title: Kupffer phase image of Sonazoid-enhanced US is useful in predicting a hypervascularization of non-hypervascular hypointense hepatic lesions detected on Gd-EOB-DTPA-enhanced MRI: a multicenter retrospective study.
abstract: BACKGROUND
  It remains unknown whether Kupffer-phase images in Sonazoid-enhanced ultrasonography (US) can be used to predict hypervascularization of borderline lesions. Therefore, we aimed to clarify whether Kupffer-phase images in Sonazoid-enhanced ultrasonography can predict subsequent hypervascularization in hypovascular borderline lesions detected on hepatobiliary-phase gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging.
  
  
  METHODS
  From January 2008 to March 2012, 616 low-intensity hypovascular nodules were detected in hepatobiliary-phase images of Gd-EOB-DTPA-enhanced MRI at nine institutions. Among these, 167 nodules, which were confirmed as hypovascular by Gd-EOB-DTPA-enhanced MRI and Sonazoid-enhanced US, were evaluated in this study. Potential hypervascularization factors were selected based on their clinical significance and the results of previous reports. The Kaplan-Meier model and log-rank test were used for univariate analysis and the Cox regression model was used for multivariate analysis.
  
  
  RESULTS
  The cumulative incidence of hypervascularization of borderline lesions was 18, 37, and 43 % at 1, 2, and 3 years, respectively. Univariate analyses showed that tumor size (p = 0.0012) and hypoperfusion on Kupffer-phase images in Sonazoid-enhanced US (p = 0.004) were associated with hypervascularization of the tumor. Multivariate analysis showed that tumor size [HR: 1.086, 95 % confidence interval = 1.027-1.148, p = 0.004] and hypo perfusion on Kupffer-phase images [HR: 3.684, 95 % confidence interval = 1.798-7.546, p = 0.0004] were significantly different.
  
  
  CONCLUSIONS
  Kupffer-phase images in Sonazoid-enhanced US and tumor diameter can predict hypervascularization of hypointense borderline lesions detected on hepatobiliary-phase Gd-EOB-DTPA-enhanced MRI.
authors.affiliation: Department of Gastroenterology and Hepatology, Kinki University School of Medicine, 377-2, Ohno-Higashi, Osaka-Sayama, 589-8511, Osaka, Japan. tatsuoinouejp@yahoo.co.jp.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Inoue
authors.affiliation: Department of Diagnostic Radiology, Kinki University School of Medicine, 377-2, Ohno-Higashi, Osaka-Sayama, 589-8511, Osaka, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Hyodo
authors.affiliation: Department of Hepatology and Pancreatology, Kawasaki Medical School, Kurashiki, Japan.|Department of Gastroenterology and Hepatology, Kohnodai Hospital, National Center for Global Health and Medicine, Chiba, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Korenaga
authors.affiliation: Department of Diagnostic Radiology, Kinki University School of Medicine, 377-2, Ohno-Higashi, Osaka-Sayama, 589-8511, Osaka, Japan.
authors.forename: Takamichi
authors.initials: T
authors.lastname: Murakami
authors.affiliation: Department of Gastroenterology, Ikeda Municipal Hospital, Osaka, Japan.
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Imai
authors.affiliation: Department of Hepatology and Pancreatology, Kawasaki Medical School, Kurashiki, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Higaki
authors.affiliation: Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Suda
authors.affiliation: Division of Radiation Oncology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Takano
authors.affiliation: Division of Medicine and Clinical Science, Department of Multidisciplinary Internal Medicine, Tottori University, Tottori, Japan.
authors.forename: Kennichi
authors.initials: K
authors.lastname: Miyoshi
authors.affiliation: Division of Medicine and Clinical Science, Department of Multidisciplinary Internal Medicine, Tottori University, Tottori, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Koda
authors.affiliation: Ultrasound Imaging Center, Hyogo College of Medicine, Nishinomiya, Japan.|Division of Hepatobiliary and Pancreatic Disease, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Tanaka
authors.affiliation: Ultrasound Imaging Center, Hyogo College of Medicine, Nishinomiya, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Iijima
authors.affiliation: Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Matsuyama, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Ochi
authors.affiliation: Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Matsuyama, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Hirooka
authors.affiliation: Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Japan.
authors.forename: Kazushi
authors.initials: K
authors.lastname: Numata
authors.affiliation: Department of Gastroenterology and Hepatology, Kinki University School of Medicine, 377-2, Ohno-Higashi, Osaka-Sayama, 589-8511, Osaka, Japan. m-kudo@med.kindai.ac.jp.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Kudo
mesh_terms: D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000098:blood supply* / Q000175:diagnosis / Q000473:pathology; D003287:Contrast Media; D018450:Disease Progression; D005260:Female; D005290:Ferric Compounds; D019786:Gadolinium DTPA; D006801:Humans; D007501:Iron; D053208:Kaplan-Meier Estimate; D007728:Kupffer Cells / Q000000981:diagnostic imaging; D008113:Liver Neoplasms / Q000098:blood supply* / Q000175:diagnosis / Q000473:pathology; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000000981:diagnostic imaging*; 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
keywords: Gadolinium ethoxybenzyl-diethylenetriamine-pentaacetic acid-enhanced MRI; Hepatocellular carcinoma; Hypervascular transformation; Kupffer phase; Sonazoid-enhanced ultrasonography