用于肿瘤治疗的高强度聚焦超声换能器及其温度场测量

高强度聚焦超声（HIFU）作为一种具有巨大潜力的、无损的、有效的肿瘤治疗手段,已得到普遍认同。本文介绍了所研制的HIFU治疗系统,对其关键部分高强度聚焦超声换能器的温度场特性,从理论上和实验上进行了深入的研究,并提出了超声声场的理论算法.     

双频高强度聚焦超声换能器应用研究进展

高强度聚焦超声(High Intensity Focused Ultrasound,HIFU)消融实体肿瘤已在临床治疗中展示出良好的应用前景。HIFU消融肿瘤技术由于其使靶区肿瘤组织瞬时升温至60℃以上,产生不可逆性凝固性坏死,同时不影响靶区外正常组织而被广泛应用。目前治疗用超声主要使用单频率高强度聚焦超声,但其临床应用的主要限制是靶区组织消融时间较长,靶区外正常组织损伤风险较大。缩短靶区组织消融时间,对于提高HIFU治疗效率,更好地应用于临床较为关键。在总结HIFU换能器的特性和影响HIFU治疗因素的基础上,综述了应用不同类型的双频HIFU换能器强空化和缩短靶区组织消融时间等方面的研究进展。     

高强度聚焦超声换能器的新型设计

采用高强度聚焦超声（HIFU）治疗局部肿瘤，如何增强对病变区域的辐照效果，而尽量减少对健康区域的辐照损伤是一个很重要的问题。文章基于目前常用的凹球面自聚焦换能器，提出了解决上述问题的方案，设计了新型的换能器，对其工作方式及声场特性进行了研究。结果表明：采用多换能器轮流发射的方式进行治疗是一种行之有效的解决方案。     

开口凹球面聚焦声场分析

高强度聚焦超声（HIFU）治疗局部肿瘤存在聚焦换能器和定位探头同时旋转的问题，考虑到实际工程中必须考虑B超探头的放置对聚焦声场的影响。文章就此进行了研究。结果表明：开口的凹球面会降低焦区声压幅度。随着开孔半径的变大。焦区声压呈下降的趋势，焦区越长，越不利于聚焦；随着开孔位置距轴线的距离变大。焦区声压呈下降的趋势，而焦区的位置变化不大，文章同时对相应的温度场也进行了相关的分析。     

高强度聚焦超声肿瘤治疗系统专项技术研究

本文通过对高强度聚焦超声治疗基本原理介绍,对HY2900聚焦超声肿瘤治疗系统实际工作几项特色专项技术HIFU声场分布参数测量、HIFU温度场测量、三维重建技术中任意方位切面图像浏览及边界轮廓的实现方法等进行讨论,介绍相关技术及方法.     

超声阵列换能器设计及声场模拟

聚焦超声采用的聚焦方式有许多种,电子聚焦是其中之一,与其它聚焦方式相比,电子聚焦技术有很多优点,然而一些相互矛盾的条件对其设计有很大影响。通过用快速算法对阵元声场、以及频率对场的影响进行模拟,对阵列设计中的几个主要考虑方面进行了分析,提供了一般设计思路。采用伪逆矩阵算法,对变迹技术和多焦点技术进行计算机模拟,为焦域控制提供了新的思路,结果表明：将电子聚焦阵列换能器用于高强度聚焦超声治疗设备,比其它     

HIFU治疗裸鼠皮下移植瘤超声和磁共振变化的初步观察

目的初步探讨高强度聚焦超声对裸鼠卵巢癌皮下移植瘤治疗前后的超声和磁共振变化.方法HIFU治疗裸鼠卵巢癌模型12例,高强度聚焦超声治疗肿瘤外侧1/2,治疗前后进行超声和磁共振检查.结果(1)治疗前肿瘤组织超声表现为低回声,彩色和能量多普勒检测肿瘤内部及周边均有少许血流信号;治疗后肿瘤组织回声增强,彩色和能量多普勒检测肿瘤治疗区域内部及周边均无血流信号.(2)磁共振检查治疗区域肿瘤组织增强后未见明显强化.结论HIFU能准确破坏卵巢肿瘤,治疗过程中超声定位准确、方便,治疗后磁共振有助于评价其疗效,为临床应用提供实验依据.     

高强度治疗超声（HITU）测量标准化的进展

高强度聚焦超声（HIFU）的医学应用研究和临床实践,经过20多年的发展,不断提高,逐步完善,取得长足进步。各种高强度治疗超声（HITU）设备产品纷纷涌现。促成了2005年我国国家标准《GB/T19890—2005高强度聚焦超声（HIFU）声功率和声场特性的测量》的制定,也引起了国际电工委员会（IEC）87技术委员会（TC87：超声学）第六工作组（WG6：聚焦换能器）和第八工作组（WG8：超声场测量）以及国际同行专家的重视。     

基于反射探针的聚焦超声测量传感器设计和方法研究

基于钨钢探针和PVDF压电薄膜材料,设计研制了一种用于聚焦超声测量的新型传感器。同时,通过理论分析和有限元分析软件建立了传感器物理模型,并对传感器的内部声场及反射状况进行了模拟仿真,获得传感器输出信号的波形和幅值。最后,利用研制的传感器对聚焦换能器焦域声压和声强进行检测,并将检测结果与理论仿真结果对比,在10W的声功率范围内,证明了新型传感器及其测量理论和方法在聚焦超声测量中的可行性与可靠性。该新型反射探针传感器将为高强度聚焦超声声场的测量提供一种新的方法。     

超声造影早期评价HIFU治疗兔移植性骨肿瘤的初步研究

目的:观察兔VX2移植性骨肿瘤经高强度聚焦超声(High Intensity Focused Ultrasound,HIFU)治疗前后超声造影的图像变化,以评价高强度聚焦超声治疗骨肿瘤的疗效。方法:将VX2瘤块植入20只兔的右侧胫骨髓腔内,三周后进行HIFU治疗。治疗前后均推注超声微泡造影剂,对肿瘤治疗前后的超声造影图像进行比较。结果:治疗前超声造影显示,右侧胫骨髓内肿瘤快速、明显强化,与周边组织分界清楚,测得病灶平均大小为,上下径(17.614±0.955)mm,前后径(10.414±1.142)mm。治疗后造影,治疗区域显示为造影剂灌注缺损区,平均范围为上下径(8.010±0.584)mm,前后径(7.540±0.499)mm,未经治疗的肿瘤组织仍有超声造影剂灌注。结论:超声造影成像清楚地显示肿瘤范围以及治疗后灌注缺损区的大小,通过反映治疗后肿瘤的血供改变来评价HIFU治疗肿瘤的疗效。     

高强度聚焦超声联合全氟戊烷液滴在乳腺癌治疗增效中的实验研究

目的:探讨高强度聚焦超声(High-Intensity Focused Ultrasound,HIFU)联合全氟戊烷液滴(Perfluoropentane droplets,PFP),对小鼠乳腺癌4T1细胞治疗的增效作用。方法:制备PFP,检测其平均粒径及形态结构。试验设立三组:HIFU假照组,单纯HIFU治疗组,HIFU联合PFP治疗组。流式细胞仪检测HIFU分组治疗乳腺癌细胞后细胞存活率及死亡率;体内动物试验分组处理后,二维超声观察HIFU辐照前后肿瘤回声灰度变化情况,超声造影剂灌注缺损面积占总面积百分比评价不同治疗方式对裸鼠皮下移植瘤的消融能力。结果:所制备的PFP平均粒径为1.2μm,形态呈规则球形。细胞试验显示,HIFU联合PFP治疗组乳腺癌细胞死亡率(23.50±1.34)%显著高于单纯HIFU治疗组(14.34±0.55)%和HIFU假照组(11.76±0.62)%(P<0.05);动物试验显示HIFU联合PFP治疗组肿瘤消融面积占总面积百分比(84.03±4.47)%显著高于单纯HIFU治疗组(41.23±4.24)%(P<0.05),HIFU假照组无明显灌注缺损区域。结论:HIFU联合PFP可显著增强对乳腺癌细胞及组织的消融能力。     

A method to synchronize high-intensity, focused ultrasound with an arbitrary ultrasound imager

Ultrasound imaging is useful for monitoring high-intensity, focused ultrasound (HIFU) therapy; however, interference on the ultrasound image, caused by HIFU excitation, must be avoided. A method to synchronize HIFU excitation with ultrasound imaging is described here. Synchronization was tested with two unmodified, commercial imagers and two tissue phantoms.     

高强度聚焦超声治疗裸鼠胰腺癌皮下移植瘤的初步研究

目的：观察高强度聚焦超声（HIFU）治疗裸鼠胰腺癌皮下移植瘤后的超声回声及病理变化。方法：36只裸鼠在皮下接种SW1990人胰腺癌细胞,随机分成三组,HIFU组18只,假照组9只,对照组9只。治疗中记录肿瘤的回声变化,治疗后每隔四天采用超声观察肿瘤的大小及回声变化,共随访4周。HIFU治疗后于靶区取样进行光镜和电镜检查。结果：HIFU治疗2周后,HIFU组肿瘤体积都有缩小,而假照组和对照组肿瘤继续生长。镜下可见HIFU组靶区内肿瘤组织完全凝固性坏死。结论：HIFU能够有效治疗裸鼠胰腺癌皮下移植瘤,可望成为治疗晚期胰腺癌的有效方法。     

Pathophysiological mechanisms of high-intensity focused ultrasound-mediated vascular occlusion and relevance to non-invasive fetal surgery

High-intensity focused ultrasound (HIFU) is a non-invasive technology, which can be used occlude blood vessels in the body. Both the theory underlying and practical process of blood vessel occlusion are still under development and relatively sparse in vivo experimental and therapeutic data exist. HIFU would however provide an alternative to surgery, particularly in circumstances where serious complications inherent to surgery outweigh the potential benefits. Accordingly, the HIFU technique would be of particular utility for fetal and placental interventions, where open or endoscopic surgery is fraught with difficulty and likelihood of complications including premature delivery. This assumes that HIFU could be shown to safely and effectively occlude blood vessels in utero. To understand these mechanisms more fully, we present a review of relevant cross-specialty literature on the topic of vascular HIFU and suggest an integrative mechanism taking into account clinical, physical and engineering considerations through which HIFU may produce vascular occlusion. This model may aid in the design of HIFU protocols to further develop this area, and might be adapted to provide a non-invasive therapy for conditions in fetal medicine where vascular occlusion is beneficial.     

高强度聚焦超声消融滋养动脉治疗子宫肌瘤的临床价值

目的：探讨高强度聚焦超声消融滋养动脉治疗子宫肌瘤的可行性及有效性。方法：47例直径4~10cm肌壁间肌瘤,高强度聚焦超声治疗前通过彩色多普勒及超声造影确定肌瘤滋养动脉的蒂,对该区域进行消融,观察治疗前后肌瘤内部彩色多普勒及超声造影等影像学变化、随访临床症状及并发症。结果：治疗后肌瘤体积有不同程度的缩小,瘤体假包膜环状血流信号消失,肌瘤内部处于持续无灌注状态,部分患者临床症状消失或明显改善。结论：HIFU消融滋养动脉治疗子宫肌瘤能够缩短治疗时间,减少并发症,是一种微创和有效的方法。     

Feasibility of MR-temperature mapping of ultrasonic heating from a CMUT

In the last decade, high intensity focused ultrasound (HIFU) has gained popularity as a minimally invasive and noninvasive therapeutic tool for treatment of cancers, arrhythmias, and other medical conditions. HIFU therapy is often guided by magnetic resonance imaging (MRI), which provides anatomical images for therapeutic device placement, temperature maps for treatment guidance, and postoperative evaluation of the region of interest. While piezoelectric transducers are dominantly used for MR-guided HIFU, capacitive micromachined ultrasonic transducers (CMUTs) show competitive advantages, such as ease of fabrication, integration with electronics, improved efficiency, and reduction of self-heating. In this paper, we will show our first results of an unfocused CMUT transducer monitored by MR-temperature maps. This 2.51 mm by 2.32 mm, unfocused CMUT heated a HIFU phantom by 14 degrees C in 2.5 min. This temperature rise was successfully monitored by MR thermometry in a 3.0 T General Electric scanner.     

高强度聚焦超声热疗中组织损伤的一种监测方法

用特定频率和功率的高强度聚焦超声（HIFU）照射离体猪肉组织,研究了焦点区域的B超图像变化与HIFU导致的组织损伤之间的关系,并研究了M超信号变化和温度的相关性。结果表明：逐渐增加HIFU照射次数,焦点区域组织变性,B超图像发生明显改变。靶区内灰度超过设定的阈值的区域面积增大,区域内灰度升高,两者均与照射次数成近似线性关系;模拟加热实验中M超信号也随温度升高而变化,其变化较B超更显著。与以往的方法相比,实验系统可以实时地检测到组织损伤的程度和范围,提供了一种新的可视化的HIFU治疗实时监测方法。     

An Intelligent Nanotheranostic Agent for Targeting,Redox‐Responsive Ultrasound Imaging,and Imaging‐Guided High‐Intensity Focused Ultrasound Synergistic Therapy

A novel multifunctional nanotheranostic agent with targeting, redox‐responsive ultrasound imaging and ultrasound imaging‐guided high‐intensity focused ultrasound (HIFU) therapy (MSNC‐PEG‐HA_SS‐PFH, abbreviated as MPH_SS‐PFH) capabilities is developed. The redox‐responsive guest molecule release and ultrasound imaging functions can be both integrated in such a “smart” theranostic agent, which is accomplished by the redox‐triggered transition from the crosslinking state to retrocrosslinking state of the grafted polyethylene glycol‐disulfide hyaluronic acid molecules on the particle surface when reaching a reducing environment in vitro. More importantly, under the tailored ultrasound imaging guiding, in vivo Hela tumor‐bearing nude mice can be thoroughly and spatial‐accurately ablated during HIFU therapy, due to the targeted accumulation, responsive ultrasound imaging guidance and the synergistic ablation functions of nanotheranostic agent MPH_SS‐PFH in the tumors. This novel multifunctional nano‐platform can serve as a promising candidate for further studies on oncology therapy, due to its high stability, responsive and indicative ultrasound imaging of tumors, and enhanced HIFU therapeutic efficiency and spatial accuracy under ultrasound‐guidance.