Gadoxetate-enhanced MR imaging and compartmental modelling to assess hepatocyte bidirectional transport function in rats with advanced liver fibrosis

• Published in: European radiology 2017-05, Vol.27 (5), p.1804-1811
• Main Authors: Giraudeau, Céline, Leporq, Benjamin, Doblas, Sabrina, Lagadec, Matthieu, Pastor, Catherine M., Daire, Jean-Luc, Van Beers, Bernard E.
• Format: Article
• Language: English
• Subjects: Acids; Animals; Bile Ducts, Intrahepatic - diagnostic imaging; Bile Ducts, Intrahepatic - metabolism; Bioengineering; Biomarkers; Biomarkers - metabolism; Carbon Tetrachloride - toxicity; Case-Control Studies; Catheters; Contrast agents; Contrast Media; Diagnostic Radiology; Disease Models, Animal; Engineering Sciences; Gadolinium DTPA; Hepatobiliary-Pancreas; Hepatocytes - metabolism; Human health and pathology; Hépatology and Gastroenterology; Image Processing, Computer-Assisted; Imaging; Internal Medicine; Interventional Radiology; Life Sciences; Liver - diagnostic imaging; Liver - metabolism; Liver cirrhosis; Liver Cirrhosis - chemically induced; Liver Cirrhosis - diagnostic imaging; Liver Cirrhosis - metabolism; Magnetic Resonance Imaging - methods; Male; Medicine; Medicine & Public Health; Membrane Transport Proteins - metabolism; Neuroradiology; Pharmacokinetics; Radiology; Rats; Rats, Wistar; Scintigraphy; Signal and Image processing; Ultrasound
• ISSN: 0938-7994; 1432-1084
• DOI: 10.1007/s00330-016-4536-7

Objectives Changes in the expression of hepatocyte membrane transporters in advanced fibrosis decrease the hepatic transport function of organic anions. The aim of our study was to assess if these changes can be evaluated with pharmacokinetic analysis of the hepatobiliary transport of the MR contrast agent gadoxetate. Methods Dynamic gadoxetate-enhanced MRI was performed in 17 rats with advanced fibrosis and 8 normal rats. After deconvolution, hepatocyte three-compartmental analysis was performed to calculate the hepatocyte influx, biliary efflux and sinusoidal backflux rates. The expression of Oatp1a1, Mrp2 and Mrp3 organic anion membrane transporters was assessed with reverse transcription polymerase chain reaction. Results In the rats with advanced fibrosis, the influx and efflux rates of gadoxetate decreased and the backflux rate increased significantly (p = 0.003, 0.041 and 0.010, respectively). Significant correlations were found between influx and Oatp1a1 expression (r = 0.78, p