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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.

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.

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

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.

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.

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.

Purpose: In local hyperthermia, precise temperature control throughout the entire target region is key for swift, safe, and effective treatment. In this article, we present a model predictive control (MPC) algorithm providing voxel-level temperature control in magnetic resonance-guided high intensity focused ultrasound (MR-HIFU) and assess the improvement in performance it provides over the current state of the art. Materials and methods: The influence of model detail on the prediction quality and runtime of the controller is evaluated and a tissue mimicking phantom is characterized using the resulting model. Next, potential problems arising from modeling errors are evaluated in silico and in the characterized phantom. Finally, the controller’s performance is compared to the current state-of-the-art hyperthermia controller in side-by-side experiments. Results: Modeling diffusion by heat exchange between four neighboring voxels achieves high predictive performance and results in runtimes suited for real-time control. Erroneous model parameters deteriorate the MPC’s performance. Using models derived from thermometry data acquired during low powered test sonications, however, high control performance is achieved. In a direct comparison with the state-of-the-art hyperthermia controller, the MPC produces smaller tracking errors and tighter temperature distributions, both in a homogeneous target and near a localized heat sink. Conclusion: Using thermal models deduced from low-powered test sonications, the proposed MPC algorithm provides good performance in phantoms. In direct comparison to the current state-of-the-art hyperthermia controller, MPC performs better due to the more finely tuned heating patterns and therefore constitutes an important step toward stable, uniform hyperthermia.

Background: Magnetic resonance-guided focused ultrasound surgery (MRgFUS) is an alternative local therapy for patients with painful bone metastasis. However, little is known about the prognostic and predictive factors of MRgFUS in treating bone metastasis. Materials and methods: This retrospective study analyzed the performance status, treated site, pretreatment pain score, pretreatment tumor volume and lesion coverage volume factor (CVF) of 31 patients who underwent MRgFUS. A numerical rating scale for pain was used at the same time to assess the clinical response. Radiographic responses were evaluated using a modified version of The University of Texas MD Anderson Cancer Center criteria and reference to the MR imaging or computed tomography scans obtained 3 months after treatment. Univariate and multivariate logistic regression analyses were conducted to examine the effect of variables on clinical and radiographic responses. Results: The overall clinical response rate was 83.9% and radiographic response rate was 67.7%. Multivariate logistic regression analysis revealed that the better pretreatment Karnofsky performance status (KPS) (odds ratio: 1.220, 95% confidence interval (CI): 1.033–1.440; p = 0.019) was significantly associated with a more positive clinical response, and that the lesion CVF (odds ratio: 1.183, 95% CI: 1.029–1.183; p = 0.0055) was an independent prognostic factor for radiographic responses. The radiographic response of patients with lesion CVF ≥70% and CVF

Objective: To develop and evaluate a combined motion-assisted/gated MRHIFU heating strategy designed to accelerate the treatment procedure by reducing the required number of sonications to ablate a target volume in the pancreas. Methods: A planning method for combined motion-assisted/gated MRHIFU using 4D-MRI and motion characterization is introduced. Six healthy volunteers underwent 4D-MRI for target motion characterization on a 3.0-T clinical scanner. Using displacement patterns, simulations were performed for all volunteers for three sonication approaches: gated, combined motion-assisted/gated, and static. The number of sonications needed to ablate the pancreas head was compared. The influence of displacement amplitude and target volume size was investigated. Spherical target volumes (8, 15, 20 and 34 mL) and displacement amplitudes ranging from 5 to 25 mm were evaluated. For this case, the number of sonications required to ablate the whole target was determined. Results: The number of required sonications was lowest for a static target, 62 on average (range 49–78). The gated approach required most sonications, 126 (range 97–159). The combined approach was almost as efficient as the hypothetical static case, with an average of 78 (range 53–123). Simulations showed that with a 5-mm displacement amplitude, the target could be treated by making use of motion-assisted MRHIFU sonications only. In that case, this approach allowed the lowest number of sonication, while for 10 mm and above, the number of required sonications increased. Conclusion: The use of a combined motion-assisted/gated MRHIFU strategy may accelerate tumor ablation in the pancreas when respiratory-induced displacement amplitudes are between 5 and 10 mm.

Purpose: The objective of this study was to investigate the bactericidal effects of high intensity focused ultrasound (HIFU) on Bacillus Calmette–Guerin (BCG, a substitute for Mycobacterium tuberculosis) in vitro and in vivo, and to explore the underlying mechanisms. Materials and methods: HIFU, at a fixed frequency of 1 MHz, was applied to both BCG culture suspensions and subcutaneous BCG abscesses in rats. Results: HIFU irradiation significantly reduced the bacterial survival rate and caused temperature elevations both in vitro and in vivo. Furthermore, BCG suspensions irradiated for 15 s at 3185 and 6369 W/cm2 had increased cell wall damage, which resulted in morphological changes compared to the untreated control group. Additionally, we observed histological changes in the rat subcutaneous abscesses after HIFU ablation at 6369 W/cm2. H&E staining of infected lesions showed coagulative necrosis with central nucleus dissolution and increased infiltration of inflammatory cells, as well as nuclear pyknosis and nuclear fragmentation in the periphery. The volumes of the subcutaneous abscesses in the HIFU-treated group were significantly lower than those in the sham-treated group. Conclusion: HIFU has the therapeutic potential to treat BCG-infected tissues in rats. We theorize that a combination of mechanical, cavitation, and thermal effects most efficiently inactivate BCG bacteria via HIFU. This study is expected to provide a bio-plausible basis for a noninvasive and effective treatment for tuberculosis.

Objective: To evaluate the outcomes of subsequent pregnancies in patients with a history of cesarean scar pregnancy (CSP) treated with high intensity focused ultrasound (HIFU) followed by ultrasound-guided dilation and curettage (USg-D&C). Methods: A retrospective analysis was performed on data collected from 154 patients with CSP who were treated by HIFU followed by USg-D&C in Suining Central Hospital between January 2015 and January 2018. Among them, 28 patients wanted to conceive following treatment. Baseline characteristics, treatment results, intraoperative hemorrhages during USg-D&C, post-curettage serum beta human chorionic gonadotropin (β-hCG) levels and vaginal bleeding were investigated. Subsequent pregnancy outcomes, including intervals between pregnancy and treatment of CSP, complications during pregnancy, and outcomes of newborns were evaluated. Results: All patients with CSP were successfully treated by HIFU combined with USg-D&C. Of the 28 CSP patients who intended to conceive after the treatment, 23 patients (82.14%) successfully conceived. The average interval between conception and HIFU treatment was 18.38 ± 10.04 months. Eighteen patients (78.26%) had an intrauterine pregnancy, in which 12 had delivery by cesarean section, 1 had an ongoing pregnancy, and 5 had an abortion in the first trimester. Among the other 5 women, 3 had tubal ectopic pregnancy and 2 had recurrent CSP. These five patients underwent laparoscopy within the first trimester. Conclusion: HIFU followed by USg-D&C is an effective and safe treatment for patients with CSP who wish to conceive. Prospective multi-center studies with larger sample sizes and longer follow-up periods are needed to compare this treatment with others.

Objective: To evaluate the safety and feasibility of combined procedures: HIFU combined with systemic MTX followed by ultrasound-guided curettage or hysteroscopic resection while treating placenta accreta (PA). Method: This study included 21 patients diagnosed with retained PA with marked vascularity after abortion or delivery from July 2015 to December 2017. Patients with high serum β-hCG level (≥100 mIU/mL) received systemic MTX + HIFU treatment for 3 days and the ones with low β-hCG level (

Purpose: Osteomyelitis is one of the most serious complications linked to diabetes and increases the possibility of limb amputation considerably. There exists an important clinical need to improve management of osteomyelitis, especially for diabetic patients who are more susceptible to failures, relapses and chronicity of multiple bone infections. Magnetic resonance-guided focused ultrasound (MRgFUS) can offer a clinical management option for patients with osteomyelitis by providing a non-surgical and potentially rapid-recovery treatment option. Material and Methods: A retrospective study with patients with confirmed osteomyelitis (n = 75) was performed at evaluating the feasibility to target bone infection sites with a clinically approved MRgFUS device (Sonalleve, Profound Medical, Mississauga, ON, Canada). The developed methodology allows using preexisting diagnostic magnetic resonance imaging (MRI) or computed tomography (CT) scans to evaluate the treatment feasibility directly using a MRgFUS treatment planning software. Results: 74.7% of the cases included in our study passed the targetability criteria. Cases were deemed non-targetable if the target was less than 1 cm from the skin or close to a neuro-vascular bundle, metallic implants, or in the way of a defect in the overlying skin. For cases that passed the targetability criteria, an average among patients of 92.7 ± 5.2% of the gross treatment volume could be reached using treatment cells available at the Sonalleve system. Conclusion: The retrospective study presented here is the first step to demonstrate the feasibility of utilizing MRgFUS for the thermal treatment of osteomyelitis.

Background: The use of magnetic resonance imaging-guided high-intensity focused ultrasound (MR-HIFU) to deliver mild hyperthermia requires stable temperature mapping for long durations. This study evaluates the effects of respiratory motion on MR thermometry precision in pediatric subjects and determines the in vivo feasibility of circumventing breathing-related motion artifacts by delivering MR thermometry-controlled HIFU mild hyperthermia during repeated forced breath holds. Materials and methods: Clinical and preclinical studies were conducted. Clinical studies were conducted without breath-holds. In phantoms, breathing motion was simulated by moving an aluminum block towards the phantom along a sinusoidal trajectory using an MR-compatible motion platform. In vivo experiments were performed in ventilated pigs. MR thermometry accuracy and stability were evaluated. Results: Clinical data confirmed acceptable MR thermometry accuracy (0.12–0.44 °C) in extremity tumors, but not in the tumors in the chest/spine and pelvis. In phantom studies, MR thermometry accuracy and stability improved to 0.37 ± 0.08 and 0.55 ± 0.18 °C during simulated breath-holds. In vivo MR thermometry accuracy and stability in porcine back muscle improved to 0.64 ± 0.22 and 0.71 ± 0.25 °C during breath-holds. MR-HIFU hyperthermia delivered during intermittent forced breath holds over 10 min duration heated an 18-mm diameter target region above 41 °C for 10.0 ± 1.0 min, without significant overheating. For a 10-min mild hyperthermia treatment, an optimal treatment effect (TIR > 9 min) could be achieved when combining 36–60 s periods of forced apnea with 60–155.5 s free-breathing. Conclusion: MR-HIFU delivery during forced breath holds enables stable control of mild hyperthermia in targets adjacent to moving anatomical structures.