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.     

Therapeutic ultrasound an overview

Therapeutic ultrasound is defined as the use of ultrasound for the treatment of diseased or injured organs or bodily structures and is quite distinct from diagnostic ultrasound. There were many early attempts in the past to use ultrasound in therapy for a variety of applications and while some of these have not been pursued others have led on to clinical applications which are now used routinely. Such progress has been made possible by a number of factors including advances in transducer design, more accurate measurement and calibration of acoustic power and careful experiments to determine the precise nature of chemical processes taking place during and following the exposure of tissue to ultrasound. Major advances have been made in some fields where ultrasound is used such as physiotherapy, surgical instruments, chemotherapy, drug delivery and more recently, high intensity focused ultrasound (HIFU). The last of these has seen enormous activity leading to the formation of the International Society of Therapeutic Ultrasound and a number of very well attended regular specialist meetings. In this review some historical perspectives of therapeutic ultrasound and progress in the field since the early 1990's will be presented.     

Recent advances in applications of power ultrasound for petroleum industry

Power ultrasound, as an emerging green technology has received increasing attention of the petroleum industry. The physical and chemical effects of the periodic oscillation and implosion of acoustic cavitation bubbles can be employed to perform a variety of functions. Herein, the mechanisms and effects of acoustic cavitation are presented. In addition, the applications of power ultrasound in the petroleum industry are discussed in detail, including enhanced oil recovery, oil sand extraction, demulsification, viscosity reduction, oily wastewater treatment and oily sludge treatment. From the perspective of industrial background, key issue and resolution mechanism, current applications and future development of power ultrasound are discussed. In addition, the effects of acoustic parameters on treatment efficiency, such as frequency, acoustic intensity and treatment time are analyzed. Finally, the challenges and outlook for industrial application of power ultrasound are discussed.     

A derating method for therapeutic applications of high intensity focused ultrasound

Current methods of determining high intensity focused ultrasound (HIFU) fields in tissue rely on extrapolation of measurements in water assuming linear wave propagation both in water and in tissue. Neglecting nonlinear propagation effects in the derating process can result in significant errors. A new method based on scaling the source amplitude is introduced to estimate focal parameters of nonlinear HIFU fields in tissue. Focal values of acoustic field parameters in absorptive tissue are obtained from a numerical solution to a KZK-type equation and are compared to those simulated for propagation in water. Focal wave-forms, peak pressures, and intensities are calculated over a wide range of source outputs and linear focusing gains. Our modeling indicates, that for the high gain sources which are typically used in therapeutic medical applications, the focal field parameters derated with our method agree well with numerical simulation in tissue. The feasibility of the derating method is demonstrated experimentally in excised bovine liver tissue.     

The effect of acoustic absorber's physical parameters on estimating acoustic intensity in high intensity focused ultrasound field using infrared thermometry

The physical parameters of acoustic absorber play an important role in estimating acoustic intensity in high intensity focused ultrasound (HIFU) using infrared ...     

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.     

柔性超声换能器在生物医学中的研究进展*

传统超声换能器存在体积大、表面刚性的缺点,无法用于人体复杂皮肤表面和可穿戴器件的设计。为使换能器具有灵活、体积小,满足可穿戴的特点,将其压电元件、电极和封装等各组成部分重组为柔性换能器。相比于传统换能器,它有两个优点：首先,不需要专业人员操作,可实现持续性的超声监控或治疗。其次,通过更全面的皮肤表面覆盖,扩大声场范围。在超声诊断方面,改善声信号采集,获得更全面的检测信息;在超声治疗方面,增加声能量沉积,提高疗效。柔性换能器使超声医疗应用场景多元化,可实现连续超声诊断或超声治疗。该文首先概述了其在设计和加工方面的最新进展,然后重点介绍了其在诊断和治疗方面的应用,最后讨论了这一领域所面临的挑战并对发展前景进行展望。     

Calibration and measurement issues for therapeutic ultrasound

This review paper examines some of the issues relating to calibration and measurement of therapeutic medical ultrasonic equipment (MUE). This is not intended to be an all-encompassing review of all aspects of characterising therapeutic ultrasound. Instead it concentrates on issues related to the acoustic output of two applications: physiotherapy and high intensity focused ultrasound surgery (HIFUS or HIFU; also referred to as high intensity therapeutic ultrasound, HITU). Physiotherapy has a well-established standards infrastructure for calibration: the requirements are small in number and well-defined. The issue for physiotherapy is not so much 'How to calibrate?' but rather, 'How to ensure that equipment IS calibrated?' The situation in the much newer area of HIFU is very different: the first steps towards writing standards are just starting and even the very basic questions of what to measure and with what type of sensor are open for debate. Readers whose main interest is in other ultrasound therapies will find ideas of relevance to their own specialty.     

Phase transitions of perfluorocarbon nanoemulsion induced with ultrasound: A mathematical model

While ultrasound has been used in many medical and industrial applications, only recently has research been done on phase transformations induced by ultrasound. This paper presents a numerical model and the predicted results of the phase transformation of a spherical nanosized droplet of perfluorocarbon in water. Such a model has applications in acoustic droplet vaporization, the generation of gas bubbles for medical imaging, therapeutic delivery and other biomedical applications.The formation of a gas phase and the subsequent bubble dynamics were studied as a function of acoustic parameters, such as frequency and amplitude, and of the physical aspects of the perfluorocarbon nanodroplets, such as chemical species, temperature, droplet size and interfacial energy. The model involves simultaneous applications of mass, energy and momentum balances to describe bubble formation and collapse, and was developed and solved numerically. It was found that, all other parameters being constant, the maximum bubble size and collapse velocity increases with increasing ultrasound amplitude, droplet size, vapor pressure and temperature. The bubble size and collapse velocity decreased with increasing surface tension and frequency. These results correlate with experimental observations of acoustic droplet vaporization.     

球形集声器在生物组织中形成的组织损伤

球形集声器可在亚波长焦域内形成高强度声压,在高强度聚焦超声治疗中具有潜在应用前景.本文结合非线性声传播理论及生物传热学理论,研究球形集声器在生物组织中形成的组织损伤.实验中采用430 kHz,内径为240 mm的球形集声器对肝组织作用,结果表明:集声器表面声压为53 kPa时作用2 s,可以形成小于波长尺度的组织损伤.理论计算结果与实验结果符合得较好,并且理论模型可优化球形集声器的开口孔径.研究结果表明,球形集声器可应用于肿瘤的精细超声治疗.     

A reduced-order, single-bubble cavitation model with applications to therapeutic ultrasound

Cavitation often occurs in therapeutic applications of medical ultrasound such as shock-wave lithotripsy (SWL) and high-intensity focused ultrasound (HIFU). Because cavitation bubbles can affect an intended treatment, it is important to understand the dynamics of bubbles in this context. The relevant context includes very high acoustic pressures and frequencies as well as elevated temperatures. Relative to much of the prior research on cavitation and bubble dynamics, such conditions are unique. To address the relevant physics, a reduced-order model of a single, spherical bubble is proposed that incorporates phase change at the liquid-gas interface as well as heat and mass transport in both phases. Based on the energy lost during the inertial collapse and rebound of a millimeter-sized bubble, experimental observations were used to tune and test model predictions. In addition, benchmarks from the published literature were used to assess various aspects of model performance. Benchmark comparisons demonstrate that the model captures the basic physics of phase change and diffusive transport, while it is quantitatively sensitive to specific model assumptions and implementation details. Given its performance and numerical stability, the model can be used to explore bubble behaviors across a broad parameter space relevant to therapeutic ultrasound.     

球形腔聚焦换能器的非线性声场建模

球形腔聚焦换能器是一种特殊形式的聚焦换能器。为理论证实球形腔聚焦换能器能突破传统超声聚焦在聚焦精度和聚焦增益上的限制,采用Westervelt非线性方程并结合时域有限差分法,建立了球形腔聚焦换能器的非线性声场的数值模型。数值计算了直径为120 mm的0.6 MHz球形腔聚焦换能器的非线性声场,并与传统球壳形聚焦换能器进行了对比。当激励声压为100 kPa时,球形腔聚焦换能器与同尺寸壳形聚焦换能器相比,焦点正声压增益提高约8.5倍,且焦域精度更高,-6 dB聚焦区域在z方向减小约20倍,达到次波长尺度。研究表明球形腔聚焦换能器在高强度聚焦超声精细治疗上具有潜在的应用前景。     

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。     

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.     

Characterization of high intensity focused ultrasound transducers using acoustic streaming

A new approach for characterizing high intensity focused ultrasound (HIFU) transducers is presented. The technique is based upon the acoustic streaming field generated by absorption of the HIFU beam in a liquid medium. The streaming field is quantified using digital particle image velocimetry, and a numerical algorithm is employed to compute the acoustic intensity field giving rise to the observed streaming field. The method as presented here is applicable to moderate intensity regimes, above the intensities which may be damaging to conventional hydrophones, but below the levels where nonlinear propagation effects are appreciable. Intensity fields and acoustic powers predicted using the streaming method were found to agree within 10% with measurements obtained using hydrophones and radiation force balances. Besides acoustic intensity fields, the streaming technique may be used to determine other important HIFU parameters, such as beam tilt angle or absorption of the propagation medium.     

Impact of cavitation on lesion formation induced by high intensity focused ultrasound

High intensity focused ultrasound(HIFU) has shown a great promise in noninvasive cancer therapy. The impact of acoustic cavitation on the lesion formation induced by HIFU is investigated both experimentally and theoretically in transparent protein-containing gel and ex vivo liver tissue samples. A numerical model that accounts for nonlinear acoustic propagation and heat transfer is used to simulate the lesion formation induced by the thermal effect. The results showed that lesions could be induced in the samples exposed to HIFU with various acoustic pressures and pulse lengths. The measured areas of lesions formed in the lateral direction were comparable to the simulated results, while much larger discrepancy was observed between the experimental and simulated data for the areas of longitudinal lesion cross-section. Meanwhile,a series of stripe-wiped-off B-mode pictures were obtained by using a special imaging processing method so that HIFUinduced cavitation bubble activities could be monitored in real-time and quantitatively analyzed as the functions of acoustic pressure and pulse length. The results indicated that, unlike the lateral area of HIFU-induced lesion that was less affected by the cavitation activity, the longitudinal cross-section of HIFU-induced lesion was significantly influenced by the generation of cavitation bubbles through the temperature elevation resulting from HIFU exposures. Therefore, considering the clinical safety in HIFU treatments, more attention should be paid on the lesion formation in the longitudinal direction to avoid uncontrollable variation resulting from HIFU-induced cavitation activity.     

A feasibility study of temperature rise measurement in a tissue phantom as an alternative way for characterization of the therapeutic high intensity focused ultrasonic field

The feasibility that temperature field measurements in vitro as an alternative way to characterize the high intensity focused ultrasound (HIFU) field used in therapeutic applications has been explored in a phantom study. Thermocouples (copper-constantan, diameter 0.125 mm) are embedded in a phantom filled with tissue mimicking material that simulates the thermal and acoustic properties of soft-tissue. The temperature rises as a function of ultrasound exposure time near the focus of a HIFU transducer (1.1 MHz, active radius a = 32 mm, geometric focal length = 62 mm) of various acoustic powers up to 30 W are measured and compared with predicted values using a simple nonlinear Gaussian model. The experimental results can be explained well by the model if no acoustic cavitation takes place. When the acoustic power become higher (>5 W) and the local temperature elevation >15 °C and the local temperature is >40 °C at the focal point, cavitation vapor bubbles appear. The presence of the cavitation bubbles may increase the temperature rise rate initially. The bubble aggregates may form along the beam axis under sonication and then eventually makes the temperature elevation reach a saturated value. When acoustic cavitation occurs, the bubble-assisted enhancement of the initial temperature rise (exposure time t < 2 s) can still be predicted by the theory.     

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.     

Sonodynamic therapy

Recently, there have been numerous reports on the application of non-thermal ultrasound energy for treating various diseases in combination with drugs. Furthermore, the introduction of microbubbles and nanobubbles as carriers/enhancers of drugs has added a whole new dimension to therapeutic ultrasound. Non-thermal mechanisms for effects seen include various forms of energy due to cavitation, acoustic streaming, micro jets and radiation force which increases possibilities for targeting tissue with drugs, enhancing drug effectiveness or even chemically activating certain materials. Examples such as enhancement of thrombolytic agents by ultrasound have proven to be beneficial for acute stroke patients and peripheral arterial occlusions. Non-invasive low intensity focused ultrasound in conjunction with anti-cancer drugs may help to reduce tumor size and lessen recurrence while reducing severe drug side effects. Chemical activation of drugs by ultrasound energy for treatment of atherosclerosis and tumors is another new field recently termed as “Sonodynamic therapy”. Lastly, advances in molecular imaging have aroused great expectations in applying ultrasound for both diagnosis and therapy simultaneously. Microbubbles or nanobubbles targeted at the molecular level will allow medical doctors to make a final diagnosis of a disease using ultrasound imaging and then immediately proceed to a therapeutic ultrasound treatment.