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The natural history of streptozotocin-stimulated non-alcoholic steatohepatitis mice followed by Gd-EOB-DTPA-enhanced MRI: Comparison with simple steatosis mice
Institution:1. Department of Radiology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan;2. Department of Pathology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan;3. Department of Radiology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan;4. Department of Diagnostic Radiology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan;1. Computational BioMedicine Laboratory, FORTH-ICS, Heraklion, Crete, Greece;2. Department of Medical Physics, University of Crete, Heraklion, Crete, Greece;3. Department of Radiology, University of Crete, Heraklion, Greece;1. Magnetic Resonance Imaging Laboratory, Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology, Daejeon, South Korea;2. Department of Electrical Engineering, Korea Advanced Institute of Science and Technology, Daejeon, South Korea;1. Ohio Musculoskeletal and Neurological Institute, Ohio University, Athens, OH 45701, United States;2. Department of Biomedical Sciences, Ohio University, Athens, OH 45701, United States;3. Department of Mechanical Engineering, Ohio University, Athens, OH 45701, United States;4. School of Rehabilitation and Communication Sciences, Ohio University, Athens, OH 45701, United States;5. Department of Geriatric Medicine, Ohio University, Athens, OH 45701, United States;1. Department of Diagnostic Radiology and Nuclear Medicine, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan;2. Department of Oral and Maxillofacial Radiology, Tokyo Medical and Dental University, Tokyo, Japan;3. Okinawa Institute of Science and Technology Graduate University, Okinawa, Japan;4. Department of Comprehensive Reproductive Medicine, Tokyo Medical and Dental University, Tokyo, Japan;5. Department of Colorectal Surgery, Tokyo Medical and Dental University, Tokyo, Japan;6. Department of Pathology, Tokyo Medical and Dental University, Tokyo, Japan
Abstract:PurposeTo clarify the development of HCC, temporal change of steatosis and Gd-EOB-DTPA enhancement of non-alcoholic steatohepatitis (NASH) model mice by magnetic resonance imaging (MRI).Materials and methodsAll animal experiments were approved by the institution's Animal Research Committee. MRI was performed on six NASH and six simple steatosis (SS) model mice every 2 weeks from the ages of 8 weeks to 16 weeks. The sequential changes in the number and size of the focal liver lesions detected on Gd-EOB-DTPA-enhanced MRI were evaluated. Additionally, the hepatic fat fraction (HFF), contrast-to-noise ratio (CNR) and relative enhancement (RE) were calculated at each time point. The temporal changes and correlations in these parameters were evaluated.ResultsAll alive NASH model mice demonstrated focal liver lesions from week 10, at the latest. Number of the lesions increased with time, and all the lesion enlarged with time. All the lesions larger than 1 mm were confirmed as hepatocellular carcinoma (HCC) pathologically. While the HFF remained constant in NASH model mice, HFF in SS model mice dramatically increased with time. CNR of the NASH model mice remained constant through the study period, while CNR in SS model mice decreased with time. Although no correlation was seen in NASH model mice, the HFF showed a negative correlation against CNR and RE in SS model mice.ConclusionDevelopment of HCC was observed using Gd-EOB-DTPA-enhanced MRI only in NASH model mice. Degree of steatosis and hepatic enhancement by Gd-EOB-DTPA was both constant in NASH model mice, while steatosis increased and hepatic enhancement decreased with time in SS model mice.
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