title: Pre-Hepatectomy Assessment of Bile Transporter Expression by Gadoxetic Acid-Enhanced MRI in a Rat Model of Liver Cirrhosis.
abstract: BACKGROUND
  Gadoxetic acid is a liver-specific intravenous T1 magnetic resonance (MR) contrast agent that is excreted via the hepatobiliary system. We hypothesize that hepatocyte expressions of bile transporters (OATP1 and MRP2) correlate with dynamic profile of Gadoxetic acid enhanced (GE)-MR imaging (MRI).
  
  
  METHODS
  Two groups of rats, control (n = 6) and cirrhosis (n = 12), received gadoxetic acid enhanced MRI followed by 70% hepatectomy. The change in MR signal intensity from the baseline before the contrast injection (ΔSI) was analyzed every minute for 30 min. Dynamic signal intensity retention ratio (DSR) was defined as the mean ΔSI of the third 10-minmin period divided by the first 10-minmin period. Real-time PCR was utilized to quantify mRNA expressions.
  
  
  RESULTS
  Compared to the control, cirrhosis group demonstrated lower mRNA levels of OATP1 (0.038 ± 0.020 vs. 0.232 ± 0.0979; p = 0.004), MRP2 (0.201 ± 0.084 vs. 0.7567 ± 0.254; p = 0.002), and OATP1/MRP2 mRNA ratio (0.193 ± 0.065 vs. 0.342 ± 0.206; p = 0.032). DSR was higher in the cirrhosis group (0.678 ± 0.554 vs -0.125 ± 0.839; p = 0.033). In the cirrhosis group, there was an inverse correlation between the ratios of OATP1/MRP2 mRNA and DSR (R = -0.709, p = 0.01).
  
  
  CONCLUSIONS
  Bile transporters OATP1/MRP2 mRNA expression ratio in rat liver tissue decreased with DMN-induced liver injury. The expressions of bile transporters correlated with GE-MRI DSR. The GE-MRI DSR has potential utility in qualifying OATP1/MRP2 mRNA expression.
authors: a Division of Transplant Surgery, Department of Surgery , Medical College of Wisconsin , Milwaukee , Wisconsin , USA.|b The Transplant Center at Froedtert and Medical College of Wisconsin , Children's Hospital of Wisconsin and The Blood Center of Wisconsin , Milwaukee , Wisconsin , USA.
authors: Joohyun
authors: J
authors: Kim
authors: c Department of Biomedical Science and Engineering , Gwangju Institute of Science and Technology , Gwangju , South Korea.
authors: Tae
authors: T
authors: Kim
authors: d Division of MR Research , Korea Basic Science Institute , Cheongwon , South Korea.
authors: Kwan Soo
authors: KS
authors: Hong
authors: d Division of MR Research , Korea Basic Science Institute , Cheongwon , South Korea.
authors: Hyeyoung
authors: H
authors: Moon
authors: e Department of Surgery , College of Medicine, Kyung Hee University , Seoul , South Korea.
authors: In-Kyung
authors: IK
authors: Oh
authors: e Department of Surgery , College of Medicine, Kyung Hee University , Seoul , South Korea.
authors: Sang Mok
authors: SM
authors: Lee
authors: f Department of Radiology , Medical College of Wisconsin , Wisconsin , USA.
authors: Mark D
authors: MD
authors: Hohenwalter
authors: a Division of Transplant Surgery, Department of Surgery , Medical College of Wisconsin , Milwaukee , Wisconsin , USA.|b The Transplant Center at Froedtert and Medical College of Wisconsin , Children's Hospital of Wisconsin and The Blood Center of Wisconsin , Milwaukee , Wisconsin , USA.
authors: Michael A
authors: MA
authors: Zimmerman
authors: a Division of Transplant Surgery, Department of Surgery , Medical College of Wisconsin , Milwaukee , Wisconsin , USA.|b The Transplant Center at Froedtert and Medical College of Wisconsin , Children's Hospital of Wisconsin and The Blood Center of Wisconsin , Milwaukee , Wisconsin , USA.
authors: David C
authors: DC
authors: Cronin
authors: a Division of Transplant Surgery, Department of Surgery , Medical College of Wisconsin , Milwaukee , Wisconsin , USA.|b The Transplant Center at Froedtert and Medical College of Wisconsin , Children's Hospital of Wisconsin and The Blood Center of Wisconsin , Milwaukee , Wisconsin , USA.
authors: Johnny C
authors: JC
authors: Hong
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000818:Animals; D019786:Gadolinium DTPA; D006498:Hepatectomy / Q000401:mortality; D008106:Liver Cirrhosis, Experimental / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000401:mortality; D008279:Magnetic Resonance Imaging; D008297:Male; D029362:Organic Anion Transporters, Sodium-Independent / Q000378:metabolism*; D017207:Rats, Sprague-Dawley
chemical_list: D018528:ATP-Binding Cassette Transporters; C423013:Abcc2 protein, rat; D029362:Organic Anion Transporters, Sodium-Independent; C421102:Slco1a1 protein, rat; C073590:gadolinium ethoxybenzyl DTPA; D019786:Gadolinium DTPA
keywords: bile transporter; gacoxetic acid; hepatic function test; liver cirrhosis; magnetic resonance imaging; posthepatectomy liver failure