title: Gas-generating polymeric microspheres for long-term and continuous in vivo ultrasound imaging.
abstract: 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.
authors: School of Life Science and Biotechnology, Korea University, 1 Anam-dong, Seongbuk-gu, Seoul 136-701, Republic of Korea.
authors: Hyun Su
authors: HS
authors: Min
authors: Eunah
authors: E
authors: Kang
authors: Heebeom
authors: H
authors: Koo
authors: Jaeyoung
authors: J
authors: Lee
authors: Kwangmeyung
authors: K
authors: Kim
authors: Rang-Woon
authors: RW
authors: Park
authors: In-San
authors: IS
authors: Kim
authors: Youngseok
authors: Y
authors: Choi
authors: Ick Chan
authors: IC
authors: Kwon
authors: Moonhee
authors: M
authors: Han
mesh_terms: D000818:Animals; D003287:Contrast Media; D005740:Gases / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008863:Microspheres; D011076:Polycarboxylate Cement / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D014463:Ultrasonography / Q000379:methods*
chemical_list: D003287:Contrast Media; D005740:Gases; D011076:Polycarboxylate Cement; D011108:Polymers; C005506:polycarbonate