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Research Papers: Imaging

Ex vivo imaging and quantification of liver fibrosis using second-harmonic generation microscopy

[+] Author Affiliations
Tzu-Lin Sun, Yuan Liu, Ming-Chin Sung

National Taiwan University, Department of Physics, Taipei, 10617 Taiwan

Hsiao-Ching Chen

National Taiwan University Hospital, Department of Internal Medicine, Taipei, 100 Taiwan and National Taiwan University, College of Medicine, Taipei, 100 Taiwan

Chun-Hui Yang, Vladimir Hovhannisyan

National Taiwan University, Department of Physics, Taipei, 10617 Taiwan

Wei-Chou Lin, Yung-Ming Jeng

National Taiwan University Hospital and National Taiwan University, College of Medicine, Department of Pathology, Taipei, 10002 Taiwan

Wei-Liang Chen

National Taiwan University, Department of Physics, Taipei, 10617 Taiwan

Ling-Ling Chiou, Guan-Tarn Huang

National Taiwan University Hospital, Department of Internal Medicine, Taipei, 100 Taiwan and National Taiwan University, College of Medicine, Taipei, 100 Taiwan

Ki-Hean Kim, Peter T. C. So

Massachusetts Institute of Technology, Department of Mechanical Engineering and Division of Bioengineering, Cambridge, Massachusetts 02139

Yang-Fang Chen

National Taiwan University, Department of Physics, Taipei, 10617 Taiwan

Hsuan-Shu Lee

National Taiwan University, Institute of Biotechnology and National Taiwan University Hospital, Department of Internal Medicine and National Taiwan University, College of Medicine, Taipei, 100 Taiwan

Chen-Yuan Dong

National Taiwan University, Department of Physics and , Center for Quantum Science and Engineering and , Division of Genomic Medicine, Research Center for Medical Excellence, Biomedical Molecular Imaging Core, Taipei, 100 Taiwan

J. Biomed. Opt. 15(3), 036002 (June 30, 2010). doi:10.1117/1.3427146
History: Received November 12, 2009; Revised February 25, 2010; Accepted March 09, 2010; Published June 30, 2010; Online June 30, 2010
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Conventionally, liver fibrosis is diagnosed using histopathological techniques. The traditional method is time-consuming in that the specimen preparation procedure requires sample fixation, slicing, and labeling. Our goal is to apply multiphoton microscopy to efficiently image and quantitatively analyze liver fibrosis specimens bypassing steps required in histological preparation. In this work, the combined imaging modality of multiphoton autofluorescence (MAF) and second-harmonic generation (SHG) was used for the qualitative imaging of liver fibrosis of different METAVIR grades under label-free, ex vivo conditions. We found that while MAF is effective in identifying cellular architecture in the liver specimens, it is the spectrally distinct SHG signal that allows the characterization of the extent of fibrosis. We found that qualitative SHG imaging can be used for the effective identification of the associated features of liver fibrosis specimens graded METAVIR 0 to 4. In addition, we attempted to associate quantitative SHG signal to the different METAVIR grades and found that an objective determination of the extent of disease progression can be made. Our approach demonstrates the potential of using multiphoton imaging in rapid classification of ex vivo liver fibrosis in the clinical setting and investigation of liver fibrosis–associated physiopathology in animal models in vivo.

Figures in this Article
E800, Nikon, Tokyo, Japan

Citation

Tzu-Lin Sun ; Hsiao-Ching Chen ; Chun-Hui Yang ; Wei-Chou Lin ; Wei-Liang Chen, et al.
"Ex vivo imaging and quantification of liver fibrosis using second-harmonic generation microscopy", J. Biomed. Opt. 15(3), 036002 (June 30, 2010). ; http://dx.doi.org/10.1117/1.3427146


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