title: Gadoxetic acid-enhanced MRI and sonoelastography: non-invasive assessments of chemoprevention of liver fibrosis in thioacetamide-induced rats with Sho-Saiko-To.
abstract: BACKGROUND
  This study aimed to compare the performance of gadoxetic acid -enhanced magnetic resonance imaging (MRI) and sonoelastography in evaluating chemopreventive effects of Sho-Saiko-To (SST) in thioacetamide (TAA)-induced early liver fibrosis in rats.
  
  
  METHODS
  Ten of Sprague-Dawley rats receiving TAA (200 mg/kg of body weight) intraperitoneal injection were divided into three groups: Group 1 (TAA only, n = 3), Group 2 (TAA +0.25 g/kg SST, n = 4) and Group 3 (TAA+1 g/kg SST, n = 3). Core needle liver biopsy at week 2 and liver specimens after sacrifice at week 6 confirmed liver fibrosis using histological examinations, including Sirius red staining, Ishak and Metavir scoring systems. Gadoxetic acid-enhanced MRI and shear-wave sonoelastography were employed to evaluate liver fibrosis. The expression of hepatic transporter organic anion transporter 1 (Oatp1), multidrug-resistant protein 2 (Mrp2) and alpha-smooth muscle actin (α-Sma) were also analyzed in each group by immunohistochemistry (IHC) and Western blot.
  
  
  RESULTS
  According to histological grading by Sirius red staining, Ishak scores of liver fibrosis in Groups 1, 2 and 3 were 3, 2 and 1, respectively. As shown in gadoxetic acid-enhanced MRI, the ratio of relative enhancement was significantly lower in Group 1 (1.87 ± 0.21) than in Group 2 of low-dose (2.82 ± 0.25) and Group 3 of high-dose (2.72 ± 0.12) SST treatment at 10 minutes after gadoxetic acid intravenous injection (p < 0.05). Sonoelastography showed that the mean difference before and after experiments in Groups 1, 2 and 3 were 4.66 ± 0.1, 4.4 ± 0.57 and 3 ± 0.4 KPa (p < 0.1), respectively. Chemopreventive effects of SST reduced the Mrp2 protein level (p < 0.01) but not Oatp1 and α-Sma levels.
  
  
  CONCLUSIONS
  Sonoelastography and gadoxetic acid-enhanced MRI could monitor the treatment effect of SST in an animal model of early hepatic fibrosis.
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Miaoli, 350, Taiwan; Graduate Institute of Basic Medical Science, China Medical University, Taichung, 404, Taiwan.
authors.forename: Ya-Wen
authors.initials: YW
authors.lastname: Chen
authors.affiliation: Department of Radiology, Kaohsiung Veterans General Hospital, Kaohsiung, 813, Taiwan; School of Medicine, National Yang-Ming University, Taipei, 112, Taiwan.
authors.forename: Meng-Yuan
authors.initials: MY
authors.lastname: Tsai
authors.affiliation: Department of Radiology, Kaohsiung Veterans General Hospital, Kaohsiung, 813, Taiwan; School of Medicine, National Yang-Ming University, Taipei, 112, Taiwan; Department of Medical Imaging and Radiological Sciences, I-Shou University, Kaohsiung, 824, Taiwan.
authors.forename: Huay-Ben
authors.initials: HB
authors.lastname: Pan
authors.affiliation: School of Medicine, National Yang-Ming University, Taipei, 112, Taiwan; Department of Pathology, Kaohsiung Veterans General Hospital, Kaohsiung, 813, Taiwan.
authors.forename: Hui-Hwa
authors.initials: HH
authors.lastname: Tseng
authors.affiliation: Department of Radiology, Kaohsiung Veterans General Hospital, Kaohsiung, 813, Taiwan.
authors.forename: Yu-Ting
authors.initials: YT
authors.lastname: Hung
authors.affiliation: Department of Radiology, Kaohsiung Veterans General Hospital, Kaohsiung, 813, Taiwan; School of Medicine, National Yang-Ming University, Taipei, 112, Taiwan; Department of Medical Laboratory Sciences and Biotechnology, Fooyin University, Kaohsiung, 807, Taiwan.
authors.forename: Chen-Pin
authors.initials: CP
authors.lastname: Chou
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis; D003287:Contrast Media / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000737:chemistry*; D054459:Elasticity Imaging Techniques / Q000379:methods*; D019786:Gadolinium DTPA / Q000493:pharmacokinetics*; D007124:Immunoenzyme Techniques; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008111:Liver Function Tests; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D010936:Plant Extracts / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013853:Thioacetamide / Q000633:toxicity*; D014018:Tissue Distribution
chemical_list: D015415:Biomarkers; D003287:Contrast Media; D004365:Drugs, Chinese Herbal; D010936:Plant Extracts; C073590:gadolinium ethoxybenzyl DTPA; C461320:shosaiko-to; D013853:Thioacetamide; D019786:Gadolinium DTPA