Jingfeng Guan

Estimating the shell parameters of SonoVue ® microbubbles using light scattering

Experiments were performed to measure the dynamical response of individual SonoVue microbubbles subjected to pulsed ultrasound. Three commonly used bubble dynamic models (i.e., Hoffs, Sarkars, and linearized Marmottants models) were compared to determine the most appropriate model for fitting to the experimental data. The models were evaluated against published optical microscopy data. The comparison suggests that it is difficult to rank these models for lipid-shelled microbubbles undergoing small-amplitude oscillations, because under these conditions the shell parameters in these models are closely related. A linearized version of the Marmottant model was used to estimate the shell parameters (i.e., shear modulus and shear viscosity) of SonoVue microbubbles from the experimental light scattering data, as a function of ambient microbubble radius. The SonoVue microbubble shell elasticity and dilatational viscosity increase with ambient bubble radius, in agreement with previously published data. The results suggest that light scattering, used in conjunction with one of several popular bubble dynamics models, is effective at characterizing microbubble response and evaluating shell parameters.

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.

Monitoring bubble growth in supersaturated blood and tissue ex vivo and the relevance to marine mammal bioeffects

There have been several recent reports that active sonar systems can lead to serious bioeffects in marine mammals, particularly beaked whales, resulting in strandings, and in some cases, to their deaths. We have devised a series of experiments to determine the potential role of low-frequency acous- tic sources as a means to induce bubble nucleation and growth in supersatu- rated ex vivo bovine liver and kidney tissues, and blood. Bubble detection was achieved with a diagnostic ultrasound scanner. Under the conditions of this experiment, supersaturated tissues and blood led to extensive bubble produc- tion when exposed to short pulses of low frequency sound. right whales. 5 Although these cetaceans have not been associated with mass stranding events related to navy sonar systems, it is likely that other cetaceans will also undergo significant changes in behavior when subjected to high-intensity acoustic pulses. Rapid surfacing from a deep dive may lead to decompression sickness. In addition, it is known that exercising after diving can lead to decompression sickness in humans. 6 Analogously, abnormal extended activity resulting from sonar may induce decompression sickness in cetaceans. To address the role of direct bubble nucleation in tissue by a sound pulse, it is worthwhile to discuss the bioeffects induced by diagnostic ultrasound systems, used routinely worldwide to image the progress of healthy as well as pathological conditions in the human patient. It is no surprise, then, to recognize that ultrasound-induced bioeffects in human tissue have been studied extensively. To this date, no repeatable effects of diagnostic ultrasound exams have been reported in the general literature. This paucity of observable bioeffects was at first surprising because the acoustic pressure amplitudes used in imaging devices are in excess of the threshold for bubble nucleation and growth, i.e., cavitation—the most likely ultrasound-induced

Imaging the destruction of individual ultrasound contrast microbubbles with diagnostic ultrasound

Ultrasound imaging of ultrasound contrast agent fragmentation in a water bath was performed with the color Doppler mode of the HDI 5000 (Phillips Ultrasound). A highly diluted suspension of ultrasound contrast microbubbles (Optison®) was injected into the water bath such that individual microbubbles passed through the image plane every few seconds. Decorrelation of the signal, along with the appearance of multiple signals, suggests that single microbubble fragmentation was observed, with daughter bubbles being formed from the original microbubbles, depending on the applied acoustic pressure.

Understanding the pulse-to-pulse evolution of microbubble clouds using light scattering

Measurements of the dynamical response of ultrasound contrast agents to diagnostic and therapeutic ultrasound pulses have been accomplished with light scattering. Light-scattering can be used to resolve the instantaneous motion of single microbubbles and provide information about the bubble evolution over many acoustic cycles. We applied this same technique to monitor the evolution of clouds of Optison microbubbles subjected to pulsed ultrasound from a diagnostic ultrasound system. Bubble oscillations were measured by focusing a 30-mW laser beam through the suspension. At low MI settings, bubble oscillations were relatively linear. In some cases, we observed an increase in the background light scatter amplitude, suggesting that bubble coalescence or gas diffusion occurred. At higher MI settings, the motion was nonlinear. Bubble fragmentation could be observed as the background light scattered signal decreased significantly from pulse to pulse.

Acoustical and optical monitoring of contrast microbubbles

We have undertaken a series of studies to better understand the response of ultrasound contrast microbubbles to pulsed ultrasound. Toward this end we have used acoustical and optical scattering techniques. The acoustic interrogation of shell‐disrupted microbubbles immediately following HIFU was used to monitor microbubble (or fragmented daughter) dissolution. Results were compared to calculations, assuming a simple Gaussian distribution of fragmented microbubbles and the dissolution characteristics of a mixed‐gas system (such as a perfluorocarbon gas bubble in air‐saturated water). Good results were obtained by considering a multi‐modal bubble size distribution. That is, the HIFU pulse created a distribution of smaller bubbles. In order to follow the instantaneous motion of a single microbubble during pulsed ultrasound, light scattering was employed. For this experiment, a diagnostic ultrasound system was used to force the microbubble into oscillation. Light scattered off the microbubble was collected by ...

Light‐scattering measurements of cavitation from ultrasound contrast agent bubbles

Ultrasound contrast agents are typically micron‐sized gas bodies with stabilizing shell coatings. The shell prevents the gas bubble from dissolving. The shell also changes a bubble’s scattering properties and affects a bubble’s destruction. Optimization of the shell can be beneficial for diagnostic imaging and therapeutic ultrasound applications. Thus, understanding agent response to pulsed ultrasound is important. However, because the agents are so small, their response to pulsed ultrasound is difficult to measure. Until recently, the only tool available for measuring contrast agent dynamics was a very expensive high‐speed camera. We have been investigating the use of light‐scattering to measure aspects of cavitation from contrast agents in which a small HeNe laser beam scatters off a bubble and is focused onto a photomultiplier tube detector. Previous experiments have involved clusters of agents, where collective bubble oscillations and destruction were observed. Our current apparatus is designed to obs...

Time‐scales for quenching single‐bubble sonoluminescence in the presence of alcohols

A small amount of alcohol added to water dramatically decreases the light intensity from single‐bubble sonoluminescence [Weninger et al., J. Phys. Chem. 99, 14195–14197 (1995)]. From an excess accumulation at the bubble surface [Ashokkumar et al., J. Phys. Chem. 104, 8462–8465 (2000)], the molecules evaporate into the bubble interior, reducing the effective adiabatic exponent of the gas, and decreasing the bubble temperature and light output [Toegel et al., Phys. Rev. Lett. 84, 2509–2512 (2000)]. There is a debate as to the rate at which alcohol is injected into the bubble interior. One camp favors the notion that molecules must be repetitively injected over many acoustic cycles. Another camp favors the notion that most quenching occurs during a single collapse. An experiment has been conducted in order to resolve the debate. Quenching rates were measured by recording the instantaneous bubble response and corresponding light emission during a sudden increase in pressure. It was found that complete quenchi...