging technology and the "main focus" theory, focal therapy techniques have been greatly developed. Focal therapy (FT) is a treatment method for localized prostate cancer (Pca), which mainly targets low and medium-risk localized disease to reduce whole-gland treatment. Such as radical prostatectomy (RP) or the adverse effects of radical external radiotherapy, FT has the advantage of preserving more sexual and bladder function while controlling the tumor. The current focal therapy techniques used in clinic mainly include high-intensity focused ultrasound, focal laser ablation, cryotherapy, irreversible electroporation, and photodynamic therapy. In this study, we reviewed the clinical trials of focal therapy in recent years and found that high-intensity focused ultrasound and focal laser ablation have better failure-free survival and postoperative functional control.

AbstractIn transabdominal histotripsy, ultrasound pulses are focused into the body to noninvasively destroy soft tissues via cavitation. However, the ability to focus is limited by phase aberration, or decorrelation of the ultrasound pulses due to spatial variation in the speed of sound throughout heterogeneous tissue. Phase aberration shifts, broadens, and weakens the focus, thereby reducing the safety and efficacy of histotripsy therapy. This paper reviews and discusses aberration effects in histotripsy and in related therapeutic ultrasound techniques (e.g., high intensity focused ultrasound), with an emphasis on aberration by soft tissues. Methods for aberration correction are reviewed and can be classified into two groups: model-based methods, which use segmented images of the tissue as input to an acoustic propagation model to predict and compensate phase differences, and signal-based methods, which use a receive-capable therapy array to detect phase differences by sensing acoustic signals backpropagating from the focus. The relative advantages and disadvantages of both groups of methods are discussed. Importantly, model-based methods can correct focal shift, while signal-based methods can restore substantial focal pressure, suggesting that both methods should be combined in a 2-step approach. Aberration correction will be critical to improving histotripsy treatments and expanding the histotripsy treatment envelope to enable non-invasive, non-thermal histotripsy therapy for more patients.

AbstractPurpose Surgical resection of the tendon is an effective treatment for severe contracture. Magnetic Resonance-guided Focused Ultrasound (MRgFUS) is a non-invasive ultrasonic therapy which produces a focal increase in temperature, subsequent tissue ablation and disruption. We evaluated MRgFUS as a clinically translatable treatment modality to non-invasively disrupt in vivo porcine tendons.Material and methods In vivo Achilles tendons (n = 28) from 15–20kg Yorkshire pigs (n = 16) were randomly assigned to 4 treatment groups of 600, 900, 1200 and 1500 J. Pretreatment range of motion (ROM) of the ankle joint was measured with the animal under general anesthesia. Following MRgFUS treatment, success of tendon rupture, ROM increase, temperature, thermal dosage, skin burn, and histology analyses were performed.Results Rupture success was found to be 29%, 86%, 100% and 100% for treatment energies of 600, 900, 1200 and 1500 J respectfully. ROM difference at 90° flexion showed a statistically significant change in ROM between 900 J and 1200 J from 16° to 27°. There was no statistical significance between other groups, but there was an increase in ROM as more energy was delivered in the treatment. For each of the respective treatment groups, the maximal temperatures were 58.4 °C, 63.3 °C, 67.6 °C, and 69.9 °C. The average areas of thermal dose measured were 24.3mm2, 53.2mm2, 77.8mm2 and 91.6mm2. The average areas of skin necrosis were 5.4mm2, 21.8mm2, 37.2mm2, and 91.4mm2. Histologic analysis confirmed tissue ablation and structural collagen fiber disruption.Conclusions This study demonstrated that MRgFUS is able to disrupt porcine tendons in vivo without skin incisions.

AbstractSince its inception about two decades ago, histotripsy – a non-thermal mechanical tissue ablation technique – has evolved into a spectrum of methods, each with distinct potentiating physical mechanisms: intrinsic threshold histotripsy, shock-scattering histotripsy, hybrid histotripsy, and boiling histotripsy. All methods utilize short, high-amplitude pulses of focused ultrasound delivered at a low duty cycle, and all involve excitation of violent bubble activity and acoustic streaming at the focus to fractionate tissue down to the subcellular level. The main differences are in pulse duration, which spans microseconds to milliseconds, and ultrasound waveform shape and corresponding peak acoustic pressures required to achieve the desired type of bubble activity. In addition, most types of histotripsy rely on the presence of high-amplitude shocks that develop in the pressure profile at the focus due to nonlinear propagation effects. Those requirements, in turn, dictate aspects of the instrument design, both in terms of driving electronics, transducer dimensions and intensity limitations at surface, shape (primarily, the F-number) and frequency. The combination of the optimized instrumentation and the bio-effects from bubble activity and streaming on different tissues, lead to target clinical applications for each histotripsy method. Here, the differences and similarities in the physical mechanisms and resulting bioeffects of each method are reviewed and tied to optimal instrumentation and clinical applications.

AbstractObjectives Our study aims at the comprehensive analysis of adverse events (AEs) in patients with symptomatic uterine fibroids (UFs) who underwent magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) in the last 6 years in one of the major Polish centers performing this type of therapy.Methods The presented retrospective case-control study was conducted in the Department of Obstetrics and Gynecology, Pro-Familia Hospital, Rzeszów in cooperation with the Second Department of Obstetrics and Gynecology, Center of Postgraduate Medical Education, Warsaw. The study enrolled 372 women with symptomatic UFs who underwent MR-HIFU and reported AEs during or after the procedure. The occurrence of particular AEs was analyzed. Statistical comparison of two cohorts (patients with and without AEs) was conducted based on epidemiological factors, UF characteristics, fat layer thickness, the presence of abdominal scars and technical parameters of the procedure.Results The overall mean occurrence rate of AEs was 8.9% (n = 33). No major AEs were reported. The only statistically significant risk factor of AEs was the treatment of type II UFs according to Funaki (OR 2.12, CI 95%, p = 0.043). Other investigated factors did not have a statistically significant influence on AE occurrence. Abdominal pain was the most common AE.Conclusion Our data showed that MR-HIFU seemed to be a safe procedure. The AE rate after the treatment is relatively low. According to the obtained data it seems that the occurrence of AEs does not depend on the technical parameters of the procedure and the volume, position and location of UFs. Further prospective, randomized studies and with long follow-up are necessary to confirm the final conclusions.

AbstractBackground Due to resistance and intolerance to chemotherapy, localized lesion resection may be required in some patients with Gestational trophoblastic neoplasia (GTN), which may lead to massive bleeding. In this case report, we describe the successful use of high-intensity focused ultrasound (HIFU) as an effective pretreatment method for surgical procedure in a patient with GTN to reduce the perioperative risk and the impact on fertility.Case presentation A 26-year-old woman was diagnosed with high-risk GTN (FIGO Stage III: 12 prognostic scores) after a hydatidiform mole. The fifth chemotherapy cycle was interrupted due to severe chemotherapy toxicity. However, the uterine lesion was still present and the beta-human chorionic gonadotropin (β-hCG) level was not restored to normal. Therefore, ultrasound-guided HIFU was performed as a pretreatment method to shrink the lesion and prevent massive bleeding during localized lesion resection. The effectiveness of ablation was evaluated immediately using contrast-enhanced ultrasound and Color Flow Doppler ultrasonography. One month after HIFU treatment, the uterine lesion was completely resected under hysteroscopic surgery. During the surgery, HIFU was found to have shrunk the lesion and there was minimal bleeding (5 mL). The uterine cavity morphology and menstruation returned to normal after surgery. The patient has showed no signs of recurrence as of one-year follow-up.Conclusion Ultrasound-guided HIFU ablation may be a new choice for high-risk GTN patients with chemoresistance or chemo-intolerance. As a noninvasive pretreatment method, HIFU can shrink the uterine lesion, and reduce the risk of bleeding with no obvious effect on fertility.

Abstract Background The treatment of gestational trophoblastic neoplasia (GTN) is one of the success stories in medical oncology. GTN in the cesarean scar is a rare entity, but most cases need to be treated with hysterectomy or localized uterine lesion resection because of chemoresistant lesions and/or massive bleeding. We present a patient with post-molar GTN in the cesarean scar who was non-invasively treated with ultrasound-guided high intensity focused ultrasound (HIFU) to preserve the uterus and fertility. Case presentation A 32-year-old woman was diagnosed with low-risk GTN (FIGO Stage I: 2 prognostic score) after partial hydatidiform mole. The 5th cycle of chemotherapy was interrupted because of persistent hepatic toxicity and impaired ovarian reserve function. However, the uterine lesion persisted (diameter of residual uterine lesion in the cesarean scar: 2.0 cm). Therefore, ultrasound-guided HIFU treatment was performed. A significant gray-scale change was observed during the HIFU treatment. Color Doppler ultrasonography and contrast-enhanced ultrasound (CEUS) was performed to evaluate the ablation effectiveness. Color Doppler ultrasonography showed disappearance of the signal of vascularity and CEUS showed no perfusion in the lesion located in the cesarean scar. The uterine lesion was obviously shrunken one month after HIFU treatment. Menstrual cycle resumed 48 days after HIFU. HIFU treatment decreased the number of chemotherapy cycles and there was complete disappearance of the GTN lesion at 4-month follow-up. The patient has shown no signs of recurrence as of 58-month follow-up. Conclusion Ultrasound-guided HIFU may be a useful alternative to lesion resection for GTN in the cesarean scar in patients who show chemoresistance or are not suitable for chemotherapy. It has the potential to ablate the residual uterine lesion noninvasively to preserve the uterus and fertility, avoiding perioperative risks of lesion resection, especially acute bleeding.

Objective To investigate the clinical efficacy and safety of high intensity focused ultrasound (HIFU) combined with ultrasound-guided suction curettage in patients with type I/II/III cesarean scar pregnancy (CSP).Methods A total of 153 patients with CSP were enrolled and classified according to the type of CSP. All of them were treated by HIFU combined with ultrasound-guided suction curettage. When active uterine bleeding was observed after curettage, a Foley balloon was used for hemostasis by compression. Baseline characteristics, technical parameters of HIFU, intraoperative blood loss in suction curettage, the time for serum β-HCG to return to normal levels, reproductive outcomes, and adverse effects were recorded and analyzed.Results 152 patients completed one session of HIFU combined with suction curettage except one patient transferred to surgery. Total energy used for ablation and the time for serum β-HCG return to normal level in type II and III were significantly higher than type I (p < .05). The treatment time and sonication time of HIFU in type III were significantly longer than type I (p < .05). Vaginal bleeding after curettage and the rate of using Foley catheter balloon in type III was larger than type I and II.Conclusions HIFU combined with ultrasound-guided suction curettage is a safe and effective treatment option for patients with type I/II/III CSP and desire for fertility. Patients with type III CSP were more dependent on Foley catheter balloon compression therapy than the other two types after HIFU combined with curettage.

Objective To investigate the effectiveness and safety of high-intensity focused ultrasound (HIFU) ablation for patients with colorectal liver metastases (CRLMs) who were unsuitable for hepatectomy.Methods This is a multicenter retrospective study. 238 CRLM patients underwent ultrasound-guided HIFU (USgHIFU) ablation in three medical centers from October 2014 to December 2020. Patients who had complete colorectal cancer resection, but exhibited extra-hepatic metastasis were excluded from this study. HIFU ablation procedure was performed, and contrast-enhanced MR imaging and/or contrast-enhanced CT examinations were conducted and mRECIST was used for the assessment of tumor ablation effectiveness before and after treatment, and every 3 months thereafter. Adverse events and complications were recorded.Results 43 CRML patients (27 male, 16 female, aged 29–82 years) were enrolled and underwent a USgHIFU ablation procedure. CR (complete response) was achieved in 21 patients, while PR (partial response) was observed in 21 patients and SD (stable disease) was achieved in one patient, respectively. The objective response rate was 97.7%. Median OS (overall survival) was estimated to be 31 months, and1-year and 18-month overall survival was 90.7% (39/43) and 72.1% (31/43), respectively. For CR and PR patients, the median OS was 35 months and 23 months, respectively (p = 0.00). The majority of adverse events were pain in 22 cases (51.2%) and local skin edema in 33 cases (76.7%). No severe adverse events or complications were reported and recorded.Conclusions USgHIFU ablation is a safe and effective treatment option for CRLM patients, especially for patients who are unsuitable for hepatectomy.

Objective To explore the learning curve of high intensity focus ultrasound (HIFU) treatment for breast fibroadenoma.Methods A database of 110 patients with 255 breast fibroadenomas who underwent HIFU treatment at two different clinical centers (Center 1 and 2) were retrospectively analyzed. The learning curves of HIFU treatment for breast fibroadenoma were drawn by CUSUM analysis in two centers, respectively. According to the inflection point of the learning curves, the treatment was divided into two groups: initial phase and consolidation phase. HIFU treatment parameters were compared between two groups. The effectiveness and safety results were also evaluated.Results The inflection points of the learning curves were the 60th treatment in Center 1 and the 65th treatment in Center 2. The screening time, treatment time, sonication time and hyperechoic scale change time were significantly shorter in consolidation phase than those in initial phase of the two centers (p

Background Abdominal wall endometriosis（AWE）is an unusual extra-pelvic endometriosis. Currently, multiple treatment modalities are available, but no clear guidelines exist for the management of large AWE.Materials and methods We present a 36-year-old female patient with a large AWE lesion who underwent cesarean section due to abnormal fetal position 8 years ago. The mass lesion of AWE located in rectus muscle fascia and rectus muscle with a size of 61 × 25 × 49mm.Results HIFU treatment was completed in one session. One day post-HIFU MRI showed the mass was completely ablated. After HIFU treatment, the cyclical abdominal pain disappeared. The mass lesion shrank during follow-up period and disappeared in 1 year after HIFU. No complication was observed after HIFU.Conclusion Surgical resection of AWE remains the standard of care. In patients with large AWE lesion located in rectus muscle fascia and rectus muscle where the muscle and fascia must be excised, HIFU treatment should be considered to avoid mesh implantation.

Objective To investigate the factors influencing the sonication dosage and efficiency of ultrasound-guided high intensity focused ultrasound (USgHIFU) for breast fibroadenomas.Materials and Methods Forty-nine patients with 78 breast fibroadenomas who underwent USgHIFU were retrospectively analyzed. The energy efficiency factor (EEF) was set as dependent variable, and the factors possibly influencing the sonication dosage, including age, body mass index (BMI), fibroadenoma size, distance from the shallow margin of the fibroadenoma to skin, distance from the deep margin of the fibroadenoma to pectoralis major, types of near field acoustic pathway, and Adler blood flow classification of ultrasound, were set as independent variables. The correlation between EEF and these independent variables were analyzed, and an optimal scaling regression model was established.Results Fibroadenoma size, distance from the shallow margin of the fibroadenoma to skin and type of near field acoustic pathway had significant correlation with EEF (p

BackgroundOur previous studies found that high-intensity focused ultrasound (HIFU) stimulated tumor-specific T cells in a mouse H22 tumor model, and adoptive transfer of the T cells from HIFU-treated mice could subsequently elicit stronger inhibition on the growth and progression of the implanted tumors. The aim of this study was to investigate the mechanism of T cells from focused ultrasound ablation in HIFU-mediated immunomodulation.MethodsSixty H22 tumor-bearing mice were treated by either HIFU or sham-HIFU, and 30 naïve syngeneic mice served as controls. All mice were euthanized on day 14 after HIFU and splenic T cell suspensions were obtained in each group. Using an adoptive cell transfer model, a total of 1 × 106 T cells from HIFU treated-mice were intravenously injected into each syngeneic H22 tumor-bearing mouse twice on day 3 and 4, followed by the sacrifice for immunological assessments at 14 days after the adoptive transfer.ResultsT cells from HIFU-treated mice could significantly enhance the cytotoxicity of CTLs (p < 0.001), with a significant increase of TNF-α (p < 0.001) and IFN-γ secretion (p < 0.001). Compared to control and sham-HIFU groups, the number of Fas ligand+ and perforin+ tumor-infiltrating lymphocytes (TILs) and apoptotic H22 tumor cells were significantly higher (p < 0.001) in the HIFU group. There were linear correlations between apoptotic tumor cells and Fas ligand+ TILs (r = 0.9145, p < 0.001) and perforin+ TILs (r = 0.9619, p < 0.001).ConclusionT cells from HIFU-treated mice can subsequently mediate cellular antitumor immunity, which may play an important role in the HIFU-based immunomodulation.

This review article reviews the published results of the clinical use of intravaginal non-invasive HIFU therapy for the treatment of urogenital atrophy, stress urinary incontinence, and wide vagina syndrome. Vaginal distension and genitourinary syndromes of menopause create physical, psychological, and functional problems for women and their partners. Existing invasive treatments can lead to certain complications, so safer and more effective minimally invasive medicine is desirable. Our goal was to evaluate the efficacy and safety of microfocus ultrasound therapy as a form of non-invasive HIFU therapy administered in the vaginal canal in female patients. This review uses the results of a number of recent studies from Argentina, Poland, Japan and other countries using medical devices: Feminine HIFU, manufactured by Sveltia, Argentina, and Ultra Vera, manufactured by Hironic, Republic of Korea.The purpose of the study is to study the results of the clinical application of high-intensity focused ultrasound as a new treatment method in the field of gynecology.High Intensity Focused Ultrasound (HIFU) is a new technology in gynecology that involves regenerative thermal effects on deeper layers of vaginal tissues that cannot be achieved with laser and radio frequency equipment. The results of studies with a total number of participants in more than 100 patients from several groups who underwent clinical examination support suggestions for a potential therapeutic effect as a preferred method of therapy or an addition to laser and other methods of treatment, supported by an evidence base.The value of the study is to provide effective treatment of pathologies due to the formation of new collagen fibers that create a structural framework in the fascial plate of the vagina and adjacent fascia, and the muscles of the small pelvis due to a certain mode of HIFU exposure. The results are promising and motivate further research.

This review article reviews the published results of the clinical use of intravaginal non-invasive HIFU therapy for the treatment of urogenital atrophy, stress urinary incontinence, and wide vagina syndrome. Vaginal distension and genitourinary syndromes of menopause create physical, psychological, and functional problems for women and their partners. Existing invasive treatments can lead to certain complications, so safer and more effective minimally invasive medicine is desirable. Our goal was to evaluate the efficacy and safety of microfocus ultrasound therapy as a form of non-invasive HIFU therapy administered in the vaginal canal in female patients. This review uses the results of a number of recent studies from Argentina, Poland, Japan and other countries using medical devices: Feminine HIFU, manufactured by Sveltia, Argentina, and Ultra Vera, manufactured by Hironic, Republic of Korea.The purpose of the study is to study the results of the clinical application of high-intensity focused ultrasound as a new treatment method in the field of gynecology.High Intensity Focused Ultrasound (HIFU) is a new technology in gynecology that involves regenerative thermal effects on deeper layers of vaginal tissues that cannot be achieved with laser and radio frequency equipment. The results of studies with a total number of participants in more than 100 patients from several groups who underwent clinical examination support suggestions for a potential therapeutic effect as a preferred method of therapy or an addition to laser and other methods of treatment, supported by an evidence base.The value of the study is to provide effective treatment of pathologies due to the formation of new collagen fibers that create a structural framework in the fascial plate of the vagina and adjacent fascia, and the muscles of the small pelvis due to a certain mode of HIFU exposure. The results are promising and motivate further research.

Whilst sonothrombolysis is a promising and noninvasive ultrasound technique for treating blood clots, bleeding caused by thrombolytic agents used for dissolving clots and potential obstruction of blood flow by detached clots (i.e., embolus) are the major limitations of the current approach. In the present study, a new sonothrombolysis method is proposed for treating embolus without the use of thrombolytic drugs. Our proposed method involves (a) generating a spatially localised acoustic radiation force in a blood vessel against the blood flow to trap moving blood clots (i.e., generation of an acoustic net), (b) producing acoustic cavitation to mechanically destroy the trapped embolus, and (c) acoustically monitoring the trapping and mechanical fractionation processes. Three different ultrasound transducers with different purposes were employed in the proposed method: (1) 1-MHz dual focused ultrasound (dFUS) transducers for capturing moving blood clots, (2) a 2-MHz High Intensity Focused Ultrasound (HIFU) source for fractionating blood clots and (3) a passive acoustic emission detector with broad bandwidth (10 kHz to 20 MHz) for receiving and analysing acoustic waves scattered from a trapped embolus and acoustic cavitation. To demonstrate the feasibility of the proposed method, in vitro experiments with an optically transparent blood vessel-mimicking phantom filled with a blood mimicking fluid and a blood clot (1.2 to 5 mm in diameter) were performed with varying the dFUS and HIFU exposure conditions under various flow conditions (from 1.77 to 6.19 cm/s). A high-speed camera was used to observe the production of acoustic fields, acoustic cavitation formation and blood clot fragmentation within a blood vessel by the proposed method. Numerical simulations of acoustic and temperature fields generated under a given exposure condition were also conducted to further interpret experimental results on the proposed sonothrombolysis. Our results clearly showed that fringe pattern-like acoustic pressure fields (fringe width of 1 mm) produced in a blood vessel by the dFUS captured an embolus (1.2 to 5 mm in diameter) at the flow velocity up to 6.19 cm/s. This was likely to be due to the greater magnitude of the dFUS-induced acoustic radiation force exerted on an embolus in the opposite direction to the flow in a blood vessel than that of the drag force produced by the flow. The acoustically trapped embolus was then mechanically destructed into small pieces of debris (18 to 60 μm sized residual fragments) by the HIFU-induced strong cavitation without damaging the blood vessel walls. We also observed that acoustic emissions emitted from a blood clot captured by the dFUS and cavitation produced by the HIFU were clearly distinguished in the frequency domain. Taken together, these results can suggest that our proposed sonothrombolysis method could be used as a promising tool for treating thrombosis and embolism through capturing and destroying blood clots effectively.

Abstract Objective To investigate the safety and feasibility of high intensity focused ultrasound (HIFU) ablation followed by ultrasound-guided dilation and curettage (USg-D&C) for two types patients with cesarean scar pregnancy (CSP-I and CSP-II). Materials and methods This study was a retrospective analysis of 101 CSP-I patients and 52 CSP-II patients who received HIFU ablation followed by USg-D&C from Jun 2014 to Oct 2020. The diameter of gestational sac/mass, thickness of the intervening myometrium, intraoperative blood loss, operation time, length of hospital stays, adverse effects and β-HCG level in the two groups were compared. Results All patients successfully received HIFU ablation under conscious sedation. The median total treatment time of HIFU ablation and median USg-D&C time in the CSP-I group were statistically longer than those in the CSP-II group (P 0.05). The average time needed for β-HCG return to normal levels was 26.08 ± 5.02. and 28.15 ± 4.99 days for CSP-I and CSP-II, respectively (P > 0.05). The percentage of adverse effects and complications was not significantly different between the two groups (P > 0.05). Conclusions HIFU ablation followed by USg-D&C was safe and effective in treating the CSP-I patients and CSP-II patients, which may be a potential noninvasive therapeutic option for patients with CSP.

IntroductionBoiling histotripsy (BH) is a promising High Intensity Focused Ultrasound (HIFU) technique that can be used to mechanically fractionate solid tumours at the HIFU focus noninvasively, promoting tumour immunity. Because of the occurrence of shock scattering phenomenon during BH process, the treatment accuracy of BH is, however, somewhat limited. To induce more localised and selective tissue destruction, the concept of pressure modulation has recently been proposed in our previous in vitro tissue phantom study. The aim of the present study was therefore to investigate whether this newly developed histotripsy approach termed pressure-modulated shockwave histotripsy (PSH) can be used to induce localised mechanical tissue fractionation in in vivo animal model.MethodsIn the present study, 8 Sprague Dawley rats underwent the PSH treatment and were sacrificed immediately after the exposure for morphological and histological analyses (paraffin embedded liver tissue sections were stained with H&E and MT). Partially exteriorised rat’s left lateral liver lobe in vivo was exposed to a 2.0 MHz HIFU transducer with peak positive (P+) and negative (P-) pressures of 89.1 MPa and –14.6 MPa, a pulse length of 5 to 34 ms, a pressure modulation time at 4 ms where P+ and P- decreased to 29.9 MPa and – 9.6 MPa, a pulse repetition frequency of 1 Hz, a duty cycle of 1% and number of pulses of 1 to 20. Three lesions were produced on each animal. For comparison, the same exposure condition but no pressure modulation was also employed to create a number of lesions in the liver.Results and DiscussionExperimental results showed that a partial mechanical destruction of liver tissue in the form of an oval in the absence of thermal damage was clearly observed at the HIFU focus after the PSH exposure. With a single pulse length of 7 ms, a PSH lesion created in the liver was measured to be a length of 1.04 ± 0.04 mm and a width of 0.87 ± 0.21 mm which was 2.37 times in length (p = 0.027) and 1.35 times in width (p = 0.1295) smaller than a lesion produced by no pressure modulation approach (e.g., BH). It was also observed that the length of a PSH lesion gradually grew towards the opposite direction to the HIFU source along the axial direction with the PSH pulse length, eventually leading to the generation of an elongated lesion in the liver. In addition, our experimental results demonstrated the feasibility of inducing partial decellularisation effect where liver tissue was partially destructed with intact extracellular matrix (i.e., intact fibrillar collagen) with the shortest PSH pulse length. Taken together, these results suggest that PSH could be used to induce a highly localised tissue fractionation with a desired degree of mechanical damage from complete tissue fractionation to tissue decellularisation through controlling the dynamics of boiling bubbles without inducing the shock scattering effect.

BackgroundNo reports on Letrozole as a pretreatment before ablation of uterine fibroid with high intensity focused ultrasound (HIFU), so a retrospective observation study was performed to evaluate the response of different pre-HIFU medication.MethodsWe collected patients with single uterine fibroid receiving HIFU ablation from January 2018 to April 2021. All enrolled patients were classified into three group: group A (no pre-HIFU medication use), group B (Pre-HIFU letrozole use), group C (pre-HIFU gonadotrophin releasing hormone analog, GnRHa). Further associated clinical data and treatment response after HIFU treatment were reviewed and evaluated.ResultsA total of 39 patients including 21, 7, and 11 in group A, B, and C were collected respectively. After pre-HIFU medication, no difference of fibroid volume was found (A: 251.4, B: 360.6, C: 409.4 cm3, p = 0.250), and GnRHa group had significantly larger volume reduction than Letrozole users (38.6% vs. 16.4%, p = 0.007). The incidence of hypoestrogenic symptoms was higher in GnRHa group than in letrozole users (27.3% vs. 0, p = 0.170). GnRHa group had more sonication time (p = 0.001), treatment duration (p = 0.002), and ablated energy (p = 0.001) than group A and B. The treatment efficiency was higher in letrozole group than that in other 2 groups (4.52 vs. 2.39 vs. 2.34 cm3/min, p = 0.050). For patients with fibroid over 10 cm in diameter, letrozole group had even better energy efficiency (p = 0.067), treatment speed (p = 0.007), treatment efficiency (p = 0.001), NPV per energy (p = 0.005), and NPV per sonication (p = 0.004) than other 2 groups.ConclusionLetrozole as a pretreatment medication before HIFU treatment might increase the energy efficiency and treatment efficiency of its ablation of uterine leiomyoma, especially for fibroid over 10 cm. Future study of larger patient number is needed to confirm our results.

Objective To investigate the MRI features and clinical outcomes of unexpected uterine sarcomas in patients after high-intensity focused ultrasound (HIFU) ablation for presumed uterine fibroids. Materials and methods 15,759 consecutive patients who came for HIFU treatment, from November 2008 to September 2019, for presumed uterine fibroids were retrospectively reviewed. All the patients had completed a pre-HIFU MRI. All MRI images were independently analyzed and interpreted by two radiologists in every center. Results According to the T2WI MRI features of hyperintensity, accompanied by irregular margins, necrosis or cystic degeneration, multi-lobulated lesion with internal septation, 46 patients were suspected to be uterine sarcomas before HIFU. Eleven patients were histologically diagnosed as uterine sarcomas after laparotomy. Among the 15713 patients who received HIFU treatment for presumed uterine fibroids, 8 patients were found to have occult recurrence during the follow-up period, and 6 were confirmed histologically as uterine sarcomas after laparotomy. The incidence rate of uterine sarcomas was 0.108% (17/15759). Among them, 12 cases were low-grade endometrial stromal sarcoma (LG-ESS) and 5 cases were uterine leiomyosarcoma (LMS). No histological dissemination of the sarcoma was detected in patients with unexpected uterine sarcomas. Conclusion Although some MRI features of uterine sarcomas and uterine fibroids overlapped, MRI is valuable in distinguishing between uterine fibroids and uterine sarcomas. HIFU does not seem to cause histological dissemination of the sarcoma, but follow-up visits should be strictly adhered to in order to detect unexpected uterine sarcomas at an early stage and to treat them in a timely manner.

High-intensity focused ultrasound (HIFU) has been shown to be a valuable tool in the management of small liver tumors such as hepatocellular carcinoma (HCC). It has been shown to be a safe and effective means to ablate small HCC even in the presence of advanced cirrhosis. This review examines the challenges faced during HIFU ablation when the target tumors are located in difficult locations such as the liver dome, close to the rib cage, near large blood vessels or the heart, or adjacent to hollow viscera; and the special maneuvers employed to tackle such lesions.

High Intensity Focused Ultrasound (HIFU) capably bridges the disciplines of surgery, oncology and biomedical engineering science. It provides the precision associated with a surgical tool whilst remaining a truly non-invasive technique. Oxford has been a centre for both clinical and preclinical research in HIFU over the last twenty years. Research into this technology in the UK has a longer history, with much of the early research being carried out by Professor Gail ter Haar and her team at the Institute of Cancer Research at Sutton in Surrey. A broad range of potential applications have been explored extending from tissue ablation to novel drug delivery. This review presents Oxford’s clinical studies and applications for the development of this non-invasive therapy. This includes treatment of solid abdominal tumours comprising those of the liver, kidney, uterus, pancreas, pelvis and prostate. It also briefly introduces preclinical and translational works that are currently being undertaken at the Institute of Biomedical Engineering, University of Oxford. The safety, wide tolerability and effectiveness of this technology is comprehensively demonstrated across these studies. These results can facilitate the incorporation of HIFU as a key clinical management strategy.

Abstract Background The purpose of this study was to explore the efficacy and safety of high intensity focused ultrasound (HIFU) in gastric cancer with liver metastasis (GCLM) patients who were contraindicated for either hepatectomy or radiofrequency ablation (RFA). Methods This is a prospective, observational study on GCLM patients with 1–3 liver metastases. The primary gastric lesions were thoroughly resected and any case that exhibited extra-hepatic metastasis was excluded. A 1:2:2 propensity score-matching analysis was performed using a logistic regression model on the HIFU group, best supportive care (BSC) group, and palliative chemotherapy (PC) group. The primary endpoints include progression-free survival (PFS) and overall survival (OS). Results Forty patients were finally included, there were 8 cases in HIFU group, 16 cases in BSC group, and 16 cases in PC group. The median follow-up time for the entire cohort was 10 months. The median PFS was 16.5 months in HIFU group, 2 months in BSC group, and 5 months in PC group. The median OS was 27.5 months in the HIFU group, 7 months in the BSC group, and 11.5 months in the PC group. Additionally, no grade 3 or higher adverse events occurred in the HIFU group. Conclusion The results of this study showed that HIFU treatment could improve the long-term prognosis of GCLM patients without a significant increase in the occurrence of adverse events. Compared with PC and BSC, HIFU is the preferred treatment option when GCLM patients without extra-hepatic metastasis are unable to undergo either surgery or RFA.

Yu Tang, Chun Chen, Binglei Jiang, Lu Wang, Fujie Jiang, Disen Wang, Yaotai Wang, Haiyan Yang, Xia Ou, Yan Du, Qi Wang, Jianzhong Zou State Key Laboratory of Ultrasound in Medicine and Engineering, Chongqing Key Laboratory of Biomedical Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing, 400016, People’s Republic of ChinaCorrespondence: Jianzhong ZouState Key Laboratory of Ultrasound in Medicine and Engineering, Chongqing Key Laboratory of Biomedical Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing, 400016, People’s Republic of ChinaTel +86-13708302390Email zoujzh@cqmu.edu.cnPurpose: Hypoxia is considered to be obstructive to tumor treatment, but the reduced oxygen surroundings provide a suitable habitat for Bifidobacterium bifidum (BF) to colonize. The anaerobe BF selectively colonizes into tumors following systemic injection due to its preference for the hypoxia in the tumor cores. Therefore, BF may be a potential targeting agent which could be used effectively in tumor treatment. We aimed to determine whether a novel BF-mediated strategy, that was designed to deliver AP-PFH/PLGA NPs (aptamers CCFM641-5-functionalized Perfluorohexane (PFH) loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles) by aptamer-directed approach into solid tumor based on the tumor-targeting ability of BF, could improve efficiency of high intensity focused ultrasound (HIFU) treatment of breast cancer.Methods: We synthesized AP-PFH/PLGA NPs using double emulsion method and carbodiimide method. Then, we evaluated targeting ability of AP-PFH/PLGA NPs to BF in vivo. Finally, we studied the efficacy of HIFU ablation based on BF plus AP-PFH/PLGA NPs (BF-mediated HIFU ablation) in tumor.Results: The elaborately designed AP-PFH/PLGA NPs can target BF colonized in tumor to achieve high tumor accumulation, which can significantly enhance HIFU therapeutic efficiency. We also found that, compared with traditional chemotherapy, this therapy not only inhibits tumor growth, but also significantly prolongs the survival time of mice. More importantly, this treatment strategy has no obvious side effects.Conclusion: We successfully established a novel therapy method, BF-mediated HIFU ablation, which provides an excellent platform for highly efficient and non-invasive therapy of tumor.Keywords: high intensity focused ultrasound, aptamers, nanoparticles, Bifidobacterium bifidum, tumor treatment

Epilepsy affects about 1% of the population. Approximately one third of patients with epilepsy are drug-resistant (DRE). Resective surgery is an effective treatment for DRE, yet invasive, and not all DRE patients are suitable resective surgery candidates. Focused ultrasound, a novel non-invasive neurointerventional method is currently under investigation as a treatment alternative for DRE. By emitting one or more ultrasound waves, FUS can target structures in the brain at millimeter resolution. High intensity focused ultrasound (HIFU) leads to ablation of tissue and could therefore serve as a non-invasive alternative for resective surgery. It is currently under investigation in clinical trials following the approval of HIFU for essential tremor and Parkinson’s disease. Low intensity focused ultrasound (LIFU) can modulate neuronal activity and could be used to lower cortical neuronal hyper-excitability in epilepsy patients in a non-invasive manner. The seizure-suppressive effect of LIFU has been studied in several preclinical trials, showing promising results. Further investigations are required to demonstrate translation of preclinical results to human subjects.

Cancer immunotherapy, which enhances the body's immune response and inhibits immune escape to eliminate or combat tumors, holds great promise for cancer treatment. However, it still faces many challenges, such as low response rate and immune-related adverse events, which limit its clinical applications. Ultrasound, as a safe, effective and non-invasive technique, has been widely used in diagnostics and therapeutics of tumors. In recent years, many studies have confirmed that ultrasound can also mediate tumor immunotherapy. High intensity focused ultrasound can destroy tumor tissue and lead to the in situ production of tumor fragments at the same time, which can be used as antigens of the immune system to form in situ vaccines to induce a systemic immune response. The ultrasound-targeted microbubble destruction technique with microbubbles as the carrier mediates the targeted delivery of immunomodulatory adjuvants to tumor cells or immune cells. It can not only enhance the host immune response and improve immunotherapy efficacy, but also reduce the dosage of immunoregulatory adjuvants and side effects. Sonodynamic therapy can induce immunogenic cell death to elicit an immune response and the combination with immunotherapy can achieve higher therapeutic efficacy. In this review, research advances in ultrasound-mediated tumor immunotherapy are summarized, and the potential and challenges of its application are discussed.

Focused ultrasound (FUS) has been utilized for the treatment of localized prostate cancer. Initially, FUS was performed as a whole-gland treatment comparable to radical prostatectomy or radiation therapy. However, after overall downward stage migration due to health screening programs involving prostate-specific antigen testing, as well as advances in conservative or observative strategies such as active surveillance, FUS has evolved from a whole-gland treatment to a focal treatment. This new treatment technique aims to ablate tumors while preserving the normal prostate tissue, thereby ensuring better preservation of urinary and erectile function. In this article, we review the mechanism and clinical outcomes of the FUS procedure.

According to the traditional method of high intensity focused ultrasound (HIFU) treatment, the acoustic and thermal characteristic parameters of constant temperature (room temperature or body temperature) are used to predict thermal lesion. Based on the nonlinear spherical beam equation (SBE) and Pennes bio-heat transfer equation, and a new acoustic-thermal coupled model is proposed. The constant and temperature-dependent acoustic and thermal characteristic parameters are used to predict thermal lesion, and the predicted lesion area are compared with each other. Moreover, the relationship between harmonic amplitude ratio (P2/P1) and thermal lesion is studied. Combined with the known experimental data of acoustic and thermal characteristic parameters of biological tissue and data fitting method, the relationship between acoustic and thermal characteristic parameters and temperature is obtained; and the thermal lesion simulation calculation is carried out by using the acoustic and thermal characteristic parameters under constant temperature and temperature- dependent acoustic and thermal characteristic parameters, respectively. The simulation results show that under the same irradiation condition, the thermal lesion predicted by temperature-dependent acoustic and thermal characteristic parameters is larger than that predicted by traditional method, and the thermal lesion increases with the decrease of harmonic amplitude ratio.

The biological focal region (BFR) induced by a single high-intensity focused ultrasound (HIFU) exposure is considered to be the foundation of the ultrasound ablation of tumor lesions. The purpose of this study was to explore the relationship between the acoustic focal region (AFR) and the BFRs with different combinations of power and time in low-power cumulative HIFU treatment. The finite-difference time-domain (FDTD) method was used to simulate AFR and BFR during HIFU ablation. The acoustic fields, the temperature profiles, and the shapes of BFRs were calculated by the Westervelt equation, Pennes’ equation, and the equivalent thermal dose model. In order to verify the simulation rules, phantom and ex vivo bovine livers were exposed by HIFU with a different power and time. The results demonstrated that in the low-power cumulative HIFU treatment, when the lengths of BFRs and the length of AFR were approximately equal, the shape of the BFR induced by ‘high power × short time’ exposure was closer to that of AFR than the shape of the BFR induced by ‘low power × long time’ exposure, and the exposure energy required was significantly reduced. The analysis revealed the relationship between the BFR and the AFR with different acoustic power. This study provides a reference for doctors to determine power, time, and movement distance in clinical treatment.

Introduction: Endovenous techniques such as ultrasound guided foam sclerotherapy, thermal methods, or glues are generally recommended to occlude incompetent veins. However, these methods can be technically challenging and risky for patients with severe atrophic skin disorders like lipodermatosclerosis or atrophie blanche. High intensity focused ultrasound (HIFU), which has been shown to coagulate and occlude veins successfully, may offer an alternative method. This case report details ultrasound guided HIFU to occlude non-invasively a refluxing perforator vein causing active ulcers. Report: A 95 year old man presented to the Institute for Functional Phlebology (Melk, Austria) with painful recurrent ulcers in his left medial calf. His limb was scored C2,3,4a, b,6, Ep, Ap, Pr,18 according to the Clinical, Etiology, Anatomic, Pathophysiology (CEAP) classification. Lower limb ultrasound revealed a refluxing posterior tibial perforating vein, measuring 2.7 mm in diameter at the level of the fascia. Extracorporeal HIFU pulses were delivered to this vein with the Sonovein device (Theraclion, Malakoff, France). Sonication was applied for eight seconds at a mean acoustic power of 80 W. The patient was followed up for three months post-treatment and occlusion was evaluated by duplex ultrasound. There were no complications during treatment or follow up. Three months after the treatment, reflux was abolished and the two initially active ulcers had healed. Discussion: Although this is an early report, this study shows that HIFU can be successful in ablation of incompetent perforator veins in the treatment of venous leg ulcers.

Purpose The ExAblate body MRgFUS system requires advanced beamforming strategies for volumetric hyperthermia. This study aims to develop and evaluate electronic beam steering, multi-focal patterns, and sector vortex beamforming approaches in conjunction with partial array activation using an acoustic and biothermal simulation framework along with phantom experiments. Methods The simulation framework was developed to calculate the 3D acoustic intensity and temperature distribution resulting from various beamforming and scanning strategies. A treatment cell electronically sweeping a single focus was implemented and evaluated in phantom experiments. The acoustic and thermal focal size of vortex beam propagation was quantified according to the vortex modes, number of active array elements, and focal depth. Results Turning off a percentage of the outer array to increase the f-number increased the focal size with a decrease in focal gain. 60% active elements allowed generating a sonication cell with an off-axis of 10 mm. The vortex mode number 4 with 60% active elements resulted in a larger heating volume than using the full array. Volumetric hyperthermia in the phantom was evaluated with the vortex mode 4 and respectively performed with 100% and 80% active elements. MR thermometry demonstrated that the volumes were found to be 18.8 and 29.7 cm3, respectively, with 80% array activation producing 1.58 times larger volume than the full array. Conclusions This study demonstrated that both electronic beam steering and sector vortex beamforming approaches in conjunction with partial array activation could generate large volume heating for HT delivery using the ExAblate body array.

Background Patient suitability for magnetic resonance-guided high intensity focused ultrasound (MRgHIFU) therapy of pelvic tumors is currently assessed by visual estimation of the proportion of tumor that can be reached by the device’s focus (coverage). Since it is important to assess whether enough energy reaches the tumor to achieve ablation, a methodology for estimating the proportion of the tumor that can be ablated (treatability) was developed. Predicted treatability was compared against clinically achieved thermal ablation. Methods MR Dixon sequence images of five patients with recurrent gynecological tumors were acquired during their treatment. Acousto-thermal simulations were performed using k-Wave for three exposure points (the deepest and shallowest reachable focal points within the tumor, identified from tumor coverage analysis, and a point halfway in-between) per patient. Interpolation between the resulting simulated ablated tissue volumes was used to estimate the maximum treatable depth and hence, tumor treatability. Predicted treatability was compared both to predicted tumor coverage and to the clinically treated tumor volume. The intended and simulated volumes and positions of ablated tissues were compared. Results Predicted treatability was less than coverage by 52% (range: 31–78%) of the tumor volume. Predicted and clinical treatability differed by 9% (range: 1–25%) of tumor volume. Ablated tissue volume and position varied with beam path length through tissue. Conclusion Tumor coverage overestimated patient suitability for MRgHIFU therapy. Employing patient-specific simulations improved treatability assessment. Patient treatability assessment using simulations is feasible.

Objectives Fiducial markers improve accuracy in external beam radiation therapy (EBRT) for treatment of prostate cancer (PCa). However, many patients recur after EBRT necessitating additional treatment, such as MR-guided transurethral ultrasound ablation (TULSA). Residual markers may compromise TULSA through ultrasound field distortions and generation of local susceptibility artifacts. The objective was to investigate how markers affect the ablation outcome during clinical TULSA treatments. Subjects and methods A retrospective analysis was performed on nine patients with radiorecurrent PCa and residual markers who received TULSA. The MR susceptibility artifact was quantified as a function of marker type, size and orientation, in particular for thermometry. The spatial distribution of markers inside the prostate was recorded, and the resulting impact on the thermal dose was measured. The thermal dose measurements were directly compared to the residual enhancing prostatic tissue observed on the immediate and control post-TULSA contrast enhanced (CE) image. Results Successful thermal dose accumulation to the target boundary occurred for 14/20 (70%) of markers, confirmed with CE imaging. Gold markers situated simultaneously close to the urethra (≤12 mm) and far from the target boundary (≥13 mm) reduced the ultrasound depth of heating. Nitinol markers produced large, hypointense artifacts that disrupted thermometry and compromised treatment. Artifacts from gold markers were less pronounced, but when located near the target boundary, also affected treatment. Conclusion Marker composition, orientation and location inside the prostate can all potentially impact treatment outcome. Proper patient selection through detailed MRI screening is critical to ensure successful radiorecurrent PCa treatment outcomes with TULSA.

Purpose To investigate the feasibility of using an apparent diffusion coefficient (ADC) classification in predicting the technical outcome of magnetic resonance imaging-guided high-intensity focused ultrasound (MRgHIFU) treatment of symptomatic uterine fibroids and to compare it to the Funaki classification. Materials and methods Forty-two patients with forty-eight uterine fibroids underwent diffusion-weighted imaging (DWI) before MRgHIFU treatment. The DW images were acquired with five different b-values. Correlations between ADC values and treatment parameters were assessed. Optimal ADC cutoff values were determined to predict technical outcomes, that is, nonperfused volume ratios (NPVr) such that three classification groups were created (NPVr of 80%). Results were compared to the Funaki classification using receiver-operating-characteristic (ROC) curve analysis, with statistical significance being tested with the Chi-square test. Results A statistically significant negative correlation (Spearman’s ρ = –0.31, p-value < 0.05) was detected between ADC values and NPV ratios. ROC curve analysis indicated that optimal ADC cutoff values of 980 × 10−6mm2/s (NPVr > 80%) and 1800 × 10−6mm2/s (NPVr < 30%) made it possible to classify fibroids into three groups: ADC I (NPVr > 80%), ADC II (NPVr 30–80%) and ADC III (NPVr < 30%). Analysis of the whole model area under the curve resulted in values of 0.79 for the ADC classification (p-value = 0.0007) and 0.62 for the Funaki classification (p-value = 0.0527). Conclusions Lower ADC values prior to treatment correlate with higher NPV ratios. The ADC classification seems to be able to predict the NPV ratio and may even outperform the Funaki classification. Based on these results DWI and ADC maps should be included in the MRI screening protocol.

Purpose This article will report results from the in-vivo application of a previously published model-predictive control algorithm for MR-HIFU hyperthermia. The purpose of the investigation was to test the controller’s in-vivo performance and behavior in the presence of heterogeneous perfusion. Materials and methods Hyperthermia at 42°C was induced and maintained for up to 30 min in a circular section of a thermometry slice in the biceps femoris of German landrace pigs (n=5) using a commercial MR-HIFU system and a recently developed MPC algorithm. The heating power allocation was correlated with heat sink maps and contrast-enhanced MRI images. The temporal change in perfusion was estimated based on the power required to maintain hyperthermia. Results The controller performed well throughout the treatments with an absolute average tracking error of 0.27 ± 0.15 °C and an average difference of 1.25 ± 0.22 °C between and The MPC algorithm allocates additional heating power to sub-volumes with elevated heat sink effects, which are colocalized with blood vessels visible on contrast-enhanced MRI. The perfusion appeared to have increased by at least a factor of ∼1.86 on average. Conclusions The MPC controller generates temperature distributions with a narrow spectrum of voxel temperatures inside the target ROI despite the presence of spatiotemporally heterogeneous perfusion due to the rapid thermometry feedback available with MR-HIFU and the flexible allocation of heating power. The visualization of spatiotemporally heterogeneous perfusion presents new research opportunities for the investigation of stimulated perfusion in hypoxic tumor regions.

Purpose: Oral cancers are one of the commonly diagnosed tumors worldwide in human and veterinary patients. Most oral cancers are surgically resected; however, obtaining an adequate margin of safety in patients without compromising their quality of life is often challenging. Herein, we investigated the ability of non-invasive focused ultrasound (FUS) to thermally ablate a biopsy confirmed canine oral cancer. Materials and Methods: A male canine patient with a large neurilemmoma (schwannoma) mass on the left maxilla, with evidence of thinning and loss of alveolar bone and pressure necrosis, was treated with FUS ablation instead of the traditional maxillectomy procedure. FUS ablations were performed in three sessions over three weeks. Tumor remission was determined with computed tomography and histopathological examination of the treated site. Additionally, the anti-tumor immune effects of FUS were assessed by flow cytometry analysis of blood and tumor samples. Results: Complete tumor remission was noted at the treated site. Treatment related adverse events were primarily thermal burns of the buccal mucosa, which were managed with periodic hyperbaric oxygen therapy and surgical coverage of the underlying exposed bones with gingival flaps. Enhanced proliferation of adaptive immunity cells (e.g., T-cells) was observed in tumor and blood samples. Conclusion: Our limited investigation in a canine oral cancer patient suggests that FUS may avoid the need for large-scale resection of bony tissues, thus potentially improving quality of life.

AIM: To evaluate the efficacy and safety of ultrasound cycloplasty(UCP)in the treatment of neovascular glaucoma(NVG).METHODS: Thirty patients(30 eyes)with NVG who were treated with UCP at our hospital from January 2018 to December 2018 were collected. All patients received comprehensive ophthalmic examination. Visual acuity, best corrected visual acuity(BCVA), intraocular pressure(IOP), pain grade score, ocular surface, number of glaucoma drugs and complications were recorded before and 1, 3d, 1wk and 1, 2, 3, 6mo after operation, and the efficacy and safety were evaluated.RESULTS: The postoperative visual acuity was improved, the pain score was decreased, and the use of intraocular pressure-lowering drugs was decreased and the IOP decreased significantly(PThe preoperation visual acuity, pain score, use of intraocular pressure-lowering drugs and IOP was \〖1.63±0.59(LogMAR)\〗, \〖2(1,4)\〗, \〖4(4,4)\〗 and(44.19±13.72)mmHg. The postoperative IOP were decreased at different observation time within 6mo, and the differences with preoperative IOP were statistically significant(all Pr=0.928, P. The number of glaucoma drugs and pain scores were decreased, and the differences with that of preoperation were statistically significant(PPCONCLUSION: UCP is high safety and few complications for NVG treatment. It has significant effect on reducing IOP, relieving ocular pain. The higher the preoperation IOP, the greater the IOP reduction after surgery. It was a promising anti-glaucoma method.

Yaotai Wang,1 Chun Chen,1 Yong Luo,1 Jie Xiong,1 Yu Tang,1 Haiyan Yang,1 Lu Wang,1 Fujie Jiang,1 Xuan Gao,2 Die Xu,2 Huanan Li,1 Qi Wang,1 Jianzhong Zou1,2 1State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing 400016, People’s Republic of China; 2Chongqing Key Laboratory of Biomedical Engineering, Chongqing Medical University, Chongqing, 400016, People’s Republic of ChinaCorrespondence: Jianzhong ZouState Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Yuzhong District, Chongqing 400016, People’s Republic of ChinaTel +86-13708302390Email zoujzh@cqmu.edu.cnPurpose: The high-intensity focused ultrasound (HIFU) ablation of tumors is inseparable from synergistic agents and image monitoring, but the existing synergistic agents have the defects of poor targeting and a single imaging mode, which limits the therapeutic effects of HIFU. The construction of a multifunctional biological targeting synergistic agent with high biosafety, multimodal imaging and targeting therapeutic performance has great significance for combating cancer.Methods: Multifunctional biological targeting synergistic agent consisting of Bifidobacterium longum (B. longum), ICG and PFH coloaded cationic lipid nanoparticles (CL-ICG-PFH-NPs) were constructed for targeting multimode imaging, synergistic effects with HIFU and imaging-guided ablation of tumors, which was evaluated both in vitro and in vivo.Results: Both in vitro and in vivo systematical studies validated that the biological targeting synergistic agent can simultaneously achieve tumor-biotargeted multimodal imaging, HIFU synergism and multimodal image monitoring in HIFU therapy. Importantly, the electrostatic adsorption method and the targeting of B. longum to tumor tissues allow the CL-ICG-PFH-NPs to be retained in the tumor tissue, achieve the targeting ability of synergistic agent. Multimodal imaging chose the best treatment time according to the distribution of nanoparticles in the body to guide the efficient and effective treatment of HIFU. CL-ICG-PFH-NPs could serve as a phase change agent and form microbubbles that can facilitate HIFU ablation by mechanical effects, acoustic streaming and shear stress. This lays a foundation for the imaging and treatment of tumors.Conclusion: In this work, a biological targeting synergistic agent was successfully constructed with good stability and physicochemical properties. This biological targeting synergistic agent can not only provide information for early diagnosis of tumors but also realize multimodal imaging monitoring during HIFU ablation simultaneously with HIFU treatment, which improves the shortcomings of HIFU treatment and has broad application prospects.Keywords: high-intensity focused ultrasound, nanoparticles, photoacoustic imaging, fluorescence imaging, ultrasound imaging, image-guided therapy

The introduction of thermal relaxation makes non-Fourier heat transfer more effective than Pennes equation to reflect rapid bio-heat transferring during HIFU, however, the contribution of thermal relaxation in specific tissues needs to be further clarified. In this study, we first measured the thermal relaxation times of porcine muscle and porcine fat. Combining with experimental measurements, the effects of thermal relaxation on temperature elevation in the tissues were investigated by using Pennes equation, thermal wave model of bio-heat transfer (TWMBT) and dual phase-lag (DPL) bio-heat transfer. Results showed that: a) The thermal relaxation times of porcine muscle and porcine fat are experimentally determined as 5.71± 0.11 s and 5.02± 0.06 s, respectively. b) In the absence of cavitation, DPL bio-heat transfer is more accurate to predict the temperature elevation at the focus and 2 mm from the focus than Pennes equation and TWMBT. Particularly, comparing with the reported of bologna (16 s) used in most of the theoretical analysis, the utilization of the measured thermal relaxation time for a specific tissue in DPL bio-heat transfer is more effective in predicting the temperature elevation during HIFU. c) Acoustic cavitation and nonlinear propagation is easier to happen in fat, under which all bio-heat transfer models are failed to forecast the temperature elevation induced by HIFU. The results demonstrate that different tissues have different thermal relaxation, DPL bio-heat transfer with the measured thermal relaxation times of specific tissues can accurately predict the temperature elevation during HIFU without cavitation.

Objective To investigate the prevalence of pelvic adhesions in patients with uterine fibroids after high-intensity focused ultrasound (HIFU) treatment, then analyze the influencing factors of pelvic adhesions. Materials and methods From October 2010 to March 2020, a total of 2619 patients with uterine fibroids underwent either hysterectomy, myomectomy, or cesarean section in Suining Central Hospital of Sichuan province. Of the 2619 patients, 810 were excluded because of a documented history of either pelvic infections, endometriosis, prior abdominopelvic surgery, or gynecological malignancies; 1809 patients were enrolled and the data were retrospectively assessed for the prevalence and patterns of pelvic adhesions. Among them, 96 patients with uterine fibroids had had prior HIFU treatment (HIFU group), 1713 patients had not had HIFU or surgical treatments (control group). Results Among the 96 patients in the HIFU group, adhesions were detected in 42 patients, the incidence of pelvic adhesion being 43.75%; the 1713 patients in the control group, adhesions were detected in 619 patients, the prevalence of pelvic adhesion being 36.14%. No statistically significant difference in the incidence of adhesion between the two groups was observed (p = .132), no significant difference in location of pelvic adhesions between the two groups and no significant difference in the severity of adhesions between the two groups was observed (p > .05). Conclusions Based on our results with limited numbers, we concluded that HIFU treatment did not significantly increase the risk of pelvic adhesions.

Background Patient suitability for magnetic resonance-guided high intensity focused ultrasound (MRgHIFU) ablation of pelvic tumors is initially evaluated clinically for treatment feasibility using referral images, acquired using standard supine diagnostic imaging, followed by MR screening of potential patients lying on the MRgHIFU couch in a ‘best-guess’ treatment position. Existing evaluation methods result in ≥40% of referred patients being screened out because of tumor non-targetability. We hypothesize that this process could be improved by development of a novel algorithm for predicting tumor coverage from referral imaging. Methods The algorithm was developed from volunteer images and tested with patient data. MR images were acquired for five healthy volunteers and five patients with recurrent gynaecological cancer. Subjects were MR imaged supine and in oblique-supine-decubitus MRgHIFU treatment positions. Body outline and bones were segmented for all subjects, with organs-at-risk and tumors also segmented for patients. Supine images were aligned with treatment images to simulate a treatment dataset. Target coverage (of patient tumors and volunteer intra-pelvic soft tissue), i.e. the volume reachable by the MRgHIFU focus, was quantified. Target coverage predicted from supine imaging was compared to that from treatment imaging. Results Mean (±standard deviation) absolute difference between supine-predicted and treatment-predicted coverage for 5 volunteers was 9 ± 6% (range: 2–22%) and for 4 patients, was 12 ± 7% (range: 4–21%), excluding a patient with poor acoustic coupling (coverage difference was 53%). Conclusion Prediction of MRgHIFU target coverage from referral imaging appears feasible, facilitating further development of automated evaluation of patient suitability for MRgHIFU.

Background: The association between the treatment efficacy and safety of high-intensity focused ultrasound (HIFU)-based renal sympathetic denervation (RDN) and the acoustic energy dose applied has not been fully studied and may provide important understanding of the mechanism that led to failure of the WAVE IV trial. The objective of this study was to externally deliver different HIFU doses to canines for RDN treatment and to investigate the optimal energy dose for HIFU-based RDN.Methods: Thirty canines were divided into five RDN groups according to dose of acoustic energy applied, and a sham control group that consisted of four canines was used for comparisons. All animals in the RDN groups underwent the RDN procedure with different acoustic energy doses, while in the sham control group, renal arteries were harvested without being subjected to acoustic energy delivery and were imaged using color Doppler flow imaging (CDFI). Blood pressure (BP) was recorded, and blood samples were collected before the RDN procedure and at 28 days after the RDN procedure. Histological examinations and measurement of renal tissue norepinephrine concentration were performed in all retrieved samples.Results: Suppression of BP was significant in the 300 W (15.17/8.33 ± 1.47/1.21 mmHg), 250 W (14.67/9.33 ± 1.21/1.37 mmHg), and 200 W (13.17/9.17 ± 2.32/1.84 mmHg) groups. Semiquantitative histological assessment of periarterial nerves around the kidney revealed that target nerves in the 300 W (9.77 ± 0.63), 250 W (9.42 ± 0.67), and 200 W (9.58 ± 0.54) groups had the highest nerve injury scores, followed by the 150 W group (5.29 ± 0.62). Furthermore, decreased renal tissue norepinephrine concentration, together with decreased expression of tyrosine hydroxylase in the 300, 250, and 200 W groups demonstrated effective sympathetic depression following sufficient acoustic energy deposition. However, the renal artery injury score in the 300 W group (0.93 ± 0.13) was significantly higher than in the other groups (p < 0.001).Conclusion: This study provides evidence that RDN effectiveness is based on the energy dose delivered and that 200–250 W is effective and safe in normal-sized canines.