Hyperthermia Classic Commentary: ‘A scanned,focused, multiple transducer ultrasonic system for localised hyperthermia treatments’, by K. Hynynen,R. Roemer,D. Anhalt,et al., International Journal of Hyperthermia 1987;3:21–35

This commentary reviews the development of image-guided focused ultrasound treatments since the publication of the above paper. The impact of the research presented in the paper on the development of the current image-guided noninvasive surgery and treatments will also be discussed.     

高强度聚焦超声治疗子宫肌瘤和子宫腺肌瘤的临床应用

目的 探讨高强度聚焦超声(HIFU)应用于临床治疗子宫肌瘤和子宫腺肌瘤的效果和安全性.方法 以子宫肌瘤和子宫腺肌瘤患者为研究对象,采用HIFUNIT-9000型超声聚焦肿瘤消融机实施治疗.观察治疗前后患者临床症状和瘤体超声回声、血流及大小的变化.结果 共治疗子宫肌瘤和子宫腺肌瘤患者116例,治疗瘤体共192个,其中肌瘤166个,腺肌瘤26个.治疗后82例患者各种症状得到改善;瘤体缩小,瘤体超声回声增强,血流减少.治疗效果总有效率94.2%,其中显效率53.8%.结论 HIFU治疗子宫肌瘤和子宫腺肌瘤效果明显,无创、安全.     

载阿霉素液-固相变凝胶治疗HIFU消融兔VX2残余瘤

目的 研究载阿霉素液-固相变型原位凝胶(DOX凝胶)治疗高强度聚焦超声(HIFU)消融兔VX2肿瘤后残余瘤的作用.方法 制备DOX凝胶,高效液相色谱法测定其体外释药率.建立兔VX2皮下移植瘤模型,HIFU不全消融后瘤内注射DOX凝胶进行治疗.对空白组、对照组(HIFU+无药凝胶)及治疗组(HIFU+ DOX凝胶)治疗4、8d后,测量肿瘤体积,观察HE染色,免疫组化和TUNEL法检测肿瘤细胞增殖和凋亡.结果 DOX凝胶体外累积释药率为(78.92±4.68)％.治疗后,治疗组肿瘤体积较其他组小(P＜0.05),HE染色可见消融坏死区及少量肿瘤细胞,细胞增殖指数较其他组低(P＜0.05),而凋亡指数较高(P＜0.05).结论 DOX凝胶能有效治疗HIFU消融后的残余瘤,有望成为HIFU消融肿瘤后残余瘤的治疗及预防复发的新手段.     

A Tissue Mimicking Polyacrylamide Hydrogel Phantom for Visualizing Thermal Lesions Generated by High Intensity Focused Ultrasound

An optically transparent tissue-mimicking (TM) phantom whose acoustic properties are close to those of tissue was constructed for visualizing therapeutic effects by high intensity focused ultrasound (HIFU). The TM phantom was designed to improve a widely used standard bovine serum albumin (BSA) polyacrylamide hydrogel (PAG), which attenuated ultrasound far less than tissue and, unlike tissue, did not scatter ultrasound. A modified recipe has been proposed in the study by adding scattering glass beads with diameters of 40–80 μm (0.002% w/v) and by raising the concentration of acrylamide (30% v/v). The TM BSA-PAG constructed has an acoustic impedance of 1.67 MRayls, a speed of sound of 1576 m/s, an attenuation coefficient of 0.52 dB/cm at 1 MHz, a backscattering coefficient of 0.242 × 10⁻³ 1/sr/cm at 1 MHz and a nonlinear parameter (B/A) of 5.7. These parameters are close to those of liver. The thermal and optical properties are almost the same as the standard BSA-PAG. The characteristic features of the thermal lesions by HIFU were observed to be more accurately visualized in the TM BSA-PAG than in the standard BSA-PAG. In conclusion, the proposed TM BSA-PAG acoustically mimics tissue better than the standard BSA-PAG and is expected to be preferentially used for assuring if a clinical HIFU device produces the thermal lesion as planned.     

Ultrasound-induced cavitation enhances the delivery and therapeutic efficacy of an oncolytic virus in an in vitro model

We investigated whether ultrasound-induced cavitation at 0.5 MHz could improve the extravasation and distribution of a potent breast cancer-selective oncolytic adenovirus, AdEHE2F-Luc, to tumour regions that are remote from blood vessels. We developed a novel tumour-mimicking model consisting of a gel matrix containing human breast cancer cells traversed by a fluid channel simulating a tumour blood vessel, through which the virus and microbubbles could be made to flow. Ultrasonic pressures were chosen to maximize either broadband emissions, associated with inertial cavitation, or ultraharmonic emissions, associated with stable cavitation, while varying duty cycle to keep the total acoustic energy delivered constant for comparison across exposures. None of the exposure conditions tested affected cell viability in the absence of the adenovirus. When AdEHE2F-Luc was delivered via the vessel, inertial cavitation increased transgene expression in tumour cells by up to 200 times. This increase was not observed in the absence of Coxsackie and Adenovirus Receptor cell expression, discounting sonoporation as the mechanism of action. In the presence of inertial cavitation, AdEHE2F-Luc distribution was greatly improved in the matrix surrounding the vessel, particularly in the direction of the ultrasound beam; this enabled AdEHE2F-Luc to kill up to 80% of cancer cells within the ultrasound focal volume in the gel 24 hours after delivery, compared to 0% in the absence of cavitation.     

Ultrasonic Assessment of Thermal Therapy in Rat Liver

One way to assess the efficacy of thermal therapy is to quantify changes in tissue properties through ultrasonic interrogation, which requires knowledge of the acoustic properties of thermally treated tissues. In this study, estimates of ultrasonic attenuation, speed of sound, backscatter coefficient (BSC), and scattering property estimates were generated from rat liver samples submersed for 10 minutes in a saline bath that was heated to one of seven temperature values over a range of 37–70°C. The attenuation coefficient increased monotonically with exposure temperature, with a maximum increase of 90%. Speed of sound changed by <1% for the different treatment conditions. The BSC had close agreement for all thermal doses over the frequency range of 8–15 MHz. Above this frequency range, samples heated ≥55°C demonstrated an increased BSC slope, and the effective scatterer diameter and effective acoustic concentration were able to distinguish treated from nontreated cases. The findings suggest that attenuation and either BSCs or scatterer property estimates above 15 MHz were sensitive to tissue changes in excised liver caused by thermal therapy.     

Feasibility study of ultrasonic computed tomography-guided high-intensity focused ultrasound

The aim of this study was to establish a proof of concept for an ultrasonic image-guided high-intensity focused ultrasound (HIFU) breast treatment system. An ultrasonic computed tomography (UCT) scanner served as a platform for image acquisition and thermal mapping. With this system, images depicting the speed of sound (SOS) can be obtained. After HIFU activation, the resulting changes in SOS can be mapped. For the temperature range T ≤ 45°C, the temperature elevation is obtained directly from the change in SOS. For thermal ablation, monitoring is obtained by studying the temporal derivative of the SOS while continuous HIFU heating is applied. The method was implemented to in vitro tissue specimens and the ability for thermal monitoring was demonstrated. The results indicate that the suggested concept is indeed feasible.     

高能聚焦超声治疗良性前列腺增生47例临床观察

目的探讨高能聚焦超声治疗良性前列腺增生的临床疗效及安全性。方法良性前列腺增生患者47例,应用FEP—BYO2型高能聚焦超声治疗机治疗,在术前、术后3、6和12个月,经直肠超声观察前列腺和前列腺部尿道的影像学变化,通过尿液分析、国际前列腺症状评分（IPSS）、生活质量评分（QOL）、最大尿流率（PUR）和残余尿量（PVR）进行疗效评估,同时观察术后并发症。结果对47例进行了12个月的观察随访,术后IPSS评分和QOL评分降低,PVR减少,PUR明显提高（P〈0．01）,前列腺体积缩小（P〈0．05）。结论高能聚焦超声治疗良性前列腺增生是一种安全有效值得推荐的新方法。     

High intensity focused ultrasound-responsive release behavior of PLA-b-PEG copolymer micelles

Poly(lactic acid) (PLA) was synthesized by solution polycondensation of L-lactic acid and further reacted with dihydroxyl poly(ethylene glycol) (PEG) to obtain the amphiphilic block copolymer PLA-b-PEG. The biodegradable PLA-b-PEG copolymer can self-assemble into spherical micelles in aqueous solution. Nile Red, as a payload model, was used to examine the release behavior of the micelles. The hydrophobic Nile Red can be adsolubilized into the hydrophobic inner core of PLA-b-PEG micelles. With the introduction of Nile Red, the size of micelles increased. Moreover, high intensity focused ultrasound (HIFU), as a non-contact and remote control approach, was introduced to control the release behavior of PLA-b-PEG micelles containing Nile Red. The release behavior of Nile Red was monitored by fluorescence emission spectra. The results showed that HIFU can trigger the release of the encapsulated Nile Red from PLA-b-PEG micelles. By adjusting the HIFU time, intensity and location, the release behavior of Nile Red from micelles can be tuned. Base on the results, an irreversible release mechanism under HIFU was proposed. The irreversible release of Nile Red from the PLA-b-PEG micelle was attributed to a chemically breaking process of micelle structure due to the degradation of the PLA-b-PEG chain that resulted from the transient cavitation in the HIFU focal spot.