A Simple Method for Quantifying Ultrasound-Triggered Microbubble Destruction

Hung, Shuo-Hui; Yeh, Chih Kuang; Tsai, Tung Hu; Chen, Tom; Chen, Ran Chou

doi:10.1016/j.ultrasmedbio.2011.03.005

Cited by 37 publications

(25 citation statements)

References 35 publications

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“…Other studies have reported that microbubble linearized image intensity on ultrasound images is proportional to contrast agent concentration within a certain range (Lampaskis and Averkiou 2010). It was also suggested that the time-intensity curve of contrast-enhanced ultrasound (CEUS) can mimic the pharmacokinetic concentration-time curve of bubbles (Hung et al 2011). In the present study, we observed the pharmacokinetic features of nanobubbles and Definity microbubbles in tumor-bearing mice using CEUS techniques similar to the published procedures (Hung et al 2011).…”

Section: Discussionmentioning

confidence: 99%

Acoustic Characterization and Pharmacokinetic Analyses of New Nanobubble Ultrasound Contrast Agents

Rognin

Krupka

et al. 2013

Ultrasound in Medicine & Biology

127

117

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In contrast to the clinically used microbubble ultrasound contrast agents, nanoscale bubbles (or nanobubbles) may potentially extravasate into tumors that exhibit more permeable vasculature, facilitating targeted molecular imaging and drug delivery. Our group recently presented a simple strategy using the non-ionic surfactant Pluronic as a size control excipient to produce nanobubbles with a mean diameter of 200 nm that exhibited stability and echogenicity on par with microbubbles. The objective of this study was to carry out an in-depth characterization of nanobubble properties as compared with Definity microbubbles, both in vitro and in vivo. Through use of a tissue-mimicking phantom, in vitro experiments measured the echogenicity of the contrast agent solutions and the contrast agent dissolution rate over time. Nanobubbles were found to be more echogenic than Definity microbubbles at three different harmonic frequencies (8, 6.2 and 3.5 MHz). Definity microbubbles also dissolved 1.67 times faster than nanobubbles. Pharmacokinetic studies were then performed in vivo in a subcutaneous human colorectal adenocarcinoma (LS174T) in mice. The peak enhancement and decay rates of contrast agents after bolus injection in the liver, kidney and tumor were analyzed. No significant differences were observed in peak enhancement between the nanobubble and Definity groups in the three tested regions (tumor, liver and kidney). However, the decay rates of nanobubbles in tumor and kidney were significantly slower than those of Definity in the first 200-s fast initial phase. There were no significant differences in the decay rate in the liver in the initial phase or in three regions of interest in the terminal phase. Our results suggest that the stability and acoustic properties of the new nanobubble contrast agents are superior to those of the clinically used Definity microbubbles. The slower washout of nanobubbles in tumors suggests potential entrapment of the bubbles within the tumor parenchyma.

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Section: Discussionmentioning

confidence: 99%

Acoustic Characterization and Pharmacokinetic Analyses of New Nanobubble Ultrasound Contrast Agents

Rognin

Krupka

et al. 2013

Ultrasound in Medicine & Biology

127

117

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“…If a therapeutic agent is delivered directly to a target area the local concentration of a drug can be increased by reducing systemic toxicity [52]. Ultrasound can be applied to guide and achieve such deposition of small elements carried in small bubbles in the blood.…”

Section: Us-guided Interventions In the Gi Wallmentioning

confidence: 99%

High-frequency ultrasonographic imaging of the gastrointestinal wall

Ødegaard

Nesje

Lærum

et al. 2012

Expert Review of Medical Devices

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“…Sboros et al [36] reported on the backscatter of Uca suspensions as a function of concentration and pressure using definity (duPont Pharmaceutical, Waltham, Ma) and quantison (quadrant Healthcare, nottingham, UK) contrast agents and MIs < 1. Hung et al [37] quantified the destruction effects of different MIs (up to MI = 1) in vivo using SonoVue microbubbles.…”

Section: Introductionmentioning

confidence: 99%

“…When microbubble properties are investigated using a diagnostic ultrasound scanner, signal saturation can be a problem for quantification of time-intensity curves (TIcs) Manuscript [21], [37]- [39]. The dynamic range of the backscattered signals varies dramatically depending on the bubble concentration and the MI used.…”

Section: Introductionmentioning

confidence: 99%

Accurate measurement of microbubble response to ultrasound with a diagnostic ultrasound scanner

Keravnou

Mannaris

Averkiou

2015

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

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Ultrasound and microbubbles are often used to enhance drug delivery and the suggested mechanisms are extravasation and sonoporation. Drug delivery schemes with ultrasound and microbubbles at both low and high acoustic amplitudes have been suggested. A diagnostic ultrasound scanner may play a double role as both an imaging and a therapy device. It was not possible to accurately measure microbubble response with an ultrasound scanner for a large range of acoustic pressures and microbubble concentrations until now, mainly because of signal saturation issues. A method for continuously adjusting the receive gain of a scanner and limiting signal saturation was developed to accurately measure backscattered echoes from microbubbles for mechanical indexes (MIs) up to 2.1. The intensity of backscattered echoes from microbubbles increased quarticly with MI without reaching any limit. The signal intensity from microbubbles was found to be linear with concentration at both low and high MIs. However, at very high concentrations, acoustic shadowing occurs which limits the delivered acoustic pressure in deeper areas. The contrastto- tissue ratio was also measured and found to stay constant with MI. These results can be used to better guide drug delivery approaches and to also develop imaging techniques for therapy procedures.

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A Simple Method for Quantifying Ultrasound-Triggered Microbubble Destruction

Cited by 37 publications

References 35 publications

Acoustic Characterization and Pharmacokinetic Analyses of New Nanobubble Ultrasound Contrast Agents

Acoustic Characterization and Pharmacokinetic Analyses of New Nanobubble Ultrasound Contrast Agents

High-frequency ultrasonographic imaging of the gastrointestinal wall

Accurate measurement of microbubble response to ultrasound with a diagnostic ultrasound scanner

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