Experimental acoustic characterization of an endoskeletal antibubble contrast agent: First results

Abstract

An antibubble is an encapsulated gas bubble with an incompressible inclusion inside the gas phase. Current-generation ultrasound contrast agents are bubble-based: they contain encapsulated gas bubbles with no inclusions. The objective of this work is to determine the linear and nonlinear responses of an antibubble contrast agent in comparison to two bubble-based ultrasound contrast agents, that is, reference bubbles and SonoVue TM . Methods: Side scatter and attenuation of the three contrast agents were measured, using single-element ultrasound transducers, operating at 1, 2.25, and 3.5 MHz. The scatter measurements were performed at acoustic pressures of 200 and 300 kPa for 1 MHz, 300 kPa, and 450 kPa for 2.25 MHz, and 370 and 560 kPa for 3.5 MHz. Attenuation measurements were conducted at pressures of 13, 55, and 50 kPa for 1, 2.25, and 3.5 MHz, respectively. In addition, a dynamic contrast-enhanced ultrasound measurement was performed, imaging the contrast agent flow through a vascular phantom with a commercial diagnostic linear array probe. Results: Antibubbles generated equivalent or stronger harmonic signal, compared to bubble-based ultrasound contrast agents. The second harmonic sidescatter amplitude of the antibubble agent was up to 3 dB greater than that of reference bubble agent and up to 4 dB greater than that of SonoVue TM at the estimated concentration of 8 × 10 4 bubbles/mL. For ultrasound with a center transmit frequency of 1 MHz, the attenuation coefficient of the antibubble agent was 8.7 dB/cm, whereas the attenuation coefficient of the reference agent was 7.7 and 0.3 dB/cm for SonoVue TM . At 2.25 MHz, the attenuation coefficients were 9.7, 3.0, and 0.6 dB/cm, respectively. For 3.5 MHz, they were 4.4, 1.8, and 1.0 dB/cm, respectively. A dynamic contrast-enhanced ultrasound recording showed the nonlinear signal of the antibubble agent to be 31% greater than for reference bubbles and 23% lower than SonoVue TM at a high concentration of 2 × 10 6 bubbles/mL. Conclusion: Endoskeletal antibubbles generate comparable or greater higher harmonics than reference bubbles and SonoVue TM . As a result, antibubbles with liquid therapeutic agents inside the gas phase have high potential to become a traceable therapeutic agent. K E Y W O R D S harmonic imaging, linear attenuation, nonlinear scattering, pickering-stabilised bubbles, ultrasound contrast agentThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Ultrasound-Responsive Systems as Components for Smart Materials

“…An alternative carrier to conventional microbubbles has recently emerged in the form of Pickering-stabilized antibubbles. , Antibubbles consist of a liquid core surrounded by a thin gas layer that separates the core from the surrounding fluid. Recently it has been shown that the liquid core causes antibubbles to oscillate asymmetrically, which gives rise to higher harmonics with nonlinear scattering strengths comparable to or higher than those for conventional microbubble contrast agents. , The nonlinear radius oscillations may also provide a mechanism to more easily burst the antibubble and deliver a payload from the core, avoiding the surface modifications required by microbubble techniques. Further functionalities can be added to antibubbles by appropriate payload selection.…”

On the rigidity of four hundred Pickering-stabilised microbubbles

“…Microbubble populations stabilised with these hydrophobised silica particles had been studied as controls at low acoustic amplitudes. 33) These populations had been measured to have a mean radius of 3 µm. Panfilova et al estimated the bulk resonance frequency near 1 MHz.…”

“…Panfilova et al estimated the bulk resonance frequency near 1 MHz. 33) A quantity of 5 mg of freeze-dried material was deposited into a FALCON ® 15 mL…”

“…Panfilova et al estimated the bulk resonance frequency near 1 MHz. 33) A quantity of 5 mg of freeze-dried material was deposited into a FALCON® 15 ml High-Clarity Polypropylene Conical Tube (Corning Science México S.A. de C.V., Reynosa, Tamaulipas, Mexico), after which 5.0 ml of 049-16787 Distilled Water (FUJIFILM Wako Pure Chemical Corporation, Chuo-Ku, Osaka, Japan) was added. The emulsion was shaken gently by hand for 1 min.…”