Frequency relationships for ultrasonic activation of free microbubbles, encapsulated microbubbles, and gas-filled micropores.

The ultrasonic activation of free microbubbles, encapsulated microbubbles, and gas-filled micropores was explored using available linear theory. Encapsulated microbubbles, used in contrast agents for diagnostic ultrasound, have relatively high resonance frequencies and damping. At 2 MHz the resonance radii are 1.75 microns for free microbubbles, 4.0 microns for encapsulated microbubbles, and 1.84 microns for gas-filled micropores. Higher-pressure amplitudes are needed to elicit equivalent subharmonic, fundamental, or second-harmonic responses from the encapsulated microbubbles, and this behavior increases for higher frequencies. If an encapsulated microbubble becomes destabilized during exposure,the resulting liberated microbubble would be about twice the linear resonance size, which would be likely to produce subharmonic signals. Scattered signals used for medical imaging purposes may be indicative of bioeffects potential: The second harmonic signal is proportional to local shear stress for a microbubble on a boundary, and a strong subharmonic signal may imply destabilization and nucleation of free-microbubble cavitation activity. The potential for bioeffects from contrast agent gas bodies decreases rapidly with increasing frequency. This information should be valuable for understanding of the etiology of bioeffects related to contrast agents and for developing exposure indices and risk management strategies for their use in diagnostic ultrasound.     

Subharmonic imaging of contrast agents

Ultrasound contrast agents promise to improve the sensitivity and specificity of diagnostic ultrasound imaging. It is of great importance to adapt ultrasound equipment for optimal use with contrast agents e.g., by exploiting the nonlinear properties of the contrast microbubbles. Harmonic imaging is one technique that has been extensively studied and is commercially available. However, harmonic imaging is associated with problems, due to second harmonic generation and accumulation within the tissue itself. Given the lack of subharmonic generation in tissue, one alternative is the creation of subharmonic images by transmitting at the fundamental frequency (fo) and receiving at the subharmonic (fo/2). Subharmonic imaging should have a much better lateral resolution and may be suitable for scanning deep-lying structures owing to the higher transmit frequency and the much smaller attenuation of scattered subharmonic signals. In this paper, we will review different aspects of subharmonic imaging including implementation, in-vitro gray-scale imaging and subharmonic aided pressure estimation.     

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.     

生物组织成像中用反相位脉冲技术提高二次谐波信噪比的研究

本文基于有限振幅声波在介质中的非线性传播理论,分析了反相位脉冲技术对生物组织中二次谐波增强的原理.实验中利用反相位脉冲激发超声换能器,对生物组织中传播的非线性信号相加分析.结果表明反相位脉冲技术可有效抑制基波及奇次谐波信号,而可增强偶次谐波信号6dB.与滤波器滤波法相比,反相位脉冲技术在抑制基波信号的同时,可有效地提高二次谐波的信噪比,因而在生物组织的二次谐波成像中具有广阔的应用前景.     

Experimental investigation of the pulse inversion technique for imaging ultrasound contrast agents

The application of ultrasound contrast agents aims to detect low velocity blood flow in the microcirculation. To enhance discrimination between tissue and blood containing the contrast agent, harmonic imaging is used. Harmonic imaging requires the application of narrow-band signals and is obscured by high levels of native harmonics generated in an intervening medium. To improve discrimination between contrast agent and native harmonics, a pulse inversion technique has been proposed. Pulse inversion allows wide-band signals, thus preserving the axial resolution. The present study examines the interference of native harmonics and discusses the practical difficulties of wide-band pulse inversion measurements of harmonics by a single transducer. Native harmonics are not eliminated by pulse inversion. Furthermore, only even harmonics remain and are amplified by 6 dB, alleviating the requirement for selective filtering. Finally, it is shown that the contaminating third harmonic contained in the square wave activation signal leaks through in the emitted signal. The spectral location of the contaminating third harmonic is governed by the transducer spectral characteristics while the location of the native and contrast agent second harmonics is not. Thus the contaminating third harmonic and the native and contrast agent second harmonics may overlap and interfere. Optimal discrimination requires a balance between maximal sensitivity for the second harmonic at reception and minimal interference from the contaminating third harmonic.     

基于反相位脉冲技术的生物组织谐波成像研究

理论及实验研究了反相位脉冲技术在生物组织二次谐波成像中的应用。结合有限振幅声波的非线性传播理论,从理论上证明了反相位脉冲技术可有效抑制基波信号,同时二次谐波信号增强两倍,轴向及径向声场的实验测量结果基波被抑制30~50dB,二次谐波提高6dB,与理论相符。建立了相应的成像系统,对若干生物离体组织进行了基于反相位脉冲相位技术的二次谐波成像,并与常规的基波及二次谐波图像对比,进一步证明了该技术能有效提高图像的对比度和清晰度。     

Third order harmonic imaging for biological tissues using three phase-coded pulses

Compared to the fundamental and the second harmonic imaging, the third harmonic imaging shows significant improvements in image quality due to the better resolution, but it is degraded by the lower sound pressure and signal-to-noise ratio (SNR). In this study, a phase-coded pulse technique is proposed to selectively enhance the sound pressure of the third harmonic by 9.5 dB whereas the fundamental and the second harmonic components are efficiently suppressed and SNR is also increased by 4.7 dB. Based on the solution of the KZK nonlinear equation, the axial and lateral beam profiles of harmonics radiated from a planar piston transducer were theoretically simulated and experimentally examined. Finally, the third harmonic images using this technique were performed for several biological tissues and compared with the images obtained by the fundamental and the second harmonic imaging. Results demonstrate that the phase-coded pulse technique yields a dramatically cleaner and sharper contrast image.     

Automated quantitative analysis of the shift of frequency spectra generated by attenuated signals from contrast microbubbles

The ultrasound-induced harmonic microbubble response spectrum is known to shift to lower frequencies with increasing tissue attenuation. We hypothesized that this shift could be reproducibly detected in received broadband radiofrequency spectra. We used an automatic Gaussian curve-fitting technique to measure the mean harmonic response generated by three different contrast agents at six incremental levels of attenuation. Analytical curve fitting identified a consistent, reproducible, and statistically significant shift in mean harmonic frequency with increasing attenuation. The presented method could be a step toward attenuation estimation by contrast harmonic imaging; optimization of harmonic signal reception by ultrasound systems; and, ultimately, automatic detection of contrast agents in tissue.     

Detection procedures of ultrasound contrast agents

In the early days, it was believed that ultrasound contrast agents (UCA) could be sufficiently detected and imaged with the conventional imaging methods nowadays referred to as fundamental imaging. Newer imaging techniques proved to be more sensitive and are based on specific properties of the UCA. In general, these new characteristics involve non-linear and transient characteristics of contrast agents that appear at the high end of the diagnostic acoustic intensity. Imaging modalities used today for UCA are, besides fundamental imaging, second harmonic imaging, power Doppler, harmonic power Doppler, pulse inversion and pulse inversion Doppler, multi-pulse imaging and subharmonic imaging. Although the results of conventional second harmonic imaging are still not optimal for perfusion imaging applications, in combination with Doppler techniques (colour Doppler, power Doppler) it is one of the most sensitive techniques currently available in terms of agent-to-tissue ratio. Further improvements in current and future detection methods demand a complete understanding of the ultrasound-UCA interaction.     

Evidence of the harmonic Faraday instability in ultrasonic atomization experiments with a deep, inviscid fluid

A popular method for generating micron-sized aerosols is to submerge ultrasonic (ω~MHz) piezoelectric oscillators in a water bath. The submerged oscillator atomizes the fluid, creating droplets with radii proportional to the wavelength of the standing wave at the fluid surface. Classical theory for the Faraday instability predicts a parametric instability driving a capillary wave at the subharmonic (ω/2) frequency. For many applications it is desirable to reduce the size of the droplets; however, using higher frequency oscillators becomes impractical beyond a few MHz. Observations are presented that demonstrate that smaller droplets may also be created by increasing the driving amplitude of the oscillator, and that this effect becomes more pronounced for large driving frequencies. It is shown that these observations are consistent with a transition from droplets associated with subharmonic (ω/2) capillary waves to harmonic (ω) capillary waves induced by larger driving frequencies and amplitudes, as predicted by a stability analysis of the capillary waves.     

Multi-frequency harmonic arrays: initial experience with a novel transducer concept for nonlinear contrast imaging

Nonlinear contrast imaging modes such as second harmonic imaging (HI) and subharmonic imaging (SHI) are increasingly important for clinical applications. However, the performance of currently available transducers for HI and SHI is significantly constrained by their limited bandwidth. To bypass this constraint, a novel transducer concept termed multi-frequency harmonic transducer arrays (MFHA's) has been designed and a preliminary evaluation has been conducted. The MFHA may ultimately be used for broadband contrast enhanced HI and SHI with high dynamic range and consists of three multi-element piezo-composite sub-arrays (A-C) constructed so the center frequencies are 4f(A) = 2f(B) = f(C) (specifically 2.5/5.0/10.0 MHz and 1.75/3.5/7.0 MHz). In principle this enables SHI by transmitting on sub-array C receiving on B and, similarly, from B to A as well as HI by transmitting on A receiving on B and, likewise, from B to C. Initially transmit and receive pressure levels of the arrays were measured with the elements of each sub-array wired in parallel. Following contrast administration, preliminary in vitro HI and SHI signal-to-noise ratios of up to 40 dB were obtained. In conclusion, initial design and in vitro characterization of two MFHA's have been performed. They have an overall broad frequency bandwidth of at least two octaves. Due to the special design of the array assembly, the SNR for HI and SHI was comparable to that of regular B-mode and better than commercially available HI systems. However, further research on multi-element MFHA's is required before their potential for in vivo nonlinear contrast imaging can be assessed.     

Harmonic signal generation and frequency upconversion using selective sideband Brillouin amplification in single-mode fiber

Harmonic signal generation and frequency upconversion at millimeter-wave bands are experimentally demonstrated by using selective sideband Brillouin amplification induced by stimulated Brillouin scattering in a single-mode fiber. The harmonic signals and frequency upconverted signals are simultaneously generated by the beating of optical sidebands, one of which is Brillouin amplified. By using this method, we successfully demonstrate generation of third-harmonic millimeter waves at 32.55 GHz with f(LO) of 10.85 GHz and upconversion of 10 Mbps quadrature-shift keyed data at f(IF) of 1.55 GHz into a 30 GHz band with more than 17 dB RF power gain.     

Effect of coupled oscillations on microbubble behavior

Ultrasound contrast agents are encapsulated microbubbles whose nonlinear acoustic scattering signatures have been the foundation of their use in diagnostic imaging. The coupled oscillations of microbubbles along their lines of center are investigated theoretically using radial equations in the monopole approximation and an energy balance, which is obtained for the system. Coupled microbubble pairs of different initial radii are investigated numerically relative to the normal modes for the linearized system. For microbubble pairs of different size bubbles driven below the mode of the smaller bubble and above the mode of the larger bubble, it is shown that oscillations of the smaller agent are affected substantially more by the coupling than those of the larger one. For separation distances of 10 and 500 microns, a difference of approximately 10 dB occurs in the second harmonic output of a 1.0-micron radius agent coupled with a 2.2-micron radius agent forced at 2.0 MHz and 0.3 MPa. The subharmonic spectral peak is shown to decrease approximately 19 dB for the coupling of 1.5- and 2.2-micron radius agents at 10- and 500-micron distances under the same acoustic forcing conditions. These coupling effects on the radiated pressure and its spectral power are highlighted for contrast agent imaging applications.     

Measurement of the optical phase relation among subharmonic pulses in a femtosecond optical parametric oscillator

We observed the phase relation among subharmonic pulses generated by a femtosecond optical parametric oscillator (OPO). The ratio of the optical frequencies of the idler, the signal, and the pump pulses was set to 1:2:3. Under these conditions the wavelengths of the second harmonic of the signal pulse and the sum frequency between the pump and the idler pulses are the same. The beat signal between these two pulses represents the phase relationship among the pump, the signal, and the idler. The beat frequency varied when the cavity length of the OPO was changed.     

Pulse compression technique for simultaneous HIFU surgery and ultrasonic imaging: a preliminary study

In an ultrasound image-guided High Intensity Focused Ultrasound (HIFU) surgery, reflected HIFU waves received by an imaging transducer should be suppressed for real-time simultaneous imaging and therapy. In this paper, we investigate the feasibility of pulse compression scheme combined with notch filtering in order to minimize these HIFU interference signals. A chirp signal modulated by the Dolph-Chebyshev window with 3-9 MHz frequency sweep range is used for B-mode imaging and 4 MHz continuous wave is used for HIFU. The second order infinite impulse response notch filters are employed to suppress reflected HIFU waves whose center frequencies are 4 MHz and 8 MHz. The prototype integrated HIFU/imaging transducer that composed of three rectangular elements with a spherically con-focused aperture was fabricated. The center element has the ability to transmit and receive 6 MHz imaging signals and two outer elements are only used for transmitting 4 MHz continuous HIFU wave. When the chirp signal and 4 MHz HIFU wave are simultaneously transmitted to the target, the reflected chirp signals mixed with 4 MHz and 8 MHz HIFU waves are detected by the imaging transducer. After the application of notch filtering with pulse compression process, HIFU interference waves in this mixed signal are significantly reduced while maintaining original imaging signal. In the single scanline test using a strong reflector, the amplitude of the reflected HIFU wave is reduced to −45 dB. In vitro test, with a sliced porcine muscle shows that the speckle pattern of the restored B-mode image is close to that of the original image. These preliminary results demonstrate the potential for the pulse compression scheme with notch filtering to achieve real-time ultrasound image-guided HIFU surgery.     

互相关自适应加权的医学超声成像算法研究

根据超声成像系统的超声回波信号互相关性,提出互相关自适应加权超声成像算法.该算法根据散射点回波信号之间的空间相关性设置加权系数,对不同位置的散射点进行自适应加权成像,从而降低了成像系统的旁瓣,抑制了相关性较差的噪声.通过Field II仿真的点目标和吸声斑目标处理结果表明该方法成像的横向和纵向分辨率高,成像速度快.相对于延时叠加(DAS)算法,该算法对散射点成像可提高对比度16 dB,对于吸声斑成像可提高对比度0.85 dB.最后采用完备数据集进行实验,结果表明该算法成像分辨率优于DAS算法,对比度提高了17 dB.     

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.     

Multiple conversion and optical limiting in a subharmonic-pumped parametric oscillator

We demonstrate that multiple coexisting frequency-conversion processes can occur in an externally resonant second-harmonic generator under suitable conditions. Besides the generation of signal and idler waves by subharmonic-pumped parametric oscillation, sum-frequency mixing among the resonant subharmonic (1064-nm), signal, and idler waves was observed, leading to additional emission wavelengths around the harmonic wavelength (532 nm). The output waves both exhibit high frequency stability, with as long as 4 h of mode-hop-free parametric oscillation, and are continuously tunable over 2 GHz. Near degeneracy the parametric oscillator operates as an optical limiter for the harmonic wave.     

一维非线性声波传播特性

针对一维非线性声波的传播问题进行了有限元仿真和实验研究. 首先推导了一维非线性声波方程的有限元形式, 含有高阶矩阵的非线性项导致声波具有波形畸变、谐波滋生、基频信号能量向高次谐波传递等非线性特性. 编制有限元程序对一维非线性声波进行了计算并对仿真得到的畸变非线性声波信号进行处理, 分析其传播性质和物理意义. 为验证有限元计算结果, 开展了水中的非线性声波传播的实验研究, 得到了不同输入信号幅度激励下和不同传播距离的畸变非线性声波信号. 然后对基波和二次谐波的传播性质进行详细讨论, 分析了二次谐波幅度与传播距离和输入信号幅度的变化关系及其意义, 拟合出二次谐波幅度随传播距离变化的方程并阐述了拟合方程的物理意义. 结果表明, 数值仿真信号及其频谱均与实验结果有较好的一致性, 证实计算方法和结果的正确性, 并提出了具有一定物理意义的二次谐波随传播距离变化的简单数学关系. 最后还对固体中的非线性声波传播性质进行了初步探讨. 本研究工作可为流体介质中的非线性声传播问题提供理论和实验依据.     

The use of ultrasonic guided waves and wavelets analysis in pipe inspection

One of the main applications of guided waves is for pipe inspection, since its one-dimensional geometry allows inspecting long distances in a short time. As with most configurations (frequency, thickness) ultrasonic waves with many modes of propagation are generated, recent research focuses mostly on the generation and reception of specific modes, mainly by means of sophisticated arrays of transducers. In this paper this problem is addressed with a different approach, by processing ultrasonic signals with a low signal/noise ratio acquired with a single transducer in an pulse–echo configuration. In order to improve the evaluation of results, frequency bandpass filters and wavelet analysis were tested. Results showed that even when very noisy signals are utilized, signal processing improve the signal/noise (S/N) ratio up to 12 dB approximately and enhance the analysis of the results, thus demonstrating its usefulness.