Acoustic Signal Characterization of Phase Change Nanodroplets in Tissue-Mimicking Phantom Gels

Asami, Rei; Ikeda, T.; Azuma, Takashi; Umemura, Shin‐ichiro; Kawabata, Kawabata Ken-Ichi

doi:10.1143/jjap.49.07hf16

Cited by 28 publications

(25 citation statements)

References 21 publications

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“…For those investigating droplet vaporization that produces stable bubbles, the models have generally predicted a monotonic expansion that can be modulated by the influence of the vaporization pulse and inward gas diffusion, which matches experimental data for DDFP microdroplets well (Shpak et al 2013b, 2013a, Wong et al 2011). For these types of droplets, the pressure wavefront generated by the initially high expansion velocities may be able to be detected as a sign of droplet vaporization – similar to the method proposed by Asami et al (Asami et al 2010). Alternative models proposed by Qamar et al (Qamar et al 2010, 2012) have suggested that, depending on droplet size and other physical properties, droplets may over-expand as a result of momentum of expansion and then settle to a final resting diameter in an oscillatory manner, although the experimental results with DDFP microdroplets did not exhibit this behavior.…”

Section: Introductionmentioning

confidence: 87%

“…Asami et al have suggested that the impulse wavefront from droplets vaporizing adjacent to a rigid boundary could be detected and used to characterize tissue properties (Asami et al 2010). More recently, Reznik et al have suggested that as bubbles produced from vaporized dodecafluoropentane (DDFP, boiling point 29°C) droplets evolve over the course of several hundred milliseconds, the change in scattered fundamental and harmonic power over time could be used to differentiate growing bubbles (produced by recently vaporized droplets) from nearby stable bubbles (Reznik et al 2011).…”

Section: Introductionmentioning

confidence: 99%

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Phase change events of volatile liquid perfluorocarbon contrast agents produce unique acoustic signatures

2013

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Phase-change contrast agents (PCCAs) provide a dynamic platform to approach problems in medical ultrasound (US). Upon US-mediated activation, the liquid core vaporizes and expands to produce a gas bubble ideal for US imaging and therapy. In this study, we demonstrate through high-speed video microscopy and US interrogation that PCCAs composed of highly volatile perfluorocarbons (PFCs) exhibit unique acoustic behavior that can be detected and differentiated from standard microbubble contrast agents. Experimental results show that when activated with short pulses PCCAs will over-expand and undergo unforced radial oscillation while settling to a final bubble diameter. The size-dependent oscillation phenomenon generates a unique acoustic signal that can be passively detected in both time and frequency domain using confocal piston transducers with an ‘activate high’ (8 MHz, 2 cycles), ‘listen low’ (1 MHz) scheme. Results show that the magnitude of the acoustic ‘signature’ increases as PFC boiling point decreases. By using a band-limited spectral processing technique, the droplet signals can be isolated from controls and used to build experimental relationships between concentration and vaporization pressure. The techniques shown here may be useful for physical studies as well as development of droplet-specific imaging techniques.

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Section: Introductionmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Phase change events of volatile liquid perfluorocarbon contrast agents produce unique acoustic signatures

2013

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“…Their results suggest that ultrasound in the presence of microbubbles, including those created by vaporized nanodroplets, transiently permeabilizes the cell nucleus and allows penetration of therapeutic drugs into the nucleus. Asami and colleagues have also proposed that nanoscale PCCAs could be used to characterize viscoelastic properties of tumors by analyzing the waveforms received post-vaporization [114]. …”

Section: Pcca Applicationsmentioning

confidence: 99%

Phase-Change Contrast Agents for Imaging and Therapy

Sheeran¹,

Dayton²

2012

CPD

215

192

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Phase-change contrast agents (PCCAs) for ultrasound-based applications have resulted in novel ways of approaching diagnostic and therapeutic techniques beyond what is possible with microbubble contrast agents and liquid emulsions. When subjected to sufficient pressures delivered by an ultrasound transducer, stabilized droplets undergo a phase-transition to the gaseous state and a volumetric expansion occurs. This phenomenon, termed acoustic droplet vaporization, has been proposed as a means to address a number of in vivo applications at the microscale and nanoscale. In this review, the history of PCCAs, physical mechanisms involved, and proposed applications are discussed with a summary of studies demonstrated in vivo. Factors that influence the design of PCCAs are discussed, as well as the need for future studies to characterize potential bioeffects for administration in humans and optimization of ultrasound parameters.

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“…Asami et al . have shown that droplet activation behavior is influenced by the viscoelastic properties of a tissue phantom (when the droplets are embedded directly in the phantom) [52]. The peak intensity of the impulse wave was reduced with increasing tissue stiffness.…”

Section: Discussionmentioning

confidence: 99%

Dual-frequency acoustic droplet vaporization detection for medical imaging

Arena

Novell

Sheeran

et al. 2015

IEEE Trans. Ultrason., Ferroelect., Freq. Contr.

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Liquid-filled perfluorocarbon droplets emit a unique acoustic signature when vaporized into to gas-filled microbubbles using ultrasound. Here, we conducted a pilot study in a tissue-mimicking flow phantom to explore the spatial aspects of droplet vaporization and investigate the effects of applied pressure and droplet concentration on image contrast and axial and lateral resolution. Control microbubble contrast agents were used for comparison. A confocal dual-frequency transducer was used to transmit at 8 MHz and passively receive at 1 MHz. Droplet signals were of significantly higher energy than microbubble signals. This resulted in improved signal separation and high contrast-to-tissue ratios (CTR). Specifically, with a peak negative pressure (PNP) of 450 kPa applied at the focus, the CTR of B-mode images was 18.3 dB for droplets and −0.4 for microbubbles. The lateral resolution was dictated by the size of the droplet activation area, with lower pressures resulting in smaller activation areas and improved lateral resolution (0.67 mm at 450 kPa). The axial resolution in droplet images was dictated by the size of the initial droplet and independent of the properties of the transmit pulse (3.86 mm at 450 kPa). In post-processing, time-domain averaging (TDA) improved droplet and microbubble signal separation at high pressures (640 kPa and 700 kPa). Taken together, these results indicate that it is possible to generate high-sensitivity, high-contrast images of vaporization events. In the future, this has the potential to be applied in combination with droplet-mediated therapy to track treatment outcomes or as a stand-alone diagnostic system to monitor the physical properties of the surrounding environment.

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Acoustic Signal Characterization of Phase Change Nanodroplets in Tissue-Mimicking Phantom Gels

Cited by 28 publications

References 21 publications

Phase change events of volatile liquid perfluorocarbon contrast agents produce unique acoustic signatures

Phase change events of volatile liquid perfluorocarbon contrast agents produce unique acoustic signatures

Phase-Change Contrast Agents for Imaging and Therapy

Dual-frequency acoustic droplet vaporization detection for medical imaging

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