高强度聚焦超声空化效应的研究进展

高强度聚焦超声(HIFU)是一种新兴的非侵入性局部治疗技术,对HIFU的生物学效应之一——空化效应的研究较少。本文就空化效应在HIFU治疗中的应用,HIFU空化效应的预测和检测,以及HIFU空化效应的调节和控制作一综述。     

HIFU治疗中的空化效应及其应用

超声空化效应是高强度聚焦超声（HIFU）治疗中的重要生物学效应之一，在形成凝固性坏死与提高治疗效率等方面起着关键性作用。因而在HIFU治疗中是否有空化效应参与，什么条件下发生，对热效应有怎样的影响，如何评价它的利弊及怎样去控制和利用它是研究者关注的问题，本文就这些问题进行综述。     

高强度聚焦超声治疗中的空化及其与回声、热效应之间的关系

高强度聚焦超声(HIFU)正在成为医学上一种新兴的治疗技术.HIFU治疗中的空化一直是HIFU研究中的热点问题.本文介绍HIFU治疗中的空化及其与回声、热效应之间的关系.     

高强度聚焦超声治疗非肿瘤性疾病的研究进展

高强度聚焦超声(high intensity focused ultrasound,HIFU)技术属于高温治疗范畴,也称聚焦超声外科术(focused ultrasound surgery,FUS)或超声消融术(ultrasound ablation),是利用超声波的可聚焦性和组织的可穿透性等物理特性,将体外大范围较低能量的超声聚焦在体内靶区处,通过焦域区高能量超声产生60℃以上的瞬态高温、空化效应、机械效应等作用杀死靶区内细胞,以达到无创局部切除病灶的目的.     

高强度聚焦超声对H22肝癌组织的急性生物学效应

本文研究了高强度聚焦超声（HIFU）对H22肝癌组织的急性损伤效应。发现经一定声强的照射治疗后，H22肝癌细胞超微结构有一系列不可逆性损害表现，尤以细胞膜、核膜、及细胞质内膜性结构表现更为明显。讨论了HIFU对肿瘤组织的急性生物学效应和潜在的临床应用前景。HIFU高热效应、空化效应，以及其它声化学反应等综合效应可引起生物组织的急性损伤效应。上述研究为探讨HIFU治疗肿瘤的生物学效应和作用机制提供了重要的实验依据。     

高强度超声聚焦对恶性肿瘤血供作用的研究进展

自从1956年Burov将超声波聚焦后应用于肿瘤的治疗以来,超声聚焦技术在临床治疗上发展迅速,尤其在恶性肿瘤治疗方面,高强度超声聚焦( High-Intensity Focused Ultrasound,HIFU)已成为治疗恶性肿瘤的重要手段之一.其作用原理主要有热效应,机械作用,空化作用,声化学效应,与其他治疗的协同作用等.近年来研究发现HIFU对肿瘤血管有破坏作用,可栓塞肿瘤营养血管,阻断肿瘤血液供应,从而有效杀灭肿瘤细胞.查阅相关医学文献,有关HIFU对恶性肿瘤血管及供血作用的研究进展,综述如下.     

高强度聚焦超声对离体肿瘤细胞的急性生物学效应

本文应用高强度聚焦超声(HIFU)辐照肿瘤细胞的液态体模,探讨了HIFU对肿瘤细胞的急性效应及机理,治疗剂量与效应的关系。发现HIFU的热效应、空化效应是引起肿瘤细胞死亡的主要机理,治疗剂量与致死效应呈正相关关系。声强1054W/cm~2×40s是制备灭活肿瘤细胞疫苗的最佳超声剂量。     

微泡增效在高强度聚焦超声治疗子宫肌瘤中的应用

子宫肌瘤为育龄期女性最常见的良性肿瘤,高强度聚焦超声(HIFU)作为一种非侵入性治疗手段,已广泛用于实体肿瘤特别是子宫肌瘤的治疗。超声微泡可通过改变组织声学特性、增加空化等作用,增加靶区能量沉积,增大凝固性坏死面积,可作为增效剂用于HIFU治疗。本文对超声微泡在HIFU治疗子宫肌瘤中的应用作一综述。     

经阴道分娩后胎盘植入的高强度聚焦超声治疗进展

高强度聚焦超声(HIFU)是一种无创治疗技术,具有非侵入性、无放射性污染、可实时监控、治疗时间可控及治疗后恢复快等优点,现已广泛应用于多种实体肿瘤及良性病变的治疗。本文从胎盘植入的治疗现状出发,引出了HIFU治疗胎盘植入的优势,并从热效应、空化效应、机械效应以及声化学效应方面探讨了HIFU治疗的可行性;同时通过对已有治疗病例的分析,总结了HIFU治疗胎盘植入的适应证、疗效评价、可能并发症及有效性,展望了HIFU无创新技术治疗胎盘植入的良好应用前景。     

高强度聚焦超声治疗肝癌肝移植术后局部复发、转移的临床研究

近年来,高强度聚焦超声（high intensity focused ultrasound,HIFU）在肿瘤治疗领域中的应用取得了较好的效果.它利用超声波的可视性、组织穿透性和聚焦性等物理特征,通过加热效应、机械效应和空化效应从体外定位,直接破坏体内深部的肿瘤组织,而对邻近正常组织的影响较小[1].     

高强度聚焦超声联合微泡损伤山羊肝的增效性研究

目的 探讨超声造影剂SonoVue用于增强高强度聚焦超声(HIFU)损伤山羊肝组织的可行性.方法 南江黄羊15只,采用自身对照,分为HIFU治疗组(对照组)和HIFU联合造影剂治疗组(实验组).治疗深度30 mm,分别在声功率为150 W、250 W、350 W条件下对肝定点辐照15 S.辐照后24 h处死动物,解剖观察凝固性坏死情况,并作病理切片分析.结果 在相同声辐照参数下,实验组凝固性坏死发生率及凝固性坏死区域长、宽、厚、体积均明显大于对照组(P＜0.05),随功率增加实验组凝固性坏死体积增加幅度较对照组更明显,实验组能效因子(EEF)明显小于对照组.凝固性坏死区与正常肝组织分界清楚,且病理切片显示损伤为不可逆性,分界处可见大量空泡.结论 HIFU联合微泡造影剂能在山羊肝中形成完全的凝固性坏死,同时提高凝固性坏死的损伤率,增大凝固性坏死体积,提高HIFU治疗效率.     

Temporal and Spatial Detection of HIFU-Induced Inertial and Hot-Vapor Cavitation with a Diagnostic Ultrasound System

The onset and presence of inertial cavitation and near-boiling temperatures in high-intensity focused ultrasound (HIFU) therapy have been identified as important indicators of energy deposition for therapy guidance. Passive cavitation detection is commonly used to detect bubble emissions, where a fixed-focus single-element acoustic transducer is typically used as a passive cavitation detector (PCD). This technique is suboptimal for clinical applications, because most PCD transducers are tightly focused and afford limited spatial coverage of the HIFU focal region. A Terason 2000 Ultrasound System was used as a PCD array to expand the spatial detection region for cavitation by operating in passive mode, obtaining the radiofrequency signals corresponding to each scan line and filtering the contribution from scattering of the HIFU signal harmonics. This approach allows for spatially resolved detection of both inertial and stable cavitation throughout the focal region. Measurements with the PCD array during sonication with a 1.1-MHz HIFU source in tissue phantoms were compared with single-element PCD and thermocouple sensing. Stable cavitation signals at the harmonics and superharmonics increased in a threshold fashion for temperatures >90°C, an effect attributed to high vapor pressure in the cavities. Incorporation of these detection techniques in a diagnostic ultrasound platform could result in a powerful tool for improving HIFU guidance and treatment. (E-mail: cfarny@bwh.harvard.edu)     

载IR780/PFH纳米粒双模态成像及增效高强度聚焦超声消融的体外实验研究

摘 要 目的 制备一种近红外荧光多功能纳米粒,评估其体外超声、光声成像能力以及协同高强度聚焦超声（HIFU）消融牛肝的效果,通过空化检测探讨其增效HIFU的机制。方法 采用超声薄膜法制备载 IR780和全氟己烷（PFH）的脂质体纳米粒(IR780-CLs),使用透射电镜观察纳米粒的结构特征,多角度粒度分析及Zeta电位仪检测纳米粒的粒径和电位,紫外分光光度计检测IR780包封率,观察其体外超声、光声成像效果,通过离体牛肝实验评估IR780-CLs体外增效HIFU的作用,并通过被动空化检测,取宽带噪声信号幅度的均方根值（RMS）随时间的变化曲线反应实时空化信号。结果 制备的IR780-CLs纳米粒呈大小均匀的球形,平均电位(34.5 ± 3.2) mV,粒径(246.5 ± 12.4) nm,IR780包封率为88%,IR780-CLs纳米粒具有良好的体外超声、光声成像效果,纳米粒光声信号强度与浓度间存在良好的线性关系,体外牛肝实验表明其具有显著增效HIFU的作用,被动空化检测进一步验证了IR780-CLs组空化信号RMS值高于PBS组。结论 本实验成功制备多功能纳米粒IR780-CLs,具有良好的超声、光声成像能力,并能显著提高HIFU消融牛肝的效率,空化效应为增效HIFU的主要机制。     

Neoadjuvant HIFU treatment for malignant fibrous histiocytoma: report of a case

High-intensity focused ultrasound (HIFU) is an innovative, noninvasive, extracorporeal technique that induces coagulative necrosis of tumor tissue by thermal effects and cavitation. In published studies, HIFU has usually been used as an alternative to surgery, with or without other treatment modalities, to achieve curative tumor ablation or palliative tumor cytoreduction. Neoadjuvant HIFU treatment for primary inoperable malignant fibrous histiocytoma has never been reported, and neoadjuvant radiotherapy, chemoradiation, or chemotherapy is routinely under consideration. This is the first case in which HIFU ablation contributed as a neoadjuvant therapy to facilitate function-sparing resection, not as a replacement for surgery. It suggests that HIFU ablation may have some unique major advantages for treating inoperable huge soft-tissue sarcomas as a neoadjuvant local treatment modality, especially for patients for whom neoadjuvant chemotherapy or radiotherapy is not indicated.     

Hyperecho in ultrasound images of HIFU therapy: involvement of cavitation

High-intensity focused ultrasound (US), or HIFU, treatment of soft tissues has been shown to result in a hyperechoic region in B-mode US images. We report on detecting cavitation in vivo in correlation with the appearance of a hyperechoic region. The US system consisted of a HIFU transducer (3.3 MHz), a broadband A-mode transducer for active and passive cavitation detection and an US-imaging probe that were all confocal and synchronized. HIFU, at in situ intensities of 220 to 1710 W/cm(2), was applied for 10 s to pig muscles in vivo. Active and passive cavitation detection results showed a strong correlation between the onset of cavitation and the appearance of a hyperechoic region. Passive cavitation detection results showed that inertial cavitation typically occurred prior (within 0.5 s) to the appearance of a hyperechoic region. The observed cavitation activity confirms that bubbles are present during the formation of a hyperechoic region at the HIFU focus.     

Pulsed High Intensity Focused Ultrasound Mediated Nanoparticle Delivery: Mechanisms and Efficacy in Murine Muscle

High intensity focused ultrasound (HIFU) is generally thought to interact with biological tissues in two ways: hyperthermia (heat) and acoustic cavitation. Pulsed mode HIFU has recently been demonstrated to increase the efficacy of a variety of drug therapies. Generally, it is presumed that the treatment acts to temporarily increase the permeability of the tissue to the therapeutic agent, however, the precise mechanism remains in dispute. In this article, we present evidence precluding hyperthermia as a principal mechanism for enhancing delivery, using a quantitative analysis of systemically administered fluorescent nanoparticles delivered to muscle in the calves of mice. Comparisons were carried out on the degree of enhancement between an equivalent heat treatment, delivered without ultrasound, and that of the pulsed-HIFU itself. In the murine calf muscle, Pulsed-HIFU treatment resulted in a significant increase in distribution of 200 nm particles (p < 0.016, n = 6), while the equivalent thermal dose showed no significant increase. Additional studies using this tissue/agent model also demonstrated that the pulsed HIFU enhancing effects persist for more than 24 h, which is longer than that of hyperthermia and acoustic cavitation, and offers the possibility of a novel third mechanism for mediating delivery. (E-mail: vfrenkel@cc.nih.gov)     

MRI monitoring of the effect of tissue interfaces in the penetration of high intensity focused ultrasound in kidney in vivo

In this paper, we studied the effect of interfaces during the application of high intensity focused ultrasound (HIFU) ablation in rabbit kidney in vivo. In kidney ablation, mainly two types of interfaces are encountered: these are muscle-kidney and fat-kidney. It was observed that the intensity for which the probability of cavitation (POC) is one was decreased when HIFU penetrated through interfaces, meaning that an interface is a potential site of cavitation. We utilized the concept of scanning the area to be treated in two dimensions (rectangular grid) by applying low intensity ultrasound (diagnostic scan). When all the points of the grid show decrease of signal in T1-weighted fast spoiled gradient (FSPGR) which indicated heating, complete necrosis was observed in the targeted area during the application of HIFU (therapeutic scan). If ultrasound goes through an interface that includes air spaces, the diagnostic scan indicates spaces with poor ultrasound penetration and as a result, during the application of the therapeutic scan, some sites remain untreated. The muscle-kidney and fat-kidney interfaces cause reflection of ultrasound, which prevents the penetration of ultrasound. Microscopic bubbles in the interface may initiate cavitation, especially at high intensities. However, sometimes these types of interfaces do not include any bubbles and therefore the propagation of ultrasound is not inhibited.     

Real-Time Monitoring of High-Intensity Focused Ultrasound Treatment Using Axial Strain and Axial-Shear Strain Elastograms

Axial strain elastograms (ASEs) have been found to help visualize sonographically invisible thermal lesions. However, in most studies involving high-intensity focused ultrasound (HIFU)-induced thermal lesions, elastography imaging was performed separately later, after the lesion was formed. In this article, the feasibility of monitoring, in real time, tissue elasticity variation during HIFU treatment and immediately thereafter is explored using quasi-static elastography. Further, in addition to ASEs, we also explore the use of simultaneously acquired axial-shear strain elastograms (ASSEs) for HIFU lesion visualization. Experiments were performed on commercial porcine liver samples in vitro. The HIFU experiments were conducted at two applied acoustic power settings, 35 and 20 W. The experimental setup allowed us to interrupt the HIFU pulse momentarily several different times during treatment to perform elastographic compression and data acquisition. At the end of the experiments, the samples were cut along the imaging plane and photographed to compare size and location of the formed lesion with those visualized on ASEs and ASSEs. Single-lesion and multiple-lesion experiments were performed to assess the contribution of ASEs and ASSEs to lesion visualization and treatment monitoring tasks. At both power settings, ASEs and ASSEs provided accurate location information during HIFU treatment. At the low-power setting case, ASEs and ASSEs provide accurate lesion size in real-time monitoring. Lesion appearance in ASEs and ASSEs was affected by the cavitation bubbles produced at the high-power setting. The results further indicate that the cavitation bubbles influence lesion appearance more in ASEs than in ASSEs. Both ASEs and ASSEs provided accurate size information after a waiting period that allowed the cavitation bubbles to disappear. The results indicate that ASSEs not only improve lesion visualization and size measurement of a single lesion, but, under certain conditions, also help to identify untreated gaps between adjacent lesions with high contrast.     

高强度聚焦超声联合超声造影剂增强治疗效果的研究进展

高强度聚焦超声(HIFU)以其安全性、无创性、有效性的特点正日益成为治疗和辅助治疗多种肿瘤的新方法。超声造影剂(UCA)通过改变靶组织声学特性显著地提高了HIFU的治疗效果,在HIFU临床应用过程中显示了重要的应用价值。本文就HIFU联合UCA治疗的作用机理及其增强治疗效果的实验研究进展进行综述。