Broadband Attenuation Measurements of Phospholipid-Shelled Ultrasound Contrast Agents

Raymond, Jason L.; Haworth, Kevin J.; Bader, Kenneth B.; Radhakrishnan, Kirthi; Griffin, J. K.; Huang, Shaoling; McPherson, David D.; Holland, Christy K.

doi:10.1016/j.ultrasmedbio.2013.09.018

Cited by 77 publications

(112 citation statements)

References 47 publications

(91 reference statements)

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“…2(a) and 2(c) is consistent with Coulter counter measurements of the particle size distribution for this ELIP formulation, which indicated a volumeweighted mean diameter of 2 lm. 21 Previously published transmission electron microscopy images have shown liposomes on the order of 2 lm diameter 24 as well as vesicles in the nanometer size range that could not be resolved using the optical methods described here. 25,26 Atomic force microscopy 20 and fluorescence microscopy studies 26 also indicate a broad size distribution, with particle sizes ranging over three orders of magnitude from tens of nanometers to microns.…”

Section: A Experimental Setupmentioning

confidence: 79%

“…19 The exact location of the entrapped air pockets, morphology of the encapsulation, and amount of air in each carrier has not been fully ascertained. [19][20][21] The objective of the present study was to measure the damping due to the encapsulation and to estimate the shell viscosity based on the unforced response of individual ELIP exposed to a broadband acoustic impulse excitation.…”

Section: Introductionmentioning

confidence: 99%

“…The shell viscosity of individual ELIP obtained using the optical method presented here is compared to our previously reported value obtained for a population of ELIP using a broadband acoustic attenuation spectroscopy technique. 21 …”

Section: Introductionmentioning

confidence: 99%

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Impulse response method for characterization of echogenic liposomes

Raymond

Luan²,

Rooij³

et al. 2015

The Journal of the Acoustical Society of America

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An optical characterization method is presented based on the use of the impulse response to characterize the damping imparted by the shell of an air-filled ultrasound contrast agent (UCA). The interfacial shell viscosity was estimated based on the unforced decaying response of individual echogenic liposomes (ELIP) exposed to a broadband acoustic impulse excitation. Radius versus time response was measured optically based on recordings acquired using an ultra-highspeed camera. The method provided an efficient approach that enabled statistical measurements on 106 individual ELIP. A decrease in shell viscosity, from 2.1 Â 10 À8 to 2.5 Â 10 À9 kg/s, was observed with increasing dilatation rate, from 0.5 Â 10 6 to 1 Â 10 7 s À1 . This nonlinear behavior has been reported in other studies of lipid-shelled UCAs and is consistent with rheological shear-thinning. The measured shell viscosity for the ELIP formulation used in this study [j s ¼ (2.1 6 1.0) Â 10 À8 kg/s] was in quantitative agreement with previously reported values on a population of ELIP and is consistent with other lipid-shelled UCAs. The acoustic response of ELIP therefore is similar to other lipid-shelled UCAs despite loading with air instead of perfluorocarbon gas. The methods described here can provide an accurate estimate of the shell viscosity and damping for individual UCA microbubbles.

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Section: A Experimental Setupmentioning

confidence: 79%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Impulse response method for characterization of echogenic liposomes

Raymond

Luan²,

Rooij³

et al. 2015

The Journal of the Acoustical Society of America

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“…The frequency-dependent attenuation coefficient, α(f) in dB/cm, was determined using a broadband substitution technique, 35 the components of which were described U S r e c e i v e U S t r a n s m i t 36 Briefly, NOBLs were diluted (1:500) into a reservoir containing aerated phosphate-buffered saline, stirred, and allowed to flow by gravity into a sample chamber with acoustically transparent polycarbonate film windows (CLINIcell 25, Mabio, Tourcoing, France). The reservoir, sample chamber, and transducers were mounted in a test tank filled with distilled water maintained at 37°C±0.5°C using a circulating water bath (Neslab EX, Newington, NH, USA).…”

Section: Nobl Characterizationmentioning

confidence: 99%

“…(B) acoustic attenuation as a function of frequency, as determined using the system described in raymond et al 36 …”

Section: Notesmentioning

confidence: 99%

Pulsed ultrasound enhances the delivery of nitric oxide from bubble liposomes to ex vivo porcine carotid tissue

Sutton¹,

Raymond²,

Verleye³

et al. 2014

IJN

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Ultrasound-mediated drug delivery is a novel technique for enhancing the penetration of drugs into diseased tissue beds noninvasively. By encapsulating drugs into microsized and nanosized liposomes, the therapeutic can be shielded from degradation within the vasculature until delivery to a target site by ultrasound exposure. Traditional in vitro or ex vivo techniques to quantify this delivery profile include optical approaches, cell culture, and electrophysiology. Here, we demonstrate an approach to characterize the degree of nitric oxide (NO) delivery to porcine carotid tissue by direct measurement of ex vivo vascular tone. An ex vivo perfusion model was adapted to assess ultrasound-mediated delivery of NO. This potent vasodilator was coencapsulated with inert octafluoropropane gas to produce acoustically active bubble liposomes. Porcine carotid arteries were excised post mortem and mounted in a physiologic buffer solution. Vascular tone was assessed in real time by coupling the artery to an isometric force transducer. NO-loaded bubble liposomes were infused into the lumen of the artery, which was exposed to 1 MHz pulsed ultrasound at a peak-to-peak acoustic pressure amplitude of 0.34 MPa. Acoustic cavitation emissions were monitored passively. Changes in vascular tone were measured and compared with control and sham NO bubble liposome exposures. Our results demonstrate that ultrasound-triggered NO release from bubble liposomes induces potent vasorelaxation within porcine carotid arteries (maximal relaxation 31%±8%), which was significantly stronger than vasorelaxation due to NO release from bubble liposomes in the absence of ultrasound (maximal relaxation 7%±3%), and comparable with relaxation due to 12 μM sodium nitroprusside infusions (maximal relaxation 32%±3%). This approach is a valuable mechanistic tool for assessing the extent of drug release and delivery to the vasculature caused by ultrasound.

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Modulating ultrasound contrast generation from injectable nanodroplets for proton range verification by varying the degree of superheat

et al. 2021

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Purpose: Despite the physical benefits of protons over conventional photon radiation in cancer treatment, range uncertainties impede the ability to harness the full potential of proton therapy. While monitoring the proton range in vivo could reduce the currently adopted safety margins, a routinely applicable range verification technique is still lacking. Recently, phase-change nanodroplets were proposed for proton range verification, demonstrating a reproducible relationship between the proton range and generated ultrasound contrast after radiation-induced vaporization at 25°C. In this study, previous findings are extended with proton irradiations at different temperatures, including the physiological temperature of 37°C, for a novel nanodroplet formulation. Moreover, the potential to modulate the linear energy transfer (LET) threshold for vaporization by varying the degree of superheat is investigated, where the aim is to demonstrate vaporization of nanodroplets directly by primary protons. Methods: Perfluorobutane nanodroplets with a shell made of polyvinyl alcohol (PVA-PFB) or 10,12-pentacosadyinoic acid (PCDA-PFB) were dispersed in polyacrylamide hydrogels and irradiated with 62 MeV passively scattered protons at temperatures of 37°C and 50°C. Nanodroplet transition into echogenic microbubbles was assessed using ultrasound imaging (gray value and attenuation analysis) and optical images. The proton range was measured independently and compared to the generated contrast. Results: Nanodroplet design proved crucial to ensure thermal stability, as PVA-shelled nanodroplets dramatically outperformed their PCDA-shelled counterpart. At body temperature, a uniform radiation response proximal to the Bragg peak is attributed to nuclear reaction products interacting with PVA-PFB nanodroplets, with the 50% drop in ultrasound contrast being 0.17 mm AE 0.20 mm 1983

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Broadband Attenuation Measurements of Phospholipid-Shelled Ultrasound Contrast Agents

Cited by 77 publications

References 47 publications

Impulse response method for characterization of echogenic liposomes

Impulse response method for characterization of echogenic liposomes

Pulsed ultrasound enhances the delivery of nitric oxide from bubble liposomes to ex vivo porcine carotid tissue

Modulating ultrasound contrast generation from injectable nanodroplets for proton range verification by varying the degree of superheat

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