Electrical Engineering Department, Faculty of Electrical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.
Department of Urology, Amsterdam University Medical Centers location AMC, Amsterdam, The Netherlands.
Med Phys. 2021 Nov;48(11):6765-6780. doi: 10.1002/mp.15242. Epub 2021 Oct 14.
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 .
Side scatter and attenuation of the three contrast agents were measured, using single-element ultrasound transducers, operating at 1.0, 2.25, and 3.5 MHz. The scatter measurements were performed at acoustic pressures of 200 and 300 kPa for 1.0 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 1.0, 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.
Antibubbles generated equivalent or stronger harmonic signal, compared to bubble-based ultrasound contrast agents. The second 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 SonoVue at the estimated concentration of bubbles/mL. For ultrasound with a center transmit frequency of 1.0 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 . 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 at a high concentration of bubbles/mL.
Endoskeletal antibubbles generate comparable or greater higher harmonics than reference bubbles and SonoVue . As a result, antibubbles with liquid therapeutic agents inside the gas phase have high potential to become a traceable therapeutic agent.
气泡是一种封装的气体气泡，内部包含不可压缩的内含物。目前的超声对比剂是基于气泡的：它们包含封装的气体气泡，没有内含物。本工作的目的是比较一种抗气泡造影剂与两种基于气泡的超声造影剂（即参考气泡和 SonoVue）的线性和非线性响应。
使用单元素超声换能器测量三种造影剂的侧向散射和衰减，工作频率为 1.0、2.25 和 3.5 MHz。散射测量在 1.0 MHz 时的声压为 200 和 300 kPa，在 2.25 MHz 时为 300 kPa 和 450 kPa，在 3.5 MHz 时为 370 和 560 kPa。衰减测量分别在 1.0、2.25 和 3.5 MHz 时的压力为 13、55 和 50 kPa 进行。此外，还进行了动态对比增强超声测量，使用商业诊断线性阵列探头对血管仿体中的造影剂流动进行成像。
与基于气泡的超声造影剂相比，抗气泡产生了等效或更强的谐波信号。在估计的 100 万个/mL 的气泡浓度下，抗气泡造影剂的二次谐波侧向散射幅度比参考气泡造影剂高 3dB，比 SonoVue 高 4dB。对于中心发射频率为 1.0 MHz 的超声，抗气泡造影剂的衰减系数为 8.7 dB/cm，而参考造影剂的衰减系数分别为 SonoVue 的 7.7 和 0.3 dB/cm。在 2.25 MHz 时，衰减系数分别为 9.7、3.0 和 0.6 dB/cm。在 3.5 MHz 时，它们分别为 4.4、1.8 和 1.0 dB/cm。动态对比增强超声记录显示，在高浓度 100 万个/mL 的气泡下，抗气泡造影剂的非线性信号比参考气泡高 31%，比 SonoVue 低 23%。
内骨骼抗气泡产生的高次谐波与参考气泡和 SonoVue 相当或更大。因此，内部含有液体治疗剂的内骨骼抗气泡具有成为可追踪治疗剂的巨大潜力。
