Mechanism of hepatic parenchyma-specific contrast of microbubble-based contrast agent for ultrasonography: Microscopic studies in rat liver

Rira Watanabe, Manabu Matsumura, Toshiko Munemasa, Masayoshi Fujimaki, Makoto Suematsu

Research output: Contribution to journalArticle

85 Citations (Scopus)


OBJECTIVE: The objective of this study was to elucidate the mechanism of hepatic parenchyma-specific contrast of Sonazoid (microbubble contrast agent) using microscopic techniques. MATERIALS AND METHODS: Sonazoid was intravenously injected into rats to investigate the microbubble dynamics and distribution within hepatic microcirculation in exteriorized liver using intravital microscopy and to observe dose dependency of ultrasound hepatic contrast effect. In vitro and in vivo uptake of microbubbles by Kupffer cells was examined using confocal laser scanning microscopy. RESULTS: Intravital observation demonstrated freely flowing microbubbles in the sinusoid and some microbubbles co-localized with Kupffer cells. The microbubbles internalized in Kupffer cells were identified with reflected light by confocal laser scanning microscopy. The percentage of Kupffer cells taking up microbubbles was about 1% at clinical dose at which the homogeneous hepatic contrast was observed. CONCLUSIONS: The hepatic parenchyma-specific contrast by Sonazoid is due to distribution of the microbubbles in Kupffer cells.

Original languageEnglish
Pages (from-to)643-651
Number of pages9
JournalInvestigative radiology
Issue number9
Publication statusPublished - 2007 Sep 1



  • Contrast agent
  • Kupffer cell
  • Liver
  • Microbubble
  • Ultrasound

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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