高强度聚焦超声间歇式治疗中焦域温度分布的 仿真研究*

探究不同治疗深度、组织类型和治疗模式对高强度聚焦超声焦域温度场的影响。采用有限元法建立高强度聚焦超声辐照组织的二维轴对称仿真模型,通过Westervelt方程和Pennes生物热传导方程计算高强度聚焦超声焦域的声场和温度场分布。仿真结果表明:随着治疗深度的增加,焦域内温度逐渐降低,有效温升面积减小;不同组织类型在相同条件下的焦域温度不同,但焦域形状差别不大;单次治疗时间长、治疗时间间隔短的模式焦域温升速率快,有效温升面积区域大。焦域温度是高强度聚焦超声肿瘤治疗中判断治疗有效性和安全性的重要因素之一,该文通过数值仿真法,实现了预测高强度聚焦超声间歇式治疗模式下焦域组织温度场分布,有望为制定安全、有效的高强度聚焦超声术前治疗方案提供理论参考。     

高强度聚焦超声在医学超声领域中的发展与应用

高强度聚焦超声(high intensity focused ultrasound,简称HIFU)作为一种非侵入性、无毒副作用、具有巨大潜力的治疗肿瘤的手段,近年来已经越来越受到国内外学者的广泛关注。HIFU技术能将超声能量聚焦到人体组织的肿瘤内,产生高温,使肿瘤组织温度迅速上升至65℃以上,而发生不可逆转的凝固性坏死,从而达到消融肿瘤组织的目的。目前中国的HIFU肿瘤治疗技术和临床居国际领先。文章对HIFU在医学超声领域中的发展历史、现状和前景进行了探讨。     

球面矩形阵元相控阵高强度聚焦超声手术的子阵工作模式

提出了超声手术治疗肝肿瘤时非侵入性的球面矩形阵元相控阵的多种子阵工作模式:通过图像扫描来确定仅让不受肋骨遮挡的换能器子阵继续工作,并运用超声传播公式、伪逆矩阵算法和遗传算法进行声场的优化合成。结果表明:球面矩形阵元相控阵换能器的多种不同的子阵划分,不仅能够产生手术中需要的单焦点、多焦点等多种治疗模式,其声场的焦域形状和聚焦声强均达到了治疗的要求,而且能够减少肋骨上的声功率累积,避免了正常组织受损,从而可能解决高强度聚焦超声手术治疗肝肿瘤时超声波束受肋骨遮挡不能形成治疗需求声场模式的困难,拓宽治疗区域。     

基于分数导数研究高强度聚焦超声的非线性声场

在高强度聚焦超声(high intensity focused ultrasound, HIFU) 的研究中, 生物组织的衰减和色散性质会对声能量的空间分布产生影响. 本文提出应用分数导数修正非线性Khokhlov-Zabolotskaya-Kuznetsov (KZK)方程, 研究生物组织中非线性HIFU声场. 对三种生物仿体的衰减和声速色散的理论实验研究表明分数导数应用的可行性, 在此基础上通过数值仿真分析研究了衰减及声速随频率的变化对HIFU焦域分布的影响. 研究结果表明, 在计算强非线性聚焦超声时, 由于高次谐波的强色散作用, 引入分数导数来解决生物组织特殊的衰减以及色散问题可进一步提高HIFU治疗的安全性. 关键词： 分数导数 声衰减 色散 高强度聚焦超声     

基于FPGA的高强度聚焦超声相位控制系统设计*

多阵元相控阵换能器具有焦距可调和可实现经颅聚焦等优势,近来受到众多研究者的关注,其相位控制系统是决定多阵元相控换能器能否应用于临床的关键技术之一。在输出信号稳定的同时提高高强度聚焦超声相位控制系统精度是设计过程中的重点与难点。本文基于现场可编程门阵列设计了一种高强度聚焦超声相位控制系统。实测结果表明,多通道延时分辨率为1 ns,延时误差小于1 ns,可满足多阵元高强度聚焦超声治疗相控聚焦换能器延时精度的需要。     

不等间距排列的球面高强度聚焦超声相控阵列

讨论了一种新型的不等间距排列的球面高强度聚焦超声相控阵列,通过阵元间的不等间距排列明显的降低了栅瓣,使在陈元间距在 ４λ的情况下,栅瓣低于－２０ ｄＢ．通过优化设计发现在 ０．５ ＭＨｚ的发射频率时,采用 ２３１个直径为 １０ ｍｍ的圆形阵元组成的球面阵列可以在轴向 １０～ １５ ｃｍ,径向半径 ２ ｃｍ的圆柱区域形成声强 ８００ Ｗ／ｃｍ２的高强度聚焦。同时还可形成多焦点,实现大肿瘤的超声热疗。     

相控阵高强度聚焦超声的研究进展

相控阵高强度聚焦超声(high Intensity focused ultrasound,HIFU)技术可以通过电子调相自由控制聚焦区域中焦点的形状、位置、个数等,实现高精度、高效率的治疗。文章主要介绍了相控聚焦超声的原理、阵型设计、声场优化、控制算法、电路设计以及换能器材料等几个方面。     

多阵元高强度聚焦超声多目标控制方法研究

对多阵元高强度聚焦超声非侵入外科治疗采用多目标控制方法可望取得好的温度控制性能.提出和构造了闭环控制的模糊控制器,从而得到好的温度特性 为得到理想的能量空间分布,专门形成了优化声场的模式控制 另外,重要参量辨识和开关模式控制技术是十分有效的控制方法.考虑非线性效应的仿真结果显示出优越的控制性能.随后的活体实验结果显示出好的温度响应特性,同时证实了多目标控制方法的可行性 关键词： 高强度聚焦超声 多目标 模糊逻辑     

高强度聚焦超声的临床应用

高强度聚焦超声是近几年发展起来的一种新的非介入性肿瘤治疗技术,临床应用越来越广,文章就其在不同肿瘤如前列腺癌、肝癌、胰腺癌、子宫肌瘤等治疗中的应用及进展进行评述。     

变厚度聚焦换能器对声焦域轴向长度影响的研究*

针对不同厚度的病变组织,改变声焦域轴向长度能提高高强度聚焦超声在临床治疗过程中的安全性和有效性。基于多频超声波叠加原理,该文提出了变厚度(多频)聚焦换能器,并设计了两种类型变厚度聚焦换能器。根据瑞利积分法推导了变厚度聚焦换能器声场,计算和分析了变厚度聚焦换能器的声焦域轴向长度,并与等厚度(单频)聚焦换能器声焦域轴向长度进行对比。结果显示,变厚度聚焦换能器中心到边缘的厚度变化趋势与声焦域轴向长度变化相关,中间薄两边厚换能器声焦域轴向长度缩短,中间厚两边薄换能器声焦域轴向长度变长,且实验验证了理论的正确性。研究结果可为变厚度聚焦换能器声场研究和高强度聚焦超声的临床治疗提供参考。     

Prostatic tissue ablation by transrectal high intensity focused ultrasound: histological impact and clinical application

In a phase-I clinical trial the morphologic impact and safety of high-intensity focused ultrasound (HIFU) administered transrectally for tissue ablation in human prostates (n = 54) was evaluated. Location and size of the tissue lesions correlated well with the predefined target area and revealed sharply delineated coagulative necrosis in all cases. Intervening tissues, such as the rectal wall and posterior prostate capsule were invariably intact. In a subsequent phase-II clinical trial safety and efficacy of transrectal HIFU as a novel minimally invasive treatment modality for patients with symptomatic benign prostatic hyperplasia (BPH; n = 102) was determined. The maximum urinary flow rate (Qmax, ml/s) increased from 9.1+/-4.0 to 12.9+/-6.1 (3 months, n=86), 12.7+/-5.1 (6 months, n=78) and 13.3+/-6.1 (12 months, n=56). In the same time period the post void residual volume (ml) decreased from 131+/-115 to 46+/-45, 57+/-46 and 48+/-36 and the AUA symptom score decreased from 24.5+/-4.7 to 13.3+/-4.4, 13.4+/-4.7 and 10.8+/-2.5. A subset of patients (n=30) underwent multichannel pressure flow studies, which demonstrated that transrectal HIFU reduces bladder outflow obstruction. These data demonstrate that transrectal HIFU is capable of inducing coagulative necrosis in the human prostate via a transrectal approach while preserving intervening and adjacent tissue. A 48% improvement of uroflow and a 53% decrease of urinary symptoms 1 year after treatment prove that transrectal HIFU is an effective and safe minimally invasive treatment option for BPH.     

The Relationship of Cavitation to the Negative Acoustic Pressure Amplitude in Ultrasonic Therapy

The relationship between the cavitation and acoustic peak negative pressure in the high-intensity focused ultrasound(HIFU)Held is analyzed in water and tissue phantom.The peak negative pressure at the focus is determined by a hybrid approach combining the measurement with the simulation.The spheroidal beam equation is utilized to describe the nonlinear acoustic propagation.The waveform at the focus is measured by a fiber optic probe hydrophone in water.The relationship between the source pressure amplitude and the excitation voltage is determined by fitting the measured ratio of the second harmonic to the fundamental component at the focus,based on the model simulation.Then the focal negative pressure is calculated for arbitrary voltage excitation in water and tissue phantom.A portable B-mode ultrasound scanner is applied to monitor HIFU-induced cavitation in real time,and a passive cavitation detection(PCD)system is used to acquire the bubble scattering signals in the HIFU focal volume for the cavitation quantification.The results show that:(1)unstable cavitation starts to appear in degassed water when the peak negative pressure of HIFU signals reaches 13.5 MPa;and(2)the cavitation activity can be detected in tissue phantom by B-mode images and in the PCD system with HIFU peak negative pressures of 9.0 MPa and 7.8 MPa,respectively,which suggests that real-time B-mode images could be used to monitor the cavitation activity in two dimensions,while PCD systems are more sensitive to detect scattering and emission signals from cavitation bubbles.     

Acoustic power measurement of high intensity focused ultrasound in medicine based on radiation force

How to measure the acoustic power of HIFU is one of the most important tasks in its medical application. In the paper a whole series of formula for calculating the radiation force related to the acoustic power radiated by a single element focusing transducer and by the focusing transducer array were given. Various system of radiation force balance (RFB) to measure the acoustic power of HIFU in medicine were designed and applied in China. In high power experiments, the dependence of radiation force acting the absorbing target on the target position at the beam axis of focusing transducer was fined. There is a peak value of "radiation force" acting the absorbing target in the focal region when the acoustic power through the focal plane exceeds some threshold. In order to avoid this big measurement error caused by the 'peak effect' in focal region, the distance between the absorbing target of RFB and the focusing transducer or transducer array was defined to be equal to or less than 0.7 times of the focal length in the National Standard of China for the measurements of acoustic power and field characteristics of HIFU. More than six different therapeutic equipments of HIFU have been examined by RFB for measuring the acoustic power since 1998. These results show that RFB with the absorbing target is valid in the acoustic power range up to 500W with good linearity for the drive voltage squared of focusing transducer or array. The uncertainty of measurement is within +/-15%.     

Nonlinear absorption in biological tissue for high intensity focused ultrasound

In recent years the propagation of the high intensity focused ultrasound (HIFU) in biological tissue is an interesting area due to its potential applications in non-invasive treatment of disease. The base principle of these applications is the heat effect generated by ultrasound absorption. In order to control therapeutic efficiency, it is important to evaluate the heat generation in biological tissue irradiated by ultrasound. In his paper, based on the Khokhlov-Zabolotkaya-Kuznetsov (KZK) equation in frequency-domain, the numerical simulations of nonlinear absorption in biological tissues for high intensity focused ultrasound are performed. We find that ultrasound thermal transfer effect will be enhanced with the increasing of initial acoustic intensity due to the high harmonic generation. The concept of extra absorption factor is introduced to describe nonlinear absorption in biological tissue for HIFU. The theoretical results show that the heat deposition induced by the nonlinear theory can be nearly two times as large as that predicated by linear theory. Then, the influence of the diffraction effect on the position of the focus in HIFU is investigated. It is shown that the sound focus moves toward the transducer compared with the geometry focus because of the diffraction of the sound wave. The position of the maximum heat deposition is shifted to the geometry focus with the increase of initial acoustic intensity because the high harmonics are less diffraction. Finally, the temperature in the porcine fat tissue changing with the time is predicated by Pennes' equation and the experimental results verify the nonlinear theoretical prediction.     

High-speed observation of cavitation bubble cloud structures in the focal region of a 1.2 MHz high-intensity focused ultrasound transducer

Cavitation bubble clouds in the focal region of HIFU play important roles in therapeutic applications of HIFU. Temporal evolution and spatial distribution of cavitation bubble clouds generated in the focal region of a 1.2 MHz single element concave HIFU transducer in water are investigated by high-speed photography. It is found that during the initial 600 micro s insonation cavitation bubble clouds organize to the "screw-like structure" or "cap-like structure". The screw-like structure is characterized by a nearly fixed tip at the geometrical focus of the HIFU transducer, and the cap-like structure is marked by a dent formed in the direction of ultrasound transmission. After 600 micro s, another two structures are recorded - "streamer structure" and "cluster structure". The streamer structure is also featured by a nearly fixed bottom position at the focus, while the cluster structure is distinguished by agglomerations of bubbles around the focus.     

HIFU治疗中换能器驱动电功率变化机制及规律*

高强度聚焦超声(HIFU)治疗中的驱动电功率对治疗效率起着非常关键的作用,驱动电功率控制的精准性势必会影响治疗的效率和安全性。前期研究表明：HIFU治疗过程中焦域瞬态物理特性的变化会导致换能器的负载阻抗发生变化,进而影响HIFU驱动电功率,但驱动电功率与焦域瞬态物理特性之间的影响关系及规律尚不明确。该文基于电压、电流传感器、空化检测探头和温度传感器等器件,构建了一种HIFU治疗中驱动电功率实时监测及焦域声空化、温度检测系统。基于该实验研究系统,以离体牛心组织作为HIFU辐照对象,分别研究了HIFU焦域温度变化、声空化及组织损伤与驱动电功率之间的变化关系及规律。研究结果表明：当焦域温度升高时,驱动电功率缓慢上升,驱动电功率与温度变化有良好的相关性;当空化产生时,驱动电功率出现明显的波动;当组织出现损伤时,驱动电功率呈陡然下降的变化。三种情景下,驱动电功率变化有明显区别,这有望为区分HIFU治疗过程中焦域处发生损伤和空化以及实时监测靶组织损伤程度提供一种新的解决方案。     

高强度聚焦超声(HIFU)——一门多学科的研究课题

高强度聚焦超声(high intensity focused ultrasound,简称HIFU)已作为一种无创外科工具而应用于门诊治疗肿瘤。文章介绍了它的基本原理、有关的研究现状和存在的问题,以及对今后研究工作的建议。文章特别强调高强度聚焦超声是一门多学科的综合研究课题,需要各方面的科学工作者通力协作。     

微泡对高强度聚焦超声声压场影响的仿真研究*

微泡对高强度聚焦超声(HIFU)治疗焦域具有增效作用,而HIFU治疗中不同声学条件下微泡对HIFU形成声压场的影响尚不清楚。本文基于气液混合声波传播方程、Keller气泡运动方程、时域有限差分(FDTD)法和龙格-库塔(RK)法数值仿真研究输入声压、激励频率、气泡初始空隙率和气泡初始半径对HIFU形成声压场的影响。研究结果表明,随着输入声压的增大,焦点处声压升高但焦点处最大声压与输入声压的比值减小,焦点位置几乎不变;随着激励频率和气泡初始半径的增大,焦点处声压升高且焦点位置向远离换能器方向移动;随着气泡初始空隙率的增大,焦点处声压降低且焦点位置向换能器方向移动。     

Control of the dynamics of a boiling vapour bubble using pressure-modulated high intensity focused ultrasound without the shock scattering effect: A first proof-of-concept study

Boiling histotripsy is a promising High-Intensity Focused Ultrasound (HIFU) technique that can be used to induce mechanical tissue fractionation at the HIFU focus via cavitation. Two different types of cavitation produced during boiling histotripsy exposure can contribute towards mechanical tissue destruction: (1) a boiling vapour bubble at the HIFU focus and (2) cavitation clouds in between the boiling bubble and the HIFU source. Control of the extent and degree of mechanical damage produced by boiling histotripsy is necessary when treating a solid tumour adjacent to normal tissue or major blood vessels. This is, however, difficult to achieve with boiling histotripsy due to the stochastic formation of the shock scattering-induced inertial cavitation clouds. In the present study, a new histotripsy method termed pressure-modulated shockwave histotripsy is proposed as an alternative to or in addition to boiling histotripsy without inducing the shock scattering effect. The proposed concept is (a) to generate a boiling vapour bubble via localised shockwave heating and (b) subsequently control its extent and lifetime through manipulating peak pressure magnitudes and a HIFU pulse length. To demonstrate the feasibility of the proposed method, bubble dynamics induced at the HIFU focus in an optically transparent liver tissue phantom were investigated using a high speed camera and a passive cavitation detection systems under a single 10, 50 or 100 ms-long 2, 3.5 or 5 MHz pressure-modulated HIFU pulse with varying peak positive and negative pressure amplitudes from 5 to 89 MPa and −3.7 to −14.6 MPa at the focus. Furthermore, a numerical simulation of 2D nonlinear wave propagation with the presence of a boiling bubble at the focus of a HIFU field was conducted by numerically solving the generalised Westervelt equation. The high speed camera experimental results showed that, with the proposed pressure-modulated shockwave histotripsy, boiling bubbles generated by shockwave heating merged together, forming a larger bubble (of the order of a few hundred micron) at the HIFU focus. This coalesced boiling bubble then persisted and maintained within the HIFU focal zone until the end of the exposure (10, 50, or 100 ms). Furthermore, and most importantly, no violent cavitation clouds which typically appear in boiling histotripsy occurred during the proposed histotripsy excitation (i.e. no shock scattering effect). This was likely because that the peak negative pressure magnitude of the backscattered acoustic field by the boiling bubble was below the cavitation cloud intrinsic threshold. The size of the coalesced boiling bubble gradually increased with the peak pressure magnitudes. In addition, with the proposed method, an oval shaped lesion with a length of 0.6 mm and a width of 0.1 mm appeared at the HIFU focus in the tissue phantom, whereas a larger lesion in the form of a tadpole (length: 2.7 mm, width: 0.3 mm) was produced by boiling histotripsy. Taken together, these results suggest that the proposed pressure-modulated shockwave histotripsy could potentially be used to induce a more spatially localised tissue destruction with a desired degree of mechanical damage through controlling the size and lifetime of a boiling bubble without the shock scattering effect.     

The interaction of shockwaves with a vapour bubble in boiling histotripsy: The shock scattering effect

Boiling histotripsy is a High Intensity Focused Ultrasound (HIFU) technique which uses a number of short pulses with high acoustic pressures at the HIFU focus to induce mechanical tissue fractionation. In boiling histotripsy, two different types of acoustic cavitation contribute towards mechanical tissue destruction: a boiling vapour bubble and cavitation clouds. An understanding of the mechanisms underpinning these phenomena and their dynamics is therefore paramount to predicting and controlling the overall size of a lesion produced for a given boiling histotripsy exposure condition. A number of studies have shown the effects of shockwave heating in generating a boiling bubble at the HIFU focus and have studied its dynamics under boiling histotripsy insonation. However, not much is known about the subsequent production of cavitation clouds that form between the HIFU transducer and the boiling bubble. The main objective of the present study is to examine what causes this bubble cluster formation after the generation of a boiling vapour bubble. A numerical simulation of 2D nonlinear wave propagation with the presence of a bubble at the focus of a HIFU field was performed using the k-Wave MATLAB toolbox for time domain ultrasound simulations, which numerically solves the generalised Westervelt equation. The numerical results clearly demonstrate the appearance of the constructive interference of a backscattered shockwave by a bubble with incoming incident shockwaves. This interaction (i.e., the reflected and inverted peak positive phase from the bubble with the incoming incident rarefactional phase) can eventually induce a greater peak negative pressure field compared to that without the bubble at the HIFU focus. In addition, the backscattered peak negative pressure magnitude gradually increased from 17.4 MPa to 31.6 MPa when increasing the bubble size from 0.2 mm to 1.5 mm. The latter value is above the intrinsic cavitation threshold of –28 MPa in soft tissue. Our results suggest that the formation of a cavitation cloud in boiling histotripsy is a threshold effect which primarily depends (a) the size and location of a boiling bubble, and (b) the sum of the incident field and that scattered by a bubble.