Nonlinear propagation acoustics of dual-frequency wide-band excitation pulses in a focused ultrasound system

In this article, acoustic propagation effects of dual-frequency wide-band excitation pulses in a focused ultrasound system are demonstrated in vitro. A designed and manufactured dual-frequency band annular array capable of transmitting 0.9/7.5 MHz center frequency wide-band pulses was used for this purpose. The dual-frequency band annular array, has been designed using a bi-layer piezo-electric stack. Water tank measurements demonstrate the function of the array by activating the low- and high-frequency layers individually and simultaneously. The results show that the array works as intended. Activating the low- and high-frequency layers individually, results in less than -50 dB signal level from the high- and low-frequency layers respectively. Activating both layers simultaneously, produce a well defined dual-frequency pulse. The presence of the low-frequency pulse leads to compression, expansion, and a time delay of the high-frequency pulse. There is a phase shift between the low- and high-frequency pulse as it propagates from the array to the focus. This makes the latter described effects also dependent on the array configuration. By varying the low-frequency pressure, a shift of up to 0.5 MHz in center frequency of a 8.0 MHz transmitted high-frequency pulse is observed at the array focus. The results demonstrate the high propagation complexity of dual-frequency pulses.     

Stable and transient bubble formation in acoustically-responsive scaffolds by acoustic droplet vaporization: theory and application in sequential release

Acoustically-responsive scaffolds (ARSs), which are fibrin hydrogels containing monodispersed perfluorocarbon (PFC) emulsions, respond to ultrasound in an on-demand, spatiotemporally-controlled manner via a mechanism termed acoustic droplet vaporization (ADV). Previously, ADV has been used to control the release of bioactive payloads from ARSs to stimulate regenerative processes. In this study, we used classical nucleation theory (CNT) to predict the nucleation pressure in emulsions of different PFC cores as well as the corresponding condensation pressure of the ADV-generated bubbles. According to CNT, the threshold bubble radii above which ADV-generated bubbles remain stable against condensation were 0.4 µm and 5.2 µm for perfluoropentane (PFP) and perfluorohexane (PFH) bubbles, respectively, while ADV-generated bubbles of any size in perfluorooctane (PFO) condense back to liquid at ambient condition. Additionally, consistent with the CNT findings, stable bubble formation from PFH emulsion was experimentally observed using confocal imaging while PFO emulsion likely underwent repeated vaporization and recondensation during ultrasound pulses. In further experimental studies, we utilized this unique feature of ADV in generating stable or transient bubbles, through tailoring the PFC core and ultrasound parameters (excitation frequency and pulse duration), for sequential delivery of two payloads from PFC emulsions in ARSs. ADV-generated stable bubbles from PFH correlated with complete release of the payload while transient ADV resulted in partial release, where the amount of payload release increased with the number of ultrasound exposure. Overall, these results can be used in developing drug delivery strategies using ARSs.     

Enhancement of heat transfer in forced convection by using dual low-high frequency ultrasound

Combined sonication with dual-frequency ultrasound has been investigated to enhance heat transfer in forced convection. The test section used for this study consists of a channel with, on one hand, heating blocks normal to the water flow, equipped with thermocouples, and, on the other hand, two ultrasonic emitters. One is facing the heating blocks, thus the ultrasonic field is perpendicular, and the second ultrasonic field is collinear to the water flow. Two types of ultrasonic waves were used: low-frequency ultrasound (25 kHz) to generate mainly acoustic cavitation and high-frequency ultrasound (2 MHz) well-known to induce Eckart’s acoustic streaming. A thermal approach was conducted to investigate heat transfer enhancement in the presence of ultrasound. This approach was completed with PIV measurements to assess the hydrodynamic behavior modifications under ultrasound. Sonochemiluminescence experiments were performed to account for the presence and the location of acoustic cavitation within the water flow. The results have shown a synergetic effect using combined low-and-high-frequency sonication. Enhancement of heat transfer is related to greater induced turbulence within the water flow by comparison with single-frequency sonication. However, the ultrasonically-induced turbulence is not homogeneously distributed within the water flow and the synergy effect on heat transfer enhancement depends mainly on the generation of turbulence along the heating wall. For the optimal configuration of dual-frequency sonication used in this work, a local heat transfer enhancement factor up to 366% was observed and Turbulent Kinetic Energy was enhanced by up to 84% when compared to silent regime.     

高频聚焦超声声场和温度场的仿真研究*

为探究临床常用的7 MHz高频聚焦超声在多层生物组织中的声传播以及毫秒级时间内的生物传热规律问题,基于Westervelt方程和Pennes传热方程,使用有限元方法建立高频聚焦超声辐照多层组织的非线性热黏性声传播及传热模型。首先分析了线性模型和非线性模型之间的差异,然后在非线性模型下探究换能器的参数对声场和温度场的影响。仿真结果显示：在7 MHz频率下,当换能器输出声功率超过5 W时,声波传播的非线性效应不可忽视(p <0.05);当声功率从5 W增大到15 W时,非线性模型与线性模型预测的温度偏差从20%增加到34.703%;高频聚焦超声波的非线性行为比低频更加显著,基频能量向高次谐波转移的程度增大,声功率为10 W和15 W时4次谐波与基波之比分别达到7.33%和12.12%;高频换能器参数的改变对组织中声场和温度场分布的影响较大,换能器焦距从12 mm减小到11.2 mm,焦点处最高温度增加了77%。结果表明,7 MHz聚焦超声的非线性声传播需要考虑到4次谐波的影响。该文提出的多层组织非线性仿真模型可为高频聚焦超声换能器参数优化及制定安全、有效的术前治疗方案提供理论参考。     

Single-transducer dual-frequency ultrasound generation to enhance acoustic cavitation

Dual- or multiple-frequency ultrasound stimulation is capable of effectively enhancing the acoustic cavitation effect over single-frequency ultrasound. Potential application of this sonoreactor design has been widely proposed such as on sonoluminescence, sonochemistry enhancement, and transdermal drug release enhancement. All currently available sonoreactor designs employed multiple piezoelectric transducers for generating single-frequency ultrasonic waves separately and then these waves were mixed and interfered in solutions. The purpose of this research is to propose a novel design of generating dual-frequency ultrasonic waves with single piezoelectric elements, thereby enhancing acoustic cavitation. Macroscopic bubbles were detected optically, and they were quantified at either a single-frequency or for different frequency combinations for determining their efficiency for enhancing acoustic cavitation. Visible bubbles were optically detected and hydrogen peroxide was measured to quantify acoustic cavitation. Test water samples with different gas concentrations and different power levels were used to determine the efficacy of enhancing acoustic cavitation of this design. The spectrum obtained from the backscattered signals was also recorded and examined to confirm the occurrence of stable cavitation. The results confirmed that single-element dual-frequency ultrasound stimulation can enhance acoustic cavitation. Under certain testing conditions, the generation of bubbles can be enhanced up to a level of five times higher than the generation of bubbles in single-frequency stimulation, and can increase the hydrogen peroxide production up to an increase of one fold. This design may serve as a useful alternative for future sonoreactor design owing to its simplicity to produce dual- or multiple-frequency ultrasound.     

Predicting initial nucleation events occurred in a metastable nanodroplet during acoustic droplet vaporization

Acoustic droplet vaporization (ADV) capable of converting liquid perfluorocarbon (PFC) micro/nanodroplets into gaseous microbubbles has gained much attention due to its medical potentials. However, its physical mechanisms for nanodroplets have not been well understood due to the disappeared superharmonic focusing effect and the prominent Laplace pressure compared to microdroplets, especially for the initial ADV nucleation occurring in a metastable PFC nanodroplet. The classical nucleation theory (CNT) was modified to describe the ADV nucleation via combining the phase-change thermodynamics of perfluoropentane (PFP) and the Laplace pressure effect on PFP nanodroplets. The thermodynamics was exactly predicted by the Redlich–Kwong equation of state (EoS) rather than the van der Waals EoS, based on which the surface tension of the vapor nucleus as a crucial parameter in the CNT was successfully obtained to modify the CNT. Compared to the CNT, the modified CNT eliminated the intrinsic limitations of the CNT, and it predicted a larger nucleation rate and a lower ADV nucleation threshold, which agree much better with experimental results. Furthermore, it indicated that the nanodroplet properties exert very strong influences on the nucleation threshold instead of the acoustic parameters, providing a potential strategy with an appropriate droplet design to reduce the ADV nucleation threshold. This study may contribute to further understanding the ADV mechanism for PFC nanodroplets and promoting its potential theranostic applications in clinical practice.     

Effect of exposure parameters on cavitation induced by low-level dual-frequency ultrasound

In order to quantify the effects of exposure parameters under therapeutic conditions such as sonodynamic therapy, it is necessary initially to evaluate the inertial cavitation activity in vitro. In this study, the dependence of cavitation activity induced by the low-level dual-frequency ultrasound irradiation on exposure parameters has been studied. Experiments were performed in the near 150 kHz and 1 MHz fields in the progressive wave mode. It has been shown that at constant ultrasound energy the fluorescence intensity for continuous sonication is higher than for pulsed mode. With increasing the duty cycle of pulsed field, the inertial cavitation activity is increased. The activity of cavitation produced by simultaneous combined sonication by two ultrasound fields is remarkably higher than the algebraic sum of effects produced by fields separately (p-value < 0.05). This study shows that simultaneous combined dual-frequency ultrasound sonication in continuous mode is more effective in producing inertial cavitation activity at low-level intensity. Therefore, it is concluded that investigations in this combined ultrasound sonication can be useful in sonodynamic therapy for superficial tumors.     

Sonochemical reactions at 640 kHz using an efficient reactor. Oxidation of potassium iodide

Ultrasound can be used to oxidize aqueous pollutants. However, due to economic reasons higher oxidation/destruction rates and higher energy efficiency are needed. Recent studies suggest that the higher ultrasound frequencies provide better oxidation rates than the conventional 20 kHz. Another area for improvement is reactor configuration. We have tested two new reactor configurations with proper focusing and reflection of ultrasound for maximum utilization. Reactor configuration plays an important role in the overall efficiency. In the new reactors, transducers and reaction mixture are separated by a polymer acoustic window which allows efficient transfer of ultrasound energy and not the heat from the transducer to the reaction mixture. One reactor at 640 kHz provides a 100% enhancement over the best reported rate for the oxidation of potassium iodide, on a per-Watt basis. Experiments conducted at varying initial KI concentrations show interesting behavior. Increasing the KI concentration by over eight fold merely increases the iodine production rate by two fold. This suggests that in the oxidation region surrounding the bubble, the KI concentration is much different than in the bulk. It is proposed that the hydrophobic bubble region has lower and near saturation KI concentration.     

The affection on the tissue lesions of difference frequency in dual-frequency high-intensity focused ultrasound (HIFU)

The lesions induced by dual-frequency high-intensity focused ultrasound (HIFU) in freshly excised porcine livers were investigated and compared with the lesions induced by conventional single-frequency HIFU. The results have shown that using different exposure time resulted in lesions of different sizes in both dual-frequency and single-frequency HIFU modes at the same intensity level (ISAL = 808 W cm(-2)), but the dimensions of lesions in dual-frequency mode were obviously larger than those in single-frequency mode. A much possible explanation was suggested for the results and the possibilities of applications in the future were also discussed in brief.     

双锥型五模材料低频声波调控及参数设计

为有效控制噪声并进行声波调控,构造了双锥区域为TC4钛合金、节点区域为硫化橡胶的六边形排列双锥五模材料,进行能带分析发现其具有较窄的低频声子带隙和单模传输区域。为提高五模材料的低频声波调控性能,设计了正方形和三角形排列构型,结果表明三角形排列的双锥五模材料带隙的频率更低,带宽更宽,且具有单模传输性能和较好的五模特性。此外分别探究了五模材料构型的材料参数(包括双锥区和节点区的密度、泊松比和杨氏模量)以及几何参数(包括双锥宽和节点半径的变化)对带隙及单模传输区域的影响,得到带隙和单模传输区的变化规律,选择密度较轻的填充材料、较小的双锥宽和较大的节点半径不仅可以提高低频声波调控性能,而且可以降低结构质量,提高结构的稳定性。该文结果对用于低频声波传播调控的五模材料的构型和参数的设计具有一定的借鉴意义。     

Spatial and temporal observation of phase-shift nano-emulsions assisted cavitation and ablation during focused ultrasound exposure

Background: Phase-shift nano-emulsions (PSNEs) with a small initial diameter in nanoscale have the potential to leak out of the blood vessels and to accumulate at the target point of tissue. At desired location, PSNEs can undergo acoustic droplet vaporization (ADV) process, change into gas bubbles and enhance focused ultrasound efficiency. The threshold of droplet vaporization and influence of acoustic parameters have always been research hotspots in order to spatially control the potential of bioeffects and optimize experimental conditions. However, when the pressure is much higher than PSNEs’ vaporization threshold, there were little reports on their cavitation and thermal effects.Object: In this study, PSNEs induced cavitation and ablation effects during pulsed high-intensity focused ultrasound (HIFU) exposure were investigated, including the spatial and temporal information and the influence of acoustic parameters.Methods: Two kinds of tissue-mimicking phantoms with uniform PSNEs were prepared because of their optical transparency. The Sonoluminescence (SL) method was employed to visualize the cavitation activities. And the ablation process was observed as the heat deposition could produce white lesion.Results: Precisely controlled HIFU cavitation and ablation can be realized at a relatively low input power. But when the input power was high, PSNEs can accelerate cavitation and ablation in pre-focal region. The cavitation happened layer by layer advancing the transducer. While the lesion appeared to be separated into two parts, one in pre-focal region stemmed from one point and grew quickly, the other in focal region grew much more slowly. The influence of duty cycle has also been examined. Longer pulse off time would cause heat transfer to the surrounding media, and generate smaller lesion. On the other hand, this would give outer layer bubbles enough time to dissolve, and inner bubbles can undergo violent collapse and emit bright light.     

Effects of nonlinear propagation, cavitation, and boiling in lesion formation by high intensity focused ultrasound in a gel phantom

The importance of nonlinear acoustic wave propagation and ultrasound-induced cavitation in the acceleration of thermal lesion production by high intensity focused ultrasound was investigated experimentally and theoretically in a transparent protein-containing gel. A numerical model that accounted for nonlinear acoustic propagation was used to simulate experimental conditions. Various exposure regimes with equal total ultrasound energy but variable peak acoustic pressure were studied for single lesions and lesion stripes obtained by moving the transducer. Static overpressure was applied to suppress cavitation. Strong enhancement of lesion production was observed for high amplitude waves and was supported by modeling. Through overpressure experiments it was shown that both nonlinear propagation and cavitation mechanisms participate in accelerating lesion inception and growth. Using B-mode ultrasound, cavitation was observed at normal ambient pressure as weakly enhanced echogenicity in the focal region, but was not detected with overpressure. Formation of tadpole-shaped lesions, shifted toward the transducer, was always observed to be due to boiling. Boiling bubbles were visible in the gel and were evident as strongly echogenic regions in B-mode images. These experiments indicate that nonlinear propagation and cavitation accelerate heating, but no lesion displacement or distortion was observed in the absence of boiling.     

Flow boiling heat transfer enhancement under ultrasound field in minichannel heat sinks

The enhancement of the heat transfer assisted by ultrasound is considered to be an interesting and highly efficient cooling technology, but the investigation and application of ultrasound in minichannel heat sinks to strengthen the flow boiling heat transfer are very limited. Herein, a novel installation of ultrasound transducers in the flow direction of a minichannel heat sink is designed to experimentally study the characteristics of heat transfer in flow boiling and the influence of operation parameters (e.g., heat flux, mass flux rate) and ultrasound parameters (e.g., frequency, power) on the flow boiling heat transfer in a minichannel heat sink with and without ultrasound field. Bubble motion and flow pattern in the minichannel are analyzed by high-speed flow visualization, revealing that the ultrasound field induces more bubbles at the same observation position and a forward shift of the onset of nucleation boiling along the flow direction, as ultrasonic cavitation produces a large number of bubbles. Moreover, bubbles hitting the channel wall on the left and right sides are found, and the motion speed of the bubbles is increased by 31.9% under the ultrasound field. Our results demonstrate that the heat transfer coefficient obtained under the ultrasound field is 53.9% higher than in the absence of the ultrasound field under the same conditions, and the enhancement ratio is decreased in the high heat flux region due to the change of the flow regime with increasing heat flux. This study provides a theoretical basis for the application of an ultrasound field in minichannel heat sinks for the enhancement of flow boiling heat transfer.     

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。      

超声激发声信号幅值实时监测HIFU焦域组织损伤*

聚焦超声消融肿瘤过程中的损伤实时监测是临床治疗面临的一个关键难题,双频聚焦超声不仅能提高治疗效率,且能在共焦区域激发出声信号,该声信号的幅值、频率等信息与焦域组织的机械和声学特性紧密相关。本文构建了一种双频聚焦超声治疗及组织损伤实时监测系统。该系统在聚焦超声辐照离体组织过程中,通过外部水听器接收双频激发的组织声发射信号,并通过上位机进行高速数据采集、数字滤波、时频处理等,分析声发射信号幅值与离体组织损伤之间的变化规律。实验研究结果表明：随着焦域组织损伤的形成,其弹性等声学特征发生改变,导致声发射信号幅值逐渐降低,表明声发射信号幅值的变化可较好地反映靶组织声学特征和结构的变化,从而实现聚焦超声治疗中靶组织损伤的实时监测。本文提出的监测方案相比传统超声影像监控更灵敏,有望为聚焦超声临床治疗中的组织损伤监控提供一种新的实时监测方案和手段。     

Numerical investigation of acoustic vaporization threshold of microdroplets

A numerical model is presented for the acoustic vaporization threshold of a dodecafluoropentane (or perfluoropentane) microdroplet. The model is based on the Rayleigh-Plesset equation and is improved by properly treating the supercritical state that occurs when a bubble collapses rapidly and by employing the van der Waals equation of state to consider the supercritical state. The present computations demonstrate that the microdroplet vaporization behavior depends intricately on bubble compressibility, liquid inertia and phase-change heat transfer under acoustic excitation conditions. We present acoustic pressure-frequency diagrams for bubble growth regimes and the ADV threshold conditions. The effects of acoustic parameters, fluid properties and the droplet radius on the ADV threshold are investigated.     

Energetic study of ultrasonic wettability enhancement

Many industrial and biological interfacial processes, such as welding and breathing depend directly on wettability and surface tension phenomena. The most common methods to control the wettability are based on modifying the properties of the fluid or the substrate. The present work focuses on the use of high-frequency acoustic waves (ultrasound) for the same purpose. It is well known that ultrasound can effectively clean a surface by acoustic cavitation, hence ultrasonic cleaning technology. Besides the cleaning process itself, many authors have observed an important wettability enhancement when liquids are exposed to low and high (ultrasonic) frequency vibration. Ultrasound goes one step further as it can instantly adjust the contact angle by tuning the vibration amplitude, but there is still a lack of comprehension about the physical principles that explain this phenomenon. To shed light on it, a thermodynamic model describing how ultrasound decreases the contact angle in a three-phase wetting system has been developed. Moreover, an analytical and experimental research has been carried out in order to demonstrate that ultrasound is an important competitor to surfactants in terms of energy efficiency and environmental friendliness.     

Lysinoalanine formation and conformational characteristics of rice dreg protein isolates by multi-frequency countercurrent S-type sonochemical action

The influences of multi-frequency countercurrent S-type ultrasound (MFSU), with various frequency modes, on lysinoalanine (LAL) formation and conformational characteristics of rice dreg protein isolates (RDPI) were investigated. The ultrasonic operating mode with dual-frequency combination (20/40 kHz) indicated lower LAL content and higher protein dissolution rate of RDPI compared with that of other ultrasound operating modes. Under the dual-frequency ultrasound mode of 20/40 kHz, acoustic power density of 60 W/L, time of 20 min, and temperature of 35 °C, the relative reduction rate of LAL of RDPI reached the highest with its value of 26.95%, and the protein dissolution rate was 71.87%. The changes in chemical interactions between protein molecules indicated that hydrophobic interactions and disulfide bonds played a considerable role in the formation of LAL of RDPI, especially the reduction of g-g-g and g-g-t disulfide bond. Alterations in microstructure showed that ultrasonication loosened the protein structure and created more uniform protein fragments of RDPI. In conclusion, using MFSU in treating RDPI was an efficacious avenue for minimizing LAL content and modifying the conformational characteristics of RDPI.     

Simulation of the acoustic field emitted from medical linear transducer in a heterogeneous tissue

A numerical model is developed to simulate the acoustic field in heterogeneous tissue from a medical linear transducer.The coupled full-wave equation for nonlinear ultrasound is solved using a staggered-grid finite difference time domain method.The distribution of acoustic pressure and power in human abdominal wall with heterogeneities in sound speed,density,and nonlinear parameter are obtained.Compared with homogeneous medium,when sound speed in tissue is uniform and density unchanged,the acoustic energy decreases only1.8 dB in the focal region;when density in tissue is uniform and sound speed unchanged,the energy decreases 3.8 dB in the focal region,which is almost the same as heterogeneous tissue.Thus,the primary factor of the aberration of focused beam is the heterogeneous distribution of the tissue sound speed.     

应用角谱方法研究聚焦声束在层状生物组织中的非线性声传播

应用角谱方法理论研究了聚焦声束在层状生物组织中的非线性传播特性，将声波分解为角谱，可计算垂直于声轴的任意平面的非线性声场。在圆形平面活塞聚焦换能器的焦区中插入多种生物组织样品，数值计算了样品内部及外部的二次谐波声场，并通过实验测量验证了理论方法的有效性。基于快速傅氏变换的角谱方法可直观地描述非线性声传播，对非线性声成像有指导作用。