Available evidence on HIFU for focal treatment of prostate cancer: a systematic review

ABSTRACT Purpose: Prostate cancer (PCa) is the second most common oncologic disease among men. Radical treatment with curative intent provides good oncological results for PCa survivors, although definitive therapy is associated with significant number of serious side-effects. In modern-era of medicine tissue-sparing techniques, such as focal HIFU, have been proposed for PCa patients in order to provide cancer control equivalent to the standard-of-care procedures while reducing morbidities and complications. The aim of this systematic review was to summarise the available evidence about focal HIFU therapy as a primary treatment for localized PCa. Material and methods: We conducted a comprehensive literature review of focal HIFU therapy in the MEDLINE database (PROSPERO: CRD42021235581). Articles published in the English language between 2010 and 2020 with more than 50 patients were included. Results: Clinically significant in-field recurrence and out-of-field progression were detected to 22% and 29% PCa patients, respectively. Higher ISUP grade group, more positive cores at biopsy and bilateral disease were identified as the main risk factors for disease recurrence. The most common strategy for recurrence management was definitive therapy. Six months after focal HIFU therapy 98% of patients were totally continent and 80% of patients retained sufficient erections for sexual intercourse. The majority of complications presented in the early postoperative period and were classified as low-grade. Conclusions: This review highlights that focal HIFU therapy appears to be a safe procedure, while short-term cancer control rate is encouraging. Though, second-line treatment or active surveillance seems to be necessary in a significant number of patients.

Clinical efficacy of focused ultrasound ablation surgery in the treatment of internal adenomyosis / 中华妇产科杂志

Objective:To investigate the relationship between the clinical efficacy and the ablated area of endometrium in patients with internal adenomyosis treated with focused ultrasound ablation surgery (FUAS).Methods:From January 2015 to December 2018, 122 patients in Chongqing Haifu Hospital who were diagnosed as internal adenomyosis through history, clinical symptoms and enhanced magnetic resonance imaging (MRI) and treated with FUAS were enrolled in this study. According to the patient′s wishes, patients were given whether to ablate the adenomyotic lesion alone or ablate the adenomyotic lesion and the endometrium that involved in adenomyotic lesions together. The ablated area of adenomyotic lesions and endomitrium were evaluated by post-FUAS enhanced MRI. The adverse events and the changes of dysmenorrhea and menstrual volume at different follow-up points within 24 months were recorded.Results:Among the 122 patients, 32 patients chose to ablate adenomyotic lesion alone, and 90 patients chose to ablate the adenomyotic lesion and the endometrium during FUAS. No major complications such as bowel injury and nerve injury occurred after FUAS. The median non-perfused volume ratio of adenomyotic lesions was 31.7% in the group without endometrial ablation and it was 60.0% in the group with endometrium ablation ( P<0.01). The improvement of dysmenorrhea in the group with endometrium ablation was significantly better than the group without endometrial ablation ( P<0.01). The average menstrual volume score (3.4±0.9) before FUAS in the group with endometrial ablation was higher than that in the group without endometrial ablation (2.5±0.6; P<0.01), but it decreased significantly after FUAS treatment, reaching the similar menstrual volume score of the group without endometrial ablation ( P>0.05). The proportions of abnormal vaginal discharge (34.4%, 31/90) and bleeding (16.7%, 15/90) were significantly higher in the group with endometrium ablation than those in the group without endometrial ablation (all P<0.01). Conclusions:FUAS could be safely and effectively used in the treatment of patients with internal adenomyosis. It seems that ablation of adenomyotic lesion and endometrium together could obtain better therapeutic effects.

Clinical effect and influencing factors of focused ultrasound ablation surgery combined with suction curettage for the treatment of mass-type cesarean scar pregnancy / 中华妇产科杂志

Objective:To investigate the clinical effect of focused ultrasound ablation surgery (FUAS) combined with suction curettage for mass-type cesarean scar pregnancy (CSP) and to analyze the influencing factors of vaginal bleeding and readmission.Methods:From January 2014 to December 2020, 88 patients with mass-type CSP were treated by FUAS combined with suction curettage in the Third Xiangya Hospital of Central South University. The clinical results and the influencing factors of bleeding and readmission for mass-type CSP were analyzed.Results:All the patients underwent one time FUAS treatment successfully. Immediately after FUAS treatment, color Doppler ultrasound showed obvious necrosis and no perfusion area in all lesions, and the blood flow in the mass-type CSP tissue significantly decreased. The median volume of blood loss in the procedure was 20 ml (range: 5-950 ml). Thirteen patients (15%, 13/88) had vaginal bleeding≥200 ml, and 15 patients (17%, 15/88) were hospitalized again. The average time for menstruation recovery was (28±8) days (range: 18-66 days). The average time needed for serum human chorionic gonadotropin-beta subunit to return to normal levels was (22±6) days (range: 7-59 days). The risk of large vaginal bleeding of patients were related to the blood supply of the mass ( OR=5.280, 95% CI: 1.335-20.858, P=0.018) and the largest diameter of the mass ( OR=1.060, 95% CI: 1.010-1.120, P=0.030). The risk of readmission were related to the largest diameter of the mass ( OR=1.055, 95% CI: 1.005-1.108, P=0.030) and the depth of the uterus cavity ( OR=1.583, 95% CI: 1.015-2.471, P=0.043). No serious complications such as intestinal and nerve injury occurred during and after FUAS treatment. Conclusions:FUAS combined with suction curettage is safe and effective in treating patients with mass-type CSP through this preliminary study. The volume of vaginal bleeding are associated with the blood supply of the mass and the largest diameter of the mass, the risk of readmission are related to the largest diameter of the mass and the depth of the uterus cavity.

Comparison of the long-term outcomes of focused ultrasound ablation surgery for uterine fibroids and myomectomy / 中华妇产科杂志

Objective:To compare the long-term outcomes after focused ultrasound ablation surgery (FUAS) versus myomectomy for uterine fibroids.Methods:A retrospective study was conducted on women who were treated by FUAS or myomectomy for uterine fibroids at First Medical Center of Chinese PLA General Hospital from January 2007 to January 2015. Regular follow-up was conducted to evaluate the symptoms relief, symptoms recurrence, the need for re-interventions and complications of the two groups.Results:The effective rates were 95.7% (730/763) and 95.5% (1 151/1 205) in women who were treated by FUAS and myomectomy, no statistical difference was seen between the two groups ( χ2 =0.027, P=0.869). The cumulative rates of symptoms recurrence at 1 year, 3 years, 5 years, 8 years and 10 years of follow-up in FUAS group were 1.8%, 6.8%, 11.9%, 15.2% and 15.9%, respectively; and the cumulative re-intervention rates were 0.7%, 4.1%, 6.8%, 9.9% and 11.0%, respectively. The cumulative rates of symptoms recurrence at 1 year, 3 years, 5 years, 8 years and 10 years of follow-up in myomectomy group were 1.8%, 5.9%, 10.6%, 14.2% and 14.9%, respectively; and the cumulative re-intervention rates were 0.9%, 4.5%, 7.8%, 10.3% and 11.4%, respectively. No statistical differences were seen between the two groups (all P>0.05). There were no significant differences in the effective rate, symptoms recurrence rate and re-intervention rate between the two groups in patients with intermural fibroids; but the effective rate of FUAS (95.9%, 235/245) was higher than that of myomectomy (89.1%, 115/129), the symptoms recurrence rate (11.9%, 28/235) was lower than that of myomectomy (27.8%, 32/115), and the re-intervention rate (7.7%, 18/235) was lower than that of myomectomy (17.4%, 20/115) in patients with submucosal fibroids, there were significant different (all P<0.05). The effective rate of FUAS (91.0%, 132/145) was lower than that of myomectomy (97.0%, 322/332), the symptoms recurrence rate (32.6%, 43/132) was higher than that of myomectomy (9.9%, 32/322), and the re-intervention rate (22.0%, 29/132) was higher than that of myomectomy group (6.2%, 20/132) in patients with subserosal fibroids, there were significant different (all P<0.01). The incidences of total [1.8% (14/763) vs 21.9% (264/1 205)], minor and moderate adverse events were lower in FUAS group than myomectomy group (all P<0.001). Conclusion:Satisfaction with long-term outcomes after FUAS treatment or myomectomy for uterine fibroids is comparable.

Does mpMRI guidance improve HIFU partial gland ablation compared to conventional ultrasound guidance? Early functional outcomes and complications from a single center

ABSTRACT Background Focal therapy (FT) for localized prostate cancer (PCa) treatment is raising interest. New technological mpMRI-US guided FT devices have never been compared with the previous generation of ultrasound-only guided devices. Materials and Methods We retrospectively analyzed prospectively recorded data of men undergoing FT for localized low- or intermediate-risk PCa with US- (Ablatherm®-2009 to 2014) or mpMRI-US (Focal One®-from 2014) guided HIFU. Follow-up visits and data were collected using internationally validated questionnaires at 1, 2, 3, 6 and 12 months. Results We included n=88 US-guided FT HIFU and n=52 mpMRI-US guided FT HIFU respectively. No major baseline differences were present except higher rates of Gleason 3+4 for the mpMRI-US group. No major differences were present in hospital stay (p=0.1), catheterization time (p=0.5) and complications (p=0.2) although these tended to be lower in the mpMRI-US group (6.8% versus 13.2% US FT group). At 3 months mpMRI-US guided HIFU had significantly lower urine leak (5.1% vs. 15.9%, p=0.04) and a lower drop in IIEF scores (2 vs. 4.2, p=0.07). Of those undergoing 12-months control biopsy in the mpMRI-US-guided HIFU group, 26% had residual cancer in the treated lobe. Conclusion HIFU FT guided by MRI-US fusion may allow improved functional outcomes and fewer complications compared to US- guided HIFU FT alone. Further analysis is needed to confirm benefits of mpMRI implementation at a longer follow-up and on a larger cohort of patients.

Clinical effect of gemcitabine combined with high-intensity focused ultrasound in treatment of advanced pancreatic cancer: A Meta-analysis / 临床肝胆病杂志

ObjectiveTo evaluate the clinical effect and safety of high-intensity focused ultrasound (HIFU) combined with gemcitabine in the treatment of advanced pancreatic cancer. MethodsSCI, Cochrane Library, Embase, PubMed, Wanfang Data, CNKI, CBM, and VIP were searched for randomized controlled trials (RCTs) of HIFU combined with gemcitabine in the treatment of advanced pancreatic cancer, with the assistance of expanded search, and these RCTs were screened according to the inclusion criteria. Review Manager 5.3 was used to perform the Meta-analysis. A fixed effects model was used for non-heterogeneous data; heterogeneity was explained by subgroup analysis based on intervention methods, and if it could not be explained by subgroup analysis, a random effects model was used. Relative risk (RR) and 95% confidence interval (CI) were used as evaluation indices, and funnel plots were generated based on the outcome measure involved in the highest number of studies. ResultsA total of 8 RCTs with 474 patients were included. The patients in the experimental group received gemcitabine-based chemotherapy and HIFU, and those in the control group received gemcitabine-based chemotherapy alone. Compared with the control group, the experimental group had significantly better results in 3-, 6-, and 12-month survival rates (3-month: RR=1.07, 95%CI: 1.00-1.14, P＜0.05; 6-month: RR=2.19, 95%CI: 1.75-2.75, P＜0.05; 12-month: RR=235, 95%CI: 1.07-5.14, P＜0.05), tumor control (RR=1.64, 95%CI: 1.21-2.24, P=0.002), and pain control (RR=3.15, 95%CI: 2.45-4.05, P＜0.05). There were no significant differences between the two groups in the incidence rates of leukopenia (RR=1.05, 95%CI: 0.85-1.30, P＞0.05), gastrointestinal reactions (RR=0.89, 95%CI: 0.56-1.42, P＞0.05), and liver injury (RR=1.29, 95%CI: 0.95-1.75, P＞0.05). Since the outcome measure of pain control was involved in the highest number of studies, funnel plots were generated and showed no significant risk of bias. ConclusionCompared with gemcitabine alone, HIFU combined with gemcitabine can increase patients’ survival rate and improve their symptoms, with a similar incidence rate of adverse effects. Further studies are needed for this combined therapy.

Bifidobacterium combined with cationic lipid nanoparticles with liquid perflurocarbon for improving HIFU ablation effect: Experimental study / 中国介入影像与治疗学

Objective: To investigate the influence of bifidobacterium combined with cationic lipid nanoparticles with liquid fluorocarbon on HIFU ablation for tumor-bearing mice. Methods: Bifidobacterium was cultured, cationic lipid nanoparticles with liquid fluorocarbon were prepared, and the connection ratio was examined in vitro. Mice models of human breast cancer MDA-MB231 cells were established. A total of 48 tumor-bearing mice were randomly divided into 4 groups (each n=12). Different substances were injected through the tail vein twice (two days apart). Tumor-bearing mice in group A (PBS group) were injected with phosphate buffer (PBS) twice, in group B (bifidobacterium group) were injected with bifidobacterium before PBS injection, in group C (cationic lipid nanoparticles) with PBS before cationic lipid nanoparticles injection and in group D (bifidobacterium+cationic lipid nanoparticle group) with bifidobacterium before cationic lipid nanoparticles injection. Twenty-four hours after the completion of the second injection, HIFU irradiation was performed on the tumor tissue of tumor-bearing mice, and the changes between pre- and post-ablation gray scale of the tumor tissue were analyzed. Histological examination was performed 1 h before HIFU irradiation and 1 day after irradiation, respectively. The tumor targeting of bifidobacterium was observed, and the coagulative necrotic volume of tumor tissues and energy efficiency factor (EEF) of HIFU ablation were measured. Statistical analysis was performed to compare the differences among 4 groups. Results: Gram-stained bifidobacterium longum was manifested as blue-violet long rod with a surface potential of -29 mV. The cationic lipid nanoparticles were spherical and evenly distributed with average particle diameter of (280.21±60.20)nm and a surface potential of 25 mV. The differences of gray scale change (F=143.40), coagulative necrotic volume (F=243.20) and EEF (F=56.33) were statistically significant among 4 groups (all P<0.001). Gray value change and coagulative necrotic volume gradually increased in group A, B, C and D (pairwise comparison: All P<0.05), while EEF trended from high to low in group A, B, C and D (pairwise comparison: All P<0.05). There was no bifidobacterium in heart, liver, spleen, lung and kidney of tumor-bearing mice among 4 groups nor in tumors of group A and C. A quantity of bifidobacterium was found in tumor tissue of group B and D. Conclusion: Bifidobacteriaum combined with cationic lipid nanoparticles with liquid fluorocarbon can enhance the ablation effect of HIFU ablation on tumor tissue in tumor-bearing mice.

Clinical effectiveness and safety of HIFU in ablation of uterine fibroids with different MR T2WI signals / 中国介入影像与治疗学

Objective: To investigate the ablation effect and safety of HIFU for uterine fibroids with different MR T2WI signals. Methods: Totally 156 patients with 210 uterine fibroids were treated with HIFU ablation. According to preoperative MR T2WI performances, uterine fibroids were divided into low signal group, equal signal group, high signal group and mixed signal group. The preoperative fibroid volume and intraoperative therapeutic dose parameters (sound source power, irradiation time, therapeutic dose and treatment intensity), energy efficiency factor, postoperative ablation rate, fibroid reduction, as well as the incidence of intraoperative and postoperative adverse reactions were compared among 4 groups. Results: There were statistical differences of preoperative fibroid volume (χ2=14.720, P=0.002), irradiation time (F=10.422, P0.05). Conclusion: HIFU treatment is safe and effective for uterine fibroids with different signals of MR T2WI. However, uterine fibroids with high signals on MR T2WI are difficult to ablate, and the postoperative efficacy is relatively poor.

Impact on treatment safety and efficacy of seromuscular-layer injury after HIFU ablation for uterine fibroids / 中国介入影像与治疗学

Objective: To investigate the impact on treatment efficacy and safety of seromuscular-layer injury after ablation with HIFU for uterine fibroids. Methods: A total of 400 patients with uterine fibroids who underwent HIFU ablation were enrolled. All patients had completed MRI data before and after ablation. According to postoperative enhanced MR T1WI showing whether there was perfusion defect of seromuscular-layer on sagittal or axial images of whole myometrial perfusion period, the patients were divided into injured group and intact group. The patients' age, body mass index (BMI), location of uterine fibroids, type (subserous, submucous or intermural myoma), volume, distance from anterior margin of myoma to anterior abdominal wall, parameters of ablation (power and total energy), non-perfused volume (NPV) after ablation, ablation rate, energy efficiency factor (EEF), postoperative complications and pregnancy rate were compared between the two groups. Results: There were 90 cases in injured group and 310 cases in intact group. No statistical difference of patients' age, volume of uterine fibroids, distance from anterior margin of myoma to anterior abdominal wall, power of ablation nor NPV was found between the two groups (all P>0.05).There were statistical differences of location and type of uterine fibroids (both P0.05). The postoperative pregnancy rate of the injured group and the intact group was 5.56% (5/90) and 2.26% (7/310), respectively. And there was no statistical difference (χ2=1.596, P=0.206). No adverse event related to pregnancy and deliver was observed. Conclusion: HIFU ablation for uterine fibroids may lead to uterine seromuscular-layer injury, which can be observed in patients with high BMI, subserosal fibroids at the fundus of uterus and easy to ablate fibroids (low ablation energy and EEF, high ablation rate). The postoperative pregnancy and delivery are not obviously affected by seromuscular-layer injury.

Research progress of microbubble ultrasound contrast agent for treatment of uterine fibroids with high intensity focused ultrasound / 中国介入影像与治疗学

As a non-invasive thermal ablation technique, high intensity focused ultrasound (HIFU) has been widely used in treatment of uterine fibroids with affirmed efficacy. Microbubble contrast agent has important clinical value in the visualization of lesions, the evaluation of efficacy after HIFU ablation and the mechanism of synergy. The advancements of microbubble contrast agent in treatment of uterine fibroids with HIFU were reviewed in this article.

Application progresses of MRI in high intensity focused ultrasound ablation of uterine fibroids / 中国医学影像技术

High intensity focused ultrasound (HIFU) has been widely used in the treatment of uterine fibroids, and the efficacy is exact. MRI has high soft tissue resolution and obvious advantages in gynecological solid tumor detection. Multi-parameter MR imaging technology has an irreplaceable position in preoperative planning, intraoperative real-time monitoring and postoperative efficacy evaluation. The progresses of MRI parameters before, during and after HIFU ablation of uterine fibroids were reviewed in this article.

Factors affecting energy efficiency factor in high intensity focused ultrasound for adenomyosis / 中国医学影像技术

Objective: To explore the factors affecting energy efficiency factor (EEF) in high intensity focused ultrasound for adenomyosis. Methods: Data of 130 patients with adenomyosis treated with high intensity focused ultrasound were retrospectively analyzed. The factors affecting EEF in high intensity focused ultrasound were identified with difference and correlation analyses. And a multiple linear regression equation was obtained by multivariate analysis. Results: The course of disease (X1), abdominal wall scar (X2), gonadotropin releasing hormone agonist (GnRH-a) pretreatment (X3), blood flow grade (X4), abdominal wall thickness (X5) and target-skin distance (X6) were the influencing factors of EEF in high intensity focused ultrasound with the multiple linear regression equation as Y=-17.742+1.153X1+14.927X2-13.846X3+4.713X4+1.422X5+0.227X6. Conclusion: High intensity focused ultrasound treatment presents lower EEF and higher ablation efficiency in patients with adenomyosis who have short course of disease, no abdominal wall scar, GnRH-a pretreatment, little blood flow in the lesion, thin abdominal wall and short target-skin distance.

Factors Related to Successful Energy Transmission of Focused Ultrasound through a Skull: A Study in Human Cadavers and Its Comparison with Clinical Experiences

OBJECTIVE: Although magnetic resonance guided focused ultrasound (MRgFUS) has been used as minimally invasive and effective neurosurgical treatment, it exhibits some limitations, mainly related to acoustic properties of the skull barrier. This study was undertaken to identify skull characteristics that contribute to optimal ultrasonic energy transmission for MRgFUS procedures.METHODS: For ex vivo skull experiments, various acoustic fields were measured under different conditions, using five non-embalmed cadaver skulls. For clinical skull analyses, brain computed tomography data of 46 patients who underwent MRgFUS ablations (18 unilateral thalamotomy, nine unilateral pallidotomy, and 19 bilateral capsulotomy) were retrospectively reviewed. Patients' skull factors and sonication parameters were comparatively analyzed with respect to the cadaveric skulls.RESULTS: Skull experiments identified three important factors related skull penetration of ultrasound, including skull density ratio (SDR), skull volume, and incidence angle of the acoustic rays against the skull surface. In clinical results, SDR and skull volume correlated with maximal temperature (Tmax) and energy requirement to achieve Tmax (p<0.05). In addition, considering the incidence angle determined by brain target location, less energy was required to reach Tmax in the central, rather than lateral targets particularly when compared between thalamotomy and capsulotomy (p<0.05).CONCLUSION: This study reconfirmed previously identified skull factors, including SDR and skull volume, for successful MRgFUS; it identified an additional factor, incidence angle of acoustic rays against the skull surface. To guarantee successful transcranial MRgFUS treatment without suffering these various skull issues, further technical improvements are required.

Magnetic Resonance-Guided Focused Ultrasound : Current Status and Future Perspectives in Thermal Ablation and Blood-Brain Barrier Opening

Magnetic resonance-guided focused ultrasound (MRgFUS) is an emerging new technology with considerable potential to treat various neurological diseases. With refinement of ultrasound transducer technology and integration with magnetic resonance imaging guidance, transcranial sonication of precise cerebral targets has become a therapeutic option. Intensity is a key determinant of ultrasound effects. High-intensity focused ultrasound can produce targeted lesions via thermal ablation of tissue. MRgFUS-mediated stereotactic ablation is non-invasive, incision-free, and confers immediate therapeutic effects. Since the US Food and Drug Administration approval of MRgFUS in 2016 for unilateral thalamotomy in medication-refractory essential tremor, studies on novel indications such as Parkinson's disease, psychiatric disease, and brain tumors are underway. MRgFUS is also used in the context of blood-brain barrier (BBB) opening at low intensities, in combination with intravenously-administered microbubbles. Preclinical studies show that MRgFUS-mediated BBB opening safely enhances the delivery of targeted chemotherapeutic agents to the brain and improves tumor control as well as survival. In addition, BBB opening has been shown to activate the innate immune system in animal models of Alzheimer’s disease. Amyloid plaque clearance and promotion of neurogenesis in these studies suggest that MRgFUS-mediated BBB opening may be a new paradigm for neurodegenerative disease treatment in the future. Here, we review the current status of preclinical and clinical trials of MRgFUS-mediated thermal ablation and BBB opening, described their mechanisms of action, and discuss future prospects.

Clinical status of high-intensity focused ultrasound in the treatment of advanced pancreatic cancer / 国际外科学杂志

Pancreatic cancer is a common malignancy of the digestive system,which is difficult for early diagnosis and surgical resection.Currently,the main clinical treatment strategies are not effective.High-intensity focused ultrasound (HIFU),for its non-invasive characteristic,with combination therapy,such as chemotherapy,radiotherapy and traditional Chinese medicine,has made great progress in the clinical treatment of advanced pancreatic cancer.This literature will review the clinical status of HIFU in in the treatment of advanced pancreatic cancer,in order to provide references for the study of pancreatic cancer.

Factors Related to Successful Energy Transmission of Focused Ultrasound through a Skull: A Study in Human Cadavers and Its Comparison with Clinical Experiences

OBJECTIVE: Although magnetic resonance guided focused ultrasound (MRgFUS) has been used as minimally invasive and effective neurosurgical treatment, it exhibits some limitations, mainly related to acoustic properties of the skull barrier. This study was undertaken to identify skull characteristics that contribute to optimal ultrasonic energy transmission for MRgFUS procedures. METHODS: For ex vivo skull experiments, various acoustic fields were measured under different conditions, using five non-embalmed cadaver skulls. For clinical skull analyses, brain computed tomography data of 46 patients who underwent MRgFUS ablations (18 unilateral thalamotomy, nine unilateral pallidotomy, and 19 bilateral capsulotomy) were retrospectively reviewed. Patients' skull factors and sonication parameters were comparatively analyzed with respect to the cadaveric skulls. RESULTS: Skull experiments identified three important factors related skull penetration of ultrasound, including skull density ratio (SDR), skull volume, and incidence angle of the acoustic rays against the skull surface. In clinical results, SDR and skull volume correlated with maximal temperature (Tmax) and energy requirement to achieve Tmax (p<0.05). In addition, considering the incidence angle determined by brain target location, less energy was required to reach Tmax in the central, rather than lateral targets particularly when compared between thalamotomy and capsulotomy (p<0.05). CONCLUSION: This study reconfirmed previously identified skull factors, including SDR and skull volume, for successful MRgFUS; it identified an additional factor, incidence angle of acoustic rays against the skull surface. To guarantee successful transcranial MRgFUS treatment without suffering these various skull issues, further technical improvements are required.

Magnetic Resonance-Guided Focused Ultrasound : Current Status and Future Perspectives in Thermal Ablation and Blood-Brain Barrier Opening

Magnetic resonance-guided focused ultrasound (MRgFUS) is an emerging new technology with considerable potential to treat various neurological diseases. With refinement of ultrasound transducer technology and integration with magnetic resonance imaging guidance, transcranial sonication of precise cerebral targets has become a therapeutic option. Intensity is a key determinant of ultrasound effects. High-intensity focused ultrasound can produce targeted lesions via thermal ablation of tissue. MRgFUS-mediated stereotactic ablation is non-invasive, incision-free, and confers immediate therapeutic effects. Since the US Food and Drug Administration approval of MRgFUS in 2016 for unilateral thalamotomy in medication-refractory essential tremor, studies on novel indications such as Parkinson's disease, psychiatric disease, and brain tumors are underway. MRgFUS is also used in the context of blood-brain barrier (BBB) opening at low intensities, in combination with intravenously-administered microbubbles. Preclinical studies show that MRgFUS-mediated BBB opening safely enhances the delivery of targeted chemotherapeutic agents to the brain and improves tumor control as well as survival. In addition, BBB opening has been shown to activate the innate immune system in animal models of Alzheimer’s disease. Amyloid plaque clearance and promotion of neurogenesis in these studies suggest that MRgFUS-mediated BBB opening may be a new paradigm for neurodegenerative disease treatment in the future. Here, we review the current status of preclinical and clinical trials of MRgFUS-mediated thermal ablation and BBB opening, described their mechanisms of action, and discuss future prospects.

High-intensity focused ultrasound ablation as a treatment for benign thyroid diseases: the present and future

High-intensity focused ultrasound (HIFU) is a promising ablation technique for benign thyroid nodules. Current evidence has found good short- to medium-term outcomes, similar to those of better-established ablation techniques such as radiofrequency and laser ablation. The fact that it does not require insertion of a needle into the target makes HIFU a truly non-invasive treatment. Although it is not without risks, its low risk profile makes it an attractive alternative to surgery. There is much room for future development, starting from expanding the current indications to enhancing energy delivery. Relapsed Graves disease and papillary microcarcinoma are diseases that can benefit from HIFU treatment. Its role in the mediation of immune responses and synergistic effects with immunotherapy are promising in the fight against metastatic cancers.

Clinical characteristics of patients with leiomyoma who undergo surgery after high intensity focused ultrasound (HIFU)

OBJECTIVE: We evaluated the clinical characteristics of patients who underwent surgery after high intensity focused ultrasound (HIFU) to treat uterine leiomyoma. METHODS: From June 2016 to September 2017, patients at our hospital who underwent HIFU to treat uterine leiomyoma prior to surgery were enrolled. All patients underwent pelvic magnetic resonance imaging (MRI) before and after HIFU. If 6 months had passed since the last pelvic MRI was performed, imaging was performed again before the operation. RESULTS: A total of 12 patients were analyzed. The median age was 45 (range, 28–51) years. The median body mass index was 24.9 (range, 18.1–29.2) kg/m2. The median size of the leiomyoma was 10.1 (range, 7.8–14.0) cm before HIFU, which changed to 8.75 (range, 5.9–14.8) cm after HIFU. The median size increased to 9.1 (range, 5.9–18.0) cm before the operation. Surgery was planned for several reasons, including an increase in the leiomyoma size (n=6), persistent symptoms (n=4), and newly developed lesion (n=2). The median interval between HIFU and surgery was 7 (range, 3–32) months. Ten of the 12 patients underwent laparoscopic surgery, while the others underwent laparotomy; 6 patients also underwent laparoscopic myomectomy, and 4 underwent hysterectomy. Histopathologic findings showed infarction-type necrosis surrounded by granulation tissue with the infiltration of lymphocytes and macrophages in all patients. CONCLUSION: Treatment of leiomyoma with operative procedures should be considered in selected patients with tumor size greater than 10 cm, multiple tumors, and persistent symptoms after HIFU treatment.

High-Intensity Focused Ultrasound (HIFU) as salvage therapy for radio-recurrent prostate cancer: predictors of disease response

ABSTRACT Background Some men with localized radio-recurrent prostate cancer may benefit from salvage high-intensity focused ultrasound (HIFU). Herein, we describe oncologic outcomes and predictors of disease response after salvage whole gland HIFU from our prospective cohort. Materials and Methods Patients with localized radio-recurrent prostate cancer were prospectively enrolled from January 2005 to December 2014. Participants had to meet both biochemical and histological definitions of recurrence. Exclusion criteria included the receipt of prior salvage therapy, presence of metastatic disease, and administration of ADT in the 6-months prior to enrollment. Participants were treated with a single session of whole-gland HIFU ablation with the AblathermTM device (EDAP, France). The primary endpoint was recurrence-free survival (RFS), defined as a composite endpoint of PSA progression (Phoenix criteria), receipt of any further salvage therapy, receipt of ADT, clinical progression, or death. Kaplan-Meier survival analysis was used to determine the primary end-point and stratifications were used to determine the significance of 6 pre-specified predictors of improved RFS (TRUS biopsy grade, number of study entry TRUS biopsy cores positive, palpable disease at study enrollment, pre-HIFU PSA, an undetectable post-HIFU PSA nadir, and receipt of prior hormone therapy). Survival analysis was performed on participants with a minimum of 1-year follow-up. Results Twenty-four participants were eligible for study inclusion with a median follow-up of 31.0 months. Median PSA at study entry was 4.02ng/ml. Median time to PSA nadir was 3 months after treatment and median post-HIFU PSA nadir was 0.04ng/ml. Median 2-year and 5-year RFS was 66.3% and 51.6% respectively. Of our 6 prespecified predictors, an undetectable PSA nadir was the only significant predictor of improved RFS (HR 0.07, 95% CI 0.02-0.29, log-rank P<0.001). One participant underwent an intervention for a urethral stricture. No participants developed osteitis pubis or rectourethral fistulae. Conclusions Salvage HIFU allows for disease control in selected patients with localized radio-recurrent prostate cancer. An undetectable PSA nadir serves as an early predictor of disease response.