Magnetic resonance-guided focused ultrasound for essential tremor:a prospective,single center,single-arm study

The safety and effectiveness of magnetic resonance-guided focused ultrasound thalamotomy has been broadly established and validated for the treatment of essential tremor.In 2018,the first magnetic resonance-guided focused ultrasound system in Chinese mainland was installed at the First Medical Center of the PLA General Hospital.This prospective,single center,open-label,single-arm study was part of a worldwide prospective multicenter clinical trial(ClinicalTrials.gov Identifier:NCT03253991)conducted to confirm the safety and efficacy of magnetic resonance-guided focused ultrasound for treating essential tremor in the local population.From 2019 to 2020,10 patients with medication refractory essential tremor were recruited into this open-label,single arm study.The treatment efficacy was determined using the Clinical Rating Scale for Tremor.Safety was evaluated according to the incidence and severity of adverse events.All of the subjects underwent a unilateral thalamotomy targeting the ventral intermediate nucleus.At the baseline assessment,the estimated marginal mean of the Clinical Rating Scale for Tremor total score was 58.3±3.6,and this improved after treatment to 23.1±6.4 at a 12-month follow-up assessment.A total of 50 adverse events were recorded,and 2 were defined as serious.The most common intraoperative adverse events were nausea and headache.The most frequent postoperative adverse events were paresthesia and equilibrium disorder.Most of the adverse events were mild and usually disappeared within a few days.Our findings suggest that magnetic resonance-guided focused ultrasound for the treatment of essential tremor is effective,with a good safety profile,for patients in Chinese mainland.

Wideband frequency-dependent dielectric properties of rat tissues exposed to low-intensity focused ultrasound in the microwave frequency range

Tissue dielectric properties can vary upon the incident of an acoustic wave.The goal of this study is to quantify this change due to the acoustoelectric effect(AE),and to obtain the frequency-dependent dielectric properties of tissues exposed to low-intensity focused ultrasound(LIFU).The dielectric properties of the blood,brain,chest muscle,heart,kidney,leg muscle,liver,lung,pancreas,and spleen of rats were measured by an open-ended coaxial probe method.The acoustic intensity of LIFU focus was 2.97 MPa(67.6 W/cm^(2)),3.95 MPa(120 W/cm^(2)),and 5.17 MPa(204 W/cm^(2)),respectively,and the measurement frequency band was 0.1–7.08 GHz.The measurement results show that with the LIFU modulation,the conductivity and dielectric constant decreased in the high-frequency band,and on the contrary,they increased in the lowfrequency band,and the larger the acoustic intensity was,the more obvious the phenomenon was.This work contributes to a better understanding of the mechanisms by which ultrasound acts on the dielectric properties of biological tissues.It is expected that the findings from this study will provide a basis that the response of tissue to LIFU modulation can be monitored by noninvasive techniques such as microwave-induced thermoacoustic imaging(MTI)and microwave imaging,present a new idea for improving the endogenous contrast between different biological tissues in MTI and acoustoelectric imaging,and possibly lead to the development of a new imaging method based on the relaxation time of tissue after LIFU modulation.

A new method for preparing a rat intracerebral hemorrhage model by combining focused ultrasound and microbubbles

Background:We aimed to prepare a non-invasive,reproducible,and controllable rat model of intracerebral hemorrhage with focused ultrasound(FUS).Methods:A rat intracerebral hemorrhage(ICH)model was established by combining FUS and microbubbles(μBs),and edaravone was used to verify whether the free radical scavenger had a protective effect on the model.The brain tissue of each group was sectioned to observe the gross histology,blood-brain barrier(BBB)permeability,cerebral infarction volume,and histopathological changes.Results:Compared with the FUS group,the BBB permeability was significantly increased in the FUS+μBs(F&B)group(p=0.0021).The second coronal slice in the F&B group had an obvious hemorrhage lesion,and the FUS+μBs+edaravone(F&B&E)group had smaller hemorrhage areas;however,ICH did not occur in the FUS group.The cerebral infarction volume in the F&B group was significantly larger than that in the FUS group(p=0.0030)and F&B&E group(p=0.0208).HE staining results showed that nerve fibrinolysis,neuronal necrosis,microglia production,and erythrocytes were found in both the F&B group and the F&B&E group,but the areas of the nerve fibrinolysis and neuronal necrosis in the F&B group were larger than the F&B&E group.Conclusions:A rat ICH model was successfully prepared using theμBs assisted FUS treatment,and edaravone had a therapeutic effect on this model.This model can be used to study the pathophysiological mechanism of ICH-related diseases and in preclinical research on related new drugs.

Managing spindle cell sarcoma with surgery and high-intensity focused ultrasound:A case report

BACKGROUND Undifferentiated pleomorphic sarcomas,also known as spindle cell sarcomas,are a relatively uncommon subtype of soft tissue sarcomas in clinical practice.CASE SUMMARY We present a case report of a 69-year-old female patient who was diagnosed with undifferentiated spindle cell soft tissue sarcoma on her left thigh.Surgical excision was initially performed,but the patient experienced a local recurrence following multiple surgeries and radioactive particle implantations.High-intensity focused ultrasound(HIFU)was subsequently administered,resulting in complete ablation of the sarcoma without any significant complications other than bone damage at the treated site.However,approximately four months later,the patient experienced a broken lesion at the original location.After further diagnostic workup,the patient underwent additional surgery and is currently stable with a good quality of life.CONCLUSION HIFU has shown positive outcomes in achieving local control of limb spindle cell sarcoma,making it an effective non-invasive treatment option.

Lax Facial Skin Treated with High-Intensity Focused Ultrasound Devices: Efficacy and Safety Evaluations

Background: High-intensity focused ultrasound (HIFU) has been introduced to improve skin laxity in recent years. However, very few studies have evaluated the safety and effectiveness of HIFU in Chinese populations. Methods: In the study, 30 Chinese participants underwent HIFU (Bolida, Inc., Changsha, China) rejuvenation between February 1, 2022, and September 30, 2022. There were three different focal depths used depending on the area where shots were captured (4.5 mm, 4 MHz;3 mm, 7 MHz;1.5 mm, 7 MHz). After 3 months and 6 months of treatment, efficacy and safety were assessed by quantitative analysis. Results: Patients were satisfied with the clinical effects of HIFU rejuvenation after one session. In terms of effectiveness, HIFU was most successful in areas around the jawline, cheek, and perioral. In four cases, erythema was observed, in two cases, swollen gums were seen, but all of these effects were transient and mild. Conclusion: Bolida system can be safe and effective for facial tightening, additionally, they are most effective for jawline, cheek, and perioral improvements. In clinical practice, the Bolida system can be recommended as a reliable treatment option. .

High-intensity focused ultrasound ablation:An effective bridging therapy for hepatocellular carcinoma patients

AIM:To analyze whether high-intensity focused ultrasound(HIFU) ablation is an effective bridging therapy for patients with hepatocellular carcinoma(HCC).METHODS:From January 2007 to December 2010,49 consecutive HCC patients were listed for liver transplantation(UCSF criteria).The median waiting time for transplantation was 9.5 mo.Twenty-nine patients received transarterial chemoembolization(TACE) as a bringing therapy and 16 patients received no treatment before transplantation.Five patients received HIFU ablation as a bridging therapy.Another five patients with the same tumor staging(within the UCSF criteria) who received HIFU ablation but not on the transplant list were included for comparison.Patients were comparable in terms of Child-Pugh and model for end-stage liver disease scores,tumor size and number,and cause of cirrhosis.RESULTS:The HIFU group and TACE group showed no difference in terms of tumor size and tumor number.One patient in the HIFU group and no patient in the TACE group had gross ascites.The median hospital stay was 1 d(range,1-21 d) in the TACE group and two days(range,1-9 d) in the HIFU group(P < 0.000).No HIFU-related complication occurred.In the HIFU group,nine patients(90%) had complete response and one patient(10%) had partial response to the treatment.In the TACE group,only one patient(3%) had response to the treatment while 14 patients(48%) had stable disease and 14 patients(48%) had progressive disease(P = 0.00).Seven patients in the TACE group and no patient in the HIFU group dropped out from the transplant waiting list(P = 0.559).CONCLUSION:HIFU ablation is safe and effective in the treatment of HCC for patients with advanced cirrhosis.It may reduce the drop-out rate of liver transplant candidate.

Safety trial of high-intensity focused ultrasound therapy for pancreatic cancer

AIM:To evaluate the safety and clinical application of high-intensity focused ultrasound(HIFU)therapy for unresectable pancreatic cancer(PC).METHODS:Thirty PC patients(16 cases in stage III and 14 cases in stage IV)with visualized pancreatic tumors were admitted for HIFU therapy as an optional local therapy in addition to systemic chemotherapy or chemoradiotherapy.Informed consent was obtained.This study began at the end of 2008 and was approved by the ethics committee of our hospital[Institutional Review Board(IRB):890].The HIFU device used was the FEP-BY02(Yuande Bio-Medical Engineering,Beijing,China).RESULTS:The mean tumor size after HIFU therapy changed to 30.9±1.7 mm from 31.7±1.7 mm at pre-therapy.There were no significant changes in tumor size,mean number of treatment sessions(2.7±0.1 mm),or mean total treatment time(2.4±0.1 h).The rate of symptom relief effect was 66.7%.The effectiveness of primary lesion treatment was as follows:complete response,0;partial response,4;stable disease,22;progressive disease,4.Treatment after HIFU therapy included 2 operations,24 chemotherapy treatments,and 4 best supportive care treatments.Adverse events occurred in 10%of cases,namely pseudocyst formation in 2 cases and mild pancreatitis development in 1.However,no severe adverse events occurred in this study.CONCLUSION:We suggest that HIFU therapy is safe and has the potential to be a new method of combination therapy for PC.

Enhancement of antitumor vaccine in ablated hepatocellular carcinoma by high-intensity focused ultrasound

AIM:To investigate whether tumor debris created by high-intensity focused ultrasound(HIFU)could trigger antitumor immunity in a mouse hepatocellular carcinoma model. METHODS:Twenty C57BL/6J mice bearing H22 hepatocellular carcinoma were used to generate antitumor vaccines.Ten mice underwent HIFU ablation,and the remaining 10 mice received a sham-HIFU procedure with no ultrasound irradiation.Sixty normal mice were randomly divided into HIFU vaccine,tumor vaccine and control groups.These mice were immunized with HIFU-generated vaccine,tumor-generated vaccine,and saline,respectively.In addition,20 mice bearing H22 tumors were successfully treated with HIFU ablation. The protective immunity of the vaccinated mice was investigated before and after a subsequent H22 tumor challenge.Using the 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide assay,the cytotoxicity of splenic lymphocytes co-cultured with H22 cells wasdetermined in vitro before the tumor challenge,and tumor volume and survival were measured in vivo after the challenge in each group.The mechanism was also explored by loading the vaccines with bone marrowderived dendritic cells(DCs). RESULTS:Compared to the control,HIFU therapy, tumor-generated and HIFU-generated vaccines significantly increased cytolytic activity against H22 cells in the splenocytes of the vaccinated mice(P<0.001). The tumor volume was significantly smaller in the HIFU vaccine group than in the tumor vaccine group(P <0.05)and control group(P<0.01).However,there was no tumor growth after H22 rechallenge in the HIFU therapy group.Forty-eight-day survival rate was 100%in mice in the HIFU therapy group,30%in both the HIFU vaccine and tumor vaccine groups,and 20% in the control group,indicating that the HIFU-treated mice displayed significantly longer survival than the vaccinated mice in the remaining three groups(P< 0.001).After bone marrow-derived DCs were incubated with HIFU-generated and tumor-generated vaccines, the number of mature DCs expressing MHC-Ⅱ + ,CD80 + and CD86 + molecules was significantly increased,and interleukin-12 and interferon-γlevels were significantly higher in the supernatants when compared with immature DCs incubated with mouse serum(P<0.001). However,no differences of the number of mature DCs and cytokine levels were observed between the HIFU- generated and tumor-generated vaccines(P>0.05). CONCLUSION:Tumor debris remaining after HIFU can improve tumor immunogenicity.This debris releases tumor antigens as an effective vaccine to develop host antitumor immune response after HIFU ablation.

High intensity focused ultrasound,liver disease and bridging therapy

High-intensity focused ultrasound(HIFU)is a noninvasive modality that uses an extracorporeal source of focused ultrasound energy.This technique was introduced by Lynn et al and is able to induce coagulative necrosis in selected tissues without damaging adjacent structures.Although HIFU has been studied for 50years,recent technological developments now allow its use for tumours of the liver,prostate and other sites.In liver disease,HIFU has been used to treat unresectable,advanced stages of hepatocellular carcinoma(HCC)and liver metastases.Hepatocellular carcinoma is a serious health problem worldwide and is endemic in some areas because of its association with hepatitis B and C viruses(in 20%of cases).Liver transplantation(LT)has become one of the best treatments available because it removes both the tumour and the underlying liver disease such as cirrhosis(which is present in approximately 80%of cases).The prerequisite for longterm transplant success depends on tumour load and strict selection criteria regarding the size and number of tumour nodules.The need to obtain the optimal benefit from the limited number of organs available has prompted strict selection criteria limited to only those patients with early HCC who have a better long-term outcome after LT.The so-called"bridging therapy"has the aim of controlling disease burden for patients who are on the organ transplant waiting list.Amongst various treatment options,transarterial chemoembolisation and radiofrequency ablation are the most popular treatment choices.Recently,Cheung et al demonstrated that HIFU ablation is a safe and effective method for the treatment of HCC patients with advanced cirrhosis as a bridging therapy and that it reduced the dropout rate from the liver transplant waiting list.In this commentary,we discuss the current value of HIFU in the treatment of liver disease,including its value as a bridging therapy,and examine the potential advantages of other therapeutic strategies.

High-intensity focused ultrasound treatment for patients with unresectable pancreatic cancer

BACKGROUND: High-intensity focused ultrasound (HIFU) is a non-invasive method of solid tissue ablation therapy. However, only a few studies have reported the effect of HIFU for unresectable pancreatic cancer. This study aimed to evaluate the clinical benefits, survival time and complications associated with the use of HIFU ablation in patients with unresectable pancreatic cancer. METHODS: Twenty-five patients with unresectable pancreatic cancer were enrolled in our study. All patients received HIFU therapy for tumors at least once. The therapeutic effects of HIFU was evaluated in terms of Karnofsky performance status (KPS) scores, pain relief, serum CA19-9, and imaging by B-US and CT before and after the therapy. We also recorded median overall survival time and complications caused by the treatment. RESULTS: In the 25 patients, KPS scores were above 60, and increased KPS was observed in 23 patients after treatment. Pain relief occurred in 23 patients. Serum CA19-9 levels were significantly reduced one month after HIFU treatment and became negative in 5 patients. B-US revealed enhanced tumor echogenicity in 13 patients and decreased tumor blood supply in 9. Tumor necrosis was confirmed by CT in 8 patients one month after HIFU treatment. The median overall survival time was 10 months, and the 1-year survival rate was 42%. No severe complications were observed after HIFU treatment. CONCLUSION: HIFU can effectively relieve pain, increase KPS, decrease tumor growth and prolong the survival time of patients with unresectable pancreatic cancer.

High intensity focused ultrasound in clinical tumor ablation

Recent advances in high intensity focused ultrasound(HIFU),which was developed in the 1940s as a viable thermal tissue ablation approach,have increased its popularity.In clinics,HIFU has been applied to treat a variety of solid malignant tumors in a well-defined volume,including the pancreas,liver,prostate,breast,uterine fibroids,and soft-tissue sarcomas.In comparison to conventional tumor/cancer treatment modalities,such as open surgery,radio-and chemo-therapy,HIFU has the advantages of non-invasion,non-ionization,and fewer complications after treatment.Over 100 000 cases have been treated throughout the world with great success.The fundamental principles of HIFU ablation are coagulative thermal necrosis due to the absorption of ultrasound energy during transmission in tissue and the induced cavitation damage.This paper reviews the clinical outcomes of HIFU ablation for applicable cancers,and then summarizes the recommendations for a satisfactory HIFU treatment according to clinical experience.In addition,the current challenges in HIFU for engineers and physicians are also included.More recent horizons have broadened the application of HIFU in tumor treatment,such as HIFU-mediated drug delivery,vessel occlusion,and soft tissue erosion(“histotripsy”).In summary,HIFU is likely to play a significant role in the future oncology practice.

Sonablate-500^(TM) Transrectal High-intensity Focused Ultrasound (HIFU) for Benign Prostatic Hyperplasia Patients

To evaluate the safety and efficacy of transrectal high-intensity focused ultrasound （HIFU） in the treatment of benign prostatic hyperplasia （BPH）, serial studies were conducted in 150 BPH patients before and 30 min, 1, 2, 6 and 12 month（s） after Sonablate-500TM HIFU treatment. A silicon-coated indwelling 16F latex catheter was placed during the determination of the therapy zone. Preoperative and postoperative evaluations were made by using the international prostate symptom score （IPSS）, quality of life （QOL）, uroflowmetric findings and transrectal ultrasound, and incidence of complications. The cystourethrography was done in 23 patients within 1 year postoperatively. The results showed that after HIFU treatment, IPSS and QOL scores were significantly decreased at 1, 2, 6 and 12 month（s） （P〈0.01）. Maximum urine flow rate （6.0 to 17.2 mL/s, P〈0.01）, PVR （75.0 to 30.3, P〈0.01） and prostatic volume （65.0 to 38.1 mL, P〈0.05） were significantly improved 12 months after the operation. Recurrent urinary retention （17=2） and urethrorectal fistula （n=1） occurred at the 15th postoperative day. The duration of the HIFU prostate ablation was 25-90 min. The mean time for an indwelling catheter was 3-19 days. These data demonstrate that treatment of BPH with Sonab- late-500TM HIFU is safe and effective.

Sequential transcatheter arterial chemoembolization,three-dimensional conformal radiotherapy,and high-intensity focused ultrasound treatment for unresectable hepatocellular carcinoma patients

The purpose of this study was to evaluate the outcome of patients with unresectable hepatocellular carcinoma（HCC） treated by sequential therapy of transcatheter arterial chemoembolization（TACE）,three-dimensional conformal radiotherapy（3-DCRT） and high-intensity focused ultrasound（HIFU）.From October,2005 to September,2010,120 patients with unresectable HCC received the sequential treatments of several courses of TACE followed in 2-4 weeks by 3-DCRT and then a single session of HIFU with a curative intent.The median tumor irradiation dose was 40 Gy.Tumor response,toxicity and overall survival rate were analyzed.Clinicopathologic factors affecting the primary technique effectiveness and overall survival rates were investigated by univariate analysis or multivariate analysis.All 120 HCC patients were followed up by the last follow-up time.Among these patients,hepatic toxicities due to treatment were notable in 9 cases.Gastrointestinal bleeding after the overall treatment occurred in 2 cases,leukopenia of grade III was detected in 1 case,radiation-induced liver disease（RILD） was observed in 2 patients,and first-and second-degree skin burn around the HIFU treatment zone were observed in 2 patients and 1 patient,respectively.Among 120 patients,23,83 and 14 cases achieved partial response,stable disease and progressive disease,respectively.The overall survival rates at 1 year,3 years and 5 years were 70%,35% and 15%,respectively,with a median survival time of 26 months.Both Child-Pugh liver function grading and radiation dose were determined to be independent predictors for overall survival revealed by the multivariate analysis.It is concluded that the sequential therapy of TACE,3-DCRT and HIFU is a promising therapeutic regimen for unresectable HCC.

High-intensity focused ultrasound ablation as a bridging therapy for hepatocellular carcinoma patients awaiting liver transplantation

The scarcity of liver grafts in Asia leads to a significant dropout of patients from liver transplant waiting lists, particularly patients with hepatocellular carcinoma and a low model for end-stage liver disease score. In order to reduce dropping out, different bridging therapies are employed. We report the use of high-intensity focused ultrasound ablation as a bridging therapy for a patient with hepatocellular carcinoma of stage two and an extremely low platelet count (20×10 9 /L). The ablation was successful. Blood tests showed that his liver function was similar before and after the treatment. No adhesion was encountered in the liver transplantation performed six months later.

High intensity focused ultrasound: A noninvasive therapy for locally advanced pancreatic cancer

The noninvasive ablation of pancreatic cancer with high intensity focused ultrasound(HIFU) energy is received increasingly widespread interest. With rapidly temperature rise to cytotoxic levels within the focal volume of ultrasound beams, HIFU can selectively ablate a targeted lesion of the pancreas without any damage to surrounding or overlying tissues. Preliminary studies suggest that this approach is technical safe and feasible, and can be used alone or in combination with systemic chemotherapy for the treatment of patients with locally advanced pancreatic cancer. It can effectively alleviate cancer-related abdominal pain, and may confer an additional survival benefit with few significant complications. This review provides a brief overview of HIFU, describes current clinical applications, summarizes characteristics of continuous and pulsed HIFU, and discusses future applications and challenges in the treatment of pancreatic cancer.

Influence of the abdominal wall on the nonlinear propagation of focused therapeutic ultrasound

This article theoretically studies the influence of inhomogeneous abdominal walls on focused therapeutic ultrasound based on the phase screen model. An inhomogeneous tissue is considered as a combination of a homogeneous medium and a phase aberration screen. Variations of acoustic parameters such as peak positive pressure, peak negative pressure, and acoustic intensity are discussed with respect to the phase screen statistics of human abdominal walls. Results indicate that the abdominal wall can result in energy loss of the sound in the focal plane. For a typical human abdominal wall with correlation length of 7.9 mm and variance of 0.36, the peak acoustic intensity radiated from a 1MHz transmitter with a radius of 30 mm can be reduced by about 14% at the focal plane.

Experimental Study on the Effect of High-intensity Focused Ultrasound (HIFU) Using Sonablate-500 in the Ablation of Canine Prostate

To investigate the safety, feasibility and effectiveness of transrectal high-intensity focused ultrasound （HIFU） in the ablation of canine prostate, 20 dogs were divided randomly into 5 groups. Sixteen canine prostates were treated with the third-generation transrectal HIFU device （Sonablate-500^TM）. Transrectal ultrasound images of the prostate and prostatic urethra were observed preoperatively and postoperatively. Serial study was performed 30 min, 30 days, 60 days and 180 days after the therapy. The rectum, periprostatic tissues, and prostate were excised en bloc and the tissues were fixed for gross and histological analysis. Our results showed that the average maximal diameter of prostatic urethra was 0.59-0.11 cm before the operation and 2.57±0.98 cm 60 days after the operation. The volume of prostate was 6.5±3.12 cm^3 before the treatment while the volume was 4.13±0.23 cm^3 60 days after the treatment and the differences were statistically significant （P〈0.05）. Histologically, there was a clear demarcation between the necrotic area of the treated tissues and the unaffected surrounding tissues. All the necrotic tissues in the targeted zone broke off and the prostatic urethra became cavitary 60 days later. The more frequent complications were urinary retention and frequency and hematuria. No rectal injury occurred during the treatment. It is concluded that the third-generation transrectal HIFU is capable of destroying prostatic tissue, substantially increasing the width of the prostatic urethra without causing injury to the adjacent tissues. The risk of postoperative complications associated with HIFU was low. HIFU may become a safe, effective and minimally invasive alternative for the treatment of prostatic diseases.

Magnetic resonance image-guided versus ultrasound-guided high-intensity focused ultrasound in the treatment of breast cancer

Image-guided high-intensity focused ultrasound (HIFU) has been used for more than ten years, primarily in the treatment of liver and prostate cancers. HIFU has the advantages of precise cancer ablation and excellent protection of healthy tissue. Breast cancer is a common cancer in women. HIFU therapy, in combination with other therapies, has the potential to improve both oncologic and cosmetic outcomes for breast cancer patients by providing a curative therapy that conserves mammary shape. Currently, HIFU therapy is not commonly used in breast cancer treatment, and efforts to promote the application of HIFU is expected. In this article, we compare different image-guided models for HIFU and reviewed the status, drawbacks, and potential of HIFU therapy for breast cancer.

Phase Relation of Harmonics in Nonlinear Focused Ultrasound

The phase relation of harmonics in high-intensity focused ultrasound is investigated numerically and experimen- tally. The nonlinear Westervelt equation is solved to model nonlinear focused sound field by using the finite difference time domain method. Experimental waveforms are measured by a robust needle hydrophone. Then the relative phase quantity is introduced and obtained by using the zero-phase filter. The results show that the nth harmonic relative phase quantity is approximately （n - 1） π/3 at geometric center and increases along the axial direction. Moreover, the relative phase quantity decreases with the increase of source amplitude. This phase relation gives an explanation of some nonlinear phenomena such as the discrepancy of positive and negative pressure.

Treatable focal region modulated by double excitation signal superimposition to realize platform temperature distribution during transcranial brain tumor therapy with high-intensity focused ultrasound

Recently, the phase compensation technique has allowed the ultrasound to propagate through the skull and focus into the brain. However, the temperature evolution during treatment is hard to control to achieve effective treatment and avoid over-high temperature. Proposed in this paper is a method to modulate the temperature distribution in the focal region. It superimposes two signals which focus on two preset different targets with a certain distance. Then the temperature distribution is modulated by changing triggering time delay and amplitudes of the two signals. The simulation model is established based on an 82-element transducer and computed tomography （CT） data of a volunteer＇s head. A finite- difference time-domain （FDTD） method is used to calculate the temperature distributions. The results show that when the distances between the two targets respectively are 7.5-12.5 mm on the acoustic axis and 2.0-3.0 mm in the direction perpendicular to the acoustic axis, a focal region with a uniform temperature distribution （64-65 ℃） can be created. Moreover, the volume of the focal region formed by one irradiation can be adjusted （26.8-266.7 mm3） along with the uniform temperature distribution. This method may ensure the safety and efficacy of HIFU brain tumor therapy.