title: Benign Hepatocellular Nodules: Hepatobiliary Phase of Gadoxetic Acid-enhanced MR Imaging Based on Molecular Background.
abstract: Gadoxetic acid is a contrast agent for magnetic resonance (MR) imaging with hepatocyte-specific properties and is becoming increasingly important in detection and characterization of hepatocellular carcinoma and benign hepatocellular nodules, including focal nodular hyperplasia (FNH), nodular regenerative hyperplasia (NRH), hepatocellular adenoma (HCA), and dysplastic nodule. In these hepatocellular nodules, a positive correlation between the grade of membranous uptake transporter organic anion-transporting polypeptide (OATP) 1B3 expression and signal intensity in the hepatobiliary (HB) phase has been verified. In addition, it has been clarified that OATP1B3 expression is regulated by activation of β-catenin and/or hepatocyte nuclear factor 4α. On the other hand, recent studies have also revealed some of the background molecular mechanisms of benign hepatocellular nodules. FNH commonly shows iso- or hyperintensity in the HB phase with equal or stronger OATP1B3 expression, with map-like distribution of glutamine synthetase (a target of Wnt/β-catenin signaling) and OATP1B3 expression. NRH shows doughnut-like enhancement with hypointensity in the central portion in the HB phase with OATP1B3 expression. The majority of HCAs show hypointensity in the HB phase, but β-catenin-activated HCA exclusively demonstrates iso- or hyperintensity with increased expression of nuclear β-catenin, glutamine synthetase, and OATP1B3. Dysplastic nodule commonly shows iso- or hyperintensity in the HB phase with similar to increased OATP1B3 expression, but one-third of high-grade dysplastic nodules can be demonstrated as a hypointense nodule with decreased OATP1B3 expression. Knowledge of these background molecular mechanisms of gadoxetic acid-enhanced MR imaging is important not only for precise imaging diagnosis but also understanding of the pathogenesis of benign hepatocellular nodules.©RSNA, 2016.
authors.affiliation: From the Departments of Radiology (N.Y., O.M., A.K., K.K., K.Y., D.I., T.M., T.G.), Quantum Medical Imaging (S.K.), and Human Pathology (M.S.), Kanazawa University Graduate School of Medical Science, 13-1 Takaramachi, Kanazawa, Ishikawa 920-8640, Japan.
authors.forename: Norihide
authors.initials: N
authors.lastname: Yoneda
authors.affiliation: From the Departments of Radiology (N.Y., O.M., A.K., K.K., K.Y., D.I., T.M., T.G.), Quantum Medical Imaging (S.K.), and Human Pathology (M.S.), Kanazawa University Graduate School of Medical Science, 13-1 Takaramachi, Kanazawa, Ishikawa 920-8640, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Matsui
authors.affiliation: From the Departments of Radiology (N.Y., O.M., A.K., K.K., K.Y., D.I., T.M., T.G.), Quantum Medical Imaging (S.K.), and Human Pathology (M.S.), Kanazawa University Graduate School of Medical Science, 13-1 Takaramachi, Kanazawa, Ishikawa 920-8640, Japan.
authors.forename: Azusa
authors.initials: A
authors.lastname: Kitao
authors.affiliation: From the Departments of Radiology (N.Y., O.M., A.K., K.K., K.Y., D.I., T.M., T.G.), Quantum Medical Imaging (S.K.), and Human Pathology (M.S.), Kanazawa University Graduate School of Medical Science, 13-1 Takaramachi, Kanazawa, Ishikawa 920-8640, Japan.
authors.forename: Kazuto
authors.initials: K
authors.lastname: Kozaka
authors.affiliation: From the Departments of Radiology (N.Y., O.M., A.K., K.K., K.Y., D.I., T.M., T.G.), Quantum Medical Imaging (S.K.), and Human Pathology (M.S.), Kanazawa University Graduate School of Medical Science, 13-1 Takaramachi, Kanazawa, Ishikawa 920-8640, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kobayashi
authors.affiliation: From the Departments of Radiology (N.Y., O.M., A.K., K.K., K.Y., D.I., T.M., T.G.), Quantum Medical Imaging (S.K.), and Human Pathology (M.S.), Kanazawa University Graduate School of Medical Science, 13-1 Takaramachi, Kanazawa, Ishikawa 920-8640, Japan.
authors.forename: Motoko
authors.initials: M
authors.lastname: Sasaki
authors.affiliation: From the Departments of Radiology (N.Y., O.M., A.K., K.K., K.Y., D.I., T.M., T.G.), Quantum Medical Imaging (S.K.), and Human Pathology (M.S.), Kanazawa University Graduate School of Medical Science, 13-1 Takaramachi, Kanazawa, Ishikawa 920-8640, Japan.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Yoshida
authors.affiliation: From the Departments of Radiology (N.Y., O.M., A.K., K.K., K.Y., D.I., T.M., T.G.), Quantum Medical Imaging (S.K.), and Human Pathology (M.S.), Kanazawa University Graduate School of Medical Science, 13-1 Takaramachi, Kanazawa, Ishikawa 920-8640, Japan.
authors.forename: Dai
authors.initials: D
authors.lastname: Inoue
authors.affiliation: From the Departments of Radiology (N.Y., O.M., A.K., K.K., K.Y., D.I., T.M., T.G.), Quantum Medical Imaging (S.K.), and Human Pathology (M.S.), Kanazawa University Graduate School of Medical Science, 13-1 Takaramachi, Kanazawa, Ishikawa 920-8640, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Minami
authors.affiliation: From the Departments of Radiology (N.Y., O.M., A.K., K.K., K.Y., D.I., T.M., T.G.), Quantum Medical Imaging (S.K.), and Human Pathology (M.S.), Kanazawa University Graduate School of Medical Science, 13-1 Takaramachi, Kanazawa, Ishikawa 920-8640, Japan.
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Gabata
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000473:pathology; D003287:Contrast Media / Q000493:pharmacokinetics; D019317:Evidence-Based Medicine; D019786:Gadolinium DTPA / Q000493:pharmacokinetics*; D006801:Humans; D008113:Liver Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000473:pathology; D008279:Magnetic Resonance Imaging / Q000379:methods*; D057054:Molecular Imaging / Q000379:methods; D029362:Organic Anion Transporters, Sodium-Independent / Q000378:metabolism*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D000074542:Solute Carrier Organic Anion Transporter Family Member 1B3
chemical_list: D014408:Biomarkers, Tumor; D003287:Contrast Media; D029362:Organic Anion Transporters, Sodium-Independent; C421209:SLCO1B3 protein, human; D000074542:Solute Carrier Organic Anion Transporter Family Member 1B3; C073590:gadolinium ethoxybenzyl DTPA; D019786:Gadolinium DTPA