Subharmonic behavior of phospholipid-coated ultrasound contrast agent microbubbles

Coated microbubbles, unlike tissue are able to scatter sound subharmonically. Therefore, the subharmonic behavior of coated microbubbles can be used to enhance the contrast in ultrasound contrast imaging. Theoretically, a threshold amplitude of the driving pressure can be calculated above which subharmonic oscillations of microbubbles are initiated. Interestingly, earlier experimental studies on coated microbubbles demonstrated that the threshold for these bubbles is much lower than predicted by the traditional linear viscoelastic shell models. This paper presents an experimental study on the subharmonic behavior of differently sized individual phospholipid coated microbubbles. The radial subharmonic response of the microbubbles was recorded with the Brandaris ultra high-speed camera as a function of both the amplitude and the frequency of the driving pulse. Threshold pressures for subharmonic generation as low as 5 kPa were found near a driving frequency equal to twice the resonance frequency of the bubble. An explanation for this low threshold pressure is provided by the shell buckling model proposed by Marmottant et al. [J. Acoust. Soc. Am. 118, 3499-3505 (2005)]. It is shown that the change in the elasticity of the bubble shell as a function of bubble radius as proposed in this model, enhances the subharmonic behavior of the microbubbles.     

Modeling subharmonic response from contrast microbubbles as a function of ambient static pressure

Variation of subharmonic response from contrast microbubbles with ambient pressure is numerically investigated for non-invasive monitoring of organ-level blood pressure. Previously, several contrast microbubbles both in vitro and in vivo registered approximately linear (5-15 dB) subharmonic response reduction with 188 mm Hg change in ambient pressure. In contrast, simulated subharmonic response from a single microbubble is seen here to either increase or decrease with ambient pressure. This is shown using the code BUBBLESIM for encapsulated microbubbles, and then the underlying dynamics is investigated using a free bubble model. The ratio of the excitation frequency to the natural frequency of the bubble is the determining parameter--increasing ambient pressure increases natural frequency thereby changing this ratio. For frequency ratio below a lower critical value, increasing ambient pressure monotonically decreases subharmonic response. Above an upper critical value of the same ratio, increasing ambient pressure increases subharmonic response; in between, the subharmonic variation is non-monotonic. The precise values of frequency ratio for these three different trends depend on bubble radius and excitation amplitude. The modeled increase or decrease of subharmonic with ambient pressure, when one happens, is approximately linear only for certain range of excitation levels. Possible reasons for discrepancies between model and previous experiments are discussed.     

Characterization of ultrasound contrast microbubbles using in vitro experiments and viscous and viscoelastic interface models for encapsulation

Zero-thickness interface models are developed to describe the encapsulation of microbubble contrast agents. Two different rheological models of the interface, Newtonian (viscous) and viscoelastic, with rheological parameters such as surface tension, surface dilatational viscosity, and surface dilatational elasticity are presented to characterize the encapsulation. The models are applied to characterize a widely used microbubble based ultrasound contrast agent. Attenuation of ultrasound passing through a solution of contrast agent is measured. The model parameters for the contrast agent are determined by matching the linearized model dynamics with measured attenuation data. The models are investigated for its ability to match with other experiments. Specifically, model predictions are compared with scattered fundamental and subharmonic responses. Experiments and model prediction results are discussed along with those obtained using an existing model [Church, J. Acoust. Soc. Am. 97, 1510 (1995) and Hoff et al., J. Acoust. Soc. Am. 107, 2272 (2000)] of contrast agents.     

调频激励增强微气泡的次谐波理论和实验研究

超声造影剂的次谐波成像可以提高造影组织比，提供更好的图像质量. 提出一种利用调频脉冲激励以增强造影剂微气泡产生的次谐波新方法. 基于修正的Church方程，从理论上讨论了次谐波的产生与调频激励声压的关系及产生阈值，并且实验证实了优化调频信号的带宽及调频时间可以提高次谐波信号幅度及改善主瓣和旁瓣特性. 理论与实验表明，与传统脉冲信号激励相比，调频信号激励产生的次谐波幅度可提高约22dB. 关键词： 调频激励 超声造影剂 微气泡 次谐波     

Fundamental study on subharmonic imaging by irradiation of amplitude-modulated ultrasound waves

The second harmonic and subharmonic components, the frequencies of which are twice and one half the fundamental frequency, are included in echoes from contrast agents. An imaging method, which employs a second harmonic (second harmonic imaging), is widely used in medical diagnoses. On the other hand, subharmonic is expected to provide a higher contrast between biological tissues and blood flow because echo signals are generated only from blood containing the contrast agents. However, the subharmonic component echo signal power from contrast agents is relatively low. This has resulted in little progress in the field of subharmonic imaging. In this study, a new imaging method is proposed using amplitude-modulated waves as transmitted waves combined with the pulse inversion method to enhance subharmonic echo signals. Two optimal frequencies are set, including the modulated waves, F(1) and F(2), so that the subharmonic frequency of F(1) and the second harmonic frequency of F(2) may result in the same value. This allows a more powerful signal at the frequency band because the second harmonic and subharmonic components are integrated. Furthermore, a B-mode ultrasound image of an agar phantom that imitated biological tissue and showed the effectiveness of our method was reconstructed. As a result, the echo power of the subharmonic component was enhanced by approximately 11.8 dB more than the conventional method and the signal to noise ratio showed an improvement of 7.6 dB.     

Ion acoustic subharmonic excitation in a plasma

Ion acoustic subharmonic excitation in a plasma, with ion-neutral collision frequency greater than the frequency of excitation, is theoretically investigated. Two-fluid theory with source term is used to describe the system. The system exhibits either subharmonic excitation of orders 1/2 and 1/3, or subharmonic excitation of orders 1/3, 1/4 and 1/5. The resonance frequency range and the amplitude of second harmonic for each case is calculated. A comparison with experimental data can be used to obtain the values of the parameters describing the source term.     

声悬浮液滴的表面毛细波及八阶扇谐振荡

采用声悬浮方法研究了自由液滴表面的毛细波形成机理,并利用主动调制声场技术激发了液滴的八阶扇谐振荡.实验结果表明,当声场调制频率接近液滴本征频率的两倍时,液滴将由轴对称受迫振荡向非轴对称扇谐振荡模态转变.实验与理论分析证实,参数共振是毛细波与扇谐振荡的形成原因.扇谐振荡的本征频率随液滴赤道半径的增大而减小,可通过修正的Rayleigh方程来描述. 关键词： 声悬浮 液滴 毛细波 扇谐振荡     

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.     

The threshold of subharmonic parametric excitation in the bragg gap of a periodic structure

Methods of excitation of the subharmonic whose frequency lies within the forbidden band gap of a periodic structure are discussed. The dependences of threshold values of in-phase pumping on structure parameters are found.     

Dynamics of a bouncing droplet onto a vertically vibrated interface

Low viscosity (<100 cSt) silicon oil droplets are placed on a high viscosity (1000 cSt) oil bath that vibrates vertically. The viscosity difference ensures that the droplet is more deformed than the bath interface. Droplets bounce periodically on the bath when the acceleration of its sinusoidal motion is larger than a threshold value. The threshold is minimum for a particular frequency of excitation: droplet and bath motions are in resonance. The bouncing droplet has been modeled by considering the deformation of the droplet and the lubrication force exerted by the air layer between the droplet and the bath. Threshold values are predicted and found to be in good agreement with our measurements.     

Nonclassical light generation in quasi-phase-matched parametric self-frequency conversion

We present a quantum theory of the parametric self-conversion of the laser radiation frequency in active nonlinear crystals with a regular domain structure. Such crystals feature simultaneous lasing and quasi-phase-matched parametric conversion of the laser radiation frequency. These processes are described using the Heisenberg-Langevin equations in two regimes of the subharmonic generation: super-and subthreshold. The spectral properties of the quadrature components of the laser frequency and its subharmonic and the photon statistics have been studied as dependent on the pump power, crystal length, and reflectance of the laser cavity output mirror. Using the obtained analytical expressions, these characteristics are calculated for a active nonlinear Nd:Mg:LiNbO₃ crystal with a regular domain structure. In the subthreshold regime, the maximum decrease in the spectral density of fluctuations in the subharmonic quadrature component relative to the standard quantum limit may reach 90%; in the above-threshold regime, these fluctuations are virtually not suppressed. A decrease in the spectral density of fluctuations of the laser frequency quadrature does not exceed 10%. In the subthreshold excitation regime, the subharmonic photons obey a super-Poisson statistics; in the above-threshold regime, the photon statistics is Poisson-like.     

Spin wave mode excited by spin-polarized current in a magnetic nanocontact is a standing self-localized wave bullet

We demonstrate that the lowest threshold of spin-wave excitation in an in-plane magnetized magnetic nanocontact driven by spin-polarized current is achieved for a nonlinear self-localized spin-wave mode-standing spin-wave bullet--stabilized by current-induced nonlinear dissipation. This nonlinear mode has a nonpropagating evanescent character, is localized in the region comparable with the contact radius, and has a frequency that is lower than the frequency of the linear ferromagnetic resonance. The threshold current and generated frequency at the threshold theoretically calculated for this mode are in quantitative agreement with experiment.     

Resonance fluorescence spectrum of a three-level atom

We consider the excitation spectrum arising from the interaction between a three-level atom and a strong electromagnetic field in the frequency region where the two atomic transition frequencies are nearly equal to once and twice the frequency of the pump field respectively. Detailed expressions for the spectral functions are derived describing the two-, one- and zero-photon excitations as well as those arising from the coupling between them, in the limit of high photon densities. The zero-photon excitations describe low frequency modes induced by the pump field under resonance conditions.     

Effect of current modulation depth on the response of single-mode quantum-well heterolasers in the region of 1.5 μm

Numerical simulations are used to study the effect of pump current modulation depth on the response of quantum-well GaInAs–GaInAsP heterolasers at different lasing frequencies within the gain band as a function of the excess above threshold. It is shown that the amplitude-frequency characteristics of these laser emitters generally contain two local maxima. The low frequency maximum usually corresponds to a resonance for the 1/2 subharmonic and the high frequency maximum, to the fundamental. As the modulation depth is increased, the fundamental frequency decreases, while the resonance frequency for the 1/2 subharmonic can change monotonically or not. The behavior found here can be used to develop quantum-well heterolasers with specified modulation parameters.     

Position optimization of particular solution sources for distributed source boundary point method by volume velocity-matching

Choosing particular solution source and its position have great influence on accuracy of sound field prediction in distributed source boundary point method.An optimization method for determining the position of particular solution sources is proposed to get high accuracy prediction result.In this method,tripole is chosen as the particular solution.The upper limit frequency of calculation is predicted by setting 1%volume velocity relative error limit using vibration velocity of structure surface.Then,the optimal position of particular solution sources,in which the relative error of volume velocity is minimum,is determined within the range of upper limit frequency by searching algorithm using volume velocity matching.The transfer matrix between pressure and surface volume velocity is constructed in the optimal position.After that,the sound radiation of structure is calculated by the matrix.The results of numerical simulation show that the calculation error is significantly reduced by the proposed method.When there are vibration velocity measurement errors,the calculation errors can be controlled within 5% by the method.     

Nonlinear dynamics and bifurcation structure of ultrasonically excited lipid coated microbubbles

In many applications, microbubbles (MBs) are encapsulated by a lipid coating to increase their stability. However, the complex behavior of the lipid coating including buckling and rupture sophisticates the dynamics of the MBs and as a result the dynamics of the lipid coated MBs (LCMBs) are not well understood. Here, we investigate the nonlinear behavior of the LCMBs by analyzing their bifurcation structure as a function of acoustic pressure. We show that, the LC can enhance the generation of period 2 (P2), P3, higher order subharmonics (SH), superharmonics and chaos at very low excitation pressures (e.g. 1 kPa). For LCMBs sonicated by their SH resonance frequency and in line with experimental observations with increasing pressure, P2 oscillations exhibit three stages: generation at low acoustic pressures, disappearance and re-generation. Within non-destructive oscillation regimes and by pressure amplitude increase, LCMBs can also exhibit two saddle node (SN) bifurcations resulting in possible abrupt enhancement of the scattered pressure. The first SN resembles the pressure dependent resonance phenomenon in uncoated MBs and the second SN resembles the pressure dependent SH resonance. Depending on the initial surface tension of the LCMBs, the nonlinear behavior may also be suppressed for a wide range of excitation pressures.     

体积速度匹配分布源边界点法的特解源位置优化方法研究

在分布源边界点法中,选择特解源及特解源位置对声场计算的精度具有很大的影响。为减小声场计算的误差,提出了一种确定特解源位置的优化方法。在该方法中,采用三极子作为特解源,以1%体积速度相对误差对结构声辐射计算的上限频率进行预测,然后在计算上限频率范围内通过体积速度匹配搜索,得到体积速度相对误差最小意义下的特解源优化位置,在该优化位置处构造声压与表面体积速度之间的传递矩阵来计算声场,以减小计算误差。数值仿真结果表明:在求取的计算上限频率范围内,特解源处于优化位置时,计算误差得以显著减小。当振速测量存在一定误差时,采用该方法仍可将计算误差控制在5%以内。      

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.     

Soliton generation via stimulated Brillouin self-scattering under slow light conditions

Acousto-optic soliton generation via stimulated Brillouin self-scattering is predicted for light propagating at the speed of sound under electromagnetically induced transparency conditions. As in stimulated Raman self-scattering, the frequency of the electromagnetic component is gradually Stokes shifted as its intensity increases; the acoustic component has no carrier frequency. This phenomenon is explained by the possibility of forward stimulated Brillouin scattering, which is forbidden in nondispersive media. In contrast to stimulated Raman self-scattering, the Stokes shift of the electromagnetic component approaches a constant limit after the pulse has propagated to a certain distance. It is shown that the predicted soliton generation does not involve any threshold condition and can occur at extremely low input pulse intensities.     

Soliton excitation in the pass band of the transmission line based on modulation

We numerically investigate the excitation of soliton waves in the nonlinear electrical transmission line formed by many cells. When the periodic driving voltage with frequency in the pass band closing to the cutoff frequency is applied to the endpoint of the whole line, the soliton wave can be generated. The numerical results show that the soliton wave generation mainly depends on the self modulation associated with the nonlinear effect. In this study, the lower subharmonic component is also observed in the frequency spectrum. To further understand this phenomenon, we study the dependence of the subharmonic power spectrum and frequency on the forcing amplitude and frequency numerically, and find that the subharmonic frequency increases with the gradual growth of the driving amplitude.