A forward model and conjugate gradient inversion technique for low-frequency ultrasonic imaging

Emerging methods of hyperthermia cancer treatment require noninvasive temperature monitoring, and ultrasonic techniques show promise in this regard. Various tomographic algorithms are available that reconstruct sound speed or contrast profiles, which can be related to temperature distribution. The requirement of a high enough frequency for adequate spatial resolution and a low enough frequency for adequate tissue penetration is a difficult compromise. In this study, the feasibility of using low frequency ultrasound for imaging and temperature monitoring was investigated. The transient probing wave field had a bandwidth spanning the frequency range 2.5-320.5 kHz. The results from a forward model which computed the propagation and scattering of low-frequency acoustic pressure and velocity wave fields were used to compare three imaging methods formulated within the Born approximation, representing two main types of reconstruction. The first uses Fourier techniques to reconstruct sound-speed profiles from projection or Radon data based on optical ray theory, seen as an asymptotical limit for comparison. The second uses backpropagation and conjugate gradient inversion methods based on acoustical wave theory. The results show that the accuracy in localization was 2.5 mm or better when using low frequencies and the conjugate gradient inversion scheme, which could be used for temperature monitoring.     

Theoretical prediction of the scattering of spherical bubble clusters under ultrasonic excitation

Due to the nonlinear vibration of ultrasound contrast agent bubbles, a nonlinear scattered sound field will be generated when bubbles are driven by ultrasound. A bubble cluster consists of numerous bubbles gathering in a spherical space. It has been noted that the forward scattering of a bubble cluster is larger than its backscattering, and some studies have experimentally found the angular dependence of a bubble cluster’s scattering signal. In this paper, a theory is proposed to explain the difference of acoustic scattering at different directions of a bubble cluster when it is driven by ultrasound, and predicts the angular distribution of scattered acoustic pressure under different parameters. The theory is proved to be correct under circumstances of small clusters and weak interactions by comparing theoretical results with numerical simulations. This theory not only sheds light on the physics of bubble cluster scattering, but also may contribute to the improvement of ultrasound imaging technology, including ultrasonic harmonic imaging and contrast-enhanced ultrasonography.     

Difference-frequency ultrasound generation from microbubbles under dual-frequency excitation

The difference-frequency (DF) ultrasound generated by using parametric effect promises to improve detection depth owing to its low attenuation, which is beneficial for deep tissue imaging. With ultrasound contrast agents infusion, the harmonic components scattered from the microbubbles, including DF, can be generated due to the nonlinear vibration. A theoretical study on the DF generation from microbubbles under the dual-frequency excitation is proposed in formula based on the solution of the RPNNP equation. The optimisation of the DF generation is discussed associated with the applied acoustic pressure, frequency, and the microbubble size. Experiments are performed to validate the theoretical predictions by using a dual-frequency signal to excite microbubbles. Both the numerical and experimental results demonstrate that the optimised DF ultrasound can be achieved as the difference frequency is close to the resonance frequency of the microbubble and improve the contrast-to-tissue ratio in imaging.     

FDTD simulation of finite-amplitude pressure and temperature fields for biomedical ultrasound.

Full wave simulations provide a valuable tool for studying the spatial and temporal nature of an acoustic field. One method for producing such simulations is the finite-difference time-domain (FDTD) method. This method uses discrete differences to approximate derivatives in the governing partial differential equations. We used the FDTD method to model the propagation of finite-amplitude sound in a homogeneous thermoviscous fluid. The calculated acoustic pressure field was then used to compute the transient temperature rise in the fluid; the heating results from absorption of acoustic energy by the fluid. As an example, the transient temperature field was calculated in biological tissue in response to a pulse of focused ultrasound. Enhanced heating of the tissue from finite-amplitude effects was observed. The excess heating was attributed to the nonlinear generation of higher-frequency harmonics which are absorbed more readily than the fundamental. The effect of nonlinear distortion on temperature rise in tissue was observed to range from negligible at 1 MPa source pressure to an 80% increase in temperature elevation at 10 MPa source pressure.     

基于声透镜成像系统的光声层析成像

光声成像是采用“光激发-超声波成像”的新型成像技术，它是检测强散射介质内部光吸收分布的一种有效医学影像技术.用短脉冲激光照射强散射介质(如生物组织)，强散射介质由于光声效应产生超声信号，使用具有成像能力的声透镜把声压分布成像于像面上，然后利用具有空间分辨能力的阵列光声传感器，把同一像面上的光声信号强度记录下来，最后根据光声信号强度的空间分布进行图像重组.根据成像系统物像共轭原理，同一物平面的光声信号到达像面的时延相等，而不同物面的光声信号到达同一个探测器平面的时延各不相同，因此，利用BOXCAR的门控积分 关键词： 光声层析成像 声透镜 光声信号     

多参量光声成像及其在生物医学领域的应用

光声成像兼具声学成像和光学成像两者的优点, 因而成为近十年来发展最迅速的生物医学成像技术之一. 本文介绍了光声成像的特点及其相对于广泛应用的光学成像技术和声学成像技术的优点; 其次, 解释了光声成像的成像原理, 在此基础上介绍了光声断层成像和光声显微镜这两种典型的光声成像方案, 并介绍了它们的技术特点; 然后, 介绍了光声成像对生物组织的生化特性、组织力学特性、血液流速分布、温度分布参数、微结构特性等多信息参量的提取能力, 及其在生物系统的结构成像、功能成像、代谢成像、分子成像、基因成像等多领域的应用; 最后, 展望了光声成像在生物医学领域的应用潜力并讨论了其局限性.     

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。     

Modelling of nonlinear effects and the response of ultrasound contrast micro bubbles: simulation and experiment

The propagation of diagnostic ultrasonic imaging pulses in tissue and their interaction with contrast micro bubbles is a very complex physical process, which we assumed to be separable into three stages: pulse propagation in tissue, the interaction of the pulse with the contrast bubble, and the propagation of the scattered echo. The model driven approach is used to gain better knowledge of the complex processes involved. A simplified way of field simulation is chosen due to the complexity of the task and the necessity to estimate comparative contributions of each component of the process. Simulations are targeted at myocardial perfusion estimation. A modified method for spatial superposition of attenuated waves enables simulations of low intensity pulse pressure fields from weakly focused transducers in a nonlinear, attenuating, and liquid-like biological medium. These assumptions enable the use of quasi-linear calculations of the acoustic field. The simulations of acoustic bubble response are carried out with the Rayleigh-Plesset equation with the addition of radiation damping. Theoretical simulations with synthesised and experimentally sampled pulses show that the interaction of the excitation pulses with the contrast bubbles is the main cause of nonlinear scattering, and a 2-3 dB increase of second harmonic amplitude depends on nonlinear distortions of the incident pulse.     

In vivo biomicroscopy with ultrasound 2

In the first article of this series it was shown that the use of inverse scattering theory to analyse ultrasound reflections could provide high resolution images of the acoustic impedance profile of the retina. Unlike the retina, most tissue structures of interest, like small tumours and arterial plaque deposits, are shielded from view by intervening layers of tissue of appreciable acoustic impedance and attenuation. By analysing a one-dimensional model for a plaque deposit on the wall of a carotid artery embedded in a 5 cm thick layer of tissue, we demonstrate that a relatively high quality image can be recovered when compensation for the attenuation of the intervening tissue is made. We observe that because of the dearth of low frequency power in the recovered signal of ultrasound transducers, it is important that the field of view imaged is not taken to be too large. We compare the exact iterative distorted wave Born approximation inverse scattering method with the approximate but computationally faster plane wave Born approximation method and find that they give images of comparable quality for this model.     

Intense acoustic bursts as a signal-enhancement mechanism in ultrasound-modulated optical tomography

Biophotonic imaging with ultrasound-modulated optical tomography (UOT) promises ultrasonically resolved imaging in biological tissues. A key challenge in this imaging technique is a low signal-to-noise ratio (SNR). We show significant UOT signal enhancement by using intense time-gated acoustic bursts. A CCD camera captured the speckle pattern from a laser-illuminated tissue phantom. Differences in speckle contrast were observed when ultrasonic bursts were applied, compared with when no ultrasound was applied. When CCD triggering was synchronized with burst initiation, acoustic-radiation-force-induced displacements were detected. To avoid mechanical contrast in UOT images, the CCD camera acquisition was delayed several milliseconds until transient effects of acoustic radiation force attenuated to a satisfactory level. The SNR of our system was sufficiently high to provide an image pixel per acoustic burst without signal averaging. Because of the substantially improved SNR, the use of intense acoustic bursts is a promising signal enhancement strategy for UOT.     

Resonance frequencies of lipid-shelled microbubbles in the regime of nonlinear oscillations

Knowledge of resonant frequencies of contrast microbubbles is important for the optimization of ultrasound contrast imaging and therapeutic techniques. To date, however, there are estimates of resonance frequencies of contrast microbubbles only for the regime of linear oscillation. The present paper proposes an approach for evaluating resonance frequencies of contrast agent microbubbles in the regime of nonlinear oscillation. The approach is based on the calculation of the time-averaged oscillation power of the radial bubble oscillation. The proposed procedure was verified for free bubbles in the frequency range 1-4 MHz and then applied to lipid-shelled microbubbles insonified with a single 20-cycle acoustic pulse at two values of the acoustic pressure amplitude, 100 kPa and 200 kPa, and at four frequencies: 1.5, 2.0, 2.5, and 3.0 MHz. It is shown that, as the acoustic pressure amplitude is increased, the resonance frequency of a lipid-shelled microbubble tends to decrease in comparison with its linear resonance frequency. Analysis of existing shell models reveals that models that treat the lipid shell as a linear viscoelastic solid appear may be challenged to provide the observed tendency in the behavior of the resonance frequency at increasing acoustic pressure. The conclusion is drawn that the further development of shell models could be improved by the consideration of nonlinear rheological laws.     

超声造影剂微泡非线性动力学响应的机理及相关应用

随着生命科学及现代医学的发展, 一体化无创精准诊疗已经日益成为人们关注的焦点问题, 而关于超声造影剂微泡的非线性效应的相关机理、动力学建模及其在超声医学领域中的应用研究也得到了极大的推动. 本文对下列课题进行了总结和讨论, 包括: 1)基于Mie散射技术和流式细胞仪对造影剂微泡参数进行定征的一体化解决方案; 2)通过对微泡包膜的黏弹特性进行非线性修正, 构建新的包膜微泡动力学模型; 3)探索造影剂惯性空化阈值与其包膜参数之间的相关性; 以及4)研究超声联合造影剂微泡促进基因/药物转染效率并有效降低其生物毒性的相关机理.     

Interaction of a high-order Bessel beam with a submerged spherical ultrasound contrast agent shell - Scattering theory

Background and objective

Acoustic scattering properties of ultrasound contrast agents are useful in extending existing or developing new techniques for biomedical imaging applications. A useful first step in this direction is to investigate the acoustic scattering of a new class of acoustic beams, known as helicoidal high-order Bessel beams, to improve the understanding of their scattering characteristics by an ultrasound contrast agent, which at present is very limited.

Method

The transverse acoustic scattering of a commercially available albuminoidal ultrasound contrast agent shell filled with air or a denser gas such as perfluoropropane and placed in a helicoidal Bessel beam of any order is examined numerically. The shell is assumed to possess an outer radius a = 3.5 microns and a thickness of ∼105 nm. Moduli of the total and resonance transverse acoustic scattering form functions are numerically evaluated in the bandwidth 0 < ka? 3, which corresponds to a frequency bandwidth of 0-205 MHz that covers a wide range of applications for imaging with contrast agents. Particular attention is paid to the shell’s material, the content of its interior hollow region and the fluid surrounding its exterior. The contrast agent shell is assumed to be immersed in an ideal compressible fluid so the viscous corrections are not considered. Analytical equations are derived and numerical calculations of the total and resonance form functions are performed with particular emphasis on the effect of varying the half-cone angle, the order of the helicoidal Bessel beam as well as the fluid that fills the interior hollow space.

Results and conclusion

It is shown that shell wave resonance modes can be excited on an encapsulated micro-bubble. The forward and backscattering vanish for a helicoidal high-order Bessel beam. Additionally, the fluid filling the inner core affects the shell’s response significantly. Moreover, there is no monopole contribution to the axial scattering of a helicoidal Bessel beam of order m ? 1 so that the dynamics of contrast agents would be significantly altered. The main finding of the present theory is the suppression or enhancement for a particular resonance that may be used to advantage in imaging with ultrasound contrast agents for clinical applications.     

Theoretical Analysis of Shear Wave Interference Patterns by Means of Dynamic Acoustic Radiation Forces

Acoustic radiation forces associated with high intensity focused ultrasound stimulate shear wave propagation allowing shear wave speed and shear viscosity estimation of tissue structures. As wave speeds are meters per second, real time displacement tracking over an extend field-of-view using ultrasound is problematic due to very high frame rate requirements. However, two spatially separated dynamic external sources can stimulate shear wave motion leading to shear wave interference patterns. Advantages are shear waves can be imaged at lower frame rates and local interference pattern spatial properties reflect tissue's viscoelastic properties. Here a theoretical analysis of shear wave interference patterns by means of dynamic acoustic radiation forces is detailed. Using a viscoelastic Green's function analysis, tissue motion due to a pair of focused ultrasound beams and associated radiation forces are presented. Overall, this paper theoretically demonstrates shear wave interference patterns can be stimulated using dynamic acoustic radiation forces and tracked using conventional ultrasound imaging.     

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.     

Bubble nonlinear dynamics and stimulated scattering process

A complete understanding of the bubble dynamics is deemed necessary in order to achieve their full potential applications in industry and medicine. For this purpose it is first needed to expand our knowledge of a single bubble behavior under different possible conditions including the frequency and pressure variations of the sound field. In addition, stimulated scattering of sound on a bubble is a special effect in sound field, and its characteristics are associated with bubble oscillation mode. A bubble in liquid can be considered as a representative example of nonlinear dynamical system theory with its resonance, and its dynamics characteristics can be described by the Keller–Miksis equation. The nonlinear dynamics of an acoustically excited gas bubble in water is investigated by using theoretical and numerical analysis methods. Our results show its strongly nonlinear behavior with respect to the pressure amplitude and excitation frequency as the control parameters, and give an intuitive insight into stimulated sound scattering on a bubble. It is seen that the stimulated sound scattering is different from common dynamical behaviors, such as bifurcation and chaos, which is the result of the nonlinear resonance of a bubble under the excitation of a high amplitude acoustic sound wave essentially. The numerical analysis results show that the threshold of stimulated sound scattering is smaller than those of bifurcation and chaos in the common condition.     

A contrast source method for nonlinear acoustic wave fields in media with spatially inhomogeneous attenuation

Experimental data reveals that attenuation is an important phenomenon in medical ultrasound. Attenuation is particularly important for medical applications based on nonlinear acoustics, since higher harmonics experience higher attenuation than the fundamental. Here, a method is presented to accurately solve the wave equation for nonlinear acoustic media with spatially inhomogeneous attenuation. Losses are modeled by a spatially dependent compliance relaxation function, which is included in the Westervelt equation. Introduction of absorption in the form of a causal relaxation function automatically results in the appearance of dispersion. The appearance of inhomogeneities implies the presence of a spatially inhomogeneous contrast source in the presented full-wave method leading to inclusion of forward and backward scattering. The contrast source problem is solved iteratively using a Neumann scheme, similar to the iterative nonlinear contrast source (INCS) method. The presented method is directionally independent and capable of dealing with weakly to moderately nonlinear, large scale, three-dimensional wave fields occurring in diagnostic ultrasound. Convergence of the method has been investigated and results for homogeneous, lossy, linear media show full agreement with the exact results. Moreover, the performance of the method is demonstrated through simulations involving steered and unsteered beams in nonlinear media with spatially homogeneous and inhomogeneous attenuation.     

Ultrasonic bubbles in medicine: influence of the shell

Ultrasound contrast agents consist of microscopically small bubbles encapsulated by an elastic shell. These microbubbles oscillate upon ultrasound insonification, and demonstrate highly nonlinear behavior, ameliorating their detectability. (Potential) medical applications involving the ultrasonic disruption of contrast agent microbubble shells include release-burst imaging, localized drug delivery, and noninvasive blood pressure measurement. To develop and enhance these techniques, predicting the cracking behavior of ultrasound-insonified encapsulated microbubbles has been of importance. In this paper, we explore microbubble behavior in an ultrasound field, with special attention to the influence of the bubble shell. A bubble in a sound field can be considered a forced damped harmonic oscillator. For encapsulated microbubbles, the presence of a shell has to be taken into account. In models, an extra damping parameter and a shell stiffness parameter have been included, assuming that Hooke's Law holds for the bubble shell. At high acoustic amplitudes, disruptive phenomena have been observed, such as microbubble fragmentation and ultrasonic cracking. We analyzed the occurrence of ultrasound contrast agent fragmentation, by simulating the oscillating behavior of encapsulated microbubbles with various sizes in a harmonic acoustic field. Fragmentation occurs exclusively during the collapse phase and occurs if the kinetic energy of the collapsing microbubble is greater than the instantaneous bubble surface energy, provided that surface instabilities have grown big enough to allow for break-up. From our simulations it follows that the Blake critical radius is not a good approximation for a fragmentation threshold. We demonstrated how the phase angle differences between a damped radially oscillating bubble and an incident sound field depend on shell parameters.     

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。     

Improved contrast to tissue ratio at higher harmonics

The challenge in ultrasound contrast imaging is a better discrimination between the perfused tissue and the contrast bubbles, which is usually expressed by contrast to tissue ratio (CTR). Imaging based on the second harmonic frequency showed a higher CTR than imaging at the fundamental frequency. However, because of nonlinear propagation of ultrasound waves, harmonic frequencies are generated. These harmonic frequencies will be linearly reflected by the tissue and therefore limit the CTR at the second harmonic frequency. In order to reduce the scattering of tissue at harmonic frequencies and by that increase the CTR, nonlinear distortion has to be reduced. We demonstrate in this study that the CTR increases with the harmonic number. The increase is substantial when transmitting at lower frequencies. To take advantage of the higher harmonics (third, fourth, fifth and the ultraharmonics and termed here super harmonics), we have developed a new phased array transducer with a wide frequency band. In-vitro measurements using the new probe show an increase of 40 dB of the CTR for super harmonic components over the conventional second harmonic system. The increase in CTR is in agreement with the calculations using existing models for the response of encapsulated bubbles and known theory of nonlinear propagation.