title: Rat model of cholelithiasis with human gallstones implanted in cholestasis-induced virtual gallbladder.
abstract: OBJECTIVE
  To facilitate translational research on cholelithiasis, we have developed a rat model of human gallstones by exploiting the unique biliopancreatic features of this species.
  
  
  METHODS
  Under anesthesia, 16 adult rats of equal genders underwent two times of abdominal surgery. First, their common bile duct (CBD) was ligated to cause cholestasis by total biliary obstruction (TBO). On day 0, 1, 3, 7, 14, 21 and 28 after TBO, magnetic resonance imaging (MRI) was conducted to monitor the dilatation of the CBD, and blood was sampled to analyze total serum bilirubin (TSB). Secondly, on day 30, the abdomen was re-opened and gallstone(s) collected from human patients were implanted in the dilated CBD as a virtual gallbladder (VGB), which was closed by suture ligation. This rat cholelithiasis model was examined by MRI, clinical observation, microcholangiography and histology.
  
  
  RESULTS
  All rats survived two laparotomies. After ligation, the CBD was dilated to a stable size of 4 to 30 mm in diameter on day 21-28, which became a VGB. The rats initially showed signs of jaundice that diminished over time, which paralleled with the evolving TSB levels from 0.6 ± 0.3 mg/dL before ligation, through a peak of 10.9 ± 1.9 mg/dL on day 14, until a nearly normalized value after day 28. The dilated CBD with thickened wall allowed an incision for implantation of human gallstones of 1-10 mm in diameter. The rat cholelithiasis was proven by in vivo MRI and postmortem microcholangiography and histomorphology.
  
  
  CONCLUSIONS
  A rat model cholelithiasis with human gallstones has been established, which proves feasible, safe, reliable, nontoxic and cost-effective. Given the gallstones of human origin, applications of this model may be of help in translational research such as optical detection and lysis of gallstones by systemic drug administration.
authors.affiliation: Marlein Miranda Cona, Yewei Liu, Ting Yin, Yuanbo Feng, Feng Chen, Stefaan Mulier, Raymond Oyen, Yicheng Ni, Department of Imaging and Pathology, Faculty of Medicine, Biomedical Sciences Group, KU Leuven, 3000 Leuven, Belgium.
authors.forename: Marlein Miranda
authors.initials: MM
authors.lastname: Cona
authors.affiliation: Marlein Miranda Cona, Yewei Liu, Ting Yin, Yuanbo Feng, Feng Chen, Stefaan Mulier, Raymond Oyen, Yicheng Ni, Department of Imaging and Pathology, Faculty of Medicine, Biomedical Sciences Group, KU Leuven, 3000 Leuven, Belgium.
authors.forename: Yewei
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Marlein Miranda Cona, Yewei Liu, Ting Yin, Yuanbo Feng, Feng Chen, Stefaan Mulier, Raymond Oyen, Yicheng Ni, Department of Imaging and Pathology, Faculty of Medicine, Biomedical Sciences Group, KU Leuven, 3000 Leuven, Belgium.
authors.forename: Ting
authors.initials: T
authors.lastname: Yin
authors.affiliation: Marlein Miranda Cona, Yewei Liu, Ting Yin, Yuanbo Feng, Feng Chen, Stefaan Mulier, Raymond Oyen, Yicheng Ni, Department of Imaging and Pathology, Faculty of Medicine, Biomedical Sciences Group, KU Leuven, 3000 Leuven, Belgium.
authors.forename: Yuanbo
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Marlein Miranda Cona, Yewei Liu, Ting Yin, Yuanbo Feng, Feng Chen, Stefaan Mulier, Raymond Oyen, Yicheng Ni, Department of Imaging and Pathology, Faculty of Medicine, Biomedical Sciences Group, KU Leuven, 3000 Leuven, Belgium.
authors.forename: Feng
authors.initials: F
authors.lastname: Chen
authors.affiliation: Marlein Miranda Cona, Yewei Liu, Ting Yin, Yuanbo Feng, Feng Chen, Stefaan Mulier, Raymond Oyen, Yicheng Ni, Department of Imaging and Pathology, Faculty of Medicine, Biomedical Sciences Group, KU Leuven, 3000 Leuven, Belgium.
authors.forename: Stefaan
authors.initials: S
authors.lastname: Mulier
authors.affiliation: Marlein Miranda Cona, Yewei Liu, Ting Yin, Yuanbo Feng, Feng Chen, Stefaan Mulier, Raymond Oyen, Yicheng Ni, Department of Imaging and Pathology, Faculty of Medicine, Biomedical Sciences Group, KU Leuven, 3000 Leuven, Belgium.
authors.forename: Yue
authors.initials: Y
authors.lastname: Li
authors.affiliation: Marlein Miranda Cona, Yewei Liu, Ting Yin, Yuanbo Feng, Feng Chen, Stefaan Mulier, Raymond Oyen, Yicheng Ni, Department of Imaging and Pathology, Faculty of Medicine, Biomedical Sciences Group, KU Leuven, 3000 Leuven, Belgium.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Marlein Miranda Cona, Yewei Liu, Ting Yin, Yuanbo Feng, Feng Chen, Stefaan Mulier, Raymond Oyen, Yicheng Ni, Department of Imaging and Pathology, Faculty of Medicine, Biomedical Sciences Group, KU Leuven, 3000 Leuven, Belgium.
authors.forename: Raymond
authors.initials: R
authors.lastname: Oyen
authors.affiliation: Marlein Miranda Cona, Yewei Liu, Ting Yin, Yuanbo Feng, Feng Chen, Stefaan Mulier, Raymond Oyen, Yicheng Ni, Department of Imaging and Pathology, Faculty of Medicine, Biomedical Sciences Group, KU Leuven, 3000 Leuven, Belgium.
authors.forename: Yicheng
authors.initials: Y
authors.lastname: Ni
keywords: Bilirubin; Cholelithiasis; Cholestasis; Common bile duct; Gallbladder; Gallstones; Rat