Continuous Grading of Early Fibrosis in NAFLD Using Label-Free Imaging: A Proof-of-Concept Study
Autor: | Panu K. Luukkonen, Elina Ikonen, Sanja Sädevirta, Juho Pirhonen, Sanna-Maria Karppinen, Antti Isomäki, Johanna Arola, Hannele Yki-Järvinen, Mika Hukkanen, Taina Pihlajaniemi |
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Přispěvatelé: | Medicum, Department of Anatomy, Department of Pathology, Clinicum, Department of Medicine, Lipid Trafficking Lab |
Rok vydání: | 2015 |
Předmět: |
0301 basic medicine
Liver Cirrhosis Male Pathology Biopsy lcsh:Medicine Biochemistry Liver disease 0302 clinical medicine Cell Signaling Fibrosis Non-alcoholic Fatty Liver Disease Medicine and Health Sciences lcsh:Science Multidisciplinary medicine.diagnostic_test NONALCOHOLIC STEATOHEPATITIS Liver Diseases Fatty liver MICROSCOPY Middle Aged 3. Good health Signal Filtering Lipid Signaling Immunohistochemistry Engineering and Technology Liver Fibrosis 030211 gastroenterology & hepatology Female Anatomy Research Article Signal Transduction Adult medicine.medical_specialty animal structures Histology Surgical and Invasive Medical Procedures Gastroenterology and Hepatology 03 medical and health sciences SYSTEMS medicine Humans 2ND-HARMONIC GENERATION Grading (tumors) FATTY LIVER-DISEASE Label free business.industry MORTALITY lcsh:R Biology and Life Sciences Proteins Cell Biology medicine.disease Fatty Liver 030104 developmental biology Microscopy Fluorescence 3121 General medicine internal medicine and other clinical medicine Signal Processing lcsh:Q business Collagens Developmental Biology |
Zdroj: | PLoS ONE PLoS ONE, Vol 11, Iss 1, p e0147804 (2016) |
ISSN: | 1932-6203 |
Popis: | Background and Aims Early detection of fibrosis is important in identifying individuals at risk for advanced liver disease in non-alcoholic fatty liver disease (NAFLD). We tested whether second-harmonic generation (SHG) and coherent anti-Stokes Raman scattering (CARS) microscopy, detecting fibrillar collagen and fat in a label-free manner, might allow automated and sensitive quantification of early fibrosis in NAFLD. Methods We analyzed 32 surgical biopsies from patients covering histological fibrosis stages 0-4, using multimodal label-free microscopy. Native samples were visualized by SHG and CARS imaging for detecting fibrillar collagen and fat. Furthermore, we developed a method for quantitative assessment of early fibrosis using automated analysis of SHG signals. Results We found that the SHG mean signal intensity correlated well with fibrosis stage and the mean CARS signal intensity with liver fat. Little overlap in SHG signal intensities between fibrosis stages 0 and 1 was observed. A specific fibrillar SHG signal was detected in the liver parenchyma outside portal areas in all samples histologically classified as having no fibrosis. This signal correlated with immunohistochemical location of fibrillar collagens I and III. Conclusions This study demonstrates that label-free SHG imaging detects fibrillar collagen deposition in NAFLD more sensitively than routine histological staging and enables observer-independent quantification of early fibrosis in NAFLD with continuous grading. |
Databáze: | OpenAIRE |
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