Future Applications of Contrast Ultrasound

Wei, Kevin

doi:10.4250/jcu.2011.19.3.107

Cited by 10 publications

(9 citation statements)

References 42 publications

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“…The clinical translation of ultrasound molecular imaging (Klibanov et al 1997; Lindner et al 2001), using ligand-decorated microbubbles to target molecular markers expressed by angiogenesis (Tardy et al 2010), will be the ultimate application in terms of early tumor detection. Furthermore, the use of microbubbles as vehicles for local drug delivery is an emerging field under investigation in targeted cancer therapies (Wei 2011). In particular, it will allow reduction of the therapeutic dose and attenuation of systemic side effects.…”

Section: Introductionmentioning

confidence: 99%

Acoustic Characterization and Pharmacokinetic Analyses of New Nanobubble Ultrasound Contrast Agents

Rognin

Krupka

et al. 2013

Ultrasound in Medicine & Biology

128

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: Introductionmentioning

confidence: 99%

Acoustic Characterization and Pharmacokinetic Analyses of New Nanobubble Ultrasound Contrast Agents

Rognin

Krupka

et al. 2013

Ultrasound in Medicine & Biology

128

117

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“…Currently, MCA's are used clinically to monitor blood perfusion in several organs (for a recent comprehensive review on clinical applications of microbubbles, see 2) and molecular targeting in preclinical studies 2-7 and clinical trials 8. MCA's, although typically used to enhance US contrast for imaging, are becoming increasingly popular for systemically targeting drugs and genes to malignant tissue 9, 10.…”

Section: Introductionmentioning

confidence: 99%

Advances in Ultrasound Mediated Gene Therapy Using Microbubble Contrast Agents

Sirsi¹,

Borden²

2012

Theranostics

200

156

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Microbubble ultrasound contrast agents have the potential to dramatically improve gene therapy treatments by enhancing the delivery of therapeutic DNA to malignant tissue. The physical response of microbubbles in an ultrasound field can mechanically perturb blood vessel walls and cell membranes, enhancing drug permeability into malignant tissue. In this review, we discuss literature that provided evidence of specific mechanisms that enhance in vivo gene delivery utilizing microbubble contrast agents, namely their ability to 1) improving cell membrane permeability, 2) modulate vascular permeability, and 3) enhance endocytotic uptake in cells. Additionally, we review novel microbubble vectors that are being developed in order to exploit these mechanisms and deliver higher gene payloads with greater target specificity. Finally, we discuss some future considerations that should be addressed in the development of next-generation microbubbles in order to improve in vivo microbubble gene delivery. Overall, microbubbles are rapidly gaining popularity as efficient gene carriers, and combined with their functionality as imaging contrast agents, they represent powerful theranostic tools for image guided gene therapy applications.

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“…Contrast agents contain a gas with low diffusibility and solubility and a shell of lipids, albumin, or galactose to prolong their life span [9]. The microbubbles have a smaller diameter than that of red blood cells, resist arterial pressure, and remain intravascular in the intact circulation.…”

Section: Introductionmentioning

confidence: 99%

Postoperative Assessment of Myocardial Function and Microcirculation in Patients with Acute Coronary Syndrome by Myocardial Contrast Echocardiography

2017

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BackgroundPostoperative myocardial function and microcirculation of acute coronary syndrome (ACS) was assessed by myocardial contrast echocardiography (MCE).Material/MethodsEighty-nine ACS patients treated with percutaneous coronary intervention (PCI) were detected by MCE and two-dimensional ultrasonography before and a month later after PCI respectively. Their myocardial perfusion was evaluated by myocardial contrast score (MSC) and contrast score index (CSI); cross-sectional area of microvessel (A), average myocardial microvascular impairment (β), and myocardial blood flow (MBF) were analyzed by cardiac ultrasound quantitative analysis (CUSQ), and fractional flow reserve (FFR) change was observed. Left ventricular ejection fraction (LVEF), left ventricular end-diastolic dimension (LVEDD), and left ventricular end-systolic dimension (LVESD) were observed; the index of microcirculatory resistance (IMR), FFR, and coronary flow reserve (CFR) were detected to evaluate coronary microcirculation.ResultsNone of the 89 patients experienced no-reflow. Patients with normal myocardial perfusion mostly had normal or slightly decreased ventricular wall motion after PCI. A month after the operation, there was an increase in A, β, MBF, LVEF, E/A, IMR, FFR, and CFR (all P<0.05), while LVEDD, LVESD, diastolic gallop A peak, E/Ea, E/Ea×S, and Tei decreased (all P<0.05). LVEF and IMR were in positive correlations with A. LVEF, IMR, FFR and CFR were positively correlated with β and MBF (both r>0, P<0.05), while E/Ea×Sa and Tei were negatively correlated with β and MBF (r<0, P<0.05).ConclusionsMCE can safely assess post-PCI myocardial function and microcirculation of ASC.

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Future Applications of Contrast Ultrasound

Cited by 10 publications

References 42 publications

Acoustic Characterization and Pharmacokinetic Analyses of New Nanobubble Ultrasound Contrast Agents

Acoustic Characterization and Pharmacokinetic Analyses of New Nanobubble Ultrasound Contrast Agents

Advances in Ultrasound Mediated Gene Therapy Using Microbubble Contrast Agents

Postoperative Assessment of Myocardial Function and Microcirculation in Patients with Acute Coronary Syndrome by Myocardial Contrast Echocardiography

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