Noninvasive treatment efficacy monitoring and dose control for high-intensity focused ultrasound therapy using relative electrical impedance variation

As an effective therapeutic modality, high-intensity focused ultrasound(HIFU) can destroy tumour tissues by thermocoagulation with less metastasis, but it is still limited by inaccurate non-invasive temperature monitoring and efficacy evaluation. A model of electrical impedance measurement during HIFU therapy was established using the temperatureimpedance relationship. Based on the simulations of acoustic pressure, temperature, and electrical conductivity, the impedance of the phantom was calculated and experimentally demonstrated for different values of acoustic power values and treatment time. We proved that the relative impedance variation(RIV) increases linearly with the increasing treatment time at a fixed acoustic power, and the relative impedance variation rate shows a linear relationship with the acoustic power.The RIV and treatment time required for HIFU treatment efficacy are inversely proportional to the acoustic power and the square of acoustic power, respectively. The favourable results suggest that RIV can be used as an efficient indicator for noninvasive temperature monitoring and efficacy evaluation and may provide new strategy for accurate dose control of HIFU therapy.     

Gaussian representation of high-intensity focused ultrasound beams

A method for fast numerical simulation of high-intensity focused ultrasound beams is derived. The method is based on the frequency-domain representation of the Khokhlov-Zabolotskaya-Kuznetsov (KZK) equation, and assumes for each harmonic a Gaussian transverse pressure distribution at all distances from the transducer face. The beamwidths of the harmonics are constrained to vary inversely with the square root of the harmonic number, and as such this method may be viewed as an extension of a quasilinear approximation. The technique is capable of determining pressure or intensity fields of moderately nonlinear high-intensity focused ultrasound beams in water or biological tissue, usually requiring less than a minute of computer time on a modern workstation. Moreover, this method is particularly well suited to high-gain simulations since, unlike traditional finite-difference methods, it is not subject to resolution limitations in the transverse direction. Results are shown to be in reasonable agreement with numerical solutions of the full KZK equation in both tissue and water for moderately nonlinear beams.     

基于电阻抗层析成像的高强度聚焦超声温度监测技术

作为一种对正常组织无损伤且不易引起癌细胞转移的非入侵肿瘤治疗手段,高强度聚焦超声(HIFU)治疗过程中焦域的温度监测是实现剂量精准控制的关键.本文基于生物组织的温度-电阻抗的关系,将电阻抗层析成像(EIT)和HIFU治疗相结合,提出了一种利用组织焦平面的表面电压实现电阻抗重构的检测技术.建立了HIFU治疗和EIT综合系统模型,在考虑组织的声吸收条件下,对三维Helmholtz方程在柱坐标下的声场计算进行了二维简化,并引入Pennes生物热传导方程来计算HIFU焦域的声压和温升分布特性;引入生物组织的温度-电阻抗关系,基于麦克斯韦电磁场理论,建立了具有温度分布HIFU焦域的电流和电压计算模型,利用恒流注入的边界条件实现电场计算,获得焦平面的表面电压分布.在数值计算中,利用实验聚焦换能器参数,模拟了在固定声功率下组织焦域的声场和温度场分布,以及中心和偏心聚焦条件下不同治疗时刻的电导率分布;然后通过对称电极的循环电流注入,计算了组织模型焦平面内的电流密度和电势分布,获得了焦平面圆周分布的表面电极电压;进一步采用修正的牛顿-拉夫逊算法,利用32×32的表面电极电压实现了焦平面内电导率分布的重建.结果表明,基于温度-电阻抗关系的EIT电导率重建技术不但能准确定位HIFU焦域中心,还能恢复HIFU治疗中焦域的温度分布,证明了EIT用于HIFU治疗中温度监测的可行性,为其疗效评估和剂量控制提供了一种无创电阻抗测量和成像新方法.     

Perspectives in clinical uses of high-intensity focused ultrasound

Focused ultrasound holds promise in a large number of therapeutic applications. It has long been known that high intensity focused ultrasound can kill tissue through coagulative necrosis. However, it is only in recent years that practical clinical applications are becoming possible, with the development of high power ultrasound phased arrays and noninvasive monitoring methods. These technologies, combined with more sophisticated treatment planning methods allow noninvasive focusing in areas such as the brain, that were once thought to be unreachable. Meanwhile, exciting investigations are underway in microbubble-enhanced heating which could significantly reduce treatment times. These developments have promoted an increase in the number of potential applications by providing valuable new tools for medical research. This paper provides an overview of the scientific and engineering advances that are allowing the growth in clinical focused ultrasound applications. It also discusses some of these prospective applications, including the treatment of brain disorders and targeted drug delivery.     

MR monitoring of focused ultrasound surgery in a breast tissue model in vivo

The objective of this study was to investigate MRI methods for monitoring focused ultrasound surgery (FUS) of breast tumors. To this end, the mammary glands of sheep were used as tissue model. The tissue was treated in vivo with numerous single sonications which covered extended target volumes by employing a scanning technique. The ultrasound focus position was controlled by online temperature mapping based on the temperature dependence of the relaxation time T(1). This approach proved to be reliable and offers thus an alternative to proton resonance frequency methods, whose application is hampered in fatty tissues. FUS-induced tissue changes were visible on T(2)- as well as on pre- and post-contrast T(1)-weighted images. According to our initial experience, noninvasive MRI-guided FUS of breast tumors is feasible.     

The inception of cavitation bubble clouds induced by high-intensity focused ultrasound

In many therapeutic applications of high-intensity focused ultrasound (HIFU) the appearance of cavitation bubbles is unavoidable, whereas the dynamics of the bubbles induced by HIFU have not been clarified. The objective of the present work is to observe the inception process of cavitation bubble clouds generated by HIFU transducer in water using high-speed photography. Sequential images captured within 600 micros after the onset of ultrasound transmission show the dynamics of cavitation bubbles' generation, growth, deformation, expansion and collapse in the focal region. However, when the observation time is narrowed to the initial 145 micros, both the still and streak images reveal that the cavitation bubbles astonishingly stay stable in the focal region for at least 60 micros. The results imply that through adjusting the HIFU exposure time while other physical parameters are appropriately chosen, it might be possible to control the generation of stable cavitation bubbles locally in the focal region.     

Treatable focal region modulated by double excitation signal superimposition to realize platform temperature distribution during transcranial brain tumor therapy with high-intensity focused ultrasound

Recently, the phase compensation technique has allowed the ultrasound to propagate through the skull and focus into the brain. However, the temperature evolution during treatment is hard to control to achieve effective treatment and avoid over-high temperature. Proposed in this paper is a method to modulate the temperature distribution in the focal region.It superimposes two signals which focus on two preset different targets with a certain distance. Then the temperature distribution is modulated by changing triggering time delay and amplitudes of the two signals. The simulation model is established based on an 82-element transducer and computed tomography(CT) data of a volunteer's head. A finitedifference time-domain(FDTD) method is used to calculate the temperature distributions. The results show that when the distances between the two targets respectively are 7.5–12.5 mm on the acoustic axis and 2.0–3.0 mm in the direction perpendicular to the acoustic axis, a focal region with a uniform temperature distribution(64–65℃) can be created.Moreover, the volume of the focal region formed by one irradiation can be adjusted(26.8–266.7 mm~3) along with the uniform temperature distribution. This method may ensure the safety and efficacy of HIFU brain tumor therapy.     

Applications of high-intensity focused ultrasound in medicine: Spotlight on neurological applications

High-intensity focused ultrasound (HIFU) has the potential to become a modality of treatment for a wide range of clinical conditions. HIFU enables non-invasive, selective ablation of tissues including tumors and punctured vessels. Another promising area of research within the field of therapeutic ultrasound is the application of HIFU to treat neurological disorders by selectively targeting the brain, spinal cord, or nerves. This paper provides an overview of the current applications of focused ultrasound in medicine with an emphasis on its use in the fields of neurology and neurosurgery.     

高强度聚焦超声场中空化泡群的结构及其形成过程

空化是高强度聚焦超声(HIFU)引起组织损伤的作用机制之一。本文使用高速摄影技术研究了HIFU场中空化泡群结构的空间分布特征、超声功率对空化泡群结构的影响、空化泡群结构的建立过程尤其是起始过程。空化泡群的结构以空化泡在声场中的区域化分布为特征.在一定功率范围内空化泡群的结构保持稳定。从建立过程来看,空化泡群首先出现在焦区,然后在焦后区(远离换能器的区域)形成,焦前区(靠近换能器的区域)空化泡群最后形成。在对空化泡群起始的研究中发现最初拍摄到的空化泡群形状与焦区形状接近,并且观察到空化泡在焦区发生聚集然后破裂的现象。     

Hemorrhage control in arteries using high-intensity focused ultrasound: a survival study

High-intensity focused ultrasound (HIFU) has been shown to provide an effective method for hemorrhage control of blood vessels in acute animal studies. The objective of the current study was to investigate the long-term effects of HIFU-induced hemostasis in punctured arteries. The femoral arteries ( approximately 2mm in diameter) of 25 adult anesthetized rabbits were surgically exposed, and either punctured and treated with HIFU (n=15), served as control (no puncture and no HIFU application: n=7), or were punctured and left untreated (n=3). Treated animals were allowed to recover, and examined and/or sacrificed on days 0, 1, 3, 7, 14, 28, and 60 after treatment to obtain ultrasound images and samples of blood and tissue. Hemostasis (arrest of bleeding) was achieved in all 15 of the HIFU-treated arteries. Eleven of the arteries were patent after HIFU treatment, and four arteries were occluded, as determined by Doppler ultrasound. The median HIFU application time to achieve hemostasis was 20s (range 7-55 s) for the patent arteries and 110 s (range 50-134 s) for the occluded arteries. In untreated animals, bleeding had not stopped after 120 s. One of the occluded arteries had reopened by day 14. No immediate or delayed re-bleeding was observed after HIFU treatment. Maximal blood flow velocities were similar in HIFU-treated patent vessels and control vessels. No significant difference in hematocrits was found between HIFU-treated and control groups at different time points after the procedure. Light microscopy observations of the HIFU-treated arteries showed disorganization of adventitia, and coagulation and thinning of the tunica media. The general organization of the adventitia and tunica media recovered to normal appearance within 28 days, with some thinning of the tunica media observed up to day 60. Neointimal hyperplasia was observed on days 14 and 28. The results show that HIFU can produce effective and long-term (up to 60 days) hemostasis of punctured femoral arteries while preserving normal blood flow and vessel wall structure in the majority of vessels.     

Numerical simulations of partial elements excitation for hemispherical high-intensity focused ultrasound phased transducer

The hemispherical phased transducer maximizes the coverage of the skull and the ultrasonic energy per unit area of the skull is minimized, thereby reducing the risk of skull burns, but the transducer has a small focal area adjustment range, increasing the focal length of treatment is an urgent question for this type of transducer. In this paper, a three-dimensional high-intensity focused ultrasound (HIFU) transcranial propagation model is established based on the human head structure. The finite difference time domain (FDTD) is combined with the Westervelt acoustic wave nonlinear propagation equation and Penne's biological heat conduction equation for numerical simulation of the sound pressure field and temperature field. Forming a treatable focal area in a small-opening hemispherical transducer with a small amount of numerical simulation calculation focusing at a set position to determine the minimum partial excitation area ratio of focusing. And then, applying these preliminary results to a large-opening diameter hemispherical transducer and the temperature field formed by it or full excitation is studied. The results show that the focus area with the excitation area ratio of less than 22% moves forward to the transducer side when the excitation sound is formed. When the excitation area ratio is greater than or equal to 23%, it focuses at the set position. In the case of partial incentives, using 23% of the partial array, the adjustable range of the treatable focal area formed in the three-dimensional space is larger than that of the full excitation.     

Effect of acoustic nonlinearity on heating of biological tissue by high-intensity focused ultrasound

Effect of strong acoustic nonlinearity on the efficiency of heating of a biological tissue by high-intensity focused ultrasound in the modes of operation used in real clinical setups is studied. The spatial distributions of thermal sources and the corresponding temperature increments caused by ultrasonic absorption are analyzed. Numerical algorithms are developed for simulating the nonlinear focusing of ultrasound in the calculations of both the heat sources on the basis of the Khokhlov-Zabolotskaya-Kuznetsov-type equations and the temperature field in a tissue on the basis of an inhomogeneous thermal conduction equation with a relaxation term. It is demonstrated that in the mode of operation typical of acoustic surgery, the nonlinearity improves the locality of heating and leads to an increase in the power of thermal sources in the focus by approximately an order of magnitude. The diffusion phenomena in the tissue lead to a smoothing of the spatial temperature distributions, as compared to the distributions of thermal sources. In the case of one-second exposure in the nonlinear mode of focusing, the maximal temperature in the focus exceeds the values obtained in the approximation of linear wave propagation by a factor of three.     

Acoustic power calibration of high-intensity focused ultrasound transducers using a radiation force technique

To address the challenges associated with measuring the ultrasonic power from high-intensity focused ultrasound transducers via radiation force, a technique based on pulsed measurements was developed and analyzed. Two focused ultrasound transducers were characterized in terms of an effective duty factor, which was then used to calculate the power during the pulse at high applied power levels. Two absorbing target designs were used, and both gave comparable results and displayed no damage and minimal temperature rise if placed near the transducer and away from the focus. The method yielded reproducible results up to the maximum pulse power generated of approximately 230 W, thus allowing the radiated power to be calibrated in terms of the peak-to-peak voltage applied to the transducer.     

Characterization of a fiber-optic displacement sensor for measurements in high-intensity focused ultrasound fields

A fiber-optic sensor is presented that is capable of measuring the particle displacement in high-intensity focused ultrasound (HIFU) fields. For this probe, a secondary calibration was performed, and the resulting complex frequency response is discussed. As a first practical application, the setup was used to measure the pressure in the field of a weakly focusing ultrasound transducer. The result is compared with that of a membrane hydrophone measurement. The feasibility of measurements in HIFU fields is demonstrated by means of measurements of the spatial distribution of the peak particle velocity within the focus of a HIFU transducer and of the dependence of the peak values on the acoustical power level.     

Minimizing abdominal wall damage during high-intensity focused ultrasound ablation by inducing artificial ascites

High-intensity focused ultrasound (HIFU) is becoming an important tool for tumor treatment [especially hepatocellular carcinoma (HCC)] in Asian countries. A HIFU system provides unique advantages of low invasiveness and absence of nonradiation. However, if the target HCC is close to the proximal surface of the liver, HIFU may overheat diaphragm, abdominal wall or skin. To avoid this complication, a method using artificial ascites in the abdominal cavity to separate the liver from the peritoneum, and to serve as a heat sink to cool overlying structures and thereby avoid inducing permanent damage was proposed. Target tissue that was 10 mm below the liver surface was ablated in 12 New Zealand white rabbits: 6 in the experimental group and 6 in the control group. Artificial ascites was established in the experimental group by injecting normal saline into the abdominal cavity until the pressure reached 150 mm H2O. Artificial ascites not only reduced the probability and extent of thermal damage to intervening structures, but also had no adverse affect on the efficacy of HIFU ablation.     

Lysis of Chlamydomonas reinhardtii by high-intensity focused ultrasound as a function of exposure time

Efficient lysis of microalgae for lipid extraction is an important concern when processing biofuels. Historically, ultrasound frequencies in the range of 10–40 kHz have been utilized for this task. However, greater efficiencies might be achievable if higher frequencies could be used. In our study, we evaluated the potential of using 1.1 MHz ultrasound to lyse microalgae for biofuel production while using Chlamydomonas reinhardtii as a model organism. The ultrasound was generated using a spherically focused transducer with a focal length of 6.34 cm and an active diameter of 6.36 cm driven by 20 cycle sine-wave tone bursts at a pulse repetition frequency of 2 kHz (3.6% duty cycle). The time-average acoustic power output was 26.2 W while the spatial-peak-pulse-average intensity (I_SPPA) for each tone burst was 41 kW/cm². The peak compressional and rarefactional pressures at the focus were 102 and 17 MPa, respectively. The exposure time was varied for the different cases in the experiments from 5 s to 9 min and cell lysis was assessed by quantifying the percentage of protein and chlorophyll release into the supernate as well as the lipid extractability. Free radical generation and lipid oxidation for the different ultrasound exposures were also determined. We found that there was a statistically significant increase in lipid extractability for all of the exposures compared to the control. The longer exposures also completely fragmented the cells releasing almost all of the protein and chlorophyll into the supernate. The cavitation activity did not significantly increase lipid oxidation while there was a minor trend of increased free radical production with increased ultrasound exposure.     

从临床角度浅谈体外高强度聚焦超声肿瘤治疗设备的研制

本文从临床角度探讨在体外高强度聚焦超声（HIFU）治疗机的研发中应该关注的问题，指出重视HIFU的生物学效应研究、充分理解HIFU治疗肿瘤的临床意义对HIFU治疗机的研发具有的指导价值，提出了HIFU治疗机主要部件性能的临床要点，以及开发专用治疗机等构想，强调医工结合在HIFU治疗机开发中的重要性。     

Enhancement and quenching of high-intensity focused ultrasound cavitation activity via short frequency sweep gaps

This letter reports on the use of frequency sweeps to probe acoustic cavitation activity generated by high-intensity focused ultrasound (HIFU). Unprecedented enhancement and quenching of HIFU cavitation activity were observed when short frequency sweep gaps were applied in negative and positive directions, respectively. It was revealed that irrespective of the frequency gap, it is the direction and frequency sweep rate that govern the cavitation activity. These effects are related to the response of bubbles generated by the starting frequency to the direction of the frequency sweep, and the influence of the sweep rate on growth and coalescence of bubbles, which in turn affects the active bubble population. These findings are relevant for the use of HIFU in chemical and therapeutic applications, where greater control of cavitation bubble population is critical.     

高强度聚焦超声经颅脑肿瘤治疗焦域的仿真研究*

为了研究脑组织和脑肿瘤组织在HIFU治疗时形成焦域的特性及坏死肿瘤组织、不同治疗剂量参数以及多次治疗时焦点间距和时间间隔对HIFU形成焦域的影响,本文以脑胶质瘤患者为例,利用患者头颅CT图像数据建立HIFU经颅治疗的仿真模型,基于Westervelt声波非线性传播方程和Pennes生物热传导方程进行HIFU经颅治疗的仿真研究。结果表明,脑组织和脑肿瘤组织内形成HIFU焦域的差异较小,坏死肿瘤组织对HIFU温度场分布有较小影响;辐照声强越大,焦点温升达到同一温度所用时间越短,焦域长短轴越短,颅骨处温升越低;当焦点间距在一定范围内时,第一次辐照形成的温度场分布对第二个焦点温升达到同一温度所需时间影响较大;两次辐照时间间隔对颅骨处温升和两次聚焦形成60?C以上温度分布影响较小。     

随机相控高强度聚焦超声换能器的栅瓣抑制

采用3种随机排列策略形成相控阵元线性排列结构抑制高强度聚焦超声(HIFU)相控阵栅瓣。第1种和第2种策略中阵元基于规则排列随机移动,而第3种策略中阵元则直接进行随机移动,阵元可移动范围依次为:第1种<第2种<第3种。采用瑞利积分和非线性Westervelt方程分别计算了3种策略对应随机相控阵产生的线性和非线性声场,并通过归一化栅瓣最大声压、归一化栅瓣平均声强和归一化旁瓣平均声强3个参量,对栅瓣抑制效果进行评价。结果表明:线性声场中,阵元可移动范围的增加有利于栅瓣抑制,3种随机策略的归一化栅瓣最大声压相比规则排列分别降低30.7%,53.8%和55.8%;非线性声场中对于同一种随机排列策略,随机度的增加可以改善栅瓣抑制效果。例如,第3种随机策略在随机度为0.9时正负压的归一化栅瓣最大声压相比规则排列分别降低55.6%和54.8%。进一步讨论了焦点偏移时随机相控阵的非线性声场,以-8 dB作为栅瓣的安全标准,第2种和第3种随机策略可以满足要求,横向偏移分别为6 mm和10 mm。本文的工作为抑制栅瓣提供了新思路,有利于随机HIFU相控阵的设计优化。