Abstract
In medical and pharmacological research, various human disease models in small fish, such as medaka (Oryzias latipes), have been created. To investigate these disease models noninvasively, magnetic resonance imaging (MRI) is suitable because these small fish are no longer transparent as adults. However, their small body size requires a high spatial resolution, and a water pool should be avoided to maximize the strength of MRI. We developed in vivo magnetic resonance microscopy (MR microscopy) without a water pool by combining hypothermic anaesthesia and a 14.1 T MR microscope. Using in vivo MR microscopy, we noninvasively evaluated the hepatic steatosis level of a non-alcoholic fatty liver disease model in medaka and followed the individual disease progression. The steatosis level was quantified by the MRI-estimated proton density fat-fraction (MRI-PDFF), which estimates the triglyceride fat concentration in liver tissue and is recognized as an imaging biomarker. The MRI-PDFF results agreed with a histological analysis. Moreover, we optimized the hypothermic anaesthesia procedure to obtain a recovery proportion of 1 in the experiment involving MR microscopy. Recovered medaka could not be distinguished from naïve medaka after the experiment. Therefore, the in vivo MR microscopy will expand the possibilities of a human disease model in fish.
Highlights
Magnetic Resonance Imaging (MRI) is a non-invasive diagnostic imaging technique
To infer a physiological state during the imaging time of the MR microscope, we investigated the physiological changes in medaka due to the hypothermic anaesthesia
We developed in vivo MR microscopy for a disease model in medaka by combining the hypothermic anaesthesia procedure and the high-field MR microscope
Summary
Magnetic Resonance Imaging (MRI) is a non-invasive diagnostic imaging technique. Using MRI, we can visualize spatial distributions of various physical and chemical properties of internal organs. To investigate the long-term effects of the hypothermic anaesthesia procedure, we continued breeding some of uneventfully recovered medaka Using the hypothermic anaesthesia procedure, we performed MR microscopy experiments on the control and the HFD groups of medaka.
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