title: Images of Sonazoid-enhanced ultrasonography in multistep hepatocarcinogenesis: comparison with Gd-EOB-DTPA-enhanced MRI.
abstract: BACKGROUND
  Little is known about the difference in enhancement patterns of hepatocellular carcinoma (HCC) during multistep hepatocarcinogenesis between the post-vascular phase of Sonazoid-enhanced ultrasonography (SEUS) and hepatobiliary phase of gadolinium ethoxybenzyl diethylenetriamine (Gd-EOB-DTPA)-enhanced MRI, as well as uptakes of Sonazoid and Gd-EOB-DTPA by HCC.
  
  
  METHODS
  Seventy patients with 73 histologically proven HCCs (33 hypovascular well-differentiated HCCs and 40 progressed HCCs) and 9 dysplastic nodules (DNs) were enrolled. Enhancement patterns of the lesions on the post-vascular phase of SEUS and hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI were evaluated. Uptakes of Sonazoid and Gd-EOB-DTPA were assessed by Sonazoid enhancement index and EOB enhancement ratio in relation to immunohistochemistry of CD68 and organic anion transporting polypeptide 8 (OATP8), respectively.
  
  
  RESULTS
  On the post-vascular phase of SEUS, none of the 9 DNs and 3 of 33 hypovascular well-differentiated HCCs (9 %) were hypoechoic, whereas 3 of 9 DNs (33 %) and 31 of 33 hypovascular well-differentiated HCCs (94 %) showed hypointensity on the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI. Of 31 progressed HCCs, 95 and 93 % were hypoechoic and hypointense on the post-vascular phase of SEUS and hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI, respectively. Sonazoid enhancement indexes decreased in progressed HCCs, correlating with lower Kupffer cell numbers (P < 0.001). EOB enhancement ratios decreased in hypovascular well-differentiated and progressed HCCs, as OATP8 expression declined (P < 0.001).
  
  
  CONCLUSIONS
  In stepwise hepatocarcinogenesis, uptake of Sonazoid starts decreasing later than that of Gd-EOB-DTPA. Although signal reductions on the post-vascular phase of SEUS or hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI suggest HCC, hypoechoic appearance on the post-vascular phase of SEUS might be HCC-specific, particularly progressed HCC.
authors.affiliation: Department of Gastroenterology, Ikeda Municipal Hospital, 3-1-18 Johnan, Ikeda, Osaka, 563-8510, Japan.
authors.forename: Hideko
authors.initials: H
authors.lastname: Ohama
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Imai
authors.forename: Osamu
authors.initials: O
authors.lastname: Nakashima
authors.forename: Sachiyo
authors.initials: S
authors.lastname: Kogita
authors.forename: Manabu
authors.initials: M
authors.lastname: Takamura
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Hori
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Seki
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Sawai
authors.forename: Takumi
authors.initials: T
authors.lastname: Igura
authors.forename: Kazuto
authors.initials: K
authors.lastname: Fukuda
authors.forename: Yuki
authors.initials: Y
authors.lastname: Makino
authors.forename: Osakuni
authors.initials: O
authors.lastname: Morimoto
authors.forename: Masahiko
authors.initials: M
authors.lastname: Ohsawa
authors.forename: Michiie
authors.initials: M
authors.lastname: Sakamoto
authors.forename: Takamichi
authors.initials: T
authors.lastname: Murakami
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000000981:diagnostic imaging*; D003287:Contrast Media; D005260:Female; D005290:Ferric Compounds; D019786:Gadolinium DTPA; D006801:Humans; D007089:Image Enhancement / Q000379:methods; D007150:Immunohistochemistry; D007501:Iron; D008113:Liver Neoplasms / Q000000981:diagnostic imaging*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D010087:Oxides; D012189:Retrospective Studies; D014463:Ultrasonography
chemical_list: D003287:Contrast Media; D005290:Ferric Compounds; D010087:Oxides; C069727:Sonazoid; C073590:gadolinium ethoxybenzyl DTPA; D007501:Iron; D019786:Gadolinium DTPA
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