双频共焦高强度超声增强仿组织体模毁损效果的初步研究

目的：比较双频共焦模式和单频模式高强度聚焦超声（HIFU）单次辐照毁损灶的大小。方法：分别采用相同声强度的双频共焦HIFU与传统单频HIFU对透明仿组织体模进行不同时间长度的辐照，直接在透明的仿组织体模上测量HIFU毁损灶的长度和直径。结果：双频和单频模式下，随辐照时间的延长毁损灶逐渐增大；相同声强相同辐照时间下，双频HIFU产生的毁损灶显著大于单频模式所致毁损灶。结论：双频共焦模式可以增大HIFU单次辐照毁损灶的体积．为HIFU治疗效率的提高提供了一种新技术。     

高强度聚焦超声间断照射对微泡空化效应阻断毫米级兔股动脉血流的增强作用

探讨不同的高强度聚焦超声(highintensity focused ultrasound,HIFU)照射方式在对微泡空化效应阻断毫米级兔股动脉血流中的效应。将108只兔随机分成单纯HIFU照射组、HIFU联合微泡连续照射组和HIFU联合微泡间断照射组。照射后即日、7 d,用HE染色观察兔股动脉组织学变化,透射电镜观察超微结果变化,数字减影血管造影(digital subtraction angiography,DSA)观察血流变化。实验结果表明:照射后,HIFU联合微泡间断照射组所有兔股动脉内均可见血栓形成,血流中断,动脉内皮细胞局受损,组织内观察到空泡的存在;单纯HIFU照射组、HIFU联合微泡连续照射组所有兔股动脉内无血栓形成,血流连续,超微结构无明显变化。HIFU联合微泡间断照射能使毫米级的兔股动脉在较长的时间内(7 d)血栓形成,血流中断;微泡再灌注增强了空化效应。     

高强度聚焦超声治疗剂量对组织温升影响的研究

测量了高强度聚焦超声(HIFU)定点辐照新鲜离体牛肝脏时，不同声强和辐照时间下的组织焦点温升。根据Pennes传热方程，从理论上分析了高强度聚焦超声定点辐照生物组织前后组织温度变化的规律，研究结果表明；一定的声强下，总有一个辐照闻值时间存在，当辐照时间超过辐照阐值时间后，温升缓慢，声强越大，辐照阐值时同出现得更早l组织焦点温升、相对累积热剂量随声强、辐照时间的增加而增大，当治疗剂量一定时，声强对组织焦点温升的影响大于辐照时间对组织焦点温升的影响。因此，HIFU最适治疗剂量应满足：适度的声强、辐照时间为该声强下的辐照阈值时间。     

6例子宫肌瘤高强度聚焦超声治疗失败原因浅析

目的分析高强度聚聚焦超声（HIFU）体外治疗子宫肌瘤失败的原因和解决的办法。方法选择不麻醉下体外HIFU治疗子宫肌瘤效果不佳改为妇科手术切除的患者，分析HIFU治疗过程中B超复查的声图像资料。结果6例子宫肌瘤患者分别采用HIFU治疗最少3次，最多9次。每次HIFU治疗后B超复查子宫肌瘤未见有肯定的明显回声改变。彩色多普勒血流显像，肌瘤周边或肌瘤内的血流信号无明显减少。肌瘤体积无缩小，反而逐渐增大。6例子宫肌瘤患者，有5例做了切除手术，1例在B超引导下，穿刺注射硬化剂后再做HIFU治疗，肌瘤体积迅速缩小，目前仍在观察中。结论HIFU治疗子宫肌瘤失败，主要是HIFU治疗靶区焦点的声强不够。联合超声介入治疗可以增加HIFU治疗靶区的超声能量，提高HIFU治疗肌瘤的效果。     

组织声学特性对高强度聚焦超声温度场的影响

目的 数值仿真组织声学特性对高强度聚焦超声（HIFU）焦域处温度场的影响,为HIFU治疗安全性和可靠性提供理论依据.方法 以实测新鲜离体猪肝组织不同温度下的声速和衰减系数为依据,利用时域有限差分（FDTD）法数值仿真研究HIFU治疗过程中组织内声速、衰减系数的变化和温度场的分布,分析讨论声速和衰减系数变化对60 ℃以上可治疗区域大小、位置的影响.结果 随着照射时间的延长,焦域处肝组织温升增大,声速下降,声衰减系数增大.随着声速的变化,形成的可治疗区域变大,焦点位置向远离换能器方向移动;随着声衰减系数的变化,焦域大小和焦点位置几乎不变.结论 猪肝组织内声速的变化对可治疗焦域的位置和大小影响较大;声衰减系数的变化对焦域的影响较小.     

高强度聚焦超声在医学领域中应用的新进展

本文综述了国内外在高强度聚焦超声（high intensity focused ultrasound，HIFU）技术方面研究与应用的新进展。介绍了HIFU的治疗功能原理，特别给出了焦斑半径的具体计算公式和对相关组织的热效应、空化效应、机械效应，辐照效应等损伤机理，重点研究了热效应随声波频率及声强变化的规律。给出了HIFU的一般试验模型即分层组织模型以及HIFU应用与临床的情况。重点研究了HIFU源，主要讨论了换能器的聚焦方式（1）球面自聚焦换能器，（2）声透镜聚焦换能器，（3）大功率多元超声换能器，（4）电子扫描或相控阵列聚焦换能器，以及频率选择与目标深度和辐照强度的关系，并指出与其匹配的几类聚焦换能器的优缺点，列举了HIFU技术在泌尿科、肿瘤学、神经外科、眼科、妇科、止血以及其他医学领域中的最新应用。最后评价了目前HIFU在治疗方面的优势与某些不足以及可能改进的有效措施．展望了HIFU技术广阔的应用前景．     

空化增效高强度聚焦超声治疗研究进展

高强度聚焦超声（HIFU）已被证实是一种安全、有效的无创实体肿瘤消融方法,但目前面临的主要问题是治疗时间相对较长、治疗效率低。在HIFU治疗中可以通过空化实现增效,通过何种方式产生空化效应,如何提高空化对热效应的增效作用一直是研究者关注的问题。本文分别从体外引入空化核、声学驱动产生空化核两个角度,综述在HIFU治疗中通过微泡造影剂、相变纳米液滴、双频HIFU、脉冲波增强热效应、调强峰值声压增强HIFU的治疗效果。 【关键词】高强度聚焦超声;空化效应;热效应;增效;综述     

高强度聚焦超声"切除"组织的剂量学研究

运用高强度聚焦超声（High intensity focused ultrasound．HIFU）技术完整切除组织块并确立相应的能效关系，从而进行HIFU剂量学研究。按照由生物学焦域（Biological focal region，BFR）→束损伤→片损伤→块损伤的治疗原则，使用ISATA为0～27700W／cm^2，扫描速度1～4mm／s，束损伤的空间间距5～10mm，片损伤的空间间距10～20mm，在离体牛肝组织中形成不同治疗深度的束损伤、片损伤和块损伤，从而实现完整切除组织块。并把形成单位体积凝固性坏死所需的HIFU超声能量叫做HIFU治疗的能效因子（Energy—efficiency factor．EEF），用EEF量化HIFU在组织内的能量存积。研究结果表明，在不同治疗深度处形成的束损伤的EEF随治疗深度的增加而增大。形成片损伤、块损伤的EEF远远小于在不同治疗深度处形成束损伤的EEF，且形成块损伤的EEF小于形成片损伤的EEF。形成片损伤、块损伤的EEF并不是不同治疗深度的束损伤的EEF、不同治疗层面的片损伤的EEF的简单叠加，它与一个已存在的损伤改变了组织声环境有关，提示可通过改变组织声环境来改变EEF。因此，用EEF来进行HIFU的剂量学研究是一个新思路。对一个固定的聚焦超声换能器，EEF除了与声功率、辐照时间、治疗深度、组织结构和功能状态有关外，另一个重要的影响因素是H1FU治疗过程中组织声环境的改变。     

超声造影剂在高强度聚焦超声治疗肝癌中的应用

高强度聚焦超声(high-intensityfocusedultrasound,HIFU)技术是将体外低能量的超声波汇聚于体内肿瘤靶区,通过高温效应、空化效应和机械效应,使肿瘤组织产生凝固性坏死,从而达到治疗肿瘤的目的。超声造影剂(ultrasoundcontrastagents)在HIFU治疗肝癌(hepatocellularcarcinoma,HCC)中也有很大的应用价值。探讨了超声造影剂在HIFU治疗肝癌前定性、定位及治疗后疗效评定等方面的作用,尤其是造影剂在HIFU治疗过程中通过增强空化效应,改变声学环境从而提高HIFU治疗肝癌的生物学效应,使超声造影剂成为一种备受重视的HIFU增效剂。     

高强度聚焦超声换能器声场的数值仿真与实验测量

目的 高强度聚焦超声(HIFU)肿瘤治疗过程中,HIFU换能器形成的声场分布是决定其治疗效果的关键因素之一,为了提高HIFU肿瘤治疗的安全性和可靠性,需要对HIFU换能器形成的声场进行预测.方法 采用时域有限差分(FDTD)法数值仿真水体内形成的声压分布与实验测量结果对比的研究方法,分析讨论了HIFU换能器在不同激励功...     

Flooded Lung Generates a Suitable Acoustic Pathway for Transthoracic Application of High Intensity Focused Ultrasound in Liver

Background: In recent years, high intensity focused ultrasound (HIFU) has gained increasing clinical interest as a non-invasive method for local therapy of liver malignancies. HIFU treatment of tumours and metastases in the liver dome is limited due to the adjacent ultrasound blocking lung. One-lung flooding (OLF) enables complete sonography of lung and adjoining organs including liver. HIFU liver ablation passing through the flooded lung could enable a direct intercostal beam path and thus improve dose deposition in liver. In this study, we evaluate the feasibility of an ultrasound guided transthoracic, transpulmonary HIFU ablation of liver using OLF.Methods: After right-side lung flooding, ultrasound guided HIFU was applied transthoracic- transpulmonary into liver to create thermal lesions in three pigs. The HIFU beam was targeted five times into liver, two times at the liver surface and three times deeper into the tissue. During autopsy examinations of lung, diaphragm and liver located in the HIFU path were performed. The focal liver lesions and lung tissue out of the beam path were examined histologically.Results: Fifteen thermal liver lesions were generated by transpulmonary HIFU sonication in all targeted regions. The lesions appeared well-demarcated in grey color with a cigar-shaped configuration. The mean length and width of the superficial and deeper lesions were 15.8 mm (range: 13-18 mm) and 5.8 mm (range: 5-7 mm), and 10.9 mm (range: 9-13 mm) and 3.3 mm (range: 2-5 mm), respectively. Histopathological, all liver lesions revealed a homogeneous thermal necrosis lacking vitality. There were no signs of damage of the overlying diaphragm and lung tissue.Conclusions: Flooded lung is a suitable pathway for applying HIFU to the liver, thus enabling a transthoracic, transpulmonary approach. The enlarged acoustic window could enhance the ablation speed for targets in the hepatic dome.     

HIFU在牛肝组织中形成线形凝固性坏死的剂量投放研究

探讨高强度聚集超声(High ntensity focused ultrasound,HIFU)在牛肝组织中形成线形凝固性坏死的剂量投放策略。首先在辐照深度2cm处用声强(ISAL)6500W/cm2的HIFU定点辐照牛肝1s得到一横径W为3mm的点状凝固性坏死。采用单个点状凝固性坏死相互叠加形成线形凝固性坏死时,相邻的两个单次辐照的空间间距D分别为1、2、2.5、3、4.5、5mm。当采用直线扫描形成线形凝固性坏死时,扫描速度V分别为1、3、6、7mm/s,往返次数为1。辐照结束后沿长度方向剖开,直视下观察最大剖面的损伤形态、范围、程度和损伤的完整性。结果表明,当D≤W时,采用单个点状凝固性坏死相互叠加能在牛肝中形成一个完整的线形凝固性坏死,当D>W时不能在牛肝中形成一个完整的线形凝固性坏死,且中间有正常组织的残留。当运动速度V为3mm/s,往返次数为1,采用直线扫描方式能在牛肝中形成了一个边界清楚、能量分布均匀、中间没有正常组织残留的完整的线形凝固性坏死。实验结果证实:依据单个点状凝固性坏死的声辐照和其大小确定形成线形凝固性坏死的辐照参数并进行剂量投放能够在组织中形成线形凝固性坏死。     

超声弹性成像用于高强度聚焦超声损伤的检测

采用超声弹性成像的方法检测高强度聚焦超声在动物组织内产生的损伤.结果表明,聚焦超声的损伤在应变分布图(弹性图像)上表现为应变较小的区域,即损伤部位的弹性模量较周围组织的大,组织切片的损伤范围和大小也与应变分布图的结果一致.     

Real-time volumetric MRI thermometry of focused ultrasound ablation in vivo: a feasibility study in pig liver and kidney

MR thermometry offers the possibility to precisely guide high-intensity focused ultrasound (HIFU) for the noninvasive treatment of kidney and liver tumours. The objectives of this study were to demonstrate therapy guidance by motion-compensated, rapid and volumetric MR temperature monitoring and to evaluate the feasibility of MR-guided HIFU ablation in these organs. Fourteen HIFU sonications were performed in the kidney and liver of five pigs under general anaesthesia using an MR-compatible Philips HIFU platform prototype. HIFU sonication power and duration were varied. Volumetric MR thermometry was performed continuously at 1.5 T using the proton resonance frequency shift method employing a multi-slice, single-shot, echo-planar imaging sequence with an update frequency of 2.5 Hz. Motion-related suceptibility artefacts were compensated for using multi-baseline reference images acquired prior to sonication. At the end of the experiment, the animals were sacrificed for macroscopic and microscopic examinations of the kidney, liver and skin. The standard deviation of the temperature measured prior to heating in the sonicated area was approximately 1 °C in kidney and liver, and 2.5 °C near the skin. The maximum temperature rise was 30 °C for a sonication of 1.2 MHz in the liver over 15 s at 300 W. The thermal dose reached the lethal threshold (240 CEM(43) ) in two of six cases in the kidney and four of eight cases in the liver, but remained below this value in skin regions in the beam path. These findings were in agreement with histological analysis. Volumetric thermometry allows real-time monitoring of the temperature at the target location in liver and kidney, as well as in surrounding tissues. Thermal ablation was more difficult to achieve in renal than in hepatic tissue even using higher acoustic energy, probably because of a more efficient heat evacuation in the kidney by perfusion.     

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.     

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。这为进一步研究高强度聚焦超声治疗剂量学提供了实验依据     

High‐Intensity Focused Ultrasound‐Induced Thermal Effect for Solid Polymer Materials

In this study, high‐intensity focused ultrasound (HIFU)‐induced thermal effects for solid polymer materials are investigated systematically. Infrared camera imaging is used to monitor temperature changes. The effects of polymer structure, HIFU power, and sample thickness on the thermal effect are studied. The results show that the HIFU‐induced heating effect is very quickly, and can be controlled spatially and temporally. More importantly, it is obviously different for different polymers. The main reason is attributed to the various inner friction behaviors of macromolecular chains. This fundamental study is helpful to understand the interaction mechanism between HIFU and polymer, when HIFU is used as a trigger for drug release, shape memory, etc.