Abstract
Characterizing the non-linear response of microbubble contrast agents is important
for their efficacious use in imaging and therapy. In this article, we report that
the subharmonic and ultraharmonic response of lipid-shelled microbubble contrast agents
exhibits a strong temporal dependence. We characterized non-linear emissions from
Targestar-p microbubbles (Targeson Inc., San Diego, CA, USA) periodically for 60 min, at 10 MHz
excitation frequency. The results revealed a considerable increase in the subharmonic
and ultraharmonic response (nearly 12–15 and 5–8 dB) after 5–10 min of agent preparation.
However, the fundamental and the harmonic response remained almost unchanged in this
period. During the next 50 min, the subharmonic, fundamental, ultraharmonic, and harmonic
responses decreased steadily by 2–5 dB. The temporal changes in the non-linear behavior
of the agent appeared to be primarily mediated by gas-exchange through the microbubble
shell; temperature and prior acoustic excitation based mechanisms were ruled out.
Further, there was no measurable change in the agent size distribution by static diffusion.
We envisage that these findings will help obtain reproducible measurements from agent
characterization, non-linear imaging, and fluid-pressure sensing. These findings also
suggest the possibility for improving non-linear imaging by careful design of ultrasound
contrast agents.
Key Words
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Ultrasound in Medicine and BiologyAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Ultrasound-mediated destruction of contrast microbubbles used for medical imaging and drug delivery.Phys Fluids. 2005; 17: 100603
- Nondestructive subharmonic imaging.IEEE Trans Ultrason Ferroelectr Freq Control. 2002; 497: 883-892
- Subharmonic microbubble emissions for noninvasively tracking right ventricular pressures.Am J Physiol Heart Circ Physiol. 2012; 3031: H126-H132
- Compression-only behavior of phospholipid-coated contrast bubbles.Ultrasound Med Biol. 2007; 334: 653-656
- Ultrasonic characterization of ultrasound contrast agents.Med Biol Eng Comput. 2009; 478: 861-873
- Characterizing the subharmonic response of phospholipid-coated microbubbles for carotid imaging.Ultrasound Med Biol. 2011; 37: 958-970
- On the feasibility of real time, in vivo harmonic imaging with proteinaceous microspheres.J Ultrasound Med. 1996; 1512: 853-860
- Harmonic imaging with gas-filled microspheres: Initial experiences.Int J Imag Syst Tech. 1997; 81: 69-81
- Subharmonic imaging of contrast agents.Ultrasonics. 2000; 38: 93-98
- Subharmonic scattering of phospholipid-shell microbubbles at low acoustic pressure amplitudes.IEEE Trans Ultrason Ferroelectr Freq Control. 2010; 57: 1762-1771
- High frequency nonlinear b-scan imaging of microbubble contrast agents.IEEE Trans Ultrason Ferroelectr Freq Control. 2005; 52: 65-79
- Subharmonic contrast intravascular ultrasound for vasa vasorum imaging.Ultrasound Med Biol. 2007; 33: 1859-1872
- Using light scattering to measure the response of individual ultrasound contrast microbubbles subjected to pulsed ultrasound in vitro.Journal Acoust Soc Am. 2004; 116: 2832-2842
- Textbook of Medical Physiology.10th ed. WB Sanders Co., Philadelphia2000
- Subharmonic contrast microbubble signals for noninvasive pressure estimation under static and dynamic flow conditions.Ultrason Imaging. 2011; 33: 153-164
- Passive imaging with pulsed ultrasound insonations.J Acoust Soc Am. 2012; 132: 544-553
- Excitation threshold for subharmonic generation from contrast microbubbles.J Acoust Soc Am. 2011; 130: 3137-3147
- Modeling subharmonic response from contrast microbubbles as a function of ambient static pressure.J Acoust Soc Am. 2011; 129: 2325-2335
- Microbubble dissolution in a multigas environment.Langmuir. 2010; 26: 6542-6548
- Lipid monolayer dilatational mechanics during microbubble gas exchange.Soft Matter. 2012; 8: 4756-4766
- Contrast-enhanced intravascular ultrasound pulse sequences for bandwidth-limited transducers.Ultrasound Medicine Biol. 2013; 39: 706-713
- Temperature-dependent differences in the nonlinear acoustic behavior of ultrasound contrast agents revealed by high-speed imaging and bulk acoustics.Ultrasound Med Biol. 2011; 37: 1509-1517
- The influence of gas saturation on microbubble stability.Ultrasound Med Biol. 2012; 38: 1097-1100
- Surfactant shedding and gas diffusion during pulsed ultrasound through a microbubble contrast agent suspension.J Acoust Soc Am. 2013; 134: 1416-1427
- Ultrasound contrast microbubbles in imaging and therapy: Physical principles and engineering.Phys Med Biol. 2009; 546: R27-R57
- Microultrasound molecular imaging of vascular endothelial growth factor receptor 2 in a mouse model of tumor angiogenesis.Mol Imaging. 2006; 6: 289-296
- Growth and dissolution of an encapsulated contrast microbubble: Effects of encapsulation permeability.Ultrasound Med Biol. 2009; 35: 1385-1396
- Evaluation of methods for sizing and counting of ultrasound contrast agents.Ultrasound Med Biol. 2012; 38: 834-845
- Improving the sensitivity of high-frequency subharmonic imaging with coded excitation: A feasibility study.Med Phys. 2012; 39: 2049-2060
- The response of phospholipid-encapsulated microbubbles to chirp-coded excitation: Implications for high-frequency nonlinear imaging.J Acoust Soc Am. 2013; 133: 3145-3158
- Modifying the size distribution of microbubble contrast agents for high-frequency subharmonic imaging.Med Phys. 2013; 40: 082903
- Pressure dependence of subharmonic signals from contrast microbubbles.Ultrasound Med Biol. 1999; 25: 275-283
- Subharmonic behavior of phospholipid-coated ultrasound contrast agent microbubbles.J Acoust Soc Am. 2010; 128: 3239-3252
- Investigating the significance of multiple scattering in ultrasound contrast agent particle populations.IEEE Trans Ultrason Ferroelectr Freq Control. 2005; 52: 2332-2345
- Ambient pressure dependence of the ultra-harmonic response from contrast microbubbles.J Acoust Soc Am. 2012; 131: 4358-4364
- Ultrasound-mediated drug delivery for cardiovascular disease.Expert Opin Drug Del. 2013; 105: 573-592
- Quantitative contrast-enhanced ultrasound imaging: A review of sources of variability.Interface Focus. 2011; 1: 520-539
- The quasi-stable lipid shelled microbubble in response to consecutive ultrasound pulses.Appl Phys Lett. 2012; 101: 071601
- Correspondence-nonlinear oscillations of deflating bubbles.IEEE Trans Ultrason Ferroelectr Freq Control. 2012; 59: 2818-2824
- Oscillation of single microbubbles at room versus body temperature.Ultrasonics Symposium. IUS, Beijing, China2008
- Hysteretic nonlinearity of sub-harmonic emission from ultrasound contrast agent microbubbles.Chinese Physics Letters. 2011; 284: 044301
- Enhancement of subharmonic emission from encapsulated microbubbles by using a chirp excitation technique.Phys Med Biol. 2007; 52: 5531-5544
Article info
Publication history
Accepted:
January 6,
2014
Received in revised form:
November 26,
2013
Received:
August 29,
2013
Identification
Copyright
Published by Elsevier Inc.
