Streaming flow from ultrasound contrast agents by acoustic waves in a blood vessel model

Cho, Eunjin; Chung, Sang Kug; Rhee, Kyehan

doi:10.1016/j.ultras.2015.05.002

Cited by 13 publications

(20 citation statements)

References 30 publications

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“…Under the secondary radiation force, the particles are attracted toward the microbubbles (Hashmi et al, 2012), which may cause the measured value of the flow velocity to be lower than the true value. In order to avoid this influence, we chose particles that were smaller than those used by Cho et al (2015). The PRP of the 0.70 MPa group was significantly higher than that of the 0.35 MPa group, but the clustering time of the two groups were very close.…”

Section: Relationships Between the Ultrasound Parameters And Acousticmentioning

confidence: 99%

“…In contrast, UMDD uses encapsulated microbubbles with a diameter of 10 µm or less. Cho et al (2015) measured the movement speed of SonoVue microbubbles caused by primary and secondary radiation forces in a blood vessel model, but they ignored the flow fields generated by the oscillation of microbubbles and microbubble clusters. Pereno et al (2018) developed an device called a layered acoustofluidic resonator.…”

Section: Introductionmentioning

confidence: 99%

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Micro-Particle Image Velocimetry Investigation of Flow Fields of SonoVue Microbubbles Mediated by Ultrasound and Their Relationship With Delivery

Zou

Wang

et al. 2020

Front. Pharmacol.

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The flow fields generated by the acoustic behavior of microbubbles can significantly increase cell permeability. This facilitates the cellular uptake of external molecules in a process known as ultrasound-mediated drug delivery. To promote its clinical translation, this study investigated the relationships among the ultrasound parameters, acoustic behavior of microbubbles, flow fields, and delivery results. SonoVue microbubbles were activated by 1 MHz pulsed ultrasound with 100 Hz pulse repetition frequency, 1:5 duty cycle, and 0.20/0.35/0.70 MPa peak rarefactional pressure. Micro-particle image velocimetry was used to detect the microbubble behavior and the resulting flow fields. Then HeLa human cervical cancer cells were treated with the same conditions for 2, 4, 10, 30, and 60 s, respectively. Fluorescein isothiocyanate and propidium iodide were used to quantitate the rates of sonoporated cells with a flow cytometer. The results indicate that (1) microbubbles exhibited different behavior in ultrasound fields of different peak rarefactional pressures. At peak rarefactional pressures of 0.20 and 0.35 MPa, the dispersed microbubbles clumped together into clusters, and the clusters showed no apparent movement. At a peak rarefactional pressure of 0.70 MPa, the microbubbles were partially broken, and the remainders underwent clustering and coalescence to form bubble clusters that exhibited translational oscillation. (2) The flow fields were unsteady before the unification of the microbubbles. After that, the flow fields showed a clear pattern. (3) The delivery efficiency improved with the shear stress of the flow fields increased. Before the formation of the microbubble/bubble cluster, the maximum shear stresses of the 0.20, 0.35, and 0.70 MPa groups were 56.0, 87.5 and 406.4 mPa, respectively, and the rates of the reversibly sonoporated cells were 2.4% ± 0.4%, 5.5% ± 1.3%, and 16.6% ± 0.2%. After the cluster formation, the maximum shear stresses of the three groups were 9.1, 8.7, and 71.7 mPa, respectively. The former two could not mediate sonoporation, whereas the Frontiers in Pharmacology | www.frontiersin.org last one could. These findings demonstrate the critical role of flow fields in ultrasoundmediated drug delivery and contribute to its clinical applications.

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Section: Relationships Between the Ultrasound Parameters And Acousticmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Micro-Particle Image Velocimetry Investigation of Flow Fields of SonoVue Microbubbles Mediated by Ultrasound and Their Relationship With Delivery

Zou

Wang

et al. 2020

Front. Pharmacol.

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“…A separate study showed that microbubbles sonicated at center frequencies between 1 and 2.25 MHz caused fluid streaming velocities on the order of cm s −1 and triggered symmetric vortices at the focal volume outskirts (Cho et al 2015). It was argued that the fluid streaming patterns were produced by bubble clustering (Koda et al 2011) or coalescence (Postema et al 2004) and the collective microbubble translation.…”

Section: Discussionmentioning

confidence: 99%

Superharmonic microbubble Doppler effect in ultrasound therapy

Pouliopoulos

Choi

2016

Phys. Med. Biol.

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The introduction of microbubbles in focused ultrasound therapies has enabled a diverse range of non-invasive technologies: sonoporation to deliver drugs into cells, sonothrombolysis to dissolve blood clots, and blood-brain barrier opening to deliver drugs into the brain. Current methods for passively monitoring the microbubble dynamics responsible for these therapeutic effects can identify the cavitation position by passive acoustic mapping and cavitation mode by spectral analysis. Here, we introduce a new feature that can be monitored: microbubble effective velocity. Previous studies have shown that echoes from short imaging pulses had a Doppler shift that was produced by the movement of microbubbles. Therapeutic pulses are longer (>1 000 cycles) and thus produce a larger alteration of microbubble distribution due to primary and secondary acoustic radiation force effects which cannot be monitored using pulse-echo techniques. In our experiments, we captured and analyzed the Doppler shift during long therapeutic pulses using a passive cavitation detector. A population of microbubbles (5 × 104–5 × 107 microbubbles ml−1) was embedded in a vessel (inner diameter: 4 mm) and sonicated using a 0.5 MHz focused ultrasound transducer (peak-rarefactional pressure: 75–366 kPa, pulse length: 50 000 cycles or 100 ms) within a water tank. Microbubble acoustic emissions were captured with a coaxially aligned 7.5 MHz passive cavitation detector and spectrally analyzed to measure the Doppler shift for multiple harmonics above the 10th harmonic (i.e. superharmonics). A Doppler shift was observed on the order of tens of kHz with respect to the primary superharmonic peak and is due to the axial movement of the microbubbles. The position, amplitude and width of the Doppler peaks depended on the acoustic pressure and the microbubble concentration. Higher pressures increased the effective velocity of the microbubbles up to 3 m s−1, prior to the onset of broadband emissions, which is an indicator for high magnitude inertial cavitation. Although the microbubble redistribution was shown to persist for the entire sonication period in dense populations, it was constrained to the first few milliseconds in lower concentrations. In conclusion, superharmonic microbubble Doppler effects can provide a quantitative measure of effective velocities of a sonicated microbubble population and could be used for monitoring ultrasound therapy in real-time.

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“…Others show interest in the effects of the streaming induced by contrast agents in on-chip vessels. 163 Finally, streaming is also suspected to be an important mechanism for the delivery of drugs loaded on microbubbles. 113 Moreover, exploiting the acoustic radiation force on microbubbles that arises from the phase difference between the microbubble volumetric oscillations and the acoustic wave 164 is an important method for the manipulation of single bubbles, as well as an often undesired effect in vitro.…”

Section: Acoustic Excitationmentioning

confidence: 99%

In vitro methods to study bubble-cell interactions: Fundamentals and therapeutic applications

et al. 2016

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Besides their use as contrast agents for ultrasound imaging, microbubbles are increasingly studied for a wide range of therapeutic applications. In particular, their ability to enhance the uptake of drugs through the permeabilization of tissues and cell membranes shows great promise. In order to fully understand the numerous paths by which bubbles can interact with cells and the even larger number of possible biological responses from the cells, thorough and extensive work is necessary. In this review, we consider the range of experimental techniques implemented in in vitro studies with the aim of elucidating these microbubble-cell interactions. First of all, the variety of cell types and cell models available are discussed, emphasizing the need for more and more complex models replicating in vivo conditions together with experimental challenges associated with this increased complexity. Second, the different types of stabilized microbubbles and more recently developed droplets and particles are presented, followed by their acoustic or optical excitation methods. Finally, the techniques exploited to study the microbubble-cell interactions are reviewed. These techniques operate over a wide range of timescales, or even off-line, revealing particular aspects or subsequent effects of these interactions. Therefore, knowledge obtained from several techniques must be combined to elucidate the underlying processes. V C 2016 AIP Publishing LLC.

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Streaming flow from ultrasound contrast agents by acoustic waves in a blood vessel model

Cited by 13 publications

References 30 publications

Micro-Particle Image Velocimetry Investigation of Flow Fields of SonoVue Microbubbles Mediated by Ultrasound and Their Relationship With Delivery

Micro-Particle Image Velocimetry Investigation of Flow Fields of SonoVue Microbubbles Mediated by Ultrasound and Their Relationship With Delivery

Superharmonic microbubble Doppler effect in ultrasound therapy

In vitro methods to study bubble-cell interactions: Fundamentals and therapeutic applications

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