title: Mechanism of hepatic parenchyma-specific contrast of microbubble-based contrast agent for ultrasonography: microscopic studies in rat liver.
abstract: OBJECTIVE
  The objective of this study was to elucidate the mechanism of hepatic parenchyma-specific contrast of Sonazoid (microbubble contrast agent) using microscopic techniques.
  
  
  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.
authors: R&D Division, Daiichi Pharmaceutical Co., Ltd, Tokyo, Japan. watanabe.rira.vi@daiichisankyo.co.jp
authors: Rira
authors: R
authors: Watanabe
authors: Manabu
authors: M
authors: Matsumura
authors: Toshiko
authors: T
authors: Munemasa
authors: Masayoshi
authors: M
authors: Fujimaki
authors: Makoto
authors: M
authors: Suematsu
mesh_terms: D000818:Animals; D003287:Contrast Media / Q000493:pharmacokinetics*; D005290:Ferric Compounds / Q000493:pharmacokinetics*; D007501:Iron / Q000493:pharmacokinetics*; D007728:Kupffer Cells / Q000166:cytology / Q000000981:diagnostic imaging* / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000000981:diagnostic imaging* / Q000378:metabolism*; D008297:Male; D045423:Microbubbles; D009928:Organ Specificity; D010087:Oxides / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution; D014463:Ultrasonography / Q000379:methods
chemical_list: D003287:Contrast Media; D005290:Ferric Compounds; D010087:Oxides; C069727:Sonazoid; D007501:Iron