More Than Bubbles: Creating Phase-Shift Droplets from Commercially Available Ultrasound Contrast Agents

Sheeran, Paul S.; Yoo, Kimoon; Williams, Ronald J.; Yin, Melissa; Foster, F. Stuart; Burns, Peter N.

doi:10.1016/j.ultrasmedbio.2016.09.003

Cited by 41 publications

(31 citation statements)

References 38 publications

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“…Further, improvements in intratumoral pressure estimation sensitivity and accuracy using TIPE-US may also be realized by integration of MB-sensitive imaging functionality (Ghosh et al, 2017;Ghosh et al, 2019;Hoyt et al, 2015;Saini and Hoyt, 2014) and volumetric US imaging to incorporate a larger sample from 3D space (Hoyt et al, 2012a,b;Mahoney et al, 2014). While different formulation strategies exist, a recent scientific publication detailed how PCCAs can be generated directly from commercially available MB products (Sheeran et al, 2017), which could help accelerate clinical translation of any TIPE-US system.…”

Section: Figmentioning

confidence: 99%

Impact of hydrostatic pressure on phase-change contrast agent activation by pulsed ultrasound

Raut

Khairalseed

Honari

et al. 2019

The Journal of the Acoustical Society of America

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A phase-change contrast agent (PCCA) can be activated from a liquid (nanodroplet) state using pulsed ultrasound (US) energy to form a larger highly echogenic microbubble (MB). PCCA activation is dependent on the ambient pressure of the surrounding media, so any increase in hydrostatic pressure demands higher US energies to phase transition. In this paper, the authors explore this basic relationship as a potential direction for noninvasive pressure measurement and foundation of a unique technology the authors are developing termed tumor interstitial pressure estimation using ultrasound (TIPE-US). TIPE-US was developed using a programmable US research scanner. A custom scan sequence interleaved pulsed US transmissions for both PCCA activation and detection. An automated US pressure sweep was applied, and US images were acquired at each increment. Various hydrostatic pressures were applied to PCCA samples. Pressurized samples were imaged using the TIPE-US system. The activation threshold required to convert PCCA from the liquid to gaseous state was recorded for various US and PCCA conditions. Given the relationship between the hydrostatic pressure applied to the PCCA and US energy needed for activation, phase transition can be used as a surrogate of hydrostatic pressure. Consistent with theoretical predictions, the PCCA activation threshold was lowered with increasing sample temperature and by decreasing the frequency of US exposure, but it was not impacted by PCCA concentration.

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Section: Figmentioning

confidence: 99%

Impact of hydrostatic pressure on phase-change contrast agent activation by pulsed ultrasound

Raut

Khairalseed

Honari

et al. 2019

The Journal of the Acoustical Society of America

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“…Finally, homogeneous nucleation theory accurately predicts that thermal vaporization must occur at the spinodal (80%–90% of the critical temperature [34]), which marks the boundary of the region where homogeneous states are stable. Thermal vaporization at the spinodal has been observed experimentally [29], [35]. It is important to note that the homogeneous nucleation theory predicts that superheated microscale and nanoscale droplets are in a metastable kinetically trapped state owing to a local minimum in the free energy landscape.…”

Section: Governing Principlesmentioning

confidence: 99%

“…It has more recently been adapted to produce photoacoustic contrast agents [39], [55], and provides a novel opportunity to produce phase-shift droplets directly from commercially available microbubble contrast agents [35]. However, there are some limitations.…”

Section: Particle Generation Techniquesmentioning

confidence: 99%

Methods of Generating Submicrometer Phase-Shift Perfluorocarbon Droplets for Applications in Medical Ultrasonography

Sheeran

Matsuura

Borden

et al. 2017

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

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Continued advances in the field of ultrasound and ultrasound contrast agents have created new approaches to imaging and medical intervention. Phase-shift perfluorocarbon droplets, which can be vaporized by ultrasound energy to transition from the liquid to the vapor state, are one of the most highly researched alternatives to clinical ultrasound contrast agents (i.e., microbubbles). In this paper, part of a special issue on methods in biomedical ultrasonics, we survey current techniques to prepare ultrasound-activated nanoscale phase-shift perfluorocarbon droplets, including sonication, extrusion, homogenization, microfluidics, and microbubble condensation. We provide example protocols and discuss advantages and limitations of each approach. Finally, we discuss best practice in characterization of this class of contrast agents with respect to size distribution and ultrasound activation.

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“…This study takes advantage of the high temporal resolution of high-frame-rate imaging and the low activation threshold of the OFP nanodroplets to perform faster super-resolution imaging than previously demonstrated. The homemade OFP nanodroplets solution has the same composition as the commercial Definity©microbubble contrast agents [34]. This means that the condensation of Definity©microbubble contrast agents to nanodroplet solution can be used with this technique for preclinical in vivo experiments in the future and could facilitate the clinical translation of super-resolution ultrasound imaging.…”

Section: F Potential Applicationsmentioning

confidence: 99%

Fast Acoustic Wave Sparsely Activated Localization Microscopy: Ultrasound Super-Resolution Using Plane-Wave Activation of Nanodroplets

Zhang

Harput

et al. 2019

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

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Localization-based ultrasound super-resolution imaging using microbubble contrast agents and phase-change nanodroplets has been developed to visualize microvascular structures beyond the diffraction limit. However, the long data acquisition time makes the clinical translation more challenging. In this study, fast acoustic wave sparsely activated localization microscopy (fast-AWSALM) was developed to achieve superresolved frames with subsecond temporal resolution, by using low-boiling-point octafluoropropane nanodroplets and high frame rate plane waves for activation, destruction, as well as imaging. Fast-AWSALM was demonstrated on an in vitro microvascular phantom to super-resolve structures that could not be resolved by conventional B-mode imaging. The effects of the temperature and mechanical index on fast-AWSALM were investigated. The experimental results show that subwavelength microstructures as small as 190 µm were resolvable in 200 ms with plane-wave transmission at a center frequency of 3.5 MHz and a pulse repetition frequency of 5000 Hz. This is about a 3.5-fold reduction in point spread function full-width-half-maximum compared to that measured in the conventional B-mode, and two orders of magnitude faster than the recently reported AWSALM under a nonflow/very slow flow situations and other localization-based methods. Just as in AWSALM, fast-AWSALM does not require flow, as is required by current microbubblebased ultrasound super-resolution techniques. In conclusion, this study shows the promise of fast-AWSALM, a super-resolution ultrasound technique using nanodroplets, which can generate super-resolution images in milliseconds and does not require flow.

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More Than Bubbles: Creating Phase-Shift Droplets from Commercially Available Ultrasound Contrast Agents

Cited by 41 publications

References 38 publications

Impact of hydrostatic pressure on phase-change contrast agent activation by pulsed ultrasound

Impact of hydrostatic pressure on phase-change contrast agent activation by pulsed ultrasound

Methods of Generating Submicrometer Phase-Shift Perfluorocarbon Droplets for Applications in Medical Ultrasonography

Fast Acoustic Wave Sparsely Activated Localization Microscopy: Ultrasound Super-Resolution Using Plane-Wave Activation of Nanodroplets

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