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Pre-Hepatectomy Assessment of Bile Transporter Expression by Gadoxetic Acid-Enhanced MRI in a Rat Model of Liver Cirrhosis
Authors:Joohyun Kim  Tae Kim  Kwan Soo Hong  Hyeyoung Moon  In-Kyung Oh  Sang Mok Lee
Affiliation:1. Division of Transplant Surgery, Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin, USA;2. The Transplant Center at Froedtert and Medical College of Wisconsin, Children's Hospital of Wisconsin and The Blood Center of Wisconsin, Milwaukee, Wisconsin, USA;3. Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology, Gwangju, South Korea;4. Division of MR Research, Korea Basic Science Institute, Cheongwon, South Korea;5. Department of Surgery, College of Medicine, Kyung Hee University, Seoul, South Korea
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). Conclusion: 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.
Keywords:gacoxetic acid  magnetic resonance imaging  bile transporter  liver cirrhosis  posthepatectomy liver failure  hepatic function test
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