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This article examines how the acoustic and stability characteristics of single lipid-shelled microbubbles (MBs) change as a result of adherence to a target surface. For individual adherent and non-adherent MBs, the backscattered echo from a narrowband 2-MHz, 90-kPa peak negative pressure interrogation pulse was obtained. These measurements were made in conjunction with an increasing amplitude broadband disruption pulse. It was found that, for the given driving frequency, adherence had little effect on the fundamental response of an MB. Examination of the second harmonic response indicated an increase of the resonance frequency for an adherent MB: resonance radius increasing of 0.3 ± 0.1 μm for an adherent MB. MB stability was seen to be closely related to MB resonance and gave further evidence of a change in the resonance frequency due to adherence., (Copyright © 2013 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Gas microbubbles are used routinely to improve contrast in medical diagnostic imaging. The emerging fields of microbubble-enhanced quantitative imaging and microbubble-enhanced drug delivery have further enhanced the drive toward microbubble characterization and design techniques. The quest to improve efficiency, particularly in the field of drug delivery, presents a requirement to develop methods to manipulate microbubble properties to improve utility. This article presents an investigation in to the feasibility of influencing albumin shelled microbubble properties through the variation of albumin availability during fabrication. Microbubbles were fabricated from albumin suspensions of varying concentration before thorough physical and acoustic characterization. Microbubbles with shells fabricated from a 2% albumin suspension had a greater scattering to attenuation ratio (STAR) than 10% albumin preparations (4.4% and 2.2%, respectively) and approximately double the nonlinear STAR (from 0.7% to 1.5%). The 2% microbubbles also exhibited greater (up to 40%), more violent radial oscillations during high speed imaging than 5% and 10% preparations. The results show that microbubble characteristics can be simply manipulated in the lab and indicate that for a given application this may provide the opportunity to further enhance favorable characteristics., (Copyright © 2012 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Ultrasound and microbubble mediated gene transfection has great potential for site-selective, safe gene delivery. Albumin-based microbubbles have shown the greatest transfection efficiency but have not been optimised specifically for this purpose. Additionally, few studies have highlighted desirable properties for transfection specific microbubbles. In this article, microbubbles were made with 2% or 5% (w/v) albumin and 20% or 40% (w/v) dextrose solutions, yielding four distinct bubble types. These were acoustically characterised and their efficiency in transfecting a luciferase plasmid (pGL4.13) into female, CD1 mice myocardia was measured. For either albumin concentration, increasing the dextrose concentration increased scattering, attenuation and resistance to ultrasound, resulting in significantly increased transfection. A significant interaction was noted between albumin and dextrose; 2% albumin bubbles made with 20% dextrose showed the least transfection but the most transfection with 40% dextrose. This trend was seen for both nonlinear scattering and attenuation behaviour but not for resistance to ultrasound or total scatter. We have determined that the attenuation behaviour is an important microbubble characteristic for effective gene transfection using ultrasound. Microbubble behaviour can also be simply controlled by altering the initial ingredients used during manufacture., (Copyright © 2012 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Accurate acoustic characterisation is an essential component of any experimental investigation concerning the use and development of microbubble contrast agents. It is of increasing importance as applications such as therapy and molecular and quantitative imaging are investigated. Such characterisation is generally conducted in the laboratory in the form of bulk acoustic studies or optical observation of single bubbles using high speed photography in a water tank containing "out-gassed" water. The approach is widely used in acoustics to prevent inaccurate measurements being made due to the presence of gas bubbles settling on instrumentation, however, the term is often used to cover a range of water preparation techniques and the final gas content of the water is not usually stated. This technical note demonstrates the influence of gas content on the stability of microbubble contrast agents and concludes that characterisation should always be conducted in equilibrated, gas-saturated water to ensure accurate and repeatable measurements are made., (Copyright © 2012 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Previous work by the authors has established that increasing the temperature of the suspending liquid from 20°C to body temperature has a significant impact on the bulk acoustic properties and stability of an ultrasound contrast agent suspension (SonoVue, Bracco Suisse SA, Manno, Lugano, Switzerland). In this paper the influence of temperature on the nonlinear behavior of microbubbles is investigated, because this is one of the most important parameters in the context of diagnostic imaging. High-speed imaging showed that raising the temperature significantly influences the dynamic behavior of individual microbubbles. At body temperature, microbubbles exhibit greater radial excursion and oscillate less spherically, with a greater incidence of jetting and gas expulsion, and therefore collapse, than they do at room temperature. Bulk acoustics revealed an associated increase in the harmonic content of the scattered signals. These findings emphasize the importance of conducting laboratory studies at body temperature if the results are to be interpreted for in vivo applications., (Copyright © 2011 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Ultrasound and microbubble-mediated gene transfection are potential tools for safe, site-selective gene therapy. However, preclinical trials have demonstrated a low transfection efficiency that has hindered the progression of the technique to clinical application. In this paper it is shown that simple changes to the method of intravenous injection can lead to an increase in transfection efficiency when using 6-MHz diagnostic ultrasound and the ultrasound contrast agent, SonoVue. By using needles of progressively smaller gauge, i.e., larger internal diameter (ID), from 29 G (ID 0.184 mm) to 25 G (ID 0.31 mm), the transfection of a luciferase plasmid (pGL4.13) was significantly increased threefold in heart-targeted female CD1 mice. In vitro work indicated that the concentration and size distribution of SonoVue were affected by increasing needle gauge. These results suggest that the process of systemic delivery alters the bubble population and adversely affects transfection. This is exacerbated by using high-gauge needles. These findings demonstrate that the needle with the largest possible ID should be used for systemic delivery of microbubbles and genetic material., (Copyright © 2011 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Recent interest in ultrasound contrast agents (UCAs) as tools for quantitative imaging and therapy has increased the need for accurate characterization. Laboratory investigations are frequently undertaken in a water bath at room temperature; however, implications for in vivo applications are not presented. Acoustic investigation of a bulk suspension of SonoVue (Bracco Research, Geneva, Switzerland) was made in a water bath at temperatures of 20-45 degrees C. UCA characteristics were significantly affected by temperature, particularly between 20 and 40 degrees C, leading to an increase in attenuation from 1.7-2.5 dB, respectively (p = 0.002) and a 2-dB increase in scattered signal over the same range (p = 0.05) at an insonation pressure of 100 kPa. Optical data supported the hypothesis that a temperature-mediated increase in diameter was the dominant cause, and revealed a decrease in bubble stability. In conclusion, measurements made at room temperature require careful interpretation with regard to behavior in vivo., (Copyright 2010 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)