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

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...

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Main Authors: Juho Pirhonen, Johanna Arola, Sanja Sädevirta, Panu Luukkonen, Sanna-Maria Karppinen, Taina Pihlajaniemi, Antti Isomäki, Mika Hukkanen, Hannele Yki-Järvinen, Elina Ikonen
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2016-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC4726624?pdf=render
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author Juho Pirhonen
Johanna Arola
Sanja Sädevirta
Panu Luukkonen
Sanna-Maria Karppinen
Taina Pihlajaniemi
Antti Isomäki
Mika Hukkanen
Hannele Yki-Järvinen
Elina Ikonen
author_facet Juho Pirhonen
Johanna Arola
Sanja Sädevirta
Panu Luukkonen
Sanna-Maria Karppinen
Taina Pihlajaniemi
Antti Isomäki
Mika Hukkanen
Hannele Yki-Järvinen
Elina Ikonen
author_sort Juho Pirhonen
collection DOAJ
description 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.
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spelling doaj.art-5b05bc2430d14e87b34a2c9b26d39c3c2022-12-22T01:46:35ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01111e014780410.1371/journal.pone.0147804Continuous Grading of Early Fibrosis in NAFLD Using Label-Free Imaging: A Proof-of-Concept Study.Juho PirhonenJohanna ArolaSanja SädevirtaPanu LuukkonenSanna-Maria KarppinenTaina PihlajaniemiAntti IsomäkiMika HukkanenHannele Yki-JärvinenElina IkonenBACKGROUND 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.http://europepmc.org/articles/PMC4726624?pdf=render
spellingShingle Juho Pirhonen
Johanna Arola
Sanja Sädevirta
Panu Luukkonen
Sanna-Maria Karppinen
Taina Pihlajaniemi
Antti Isomäki
Mika Hukkanen
Hannele Yki-Järvinen
Elina Ikonen
Continuous Grading of Early Fibrosis in NAFLD Using Label-Free Imaging: A Proof-of-Concept Study.
PLoS ONE
title Continuous Grading of Early Fibrosis in NAFLD Using Label-Free Imaging: A Proof-of-Concept Study.
title_full Continuous Grading of Early Fibrosis in NAFLD Using Label-Free Imaging: A Proof-of-Concept Study.
title_fullStr Continuous Grading of Early Fibrosis in NAFLD Using Label-Free Imaging: A Proof-of-Concept Study.
title_full_unstemmed Continuous Grading of Early Fibrosis in NAFLD Using Label-Free Imaging: A Proof-of-Concept Study.
title_short Continuous Grading of Early Fibrosis in NAFLD Using Label-Free Imaging: A Proof-of-Concept Study.
title_sort continuous grading of early fibrosis in nafld using label free imaging a proof of concept study
url http://europepmc.org/articles/PMC4726624?pdf=render
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