The “quasi-stable” lipid shelled microbubble in response to consecutive ultrasound pulses

Thomas, David Hurst; Butler, Mairéad; Anderson, Thomas; Emmer, Marcia; Vos, Hendrik J.; Borden, Mark A.; Stride, Eleanor; Jong, Nico de; Sboros, Vassilis

doi:10.1063/1.4746258

Cited by 26 publications

(33 citation statements)

References 25 publications

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“…In addition, the shell morphology can be altered or destroyed due to multiple burst excitations. 18 A method using a single excitation would improve the efficiency of UCA characterization techniques and would minimize the effect of alterations to the microbubble shell under successive excitations.…”

Section: Introductionmentioning

confidence: 99%

Impulse response method for characterization of echogenic liposomes

Raymond

Luan²,

Rooij³

et al. 2015

The Journal of the Acoustical Society of America

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An optical characterization method is presented based on the use of the impulse response to characterize the damping imparted by the shell of an air-filled ultrasound contrast agent (UCA). The interfacial shell viscosity was estimated based on the unforced decaying response of individual echogenic liposomes (ELIP) exposed to a broadband acoustic impulse excitation. Radius versus time response was measured optically based on recordings acquired using an ultra-highspeed camera. The method provided an efficient approach that enabled statistical measurements on 106 individual ELIP. A decrease in shell viscosity, from 2.1 Â 10 À8 to 2.5 Â 10 À9 kg/s, was observed with increasing dilatation rate, from 0.5 Â 10 6 to 1 Â 10 7 s À1 . This nonlinear behavior has been reported in other studies of lipid-shelled UCAs and is consistent with rheological shear-thinning. The measured shell viscosity for the ELIP formulation used in this study [j s ¼ (2.1 6 1.0) Â 10 À8 kg/s] was in quantitative agreement with previously reported values on a population of ELIP and is consistent with other lipid-shelled UCAs. The acoustic response of ELIP therefore is similar to other lipid-shelled UCAs despite loading with air instead of perfluorocarbon gas. The methods described here can provide an accurate estimate of the shell viscosity and damping for individual UCA microbubbles.

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Section: Introductionmentioning

confidence: 99%

Impulse response method for characterization of echogenic liposomes

Raymond

Luan²,

Rooij³

et al. 2015

The Journal of the Acoustical Society of America

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“…Based on the observation of the time scale of a shedding event (several to tens of microseconds) and its strong dependence on oscillation amplitude, we assume here that lipid shedding can be caused by the surface area reduction of the lipid shedding events, which is in agreement with previous studies 181,184 . For a microbubble undergoing spherical oscillations, 30% of relative radial excursion is equivalent to 50% surface reduction of the microbubble.…”

Section: Occurrence Of Lipid Sheddingsupporting

confidence: 87%

“…They proposed that the surface area reduction caused by gas diffusion from the microbubble could lead to the expulsion of excessive shell materials. Later, Thomas et al 184 investigated the dissolution of single microbubbles as a function of the bubble radial oscillation based on ultra-high-speed imaging. The amount of microbubble dissolution was claimed to be associated with the amount of expelled lipid materials.…”

Section: Introductionmentioning

confidence: 99%

“…All of these studies were limited by 26 the following factors. First, either the time resolution (hundreds of milliseconds in Borden et al 181 ) or the recording time (10 µs in Thomas et al 184 ) of the imaging systems was not sufficient to resolve the details of lipid shedding dynamics. Second, microbubble dissolution was used as a measure of shedding.…”

Section: Introductionmentioning

confidence: 99%

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Ultrasound contrast agents: bubbles drops and particles

Lajoinie¹

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The research described in this thesis is part of the research program NanoNextNL, a micro and nanotechnology consortium of the Government of the Netherlands and 130 partners. This thesis was carried out at the Physics of Fluids group of the Faculty of Science and Technology of the University of Twente. Cover design:As a representation of a crucial goal of this work, the cover depicts a confocal microscopy image showing cells selectively porated by loaded microbubbles upon ultrasound exposure. The porated cells take up a blue fluorescent probe. By Ine Lentacker, Ine De Cock and Guillaume Lajoinie. Guide through the thesisIn this thesis, we investigate different types of innovative agents, designed for biomedical use in a context of molecular imaging. In Chapter 1, we review the agents that arouse the interest of the scientific community, most of them at the research stage of development, together with the experimental methods that can be used to study their interaction with cells. Such in vitro investigations are necessary to test on short scales the impact of the various agents on biological structures.We separate the agents in three main categories. The first group consists of stabilized microbubbles, usually by means of phospholipids that fill up the interfacial area between the gas core and the surrounding liquid (water). Such bubbles are clinically used for 40 years as contrast agents for ultrasound owing to their unique resonance behavior. When irradiated with an ultrasound pulse, a bubble experiences volumetric oscillations, that reemit an ultrasound wave back to the transducer. This process makes them unchallenged ultrasound scatterers. The role of these stable microbubbles in new biomedical research directions is discussed in Chapters 2 to 9.Phospholipid coatings were developed in the last decade to do much more than just prevent bubble dissolution. They are now a crucial tool to enrich the microbubbles with specific markers or drug payloads. In Chapter 2, we investigate the behavior of this coating when the microbubbles are subjected to an ultrasound field. We show that the coating is shed away from the microbubble, which is of major interest for molecular imaging combined with drug delivery using microbubbles. We pursue the idea in Chapter 3 where we investigate how a bubble payload, here liposomes labeled with a fluorescent dye, is released under ultrasound exposure. In Chapter 4, we link these direct observations of shedding of the previous Chapters to the subsequent dissolution of the microbubbles, no longer protected by a phospholipid shell. This dissolution, visible in the ultrasound scatter spectrum can be used to remotely quantify the effect of the microbubbles. In support of these observations, we dedicate the next Chapter (Chapter 5) to physically understand the mechanisms underlying the behavior of the phospholipid coating. The application of these findings in practice requires the production a sufficiently high production rate and with great control of such microbubbles. In Chapter 6, we th...

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“…It is well known that microbubbles can oscillate at super and sub harmonic frequencies (Leighton, 1994), and that oscillations from different frequency components (e.g., fundamental, second-harmonic) may each exhibit differential dependencies on factors such as microbubble size or transmit amplitude (Prosperetti, 2013;Shankar et al, 1998;Sijl et al, 2011;Sprague et al, 2010). This type of individual microbubble analysis is similar to that employed in previous ultra-high frame rate microscopy studies Sijl et al, 2011;Thomas et al, 2012).…”

Section: Optical-acoustical Apparatusmentioning

confidence: 68%

Individual lipid encapsulated microbubble radial oscillations: Effects of fluid viscosity

Helfield

Chen

Qin

et al. 2016

The Journal of the Acoustical Society of America

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Ultrasound-stimulated microbubble dynamics have been shown to be dependent on intrinsic bubble properties, including size and shell characteristics. The effect of the surrounding environment on microbubble response, however, has been less investigated. In particular, microbubble optimization studies are generally conducted in water/saline, characterized by a 1 cP viscosity, for application in the vasculature (i.e., 4 cP). In this study, ultra-high speed microscopy was employed to investigate fluid viscosity effects on phospholipid encapsulated microbubble oscillations at 1 MHz, using a single, eight-cycle pulse at peak negative pressures of 100 and 250 kPa. Microbubble oscillations were shown to be affected by fluid viscosity in a size-and pressure-dependent manner. In general, the oscillation amplitudes exhibited by microbubbles between 3 and 6 lm in 1 cP fluid were larger than in 4 cP fluid, reaching a maximum of 1.7-fold at 100 kPa for microbubbles 3.8 lm in diameter and 1.35-fold at 250 kPa for microbubbles 4.8 lm in diameter. Simulation results were in broad agreement at 250 kPa, however generally underestimated the effect of fluid viscosity at 100 kPa. This is the first experimental demonstration documenting the effects of surrounding fluid viscosity on microbubble oscillations, resulting in behavior not entirely predicted by current microbubble models.

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The “quasi-stable” lipid shelled microbubble in response to consecutive ultrasound pulses

Cited by 26 publications

References 25 publications

Impulse response method for characterization of echogenic liposomes

Impulse response method for characterization of echogenic liposomes

Ultrasound contrast agents: bubbles drops and particles

Individual lipid encapsulated microbubble radial oscillations: Effects of fluid viscosity

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