Characterization of Submicron Phase-change Perfluorocarbon Droplets for Extravascular Ultrasound Imaging of Cancer

Williams, Ronald J.; Wright, Clinton S.; Chérin, Emmanuel; Reznik, Nikita; Lee, Mike; Gorelikov, Ivan; Foster, F. Stuart; Matsuura, Naomi; Burns, Peter N.

doi:10.1016/j.ultrasmedbio.2012.10.004

Cited by 149 publications

(128 citation statements)

References 50 publications

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“…The pressure amplitudes required to induce the phase transition of the acoustically sensitive droplets seem to be substantial, with mechanical indices (16) reported to be as high as four (7), well above the FDA-approved limit for diagnostic ultrasound. A pronounced thresholding behavior has been observed for the activation, meaning that there is negligible probability for detection up to some peak negative pressure amplitude, after which the probability increases linearly with the applied acoustic pressure (7,17). Several groups have reported a dependence of the pressure threshold on the driving frequency (7,(17)(18)(19).…”

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confidence: 99%

“…A pronounced thresholding behavior has been observed for the activation, meaning that there is negligible probability for detection up to some peak negative pressure amplitude, after which the probability increases linearly with the applied acoustic pressure (7,17). Several groups have reported a dependence of the pressure threshold on the driving frequency (7,(17)(18)(19). The required threshold has been found to decrease with increasing frequency, whereas the cavitation threshold in liquids is expected to increase with increasing frequency (16).…”

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confidence: 99%

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Acoustic droplet vaporization is initiated by superharmonic focusing

Shpak

Verweij

Vos

et al. 2014

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

169

148

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Acoustically sensitive emulsion droplets composed of a liquid perfluorocarbon have the potential to be a highly efficient system for local drug delivery, embolotherapy, or for tumor imaging. The physical mechanisms underlying the acoustic activation of these phase-change emulsions into a bubbly dispersion, termed acoustic droplet vaporization, have not been well understood. The droplets have a very high activation threshold; its frequency dependence does not comply with homogeneous nucleation theory and localized nucleation spots have been observed. Here we show that acoustic droplet vaporization is initiated by a combination of two phenomena: highly nonlinear distortion of the acoustic wave before it hits the droplet and focusing of the distorted wave by the droplet itself. At high excitation pressures, nonlinear distortion causes significant superharmonics with wavelengths of the order of the droplet size. These superharmonics strongly contribute to the focusing effect; therefore, the proposed mechanism also explains the observed pressure thresholding effect. Our interpretation is validated with experimental data captured with an ultrahigh-speed camera on the positions of the nucleation spots, where we find excellent agreement with the theoretical prediction. Moreover, the presented mechanism explains the hitherto counterintuitive dependence of the nucleation threshold on the ultrasound frequency. The physical insight allows for the optimization of acoustic droplet vaporization for therapeutic applications, in particular with respect to the acoustic pressures required for activation, thereby minimizing the negative bioeffects associated with the use of high-intensity ultrasound.

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confidence: 99%

mentioning

confidence: 99%

Acoustic droplet vaporization is initiated by superharmonic focusing

Shpak

Verweij

Vos

et al. 2014

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

169

148

View full text Add to dashboard Cite

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“…These ligand-conjugates decorated on the outer surface of microbubbles are designed for selectivity to an individual cell type over normal cells due to the overexpression of specific receptor proteins on the surface of these cells [7]. This development of targeted microbubbles could lead to additional diagnostic applications for CEUS as well as other imaging modalities such as; 1) early detection of cancerous lesions; 2) localization of inflammation; and 3) an especially large role in emerging theranostics [8]. The main application of this work aims to use targeted microbubbles with an alternative imaging modality, multiphoton microscopy, which can potentially be translated as a diagnostic tool for use in a surgical setting.…”

Section: Introductionmentioning

confidence: 99%

Imaging of targeted lipid microbubbles to detect cancer cells using third harmonic generation microscopy

Harpel

Baker

Amirsolaimani

et al. 2016

Biomed. Opt. Express

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Abstract:The use of receptor-targeted lipid microbubbles imaged by ultrasound is an innovative method of detecting and localizing disease. However, since ultrasound requires a medium between the transducer and the object being imaged, it is impractical to apply to an exposed surface in a surgical setting where sterile fields need be maintained and ultrasound gel may cause the bubbles to collapse. Multiphoton microscopy (MPM) is an emerging tool for accurate, label-free imaging of tissues and cells with high resolution and contrast. We have recently determined a novel application of MPM to be used for detecting targeted microbubble adherence to the upregulated plectin-receptor on pancreatic tumor cells. Specifically, the third-harmonic generation response can be used to detect bound microbubbles to various cell types presenting MPM as an alternative and useful imaging method. This is an interesting technique that can potentially be translated as a diagnostic tool for the early detection of cancer and inflammatory disorders.

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“…The droplets are stabilized by surfactants such as fluorosurfactants 161,162 or by phospholipids 163,164 . While the boiling point of the perfluorcarbon is low (e.g.…”

Section: Introductionmentioning

confidence: 99%

“…At low acoustic pressures, the probability of vaporizing a droplet is negligible up to a certain threshold after which the probability increases linearly with the applied acoustic pressure 161,171 . Several groups have reported the decrease in the acoustic pressure threshold for increasing driving frequencies 161,171,173,174 . Recently, Shpak et al 175 have revealed that droplet vaporization is initiated by focusing of the nonlinear acoustic wave by the spherical droplet due to a mismatch in acoustic impedance between the PFC droplet and the surrounding water.…”

Section: Introductionmentioning

confidence: 99%

Monodisperse bubbles and droplets for medical applications

Segers¹

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Characterization of Submicron Phase-change Perfluorocarbon Droplets for Extravascular Ultrasound Imaging of Cancer

Cited by 149 publications

References 50 publications

Acoustic droplet vaporization is initiated by superharmonic focusing

Acoustic droplet vaporization is initiated by superharmonic focusing

Imaging of targeted lipid microbubbles to detect cancer cells using third harmonic generation microscopy

Monodisperse bubbles and droplets for medical applications

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