TY - JOUR
T1 - Experimental acoustic characterization of an endoskeletal antibubble contrast agent
T2 - first results
AU - Panfilova, Anastasiia
AU - Chen, Peiran
AU - van Sloun, Ruud J.G.
AU - Wijkstra, Hessel
AU - Postema, Michiel
AU - Poortinga, Albert T.
AU - Mischi, Massimo
N1 - This article is protected by copyright. All rights reserved.
PY - 2021/11
Y1 - 2021/11
N2 - PURPOSE: 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 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
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.
AB - PURPOSE: 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 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
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.
KW - harmonic imaging
KW - linear attenuation
KW - nonlinear scattering
KW - pickering-stabilised bubbles
KW - ultrasound contrast agent
UR - http://www.scopus.com/inward/record.url?scp=85116887644&partnerID=8YFLogxK
U2 - 10.1002/mp.15242
DO - 10.1002/mp.15242
M3 - Article
C2 - 34580883
SN - 0094-2405
VL - 48
SP - 6765
EP - 6780
JO - Medical Physics
JF - Medical Physics
IS - 11
ER -