Contrast Agent Microbubble Jetting during Initial Interaction with 200-kHz Focused Ultrasound

Cleve, Sarah; Inserra, Claude; Prentice, Paul

doi:10.1016/j.ultrasmedbio.2019.08.005

Cited by 16 publications

(6 citation statements)

References 11 publications

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“…2A). These asymmetric shapes were not due to jetting, which can result in the penetration of one side of the bubble through the other (23). We have also confirmed experimentally that microbubbles can coalesce within small brain microvessels.…”

Section: Resultsmentioning

confidence: 99%

Microbubble dynamics in brain microvessels

Bezer,

Prentice,

Kee Chang

et al. 2023

Preprint

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BackgroundFocused ultrasound stimulation of microbubbles is being tested in clinical trials for its ability to deliver drugs across the blood-brain barrier (BBB). This technique has the potential to treat neurological diseases by preferentially delivering drugs to targeted regions. Yet despite its potential, the physical mechanisms by which microbubbles alter the BBB permeability remain unclear, as direct observations of microbubbles oscillating in cerebral capillaries have never been previously recorded.The purpose of this study was to reveal how microbubbles respond to ultrasound when within the microvessels of living brain tissue.MethodsMicrobubbles in acute brain slices acquired from juvenile rats perfused with a concentrated solution of SonoVue® and dye were exposed to ultrasound pulses typically used in BBB disruption (center frequency: 1 MHz, peak-negative pressure: 0.2–1 MPa, pulse length: up to 10 ms) and observed using high-speed microscopy at up to 10 million frames per second.ResultsWe observed that microbubbles can exert mechanical stresses on a wide region of tissue beyond their initial location and immediate surroundings. A single microbubble can apply mechanical stress to parenchymal tissues several micrometers away from the vessel. Microbubbles can travel at high velocities within the microvessels, extending their influence across tens of micrometers during a single pulse. With longer pulses and higher pressures, microbubbles could penetrate the vessel wall and move through the parenchyma, refuting a previous assumption that microbubbles are confined to vessels. The probability of extravasation scales approximately with mechanical index, being rare at low pressures, but much more common at a mechanical index ≥ 0.6.ConclusionsThese observations provide important insight into microbubble dynamics in microvessels, and are critical leads into ultimately identifying the microbubble activities that lead to both safe drug delivery and into activities we seek to avoid, such as petechiae and other bioeffects.

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Section: Resultsmentioning

confidence: 99%

Microbubble dynamics in brain microvessels

Bezer,

Prentice,

Kee Chang

et al. 2023

Preprint

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“…The single-bubble models also do not account for the interaction of the modelled microbubble with neighbouring bubbles or with other objects, such as the vasculature. It is well established that such interactions can lead to nonspherical bubble oscillations, which promote fragmentation (Chomas et al, 2001), and asymmetric bubble collapse (Cleve et al, 2019), which can cause cell lysis (Chen et al, 2003) and sonoporation (Prentice et al, 2005;Ohl et al, 2006). Nonspherical bubble oscillations may also form for a single isolated bubble as a result of shape instabilities (Dollet et al, 2008;Lajoinie et al, 2018).…”

Section: Validity and Limitations Of The Modelling Assumptionsmentioning

confidence: 99%

Modelling lipid-coated microbubbles in focused ultrasound applications at subresonance frequencies

Gümmer,

Schenke,

Denner

2021

Preprint

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We present a computational study of the behaviour of a lipid-coated SonoVue microbubble with initial radius 1 µm ≤ R 0 ≤ 2 µm, excited at frequencies (200 − 1500 kHz) significantly below the linear resonance frequency and pressure amplitudes of up to 1500 kPa, an excitation regime used in many focused ultrasound applications. The bubble dynamics are simulated using the Rayleigh-Plesset equation and the Gilmore equation, in conjunction with the Marmottant model for the lipid monolayer coating. Also, a new continuously differentiable variant of the Marmottant model is introduced. Below the onset of inertial cavitation, a linear regime is identified in which the maximum pressure at the bubble wall is linearly proportional to the excitation pressure amplitude and, likewise, the mechanical index. This linear regime is bounded by the Blake pressure and, in line with recent in vitro experiments, the onset of inertial cavitation is found to occur approximately at an excitation pressure amplitude of 130 − 190 kPa, dependent on the initial bubble size. In the nonlinear regime the maximum pressure at the bubble wall is found to be readily predicted by the maximum bubble radius and both the Rayleigh-Plesset and Gilmore equations are shown to predict the onset of sub-and ultraharmonic frequencies of the acoustic emissions compared to in vitro experiments. Neither the surface dilatational viscosity of the lipid monolayer nor the compressibility of the liquid have a discernible influence on the studied quantities, yet accounting for the lipid coating is critical for the accurate prediction of the bubble behaviour. The Gilmore equation is shown to be valid for the considered bubbles and excitation regime, and the Rayleigh-Plesset equation also provides accurate qualitative predictions, even though it is outside its range of validity for many of the considered cases.

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“…These bubbles then scatter and absorb the energy of the subsequent pulses until they violently collapse. The collapse of individual bubbles may initiate a high-speed jet, which can develop towards neighbouring boundaries, that is, in the direction of the stone, or in the direction of the acoustic wave propagation [18] , [19] , [20] . The collapse of cavitation bubbles are known to produce shock waves and jets [21] , which both exhibit a high cavitation damage potential and are suspected to erode the calculus during lithotripsy treatments, potentially contributing to the complete ablation of the stone [22] .…”

Section: Introductionmentioning

confidence: 99%

Cavitation cloud formation and surface damage of a model stone in a high-intensity focused ultrasound field

Biasiori-Poulanges,

Lukić,

Supponen

2024

Ultrasonics Sonochemistry

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Contrast Agent Microbubble Jetting during Initial Interaction with 200-kHz Focused Ultrasound

Cited by 16 publications

References 11 publications

Microbubble dynamics in brain microvessels

Microbubble dynamics in brain microvessels

Modelling lipid-coated microbubbles in focused ultrasound applications at subresonance frequencies

Cavitation cloud formation and surface damage of a model stone in a high-intensity focused ultrasound field

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