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.

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.

Identification of denatured and normal biological tissues based on compressed sensing and refined composite multi-scale fuzzy entropy during high intensity focused ultrasound treatment

In high intensity focused ultrasound(HIFU)treatment,it is crucial to accurately identify denatured and normal biological tissues.In this paper,a novel method based on compressed sensing(CS)and refined composite multi-scale fuzzy entropy(RCMFE)is proposed.First,CS is used to denoise the HIFU echo signals.Then the multi-scale fuzzy entropy(MFE)and RCMFE of the denoised HIFU echo signals are calculated.This study analyzed 90 cases of HIFU echo signals,including 45 cases in normal status and 45 cases in denatured status,and the results show that although both MFE and RCMFE can be used to identify denatured tissues,the intra-class distance of RCMFE on each scale factor is smaller than MFE,and the inter-class distance is larger than MFE.Compared with MFE,RCMFE can calculate the complexity of the signal more accurately and improve the stability,compactness,and separability.When RCMFE is selected as the characteristic parameter,the RCMFE difference between denatured and normal biological tissues is more evident than that of MFE,which helps doctors evaluate the treatment effect more accurately.When the scale factor is selected as 16,the best distinguishing effect can be obtained.

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.

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.

High intensity focused ultrasound in combination with chemotherapy by the regime of PFC: a clinical study for advanced gastric carcinoma

Objective： To evaluate the recent curative efficacy and security of High intensity focused ultrasound （HIFU） in combination with chemotherapy（PFC） in patients with advanced gastric carcinoma. Method： Sixty patients with measurable advanced gastric carcinoma, proved pathologically, were divided into Group A and Group B. Group A： Patients were treated by HIFU（FEP-BY01） in combination with chemotherapy（PFC, paclitaxel, cisplatin and 5-fluorouracil）. Group B： Patients were treated with the single regime of PFC. Results： All cases could be evaluated, ha group A, 5 patients achieved complete response, 17 patients achieved partial response,and a response rate was 73.3%. The stable disease（SD） and the inefficiency all were 13.3% （4/30） respectively, and msurvival time（MST） was 13.9 months. In group B, 2 patients achieved complete response, 14 patients achieved partial response, and a response rate was 53.3%. The stable disease（SD） was 23.3%（7/30）. The inefficiency all were 23.3%（7/30） respectively, and median survival time was 9.6 months. There was significant difference between two groups MST（ P 〈 0.05）. Major toxicities included bone marrow depression, nausea, vomiting and alopecia, without significant differences between two groups（ P 〉 0.05）. Conclusion： This study shows that HIFU in combination with chemotherapy（PFC） was a new efficent and secure therapy for the patients with advanced gastric carcinoma. It was observed that the MST was prolonged. Prospective trials should be warranted to determine the result.

Transrectal High-Intensity Focused Ultrasound for the Treatment of Localized Prostate Cancer: Current Role

Over the past 25 years, the average life expectancy for men has increased by 4 years, and the age of prostate cancer detection has decreased an average of 10 years with diagnosis increasingly made at early-stage disease where curative therapy is possible. These changing trends in the age and extent of malignancy at diagnosis have revealed limitations in conventional curative therapies for prostate cancer, including a significant risk of aggressive cancer recurrence, and the risk of long-term genitourinary morbidity and its detrimental impact on patient quality of life (QOL). Greater awareness of the shortcomings in radical prostatectomy, external radiotherapy and brachytherapy have prompted the search for alternative curative therapies that offer comparable rates of cancer control and less treatment-related morbidity to better preserve QOL. High intensity focused ultrasound (HIFU) possesses characteristics that make it an attractive curative therapy option. HIFU is a non-invasive approach that uses precisely-delivered ultrasound energy to achieve tumor cell necrosis without radiation or surgical excision. In current urological oncology, HIFU is used clinically in the treatment of prostate cancer, and is under experimental investigation for therapeutic use in renal and breast malignancies. Clinical research on HIFU therapy for localized prostate cancer began in the 1990s, and there have now been approximately 30,000 prostate cancer patients treated with HIFU, predominantly with the Ablatherm (EDAP TMS, Lyon, France) device. Transurethral resection of the prostate (TURP) has been combined with HIFU since 2000 to reduce prostate size, facilitate tissue destruction, and to minimize side effects. Advances in imaging technologies are expected to further improve the already superior efficacy and morbidity outcomes, and ongoing investigation of HIFU as a focal therapy and in salvage and palliative indications are serving to expand the role of HIFU as a highly versatile non-invasive therapy for prostate cancer.

Salvage Transrectal High-Intensity Focused Ultrasound Therapy for Patients with Recurrence of Vesico-Urethral Anastomosis after Radical Prostatectomy

Background: Salvage radiotherapy has been used as the treatment for patients with local recurrence after radical prostatectomy. However, the therapy is time-consuming and it experiences adverse effects of some kind. Simple and less invasive treatment is highly anticipated. Objectives: To evaluate the outcomes of salvage transrectal high-intensity focused ultrasound (HIFU) therapy for patients with localized recurrence of a vesicourethral anastomosis (VUA) after radical prostatectomy. Material and methods: Sixteen patients with suspected local recurrence of a VUA after prostatectomy were treated with HIFU. All patients had prostate-specific antigen (PSA) failure (>0.2 ng/ml), positive findings of a VUA with biopsy and/or MRI, TRUS and CT, and no distant metastasis by CT, MRI and bone scintigraphy before HIFU. Recurrence after HIFU was determined by PSA failure (>0.2 ng/ml), histological findings, metastasis and start of systemic therapies. Results: HIFU treatments were performed in 16 patients, and followed-up for 7 - 159 months (median 46.5). The pre-HIFU PSA levels ranged from 0.318 to 3.1 ng/ml. Sonication time ranged from 9 - 42 min. All patients had a decline of PSA after HIFU, and 88% of the PSA nadir was Conclusion: HIFU therapy for local recurrence after prostatectomy may become a feasible salvage therapeutic option because of its ease and simple procedure. For salvage HIFU therapy, further research and additional follow-up are required to evaluate and correct the diagnosis of recurrence areas and to provide the sufficient sonication.

基于遗传算法优化VMD-ESSA的HIFU回波信号降噪研究

由于高强度聚焦超声(HIFU)信号夹杂环境噪声,提出利用遗传算法优化变分模态分解(VMD)并结合能量均值法(EAM)及奇异谱分析(SSA)来对其进行降噪。遗传算法使得VMD具有更强的抗干扰性,奇异谱分析能够弥补能量均值去噪不完善。仿真实验表明,所提方法与GA-VMD-E、GA-VMD-SSA、VMD-ESSA降噪方法相比,重构后的信号的信噪比更高,均方根误差和最大误差更小。在实测信号中从频谱和降噪率两个角度证明了该方法的优越性,为通过HIFU回波信号分析生物组织损伤提供了一种更有效的预处理方法。

基于ICEEMDAN结合MMSVC和WT的HIFU回波信号联合去噪算法

高强度聚焦超声(High intensity focused ultrasound,HIFU)已广泛应用于生物医学领域,其回波信号中的噪声处理是一个非常关键的问题。为了获得更纯净、更清晰的HIFU回波信号,提出了一种基于改进的完全自适应噪声集成经验模态分解(Improved complete ensemble empirical mode decomposition with adaptive noise,ICEEMDAN)、最小均方方差准则(Minimum mean square variance criterion,MMSVC)和小波阈值(Wavelet threshold,WT)的联合去噪方法。ICEEMDAN将信号分解为有限个本征模态函数(Intrinsic mode functions,IMF),从而避免杂散模态,减少模态中所含的噪声。MMSVC用于识别被ICEEMDAN分解得到的所有IMF,并将这些IMF分为两部分,高频IMF部分通过WT进行去噪,之后与低频IMF分量重构得到最终去噪信号。在仿真信号的实验中,与其他方法相比,本文所描述的基于ICEEMDAN-MMSVC-WT的降噪方法最大限度地保留了有用信号,大量去除了噪声成分,因而具有更好的去噪效果和应用价值。

基于振动声发射信号频移的HIFU靶组织损伤监测

高强度聚焦超声(High Intensity Focused Ultrasound,HIFU)消融技术具有无辐射、无创等优点,已被用于多种实体肿瘤的治疗。但在治疗中,基于传统的诊断超声回声变化难以精准监测靶组织的损伤,主要原因是超声回声增强更多与组织损伤、空化气泡及温度相关,解耦存在困难。基于此,利用超声激发声发射(Ultrasound Stimulated Acoustic Emission,USAE)技术,通过在HIFU治疗前后检测与靶组织弹性变化相关的振动声信号,构建了一种基于USAE信号频移的靶组织损伤监测方案。为了考察该方案的正确性和有效性,首先研究了不同仿体中的USAE信号及其频谱变化规律,进一步探究了HIFU辐照离体组织前、后USAE信号频谱特征与靶组织损伤之间的变化关系及规律。研究结果表明:靶组织损伤引起的组织弹性变化会导致USAE信号频谱的峰值偏移,基于该频移能够较好地实现靶组织损伤的检测,可望为HIFU治疗中靶组织损伤监控提供一种新的解决方案。

High-intensity focused ultrasound with large scale spherical phased array for the ablation of deep tumors

Under some circumstances surgical resection is feasible in a low percentage for the treatment of deep tumors. Nev-ertheless, high-intensity focused ultrasound (HIFU) is beginning to offer a potential noninvasive alternative to conventional therapies for the treatment of deep tumors. In our previous study, a large scale spherical HIFU-phased array was developed to ablate deep tumors. In the current study, taking into account the required focal depth and maximum acoustic power output, 90 identical circular PZT-8 elements (diameter=1.4 cm and frequency=1 MHz) were mounted on a spherical shell with a radius of curvature of 18 cm and a diameter of 21 cm. With the developed array, computer simulations and ex vivo experiments were carried out. The simulation results theoretically demonstrate the ability of the array to focus and steer in the specified volume (a 2 cm×2 cm×3 cm volume) at the focal depth of 15 to 18 cm. Ex vivo experiment results also verify the capability of the developed array to ablate deep target tissue by either moving single focal point or generating multiple foci simultaneously.

HIFU逆转人肝癌细胞HepG2/Adm多药耐药的实验研究

背景与目的:超声波能够改变细胞膜通透性,增强化疗药物对肿瘤细胞的杀伤作用。本研究评价高强度聚焦超声及其联合阿霉素(Adriamycin,ADM)对人肝癌多药耐药细胞株HepG2/Adm的效应,并探讨其作用机制。方法:取对数生长期的HepG2、HepG2/Adm细胞进行实验,分为HepG2、HepG2(超声波照射5s)、HepG2/Adm、HepG2/Adm(超声波照射5s)4组。用MTT法检测处理前后耐药细胞对抗癌药物的敏感性;用流式细胞仪检测肿瘤细胞表面mdr1基因表达产物P170的表达及细胞内阿霉素浓度;利用SP免疫组化法观察细胞膜及核膜上P-糖蛋白(P-glycoprotein,P-gp)的表达。结果:频率0.8MHz、焦域声强460W/cm2连续照射5s,能够部分逆转HepG2/Adm细胞的耐药性,HepG2/Adm细胞P-gp的表达活性下降83.1%,耐药细胞内ADM浓度增加88%,对ADM、cDDP、MMC、5-FU和MTX相对逆转效率分别为66.4%、63.4%、89.4%、72.4%和75.0%。结论:高强度聚焦超声可提高人肝癌细胞HepG2/Adm内药物浓度,降低细胞膜及核膜表面P-gp表达,从而部分逆转肿瘤细胞多药耐药。

HIFU在牛肝组织中的传播衰减研究

运用辐射压力法研究高强度聚焦超声在牛肝组织中的传播衰减。在室温 2 0℃下 ,利用 4种治疗超声换能器 ,在不同的换能器表面输出声功率下 ,分别测量 2 0、4 0、6 0、80 m m不同厚度新鲜离体牛肝在放入脱气水前后的声辐射力 F、F′,然后计算出声衰减。使用治疗超声换能器 4 ,对于不同辐照深度 ,以声强 ISATA=2 2 .0× 10 3W/cm2、辐照时间 5 s的超声剂量定点辐照新鲜离体牛肝 ,以断层方式剖开后测量凝固性坏死组织体积。研究结果表明 ,对于一个具体的治疗超声换能器 ,在牛肝厚度一定时 ,辐射力穿透率 F′/F法与换能器表面声强及样品近治疗超声换能器表面声窗面积无关。采用最小 F′/F法拟合得出辐射力穿透率随牛肝厚度增加呈指数规律递减 ,且与凝固性坏死组织体积随牛肝厚度 (辐照深度 )增加呈指数规律递减趋势一致。采用最小二乘法拟合得出高度聚集超声在牛肝组织中传播的声衰随频率近似线性增加且呈幂函数关系。

A New Full Bridge High Intensity Focused Ultrasound Power System with Harmonic Cancellation

The feasibility of a new full bridge high intensity focused ultrasound(HIFU) amplifier system with harmonic cancellation is evaluated in this study. Harmonic cancellation technique is applied to these power amplifiers, which can eliminate the 3rd harmonic and all even harmonics. Since this technique requires two channels of phase signal to control one channel of power amplifier, the signal generator is required to double its output. The transducer array proposed in this study has 100 elements. So we choose an FPGA chip to generate 200 driving signals, and each channel has a phase resolution of 2ns, less than 1°. The phase signal from the FPGA meets the requirement of driving the power amplifiers. The output waveform of one channel of power amplifier(voltage across the transducer) is evaluated, and shows fewer harmonic components.

HIFU治疗原发性肝癌的CT表现及价值

目的 探讨HIFU治疗原发性肝癌的CT表现及价值。方法 18例原发性肝癌患者HIFU治疗后行CT检查 ,对比治疗前后CT改变。 5例治疗后行病灶切除 ,观察其病理组织学改变 ,并与CT表现对照。结果 治疗后 12例 (12 / 18,6 6 .7% )病灶体积缩小。 16例 (16 / 18,88.9% )病灶密度降低 ,强化程度减弱 ,2例病灶内及周边有小片轻度增强。组织病理学检查发现HIFU治疗区内肿瘤组织出现凝固性坏死 ,病理结果与CT表现一致。结论 CT可以反映HIFU术后瘤体的组织学及血供变化 。

肋骨切除术在HIFU联合TACE治疗中晚期肝癌中的临床价值

目的:探讨肋骨切除术在高强度聚焦超声(Hihg intensity focused ultrasound,HIFU)联合经导管动脉栓塞化疗(Tran-scatheter arterial chemoembolization,TACE)治疗中晚期肝癌中的临床价值。方法:68例右叶中晚期肝癌分为肋骨切除组(36例,43病灶)和非肋骨切除组(32例,40病灶),随访两组患者HIFU联合TACE后的疗效,并进行比较。结果:总平均随访(11.9±11.4)月,两组中位生存期及1、2年生存率分别依次为13月、52.3%、21.8%与12月、46.8%、17.6%,两组比较无统计学意义(P=0.8155);其病灶完整消融率和消融体积>80%比例分别依次为46.5%、79.1%与37.5%、67.5%,两组比较无统计学意义(P>0.05)。结论:肋骨切除术不能有效提高HIFU联合TACE治疗中晚期肝癌的疗效。

HIFU治疗区域检测方法研究

提出了一种基于自适应掩模滤波和水平集方法相结合的B超图像分割方法,能较准确地从高强度聚焦超声(HIFU)辐照前后获得的B超图像的减影中检测出治疗区域。对HIFU辐照后的新鲜离体猪肉进行解剖切片,实际损伤情形基本与该方法所得结果相吻合。该方法可以帮助HIFU临床医生客观、准确地监控治疗过程,对提高HIFU疗效有实际意义。

聚焦超声换能器电阻抗谱实时在线监测系统

高强度聚焦超声(HIFU)换能器作为聚焦超声消融手术(FUAS)系统的核心部件,其电阻抗谱是确定FUAS系统工作参数的重要参考依据,故对其进行实时在线监测具有重要意义。该文采用脉冲响应时域测量方法,将探测脉冲信号与HIFU换能器的工作时序相融合,并基于LabVIEW平台构建了一套HIFU换能器电阻抗谱实时在线监测系统,实现了对HIFU换能器电阻抗幅值与相位的高重复性及准确性的实时测量。通过对长时工作在大功率、高占空比条件下HIFU换能器电阻抗谱的实时在线监测,表明该监测系统可准确反应HIFU换能器的特征频率漂移、阻抗幅值和相位的非线性变化。这为HIFU换能器电阻抗谱实时在线监测及驱动参数优化调节提供了技术方案,对HIFU换能器的设计优化和能量损耗机制研究具有重要的应用价值。

TOCE联合HIFU治疗原发性肝癌的DSA检查及意义

目的 评价TOCE联合HIFU治疗原发性肝癌的DSA表现及意义。方法 5 0例原发性肝癌患者接受TOCE联合HIFU治疗 ,比较治疗前后的DSA表现。随机选出同期 5 0例单纯TOCE治疗的患者进行对照研究。结果 研究组与对照组治疗后肿瘤血管减少、消失、不变及增多分别为 76 % (38/ 5 0 )、8% (4 / 5 0 ) ;16 % (8/ 5 0 )、0 ;6 0 % (30 /5 0 )、4% (2 / 5 0 ) ;30 % (15 / 5 0 )、6 % (3/ 5 0 ) (P <0 .0 5 )。病灶体积缩小分别为 76 % (38/ 5 0 )和 5 8% (2 9/ 5 0 ) (P <0 .0 5 )。新病灶形成分别为 4例和 6例。侧支开放为 2例和 3例。结论 TOCE联合HIFU是治疗中晚期原发性肝癌的一种有效的治疗方法 ,DSA可以准确判断治疗后肿瘤大小、血供情况 ,早期发现复发及转移灶 。