Gas-generating polymeric microspheres for long-term and continuous in vivo ultrasound imaging

Hyun Su Min, Eunah Kang, Heebeom Koo, Jaeyoung Lee, Kwangmeyung Kim, Rang Woon Park, In San Kim, Youngseok Choi, Ick Chan Kwon, Moonhee Han

Research output: Contribution to journalArticlepeer-review

38 Scopus citations


Ultrasound (US) imaging is one of the most common biomedical imaging methods, due to the easy assessment and noninvasive way. For more precise and accurate US imaging, many contrast agents have been developed in a form of microbubbles composed of inner gas and shell materials. However, microbubbles showed undesirable short half-life under acoustic field during US imaging and insufficient in vivo stability in blood flow due to diffusion or bubble destruction. Therefore, the improvement of the half-life and stability of microbubbles under in vivo condition is highly needed for long-term in vivo US imaging. Herein, we developed rationally designed gas-generating polymeric microsphere (GGPM) that can produce microbubbles without encapsulation of gas for long-term and continuous US imaging. The poly(cholesteryl γ-butyrolactone-b-propylene oxide), poly(CB-PO), with carbonate side chains was synthesized as gas-generating polymer by ring-opening polymerization of cholestryl γ-butyrolactone (CB) and propylene oxide (PO). As optimal structure for intense US signal generation, porous GGPMs (p-GGPMs) with the average size about 3-5 μm were prepared with poly(CB-PO) by double emulsion method. These p-GGPMs generated continuous US signals over 70 min, while the signals from Sonovue ®, a commercial US contrast agent were completely attenuated within 15 min. This long-term signal duration of p-GGPM was also reproduced when they were subcutaneously injected under the skin of mouse. Moreover, as advanced in vivo application, the fine US imaging of heart in rat was enabled by intravenous injection of p-GGPM. Therefore, these overall results showed the great potential of p-GGPM as gas-generating US contrast agent for in vivo biomedical imaging and diagnosis.

Original languageEnglish
Pages (from-to)936-944
Number of pages9
Issue number3
StatePublished - Jan 2012

Bibliographical note

Funding Information:
This work was financially supported by the Global Research Laboratory (GRL) Project of MEST, a grant ( A062254 ) of the Korea Health 21 R&D Project, a grant No. RTI04-01-01 from the Regional Technology Innovation Program of the Ministry of Knowledge Economy (MKE), National R&D Program for Cancer Control of Ministry for Health and Welfare ( 1020260 ), and the Intramural Research Program (Theragnosis) of KIST.


  • Contrast agent
  • Gas-generating polymer
  • Microsphere
  • Polycarbonate
  • Ultrasound imaging


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