基于磁共振温度图的高强度聚焦超声治疗热剂量研究

本实验研究基于磁共振T-Map的HIFU损伤组织的热剂量与实际凝固性坏死的关系。运用磁共振导航高强度聚焦超声治疗系统,使用1 MHz、焦距为150 mm、直径150 mm的聚焦超声换能器,定点辐照深度为20 mm的新鲜离体牛肝脏,辐照过程中用磁共振的测温序列采集各体素随时间变化的温度值并计算各体素的Eq43值,比较计算结果与发生凝固性坏死的Eq43参考阈值,判断该体素是否发生坏死。最后比较通过等效热剂量积分法得到的凝固性坏死面积和组织实际发生坏死的情况。结果表明基于磁共振T-Map的等效热剂量积分法得到的凝固性坏死的面积值能很好的反应实际发生凝固性坏死的情况,为HIFU治疗提供了一种新的判断凝固性坏死发生的方法,这种方法可以实时地反馈控制超声辐照剂量,提高了治疗的安全性。     

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。     

呼吸门控对呼吸运动引起组织位移造成靶区精度复位差的作用

背景：在常规高强度聚焦超声治疗中,如何避免呼吸运动引起的脏器组织位移从而影响辐照靶区定位精度及治疗的安全性是目前急需解决的问题。 目的：探讨在高强度聚焦超声治疗过程中,利用呼吸门控技术提高高强度聚焦超声治疗靶点定位精度的可行性。 方法：在相同声强、辐照时间情况下,利用压阻式微型呼吸传感器,基于呼吸门控技术控制高强度聚焦超声治疗设备对活体兔肝脏组织进行定点辐照,与用常规高强度聚焦超声治疗方法的定点辐照对比,并检测凝固性坏死的情况。 结果与结论：辐照后将动物解剖,取出其肝脏,找到辐照靶区,测得利用呼吸门控技术定点辐照的最大剖面焦区大小为 4.5 mm×2.0 mm,用常规的高强度聚焦超声治疗方法定点辐照的最大剖面焦区大小为9.0 mm×2.5 mm。提示呼吸门控技术能够有效消除呼吸运动引起组织移位造成的靶区定位精度的影响。     

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．     

离体组织声学特性对高强度聚焦超声剂量学预测的影响

应用高强度聚焦超声(HIFU)进行临床治疗时,主要依赖于有经验的医生主观确定辐照剂量。术前剂量投放预测一直是一个亟待解决的难题,但如果能准确预测温升变化,建立可靠的温度变化理论模型,将有助于为临床医生提供一定参考。本研究分别从声速、声衰减随温度变化的两个角度,介绍生物组织声学特性发生变化的原因,总结前人实验测得的组织声学特性的相关数据,分析离体牛肝组织声速、声衰减随温升的变化模型。在HIFU治疗中考虑靶区组织的声学特性变化,可为进一步修正HIFU剂量预测的理论模型提供一定理论依据。     

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。     

高强度聚焦超声经颅治疗温度场的数值仿真研究

数值仿真是预测高强度聚焦超声(HIFU)温度场分布的有效方法之一。本研究参照人体头颅结构建立HIFU经颅骨治疗模型,采用Westervelt声波传播方程的近似式和Pennes生物热传导方程数值仿真HIFU经颅骨治疗的温度场分布,利用时间反转法对焦域位置进行调控和颅骨温度较高处的热点消除,进而分析讨论输入声强、辐照时间、换能器与颅骨相对距离对颅内形成焦域的影响。研究结果表明,时间反转法可实现HIFU经颅治疗形成焦域位置的调控和颅骨温度较高处的热点消除,热点消除后焦点温升无明显降低;利用热点消除法可在距离颅骨20mm的颅内浅表组织中形成60℃以上的焦域,形成的焦域体积随输入声强以及辐照时间的增加而非线性增加,声强越大,达到相同大小的焦域体积所需要的辐照时间越短,且换能器与颅骨之间的距离对颅内形成焦域体积的大小有影响。     

聚焦超声对羊肝脾组织的损伤效应

背景：高强度聚焦超声可引起组织损伤。 目的：研究聚焦超声对羊肝脏和羊脾脏组织的损伤效应。 方法：用不同强度和不同方法的聚焦超声波辐照5只羊的体内肝脏、体外肝脏及体外脾脏,观察其辐照后大体及病理学改变。 结果与结论：聚焦超声辐照体外羊肝的即刻组织损伤反应较辐射治疗1周后的体内羊肝重;体内羊肝及体外羊肝在不同治疗强度下“＃”法的组织损伤反应较“=”法重;不同强度及不同方法辐照体外羊脾后均未见明显组织反应;聚焦超声Ⅲ档“＃”法辐照羊肝组织可见多个灶性的肝细胞变性及凝固性坏死;聚焦超声Ⅳ档“＃”法辐照体内羊肝组织可见被膜下炎性纤维肉芽肿性包裹结节,中心大片凝固性坏死;聚焦超声Ⅳ档“＃”法辐照体外羊肝组织可见被膜下大部分区域肝小叶结构零散不清,肝窦明显扩大,肝细胞索明显变窄,凌乱不清。说明聚焦超声Ⅲ档“＃”法能够按照设计要求选择性的损伤羊肝脏组织。     

高强度聚焦超声作用下的组织焦域能量分析及实验验证

为研究发生空化前高强度聚焦超声(HIFU)作用的最佳治疗模式,从声场和热场的仿真计算和新鲜离体牛肝实验验证出发,根据声能转化成热能的原理,分析了组织焦域温度上升造成组织损伤的变化过程;建立了与温度相关的组织损伤预测模型;计算了形成1 mm宽度的生物学焦域所吸收的能量;并在75、100、125、150 W这4种声功率下,按照350 J能量,共进行了24组新鲜离体牛肝组织的实验,验证该能量强度形成的生物学焦域尺寸。结果表明,经组织衰减后生物学焦域吸收的超声能量为350 J时,在新鲜离体牛肝组织中形成的生物学焦域宽度为(1.1±0.1)mm;当换能器物理学焦域的长短轴之比在4～10之间变动时,吸收350 J形成的生物学焦域宽度保持在(1.0±0.2) mm。在充分除气的均匀介质牛肝中,当换能器的物理学焦域长短轴比在4～10之间时,吸收350 J能量,声功率100～150 W是形成(1.0±0.2) mm宽度的生物学焦域的最佳治疗模式。     

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。     

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.     

An image-guided high intensity focused ultrasound device for uterine fibroids treatment

A high intensity focused ultrasound (HIFU) device was developed for treating uterine fibroid tumors. This prototype device enables image-guided therapy by aligning a commercially available abdominal ultrasound image probe to a vaginal HIFU transducer so the HIFU focus is in the image plane. The device was designed based on anatomical constraints of the female pelvic structures. HIFU was generated using a 3.5 MHz PZT-8 crystal, 25.4 mm in diameter, bonded to an aluminum lens. Computer simulations were performed to ensure that effective focusing was achievable at a fixed focal depth of 40 mm. Transducer efficiency was empirically determined to be 58%, and the half pressure maximum focal dimensions were 11 mm in length and 1.2 mm in width. A water-filled latex condom surrounding the transducer provided acoustic coupling, a stand-off, and allowed water circulation for transducer cooling. In vitro experiments in a tissue-mimicking gel phantom and in turkey breast demonstrated ultrasound image-guided lesion formation, or tissue necrosis, at the focus due to HIFU induced thermal and cavitation effects. The HIFU treatment site appeared as a hyperechoic spot on the ultrasound image at intensities above 1250 W/cm2. The results of in vitro experiments and in vivo ergonomic testing in six human volunteers indicated that the device has the potential of providing a nonsurgical approach for uterine fibroid treatment. Future in vivo studies in large animal models and fibroids patients are planned.     

The feasibility of interstitial ultrasound hyperthermia.

One of the most promising ways to increase the efficacy of brachytherapy is to combine it with hyperthermia. In this paper, the feasibility of using ultrasound transducers as interstitial hyperthermia sources was investigated. The ultrasound output of eight cylindrical transducers (diameter 1 mm and length 25 mm) was studied. It was found that many of these transducers were able to generate between 2 and 3 W of acoustic energy at the frequency of 9.5 MHz. The ultrasound field emitted radially was well collimated and extended the full length of the transducer. In vitro perfused liver and kidney experiments showed that an array of four transducers placed in brachytherapy catheters up to a maximum spacing of 20 mm in a square pattern could induce therapeutic temperatures. Also, the effect of flow rate into the organs and catheter cooling were investigated. These results showed that interstitial ultrasound sources are potentially the most promising way of generating therapeutic temperatures through standard interstitial radiation therapy catheters.     

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.     

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...     

Harmonic motion imaging for focused ultrasound (HMIFU): a fully integrated technique for sonication and monitoring of thermal ablation in tissues

FUS (focused ultrasound), or HIFU (high-intensity-focused ultrasound) therapy, a minimally or non-invasive procedure that uses ultrasound to generate thermal necrosis, has been proven successful in several clinical applications. This paper discusses a method for monitoring thermal treatment at different sonication durations (10 s, 20 s and 30 s) using the amplitude-modulated (AM) harmonic motion imaging for focused ultrasound (HMIFU) technique in bovine liver samples in vitro. The feasibility of HMI for characterizing mechanical tissue properties has previously been demonstrated. Here, a confocal transducer, combining a 4.68 MHz therapy (FUS) and a 7.5 MHz diagnostic (pulse-echo) transducer, was used. The therapy transducer was driven by a low-frequency AM continuous signal at 25 Hz, producing a stable harmonic radiation force oscillating at the modulation frequency. A pulser/receiver was used to drive the pulse-echo transducer at a pulse repetition frequency (PRF) of 5.4 kHz. Radio-frequency (RF) signals were acquired using a standard pulse-echo technique. The temperature near the ablation region was simultaneously monitored. Both RF signals and temperature measurements were obtained before, during and after sonication. The resulting axial tissue displacement was estimated using one-dimensional cross correlation. When temperature at the focal zone was above 48 degrees C during heating, the coagulation necrosis occurred and tissue damage was irreversible. The HMI displacement profiles in relation to the temperature and sonication durations were analyzed. At the beginning of heating, the temperature at the focus increased sharply, while the tissue stiffness decreased resulting in higher HMI displacements. This was confirmed by an increase of 0.8 microm degrees C(-1)(r=0.93, p<.005). After sustained heating, the tissue became irreversibly stiffer, followed by an associated decrease in the HMI displacement (-0.79 microm degrees C(-1), r=-0.92, p<0.001). Repeated experiments showed a reproducible pattern of the HMI displacement changes with a temperature at a slope equal to 0.8+/-0.11 and -0.79+/-0.14 microm degrees C(-1), prior to and after lesion formation in seven bovine liver samples, respectively. This technique was thus capable of following the protein-denatured lesion formation based on the variation of the HMI displacements. This method could, therefore, be applied for real-time monitoring of temperature-related stiffness changes of tissues during FUS, HIFU or other thermal therapies.     

Theoretical study of convergent ultrasound hyperthermia for treating bone tumors

This study investigates the optimal external parameters for using an ultrasound applicator for treating bone tumors. This system utilized spherically arranged applicators such as scanned focused ultrasound, and spherically focused multielement applicators. The power deposition pattern is modeled as geometric gain with exponential attenuation. The specific absorption rate ratio (SARR) criteria have been used to determine the proper heating domain of ultrasound driving frequency and therapeutic tumor diameter. The results demonstrate that the optimal driving frequency depends on tumor depth, ultrasound absorption of bone marrow, and diameter of bone, but it is independent of the acoustic window area and SARR. The treatable diameter of bone tumor increased when the absorption ratio of bone marrow to tumor, acoustic window of surface skin, and diameter of bone were elevated. However, the treatable diameter of bone tumor decreased when muscle thickness, SARR of bone tumor site to the surface skin, bone marrow, and bone declined. To deliver the ultrasound energy into the tumor site and to avoid the potential damage to the normal tissue as much as possible, the specific absorption rate (SAR) in the bone tumor site has to be three times higher than that in the surface skin, tumor/marrow, and marrow/bone interfaces. The temperature distributions can verify the SARR criteria in this model. This study provides the information for choosing the optimal operating frequency of the ultrasound transducer and the acoustic window on the skin surface, and for designing the ultrasound applicator for clinical implementation.