Experimental frequency spectra of ultrasound transmission through two-dimensional ensembles of trapped microbubbles

The frequency spectra of transmission coefficients for ultrasound passing through a sheet of gas-filled micropores have been measured using incident waves with amplitudes up to 2.4 x 10(4) Pa. It is found that as the amplitude of the incident wave is increased, the peak frequency of transmission loss through the two-dimensional trapped-bubble ensemble shifts to lower values by as much as 47%. The experiments indicate that the shifting is caused by the net displacements of air-water-membrane triple-phase lines and the air loss of the trapped bubble, which are due to the radiation force and microbubble production produced by the incident wave. Results of the experiments and possible theoretical explanations are discussed.     

Sensitization of nerve cells to ultrasound stimulation through Piezo1-targeted microbubbles

Neuromodulation by ultrasound (US) has recently drawn considerable attention due to its great advantages in noninvasiveness, high penetrability across the skull and highly focusable acoustic energy. However, the mechanisms and safety from US irradiation still remain less understood. Recently, documents revealed Piezo1, a mechanosensitive cation channel, plays key role in converting mechanical stimuli from US through its trimeric propeller-like structure. Here, we developed a Piezo1-targeted microbubble (PTMB) which can bind to the extracellular domains of Piezo1 channel. Due to the higher responsiveness of bubbles to mechanical stimuli from US, significantly lower US energy for these PTMB-binding cells may be needed to open these mechanosensitive channels. Our results showed US energy at 0.03 MPa of peak negative pressure can achieve an equivalent level of cytoplasmic Ca²⁺ transients which generally needs 0.17 MPa US intensity for the control cells. Cytoplasmic Ca²⁺ elevations were greatly reduced by chelating extracellular calcium ions or using the cationic ion channel inhibitors, confirming that US-mediated calcium influx are dependent on the Piezo1 channels. No bubble destruction and obvious temperature increase were observed during the US exposure, indicating cavitation and heating effects hardly participate in the process of Ca²⁺ transients. In conclusion, our study provides a novel strategy to sensitize the response of nerve cells to US stimulation, which makes it safer application for US-mediated neuromodulation in the future.     

Nonlinear response to ultrasound of encapsulated microbubbles

The acoustic backscatter of encapsulated gas-filled microbubbles immersed in a weak compressible liquid and irradiated by ultrasound fields of moderate to high pressure amplitudes is investigated theoretically. The problem is formulated by considering, for the viscoelastic shell of finite thickness, an isotropic hyperelastic neo-Hookean model for the elastic contribution in addition to a Newtonian viscous component. First and second harmonic scattering cross-sections have been evaluated and the quantitative influence of the driving pressure amplitude on the harmonic resonance frequencies for different initial equilibrium bubble sizes and for different encapsulating physical properties has been determined. Conditions for optimal second harmonic imaging have been also investigated and some regions in the parameters space where the second harmonic intensity is dominant over the fundamental have been identified. Results have been obtained for albumin, lipid and polymer encapsulating shells, respectively.     

Scaling of the viscoelastic shell properties of phospholipid encapsulated microbubbles with ultrasound frequency

Phospholipid encapsulated microbubbles are widely employed as clinical diagnostic ultrasound contrast agents in the 1–5 MHz range, and are increasingly employed at higher ultrasound transmit frequencies. The stiffness and viscosity of the encapsulating “shells” have been shown to play a central role in determining both the linear and nonlinear response of microbubbles to ultrasound. At lower frequencies, recent studies have suggested that shell properties can be frequency dependent. At present, there is only limited knowledge of how the viscoelastic properties of phospholipid shells scale at higher frequencies. In this study, four batches of in-house phospholipid encapsulated microbubbles were fabricated with decreasing volume-weighted mean diameters of 3.20, 2.07, 1.82 and 1.61 μm. Attenuation experiments were conducted in order to assess the frequency-dependent response of each batch, resulting in resonant peaks in response at 4.2, 8.9, 12.6 and 19.5 MHz, respectively. With knowledge of the size measurements, the attenuation spectra were then fitted with a standard linearized bubble model in order to estimate the microbubble shell stiffness S_p and shell viscosity S_f, resulting in a slight increase in S_p (1.53–1.76 N/m) and a substantial decrease in S_f (0.29 × 10⁻⁶–0.08 × 10⁻⁶ kg/s) with increasing frequency. These results performed on a single phospholipid agent show that frequency dependent shell properties persist at high frequencies (up to 19.5 MHz).     

Measurements of microwave transmission through a decaying plasmacolumn

We have studied the width and the amplitude of the transmitted radio frequency (RF) pulse, as a function of the afterglow time for argon and nitrogen plasmas. In our study, the neutral gas pressure for the case of argon was 2 torr and that for nitrogen was 0.5 torr. The RF energy of the transmitted pulse was found to reach half of its maximum value for afterglow times of about 0.1 s for argon and about 375 μs for nitrogen     

光频率调制法测量动态光栅瞬态反射谱特性

动态光栅的瞬态特性影响了单纵模掺铒光纤激光器的稳定性. 提出一种利用铒离子瞬态效应,通过对写入光施加快速频率调制测量动态光栅瞬态反射谱的新方法. 测量了线性结构动态光栅的瞬态反射谱,研究了注入光功率与端面反射率 对动态光栅响应特性的影响.结果表明, 3 m长的掺铒光纤形成的动态光栅半带宽为30 MHz, 与稳态理论值符合较好.光栅瞬态反射率相对变化随注入光功率增加和端面反射率增加而减小, 在小注入功率或低端面反射率时,最大的反射率相对变化值约为4%. 光栅建立时间随注入光功率增加而减小,当注入光功率大于4倍饱和功率时,建立时间小于1 ms. 使用双波混频过程可解释这一实验规律.     

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.     

Energy spectra of geomagnetically trapped oxygen ions

In a series of COSMOS satellite flights plastic nuclear track detectors have been exposed in low-earth orbits to monitor anomalous cosmic rays (ACR) at energies below 25 MeV/nuc. The analysis of energy spectra has now been extended to energies up to 40 MeV/nuc for two exposures aboard COSMOS 2260 in 1993 and COSMOS 2311 in 1995. Our data on trapped ACR (TACR) oxygen energy spectra might indicate the influence of energy-dependent stripping probabilities and the presence of multiply charged ACR oxygen at high energies as reported by latest SAMPEX observations.     

Interaction of microbubbles with high intensity pulsed ultrasound

High intensity pulsed ultrasound, interacting with microbubble contrast agents, is potentially useful for drug delivery, cancer treatment, and tissue ablation, among other applications. To establish the fundamental understanding on the interaction of a microbubble (in an infinite volume of water) with an ultrasound pressure field, a numerical study is performed using the boundary element method. The response of the bubble, in terms of its shape at different times, the maximum bubble radius obtained, the oscillation time, the jet velocity, and its translational movement, is studied. The effect of ultrasound intensity and initial bubble size is examined as well. One important outcome is the determination of the conditions under which a clear jet will be formed in a microbubble in its interaction with a specific sound wave. The high speed jet is crucial for the aforementioned intended applications.     

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.     

Using light scattering to measure the response of individual ultrasound contrast microbubbles subjected to pulsed ultrasound in vitro

Light scattering was used to measure the radial pulsations of individual ultrasound contrast microbubbles subjected to pulsed ultrasound. Highly diluted Optison or Sonazoid microbubbles were injected into either a water bath or an aqueous solution containing small quantities of xanthan gum. Individual microbubbles were insonified by ultrasound pulses from either a commercial diagnostic ultrasound machine or a single element transducer. The instantaneous response curves of the microbubbles were measured. Linear and nonlinear microbubble oscillations were observed. Good agreement was obtained by fitting a bubble dynamics model to the data. The pulse-to-pulse evolution of individual microbubbles was investigated, the results of which suggest that the shell can be semipermeable, and possibly weaken with subsequent pulses. There is a high potential that light scattering can be used to optimize diagnostic ultrasound techniques, understand microbubble evolution, and obtain specific information about shell parameters.     

Low frequency acoustic transmission through the walls of rectangular ducts

A simple theory is described for the transmission of low frequency sound through the walls of rectangular ducts, particularly those in air conditioning systems. The model is based on a coupled acoustic/structural wave system, and it is assumed that the duct radiates in the same way as a finite-length line source incorporating a single travelling wave. Measurements of wall transmission loss on two types of duct system are compared to theoretical predictions, and good agreement is obtained within the frequency range of validity of the theory. It is concluded that the present approach should give reliable estimates of noise transmission in practical situations.     

Nonlinear response of ultrasound contrast agent microbubbles:From fundamentals to applications

Modelling and biomedical applications of ultrasound contrast agent(UCA) microbubbles have attracted a great deal of attention. In this review, we summarize a series of researches done in our group, including(i) the development of an all-in-one solution of characterizing coated bubble parameters based on the light scattering technique and flow cytometry;(ii) a novel bubble dynamic model that takes into consideration both nonlinear shell elasticity and viscosity to eliminate the dependences of bubble shell parameters on bubble size;(iii) the evaluation of UCA inertial cavitation threshold and its relationship with shell parameters; and(iv) the investigations of transfection efficiency and the reduction of cytotoxicity in gene delivery facilitated by UCAs excited by ultrasound exposures.     

A laser frequency lock referenced to a single trapped ion

A frequency lock has been developed which frequency stabilizes a portion of the output from an ultrastable diode laser to the narrow 5s –4d transition at 445 THz (674 nm) of a single, trapped and laser cooled Sr ion. Digital processing is used to record quantum jump data and to servo the frequency applied to an acousto-optic modulator which is used to scan a portion of the laser output across two, symmetrically displaced Zeeman components. Stable locking has been obtained resulting in uncertainties in the ion transition referenced laser frequency of less than 150 Hz.     

Resonance frequency of microbubbles: effect of viscosity

The transmitted frequency at which a gas bubble of millimeter or submillimeter size oscillates resonantly in a low-viscosity liquid is approximately equal to the undamped natural frequency (referred to as the Minnaert frequency if surface tension effects are disregarded). Based on a theoretical analysis of bubble oscillation, this paper shows that such an approximation cannot be validated for microbubbles used in contrast-enhanced ultrasound imaging. The contrast-agent microbubbles represent either encapsulated bubbles of size less than 10 microm or free (nonencapsulated) bubbles of submicron size. The resonance frequency of the microbubbles deviates significantly from the undamped natural frequency over the whole range of microbubble sizes due to the increased viscous damping coefficient. The difference between these two frequencies is shown to have a tremendous impact on the resonant backscatter by the microbubbles. In particular, the first and second harmonics of the backscattered signal from the microbubbles are characterized by their own resonance frequencies, equal to neither the microbubble resonance frequency nor the undamped natural frequency.     

Measurements of sound transmission through panels of locally resonant materials between impedance tubes

We present a method for the measurements of complex transmission coefficient through high transmission loss samples using three-sensors, two impedance tubes, monotonic wave excitation, and phase sensitive detection. Having demonstrated the effectiveness of the method on perforated plates measurements have been made on locally resonant sonic materials (LRSMs). The transmission losses of perforated plates are found to decrease with decreasing frequency down to 120 Hz, following the mass law. For the LRSM’s panels with the same area mass density but different compositions, the local resonance frequency (at which the transmission loss is maximum) is found to vary according to the predesigned value. Transmission losses as high as 96.5 dB at 630 Hz and 87 dB at 250 Hz can be measured with good accuracy, with corresponding phase spectra that match the theoretical prediction of LRSMs, confirming the reliability of the transmission data.     

Design parameters of stainless steel plates for maximizing high frequency ultrasound wave transmission

This work validated, in a higher frequency range, the theoretical predictions made by Boyle around 1930, which state that the optimal transmission of sound pressure through a metal plate occurs when the plate thickness equals a multiple of half the wavelength of the sound wave. Several reactor design parameters influencing the transmission of high frequency ultrasonic waves through a stainless steel plate were examined. The transmission properties of steel plates of various thicknesses (1–7 mm) were studied for frequencies ranging from 400 kHz to 2 MHz and at different distances between plates and transducers. It was shown that transmission of sound pressure through a steel plate showed high dependence of the thickness of the plate to the frequency of the sound wave (thickness ratio). Maximum sound pressure transmission of ∼60% of the incident pressure was observed when the ratio of the plate thickness to the applied frequency was a multiple of a half wavelength (2 MHz, 6 mm stainless steel plate). In contrast, minimal sound pressure transmission (∼10–20%) was measured for thickness ratios that were not a multiple of a half wavelength. Furthermore, the attenuation of the sound pressure in the transmission region was also investigated. As expected, it was confirmed that higher frequencies have more pronounced sound pressure attenuation than lower frequencies. The spatial distribution of the sound pressure transmitted through the plate characterized by sonochemiluminescence measurements using luminol emission, supports the validity of the pressure measurements in this study.     

Attenuation of ultrasound in porous media with dispersed microbubbles

The dispersion relation for a granular bed with a small amount of fine bubbles is formulated and analyzed. It is assumed that the grain size is much larger than the bubble's radius and that their volume concentration is small. The study is motivated by the problem of acoustic diagnostics of fixed bed chemical reactors operating in multiphase flow regime.     

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.