Nonlinear Shell Behavior of Phospholipid-Coated Microbubbles

Overvelde, M.L.J.; Garbin, Valeria; Sijl, Jeroen; Dollet, Benjamin; Jong, Nico de; Lohse, Detlef; Versluis, Michel

doi:10.1016/j.ultrasmedbio.2010.08.015

Cited by 160 publications

(201 citation statements)

References 34 publications

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“…The maximum response (e f % 35%, e 2f % 11%) can be found for microbubbles with a radius of $3.4 lm, which is a typical resonant size for a driving frequency of 1 MHz, as reported previously. 23,27 The experimental data showed good agreement with the simulation results. Figures 3(c) and 3(d) illustrates the asymmetric vibrational response, indicated by the difference between the relative amplitude of the expansion and the compression phase (A exp À A com ), versus bubble size R meas .…”

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confidence: 66%

“…25,27 These phenomena were considered not only to be influenced by the resting bubble size, but also to be dependent on the initial surface tension due to the presence of the phospholipid coating, 28,29 which can greatly vary among individual bubbles. 27,30 This explains the variability in the asymmetric response among microbubbles within the same size range, see the two examples (and other bubbles) in Fig. 3(d) that nearly have the same size.…”

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confidence: 99%

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Combined optical sizing and acoustical characterization of single freely-floating microbubbles

Luan

Renaud

Raymond

et al. 2016

Applied Physics Letters

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In this study we present a combined optical sizing and acoustical characterization technique for the study of the dynamics of single freely-floating ultrasound contrast agent microbubbles exposed to long burst ultrasound excitations up to the milliseconds range. A co-axial flow device was used to position individual microbubbles on a streamline within the confocal region of three ultrasound transducers and a high-resolution microscope objective. Bright-field images of microbubbles passing through the confocal region were captured using a high-speed camera synchronized to the acoustical data acquisition to assess the microbubble response to a 1-MHz ultrasound burst. Nonlinear bubble vibrations were identified at a driving pressure as low as 50 kPa. The results demonstrate good agreement with numerical simulations based on the shell-buckling model proposed by Marmottant et al. [J. Acoust. Soc. Am. 118, 3499–3505 (2005)]. The system demonstrates the potential for a high-throughput in vitro characterization of individual microbubbles.

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confidence: 66%

mentioning

confidence: 99%

Combined optical sizing and acoustical characterization of single freely-floating microbubbles

Luan

Renaud

Raymond

et al. 2016

Applied Physics Letters

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“…Assessing the biophysics of endothelial mechanotransducers subjected to short (microseconds), large-amplitude (kilopascal) shear stresses may prove useful in illuminating downstream biological mechanisms and consequences of sonoporation, including cytoskeleton shear force transduction and shear-stress-mediated vasoregulation factors [e.g., nitric oxide production (24), reactive oxygen species]. From a translational standpoint, the development of sonication regimes in which microbubbles can be forced into a "controlled" oscillation characteristic (e.g., to generate threshold shear-stress magnitudes) requires further experimental and theoretical investigation, with particular focus on how intrinsic encapsulation heterogeneity may alter the response of an ostensibly identical microbubble to the same ultrasonic stimulus (25).…”

Section: Resultsmentioning

confidence: 99%

Biophysical insight into mechanisms of sonoporation

Helfield

Chen

Watkins

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

223

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This study presents a unique approach to understanding the biophysical mechanisms of ultrasound-triggered cell membrane disruption (i.e., sonoporation). We report direct correlations between ultrasound-stimulated encapsulated microbubble oscillation physics and the resulting cellular membrane permeability by simultaneous microscopy of these two processes over their intrinsic physical timescales (microseconds for microbubble dynamics and seconds to minutes for local macromolecule uptake and cell membrane reorganization). We show that there exists a microbubble oscillation-induced shear-stress threshold, on the order of kilopascals, beyond which endothelial cellular membrane permeability increases. The shear-stress threshold exhibits an inverse squareroot relation to the number of oscillation cycles and an approximately linear dependence on ultrasound frequency from 0.5 to 2 MHz. Further, via real-time 3D confocal microscopy measurements, our data provide evidence that a sonoporation event directly results in the immediate generation of membrane pores through both apical and basal cell membrane layers that reseal along their lateral area (resealing time of ∼<2 min). Finally, we demonstrate the potential for sonoporation to indirectly initiate prolonged, intercellular gaps between adjacent, confluent cells (∼>30-60 min). This real-time microscopic approach has provided insight into both the physical, cavitation-based mechanisms of sonoporation and the biophysical, cell-membrane-based mechanisms by which microbubble acoustic behaviors cause acute and sustained enhancement of cellular and vascular permeability.ultrasound therapy | microbubble contrast agent | endothelial membrane | gene delivery | sonoporation D elivery vehicles for therapeutic nucleic acids (e.g., siRNA, mRNA, plasmids, oligonucleotides), including nanoparticles or viruses, are intended to increase the local effectiveness of the therapeutic within a target tissue while reducing off-target effects. A major barrier to the successful delivery of molecular therapeutics in this manner is the endothelial cell membrane. Viral vectors, although able to efficiently deliver genetic material to target cells via their intracellular trafficking machinery, may elicit specific inflammatory and nonspecific antiviral immune responses (1, 2). As an alternative, nonviral vectors--for example, localized needle injection of naked therapeutic nucleic acids or lipofection--use physical forces or compounds, respectively, to deliver a genetic payload into a cell and are generally less toxic and immunogenic than viral vectors (3). However, direct needle injection into the target poses challenges in achieving homogeneous tissue distribution of the payload (4), and clinical implementation is limited by the impractical requirements of repetitive needle injections into sites which may be difficult to access. Systemically injected liposomes face the endothelial barrier, are vulnerable to intravascular destruction and/or renal excretion (depending on size), and, when endocytosed b...

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“…This system, which is not available commercially, has been extensively used to make in vitro observations of MB dynamics in US fields that have suggested that MB acoustic behaviors may have unique therapeutic and diagnostic utility in medicine. [17][18][19][20][21][22][23][24] Until recently, multi-frame high-speed cameras at million frames per second rate were capable of bright field imaging only. US-induced MB oscillations in vivo have not been visualized at Mfps rate, mainly due to low optical contrast of MBs relative to tissue and blood background.…”

Section: Introductionmentioning

confidence: 99%

Ultra-fast bright field and fluorescence imaging of the dynamics of micrometer-sized objects

Chen

Wang

Versluis

et al. 2013

Review of Scientific Instruments

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High speed imaging has application in a wide area of industry and scientific research. In medical research, high speed imaging has the potential to reveal insight into mechanisms of action of various therapeutic interventions. Examples include ultrasound assisted thrombolysis, drug delivery, and gene therapy. Visual observation of the ultrasound, microbubble, and biological cell interaction may help the understanding of the dynamic behavior of microbubbles and may eventually lead to better design of such delivery systems. We present the development of a high speed bright field and fluorescence imaging system that incorporates external mechanical waves such as ultrasound. Through collaborative design and contract manufacturing, a high speed imaging system has been successfully developed at the University of Pittsburgh Medical Center. We named the system "UPMC Cam," to refer to the integrated imaging system that includes the multi-frame camera and its unique software control, the customized modular microscope, the customized laser delivery system, its auxiliary ultrasound generator, and the combined ultrasound and optical imaging chamber for in vitro and in vivo observations. This system is capable of imaging microscopic bright field and fluorescence movies at 25 × 10 6 frames per second for 128 frames, with a frame size of 920 × 616 pixels. Example images of microbubble under ultrasound are shown to demonstrate the potential application of the system.

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Nonlinear Shell Behavior of Phospholipid-Coated Microbubbles

Cited by 160 publications

References 34 publications

Combined optical sizing and acoustical characterization of single freely-floating microbubbles

Combined optical sizing and acoustical characterization of single freely-floating microbubbles

Biophysical insight into mechanisms of sonoporation

Ultra-fast bright field and fluorescence imaging of the dynamics of micrometer-sized objects

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