Continuous Grading of Early Fibrosis in NAFLD Using Label-Free Imaging : A Proof-of-Concept Study

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Pirhonen , J , Arola , J , Sädevirta , S , Luukkonen , P , Karppinen , S-M , Pihlajaniemi , T , Isomäki , A , Hukkanen , M , Yki-Jarvinen , H & Ikonen , E 2016 , ' Continuous Grading of Early Fibrosis in NAFLD Using Label-Free Imaging : A Proof-of-Concept Study ' , PLoS One , vol. 11 , no. 1 , 0147804 . https://doi.org/10.1371/journal.pone.0147804

Title: Continuous Grading of Early Fibrosis in NAFLD Using Label-Free Imaging : A Proof-of-Concept Study
Author: Pirhonen, Juho; Arola, Johanna; Sädevirta, Sanja; Luukkonen, Panu; Karppinen, Sanna-Maria; Pihlajaniemi, Taina; Isomäki, Antti; Hukkanen, Mika; Yki-Jarvinen, Hannele; Ikonen, Elina
Contributor: University of Helsinki, Medicum
University of Helsinki, Medicum
University of Helsinki, Department of Medicine
University of Helsinki, Department of Anatomy
University of Helsinki, Medicum
University of Helsinki, Clinicum
University of Helsinki, Medicum
Date: 2016-01-25
Language: eng
Number of pages: 14
Belongs to series: PLoS One
ISSN: 1932-6203
URI: http://hdl.handle.net/10138/160977
Abstract: 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.
Subject: FATTY LIVER-DISEASE
NONALCOHOLIC STEATOHEPATITIS
2ND-HARMONIC GENERATION
MICROSCOPY
MORTALITY
SYSTEMS
3121 General medicine, internal medicine and other clinical medicine
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