Vaporization dynamics of volatile perfluorocarbon droplets: a theoretical model and in vitro validation (original) (raw)
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Initial growth and coalescence of acoustically vaporized perfluorocarbon microdroplets
Ultrasonics Symposium, 2008. …, 2008
Acoustic droplet vaporization (ADV) is a technique whereby liquid droplets are vaporized into gas bubbles using ultrasound. This process and the resulting bubbles have been proposed for embolization, drug delivery, aberration correction, and bubble-enhanced high intensity focused ultrasound. To increase the efficacy of these applications, high-speed photography was used to study the initial phase-transition process.
The Journal of the Acoustical Society of America, 2019
Phase shift liquid perfluorocarbon (PFC) droplets vaporizable by ultrasound into echogenic microbubble above a threshold pressure, termed acoustic droplet vaporization (ADV), are used for therapeutic and diagnostic applications. This study systematically investigated the effect of excitation frequency (2.25, 10, and 15 MHz) on the ADV and inertial cavitation (IC) thresholds of lipid-coated PFC droplets of three different liquid cores-perfluoropentane (PFP), perfluorohexane (PFH), and perfluorooctyl bromide (PFOB)-and of two different sizes-average diameters smaller than 3 lm and larger than 10 lm-in a tubeless setup. This study found that the ADV threshold increases with frequency for the lowest boiling point liquid, PFP, for both large and small size droplets. For higher boiling point liquids, PFH and PFOB, this study did not detect vaporization for small size droplets at the excitation levels (maximum 4 MPa peak negative) studied here. The large PFOB droplets experienced ADV only at the highest excitation frequency 15 MHz. For large PFH droplets, ADV threshold decreases with frequency that could possibly be due to the superharmonic focusing being a significant effect at larger sizes and the higher excitation pressures. ADV thresholds at all the frequencies studied here occurred at lower rarefactional pressures than IC thresholds indicating that phase transition precedes inertial cavitation. V
Acoustic vaporization threshold of lipid coated perfluoropentane droplets
The Journal of the Acoustical Society of America, 2017
Phase shift droplets vaporizable by acoustic stimulation offer the advantages of producing microbubbles as contrast agents in situ as well as higher stability and the possibility of achieving smaller sizes. Here, the acoustic droplet vaporization (ADV) threshold of a suspension of droplets with a perfluoropentane (PFP) core (diameter 400-3000 nm) is acoustically measured as a function of the excitation frequency in a tubeless setup at room temperature. The changes in scattered responsesfundamental, sub-, and second harmonic-are investigated, a quantitative criterion is used to determine the ADV phenomenon, and findings are discussed. The average threshold obtained using three different scattered components increases with frequency-1.05 6 0.28 MPa at 2.25 MHz, 1.89 6 0.57 MPa at 5 MHz, and 2.34 6 0.014 MPa at 10 MHz. The scattered response from vaporized droplets was also found to qualitatively match with that from an independently prepared lipidcoated microbubble suspension in magnitude as well as trends above the determined ADV threshold value. V
Ultrasound in Medicine & Biology, 2021
A combination of ultra high-speed optical imaging (5 x 10 6 frames/s), B-mode ultrasound and passive cavitation detection was used to study the vaporization process and determine both the acoustic droplet vaporization (ADV) and inertial cavitation (IC) thresholds of phospholipid-coated perfluorobutane nanodroplets (PFB-NDs; diameter 237 nm ± 16 nm). PFB-NDs have not previously been studied with ultra high-speed imaging and were observed to form individual microbubbles (1-10 μm) within 2-3 cycles and subsequently larger bubble clusters (10-50 μm). The ADV and IC thresholds were not statistically significantly different and decreased with increasing pulse length (20-20000 cycles), pulse repetition frequency (1-100 Hz), concentration (10 8-10 10 ND/ml), temperature (20-45 o C) and decreasing frequency (1.5-0.5 MHz). Overall, the results indicate that at frequencies of 0.5, 1.0 and 1.5 MHz, PFB-NDs can be vaporized at moderate peak negative pressures (< 2.0 MPa), pulse lengths and pulse repetition frequencies. This finding is encouraging for the use of PFB-NDs as cavitation agents, as these conditions are comparable to those required to achieve therapeutic effects with microbubbles, unlike those reported for higher boiling point NDs. The differences between the optically and acoustically determined ADV thresholds, however, suggest that application-specific thresholds should be defined according to the biological/therapeutic effect of interest.
Journal of Controlled Release, 2019
Perfluorocarbon emulsion nanodroplets containing iron oxide nanoparticles (IONPs) within their inner perfluorohexane (PFH) core were prepared to investigate potential use as an acoustically activatable ultrasound contrast agent, with the hypothesis that incorporation of IONPs into the fluorous phase of a liquid perfluorocarbon emulsion would potentiate acoustic vaporization. IONPs with an oleic acid (OA) hydrophobic coating were synthesized through chemical co-precipitation. To suspend IONP in PFH, OA was exchanged with perfluorononanoic acid (PFNA) via ligand exchange to yield fluorophilic PFNA-coated IONPs (PFNA-IONPs). Suspensions with various amounts of PFNA-IONPs (0-15% w/v) in PFH were emulsified in saline by sonication, using 5% (w/v) egg yolk phospholipid as an emulsifier. PFNA-IONPs were characterized with transmission electron microscopy (TEM), transmission electron cryomicroscopy (cryoTEM), and thermogravimetric analysis (TGA) with Fourier transform infrared spectroscopy (FTIR). IONP were between 5 and 10 nm in diameter as measured by electron microscopy, and hydrodynamic size of the PFH nanodroplets were 150 to 230 nm as measured by dynamic light scattering (DLS). Acoustic droplet vaporization of PFH nanodroplets (PFH-NDs) was induced using conversion pulses (100 cycle at 1.1 MHz and 50% duty cycle) provided by a focused ultrasound transducer, and formed microbubbles were imaged using a clinical ultrasound scanner. The acoustic pressure threshold needed for PFH-NDs vaporization decreased with increasing temperature and IONP content. PFH-NDs containing 5% w/v IONP converted to microbubbles at 42°C at 2.18 MI, which is just above the exposure limits of 1.9 MI allowed by the FDA for clinical ultrasound scanners, whereas 10 and 15% emulsion vaporized at 1.87 and 1.24 MI, respectively. Furthermore, 5% IONP-loaded PFH-NDs injected intravenously into melanomabearing mice at a dose of 120 mg PFH/kg, converted into detectable microbubbles in vivo 5 h, but not shortly after injection, indicating that this technique detects NDs accumulated in tumors.
2011
An acoustic and photoacoustic characterization of micron-sized perfluorocarbon (PFC) droplets is presented. PFC droplets are currently being investigated as acoustic and photoacoustic contrast agents and as cancer therapy agents. Pulse echo measurements at 375 MHz were used to determine the diameter, ranging from 3.2 to 6.5 μm, and the sound velocity, ranging from 311 to 406 m/s of nine droplets. An average sound velocity of 379 +/- 18 m/s was calculated for droplets larger than the ultrasound beam width of 4.0 μm. Optical droplet vaporization, where vaporization of a single droplet occurred upon laser irradiation of sufficient intensity, was verified using pulse echo acoustic methods. The ultrasonic backscatter amplitude, acoustic impedance and attenuation increased after vaporization, consistent with a phase change from a liquid to gas core. Photoacoustic measurements were used to compare the spectra of three droplets ranging in diameter from 3.0 to 6.2 μm to a theoretical model. Good agreement in the spectral features was observed over the bandwidth of the 375 MHz transducer.
Photons Plus Ultrasound: Imaging and Sensing 2011, 2011
An acoustic and photoacoustic characterization of micron-sized perfluorocarbon (PFC) droplets is presented. PFC droplets are currently being investigated as acoustic and photoacoustic contrast agents, as well as cancer therapy agents. Pulse echo measurements at 375 MHz were used to determine the PFC diameter of nine droplets, ranging from 3.2 to 6.7 µm, and the PFC sound velocity, ranging from 311 to 406 m/s. An average sound velocity of 379 ± 18 m/s was calculated if droplets smaller than the ultrasonic beam width of 4.0 µm were excluded. Optical droplet vaporization, where vaporization of a single droplet occurred upon laser irradiation of sufficient intensity (above 1.5 J/cm 2 ), was verified using acoustic methods. The ultrasonic backscatter amplitude, acoustic impedance and attenuation increased after vaporization, consistent with a phase change from a liquid to gas core. Using laser irradiation values below the vaporization threshold, photoacoustic measurements were used to compare the photoacoustic ultrasound emission spectra of three droplets of varying diameters to a theoretical model. Good agreement of the experimental results with theoretical predictions of the ultrasound spectral features were observed over the bandwidth of the 375 MHz transducer.
Vaporization of perfluorocarbon droplets using optical irradiation
2011
Micron-sized liquid perfluorocarbon (PFC) droplets are currently being investigated as activatable agents for medical imaging and cancer therapy. After injection into the bloodstream, superheated PFC droplets can be vaporized to a gas phase for ultrasound imaging, or for cancer therapy via targeted drug delivery and vessel occlusion. Droplet vaporization has been previously demonstrated using acoustic methods. We propose using laser irradiation as a means to induce PFC droplet vaporization using a method we term optical droplet vaporization (ODV). In order to facilitate ODV of PFC droplets which have negligible absorption in the infrared spectrum, optical absorbing nanoparticles were incorporated into the droplet. In this study, micron-sized PFC droplets loaded with silica-coated lead sulfide (PbS) nanoparticles were evaluated using a 1064 nm laser and ultra-high frequency photoacoustic ultrasound (at 200 and 375 MHz). The photoacoustic response was proportional to nanoparticle loading and successful optical droplet vaporization of individual PFC droplets was confirmed using photoacoustic, acoustic, and optical measurements. A minimum laser fluence of 1.4 J/cm(2) was required to vaporize the droplets. The vaporization of PFC droplets via laser irradiation can lead to the activation of PFC agents in tissues previously not accessible using standard ultrasound-based techniques.
Ultrasound in Medicine & Biology, 2015
Many studies have explored phase-change contrast agents (PCCAs) that can be vaporized by an ultrasonic pulse to form microbubbles for ultrasound imaging and therapy. However, few investigations have been published demonstrating the utility and characteristics of PCCAs as contrast agents in vivo. In this study, we examine the properties of low boiling point nanoscale PCCAs evaluated in vivo, and compare data to conventional microbubbles with respect to contrast generation and circulation properties. In order to do this, we develop a custom pulse sequence to vaporize and image PCCAs using the Verasonics research platform and a clinical array transducer. Results show that droplets can produce similar contrast enhancement to microbubbles (7.29 to 18.24 dB over baseline, depending on formulation), and can be designed to circulate for as much as 3.3 times longer than microbubbles. This study also demonstrates for the first time the ability to capture contrast wash-out kinetics of the target organ as a measure of vascular perfusion.
Optical droplet vaporization (ODV): photoacoustic characterization of perfluorocarbon droplets
… (IUS), 2010
Optical droplet vaporization (ODV) of nanoscale and micron-sized liquid perfluorocarbon (PFC) droplets via a 1064 nm laser is presented. The stability and laser fluence threshold were investigated for PFC compounds with varying boiling points. Using an external optical absorber to facilitate droplet vaporization, it was found that droplets with boiling points at 29°C and 56°C were consistently vaporized upon laser irradiation using a fluence of 0.7 J/cm 2 or greater, while those with higher boiling points did not, up to a maximum laser fluence of 3.8 J/cm 2 . Upon vaporization, the droplet rapidly expanded to approximately 10-20x the original diameter, then slowly and continuously expanded at a rate of up to 1 µm/s. Lead sulphide (PbS) nanoparticles were incorporated into perfluoropentane (PFP) droplets to facilitate vaporization. The fluence threshold to induce vaporization ranged from 0.8 to 1.6 J/cm 2 , the wide range likely due to variances of the PbS concentration within the droplets. Prior to vaporization, the photoacoustic spectral features of individual droplets 2-8 µm in diameter measured at 375 MHz agreed very well with the theoretical prediction using a liquid sphere model. In summary, the use of liquid droplets for photoacoustic imaging and cancer therapy has been demonstrated.