准实时高强度聚焦超声背向散射积分监控成像

提出一种基于超声背向散射积分(IBS)参数估计的减影成像方法,用于检测高强度聚焦超声(HIFU)治疗过程中的组织损伤.在构建的HIFU/B超准实时治疗监控成像系统上,进行了离体猪肝组织实验.得到了不同组织深度下,IBS值随治疗时间的增加而变化的情况,以及不同治疗时间的IBS减影图像.比较了两种获得减影图像的方法,讨论了空化效应对IBS值的影响.此外还采用了一种双向彩色编码模式用以识别组织运动伪像.结果表明,IBS值能够较好地检测组织的损伤,还能一定程度地反映空化效应的情况,采用时间相邻的序列减影图像的叠加所获得的减影图像效果较好,双向彩色编码模式能够较有效地识别组织运动伪像.     

仿体中超声空化效应的B超图像处理

0引言使用高强度聚焦超声(HIFU)照射组织,将产生声空化现象。在声空化过程中,声场能量于空化气泡内高度集中,当能量积累到一定阈值后,空化气泡瞬间崩溃。在气泡崩溃的瞬间能量会释放出来,形成局部的高温、高压、强冲击波等极端物理现象[1]。这将使周围的组织细胞遭到损伤。因此,对HIFU空化的监控显得尤其重要[2]。本文主要研究不同脉冲宽度的高强度聚焦超声(HIFU)在体外仿体中引起的空化气泡群面积随时间的变化。从而实现对HIFU空化的实时监控。     

HIFU治疗中生物组织对声学焦域及声的非线性影响的研究

生物分层组织是高强度聚焦超声治疗中最常见的声通道组织。通过研究生物组织对声学焦域的影响,可以为高强度聚焦超声(High Intensity Focused Ultrasound,HIFU)治疗安全性和可靠性提供理论依据。基于Westervelt方程,利用频域和时域有限元算法仿真HIFU治疗过程中超声透过分层组织后的焦域变化,并用新鲜离体猪肉组织进行实验验证。结果表明:生物组织声学特性的差异性和结构的不均一性使HIFU的声学焦域位置发生改变,尤其在声焦平面内,相对2.5mm的焦域宽度,1mm的偏移量将会对HIFU治疗精准性产生影响;声通道中存在生物组织,超声声束不会发生扩散,没有散焦现象,焦域宽度维持在2.38~2.79mm范围内;HIFU透射生物组织,声学焦域的非线性有明显的减弱,谐波次数越高,衰减程度越大,实验中基波声衰减值为9.97dB,二次谐波声衰减值为22.33dB,三次谐波声衰减值为28.05dB,四次谐波声衰减值为31.06dB,五次谐波已衰减消失。     

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。     

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。     

界面层对高强度聚焦超声所致焦斑的影响

用纳米铁磁性颗粒胶合体制作界面层,用同一剂量高强度聚焦超声(HIFU)在该界面层下方不同深度定点辐照.结果显示:焦点上缘与声学界面重合时,HIFU所致焦斑/损伤点(lesion)的体积增大,说明声学界面能够提高治疗效率；当焦点距离界面层10mm时,焦点处HIFU所致焦斑/损伤点的大小和形态与对照组相似,而界面处出现另一...     

高强度聚焦超声作用下体模组织温度上升研究

为研究高强度聚焦超声(HIFU)作用下组织温度上升规律,建立了高强度聚焦声场和组织温度场有限元仿真模型,并通过体外辐照实验对仿真模型进行了验证。通过仿真对水和组织域中的聚焦声场进行建模,计算吸收声能并将其用作热源以计算组织内的温升。进一步制备仿生物组织凝胶体模,利用热电偶进行HIFU作用下体模组织焦点处的测温。结果表明:该模型可有效预测HIFU治疗时的温度上升,与实验所得温度误差不超过 3℃;体模组织受到超声辐照时温度会立即升高,起初温升速率较快,随着辐照时间延长,温升速率逐渐降低,停止辐照后温度立即下降。     

基于超声散射回波的组织损伤程度监测方法

高强度聚焦超声(HIFU)治疗肿瘤过程中,根据组织损伤程度调整HIFU治疗剂量非常重要.本文从信号处理的角度出发,提出基于超声散射回波能量和声衰减系数并结合BP神经网络监测生物组织损伤程度的方法.将高强度聚焦超声打击新鲜猪肉组织前后获得的散射回波通过A/D转换输入到计算机,对接收到的组织散射回波信号进行预处理,再从中提取出超声散射回波能量和声衰减系数参量信息,比较不同参量对损伤程度的辨识效果.实验结果表明:综合超声散射回波能量和声衰减系数特征并输入BP神经网络,相对于仅使用某种特征参数而言能更好地监测HIFU治疗中生物组织的损伤程度,尤其在组织损伤严重时优势更加明显.     

基于回波能量的HIFU治疗区声阻抗测量方法

在高强度聚焦超声(HIFU)治疗过程中,组织声阻抗对于超声成像、表征组织特性具有重要意义.治疗区域一般位于组织内部,难以直接测出其声阻抗.本文通过建立离体猪肉组织模型,模拟超声信号在组织中的传播路径,推导出声阻抗与回波信号能量差的数学关系并应用于HIFU治疗区声阻抗的测量.为验证该方法的有效性,将上述测量的声阻抗与利用水浴锅直接测量的组织声阻抗值进行对比.实验结果表明:利用回波能量差测得的治疗区组织声阻抗与直接测量法测得的同一温度下组织声阻抗值相差较小,相对误差控制在0.5%以内,且两者随温度变化趋势表现出良好的一致性,即都随温度升高呈非线性增加趋势.     

基于超声图像小波分形维和熵监测生物组织凝固性坏死

高强度聚焦超声(HIFU)治疗肿瘤过程中,辨别组织是否发生凝固性坏死非常重要.本文从数字图像处理的角度出发,研究利用超声图像的小波分形维和熵监测生物组织变性的可行性.将高强度聚焦超声打击新鲜猪肉组织后获得的超声图像与打击前的超声图像做差值处理,截取焦域中心64×64像素的图像,然后提取其小波分形维和熵作为参量信息,比较不同参量对组织凝固性坏死的辨识效果.实验表明,提取小波分形维和熵特征并输入BP神经网络,相对于仅使用某种特征参数而言有更高的识别率,可为临床监测生物组织是否有凝固性坏死发生提供有力的依据.     

A real-time controller for sustaining thermally relevant acoustic cavitation during ultrasound therapy

A novel method for sustaining inertial cavitation during high-intensity focused ultrasound (HIFU) exposure in an agar-based tissue-mimicking material is presented. Inertial cavitation occurs during HIFU therapy when the local rarefaction pressure exceeds the inertial cavitation threshold of the insonated medium, and is characterized by broadband acoustic emissions which can be easily detected non-invasively using a passive cavitation detector (PCD). Under the right conditions, inertial cavitation has been previously shown to greatly enhance the rate of heat deposition by redistributing part of the energy carried at the fundamental HIFU frequency to higher frequencies, which are more readily absorbed by visco-elastic media such as soft tissue. However, in the absence of any cavitation control, inertial cavitation activity at the focus decays rapidly over a few seconds of exposure because of the combined effects of cavitation nuclei depletion, bubble dissolution, bubble-bubble interactions, increased vapor pressure caused by heating, and focal shielding caused by pre-focal bubble activity. The present work describes the design, validation, and testing of a real-time adaptive controller, with integrated passive localization capabilities, for sustaining inertial cavitation within the focal region of a HIFU transducer by modulation of the HIFU amplitude. Use of the controller in agar gel, originally at room temperature, has enabled therapeutically relevant temperatures in excess of 55°C to be maintained continuously in the focal region for more than 20 s using significantly less acoustic energy than is required to achieve the same temperature rise in the absence of cavitation control.     

The role of numerical simulation for the development of an advanced HIFU system

High-intensity focused ultrasound (HIFU) has been used clinically and is under clinical trials to treat various diseases. An advanced HIFU system employs ultrasound techniques for guidance during HIFU treatment instead of magnetic resonance imaging in current HIFU systems. A HIFU beam imaging for monitoring the HIFU beam and a localized motion imaging for treatment validation of tissue are introduced briefly as the real-time ultrasound monitoring techniques. Numerical simulations have a great impact on the development of real-time ultrasound monitoring as well as the improvement of the safety and efficacy of treatment in advanced HIFU systems. A HIFU simulator was developed to reproduce ultrasound propagation through the body in consideration of the elasticity of tissue, and was validated by comparison with in vitro experiments in which the ultrasound emitted from the phased-array transducer propagates through the acrylic plate acting as a bone phantom. As the result, the defocus and distortion of the ultrasound propagating through the acrylic plate in the simulation quantitatively agree with that in the experimental results. Therefore, the HIFU simulator accurately reproduces the ultrasound propagation through the medium whose shape and physical properties are well known. In addition, it is experimentally confirmed that simulation-assisted focus control of the phased-array transducer enables efficient assignment of the focus to the target. Simulation-assisted focus control can contribute to design of transducers and treatment planning.     

Noninvasive surgery of prostate tissue by high-intensity focusedultrasound

Modern ultrasound transducer material and matching layer technology has permitted us to combine the ultrasound visualization capability with production of high-intensity focused ultrasound (HIFU) on the same ceramic crystal. This development has lead to the design of a transrectal probe for noninvasive surgery of prostate tissue by HIFU. The combined capability using the same ceramic crystal simplifies treatment planning, targeting, and monitoring of tissue before and during the HIFU treatment. This mechanically scanning transrectal probe was introduced for clinical use in 1992 for noninvasive surgery of the prostate to treat benign prostatic hyperplasia (BPH) condition. This paper reviews major steps progressing from conception to the present clinical trial status of the HIFU device. During these clinical studies generation of microbubbles and cavitation were observed. Data from microbubble generation, temperature monitoring in tissue, and autopsy of HIFU-treated animal prostates are presented. Results of human clinical studies are briefly summarized to indicate performance of the device     

HIFU技术的研究

高强度聚焦超声技术起源于４０年代,当时由于缺乏高精的成像和定位技术,影响其发展,该项技术在许多方面优越于传统外科手术,具有极大的潜在临床应用价值。高强度聚焦超声对组织切换除有很高的精确性,换能器探头的选择也为灵活。该技术在对机体的生物效应包括：热效应,空化效应,与药物的相互作用和提高机体免疫机能等。该技术的应用已深入到社会科,泌尿科,等领域。     

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。     

小口径喷嘴冲击射流噪声锯齿特性及机理研究

测量了3毫米口径轴对称收缩喷嘴射流冲击大平板产生的噪声随冲击距离变化的特性。发现远场噪声随冲击距离的变化呈锯齿状，射流上游的噪声频谱上有粗缓、跨较宽频带的尖峰。根据不同唇厚喷嘴的实验对比，判断这些现象跟反馈有关，称为反馈噪声，而且正是反馈噪声与湍流噪声的相互作用，导致这种锯齿现象和射流上游的宽频尖峰。     

Using acoustic cavitation to enhance chemotherapy of DOX liposomes: experiment in vitro and in vivo

Experiments in vitro and in vivo were designed to investigate tumor growth inhibition of chemotherapeutics-loaded liposomes enhanced by acoustic cavitation. Doxorubicin-loaded liposomes (DOX liposomes) were used in experiments to investigate acoustic cavitation mediated effects on cell viability and chemotherapeutic function. The influence of lingering sensitive period after acoustic cavitation on tumor inhibition was also investigated. Animal experiment was carried out to verify the practicability of this technique in vivo. From experiment results, blank phospholipid-based microbubbles (PBM) combined with ultrasound (US) at intensity below 0.3 W/cm(2) could produce acoustic cavitation which maintained cell viability at high level. Compared with DOX solution, DOX liposomes combined with acoustic cavitation exerted effective tumor inhibition in vitro and in vivo. The lingering sensitive period after acoustic cavitation could also enhance the susceptibility of tumor to chemotherapeutic drugs. DOX liposomes could also exert certain tumor inhibition under preliminary acoustic cavitation. Acoustic cavitation could enhance the absorption efficiency of DOX liposomes, which could be used to reduce DOX adverse effect on normal organs in clinical chemotherapy.     

Monitoring of thermal therapy based on shear modulus changes: II. Shear wave imaging of thermal lesions

The clinical applicability of high-intensity focused ultrasound (HIFU) for noninvasive therapy is currently hampered by the lack of robust and real-time monitoring of tissue damage during treatment. The goal of this study is to show that the estimation of local tissue elasticity from shear wave imaging (SWI) can lead to a precise mapping of the lesion. HIFU treatment and monitoring were respectively performed using a confocal setup consisting of a 2.5-MHz single element transducer focused at 34 mm on ex vivo samples and an 8-MHz ultrasound diagnostic probe. Ultrasound-based strain imaging was combined with shear wave imaging on the same device. The SWI sequences consisted of 2 successive shear waves induced at different lateral positions. Each wave was created with pushing beams of 100 μs at 3 depths. The shear wave propagation was acquired at 17,000 frames/s, from which the elasticity map was recovered. HIFU sonications were interleaved with fast imaging acquisitions, allowing a duty cycle of more than 90%. Thus, elasticity and strain mapping was achieved every 3 s, leading to real-time monitoring of the treatment. When thermal damage occurs, tissue stiffness was found to increase up to 4-fold and strain imaging showed strong shrinkages that blur the temperature information. We show that strain imaging elastograms are not easy to interpret for accurate lesion characterization, but SWI provides a quantitative mapping of the thermal lesion. Moreover, the concept of shear wave thermometry (SWT) developed in the companion paper allows mapping temperature with the same method. Combined SWT and shear wave imaging can map the lesion stiffening and temperature outside the lesion, which could be used to predict the eventual lesion growth by thermal dose calculation. Finally, SWI is shown to be robust to motion and reliable in vivo on sheep muscle.