Experimental acoustic characterisation of an endoskeletal antibubble contrast agent: first results

International audiencePurpose: 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 encapsulted 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, i.e., reference bubbles and SonoVueᵀᴹ.Methods: Side scatter and attenuation of the three contrast agents were measured, using single-element ultrasound transducers, operating at 1 MHz, 2.25 MHz and 3.5 MHz. The scatter measurements were performed at acoustic pressures of 200 kPa and 300 kPa for 1 MHz, 300 kPa and 450 kPa for 2.25 MHz, and 370 kPa and 560 kPa for 3.5 MHz. Attenuation measurements were conducted at pressures of 13 kPa, 55 kPa and 50 kPa for 1 MHz, 2.25 MHz, 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 commertial diagnostic linear array probe.Results: Antibubbles generated equivalent or stronger harmonic signal, compared to bubble-based ultrasound contrast agents. The 2nd harmonic side-scatter 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 SonoVueᵀᴹ at the estimated concentration of 8 x 10⁴ 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 dB/cm and 0.3 dB/cm for SonoVueᵀᴹ. At 2.25 MHz the attenuation coefficients were 9.7 dB/cm, 3.0 dB/cm and 0.6 dB/cm, respectively. For 3.5 MHz, they were 4.4 dB/cm, 1.8 dB/cm and 1.0 dB/cm, respectively. We hypothesize that the antibubble agent attenuation is greater than that of the reference agent due to the solid cores in the antibubble agent. 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 SonoVueᵀᴹ at a high concentration of 2 x 10⁶ bubbles/mL.Conclusion: Endoskeletal antibubbles generate comparable or greater higher harmonics than reference bubbles and SonoVueᵀᴹ. As a result, antibubbles with liquid therapeutic agents inside the gas phase have high potential to become a traceable therapeutic agent