Non-linear optical microscopy sheds light on cardiovascular disease.

Many cardiac diseases have been associated with increased fibrosis and changes in the organization of fibrillar collagen. The degree of fibrosis is routinely analyzed with invasive histological and immunohistochemical methods, giving a limited and qualitative understanding of the tissue's morph...

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Main Authors: Valentina Caorsi, Christopher Toepfer, Markus B Sikkel, Alexander R Lyon, Ken MacLeod, Mike A Ferenczi
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0056136&type=printable
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author Valentina Caorsi
Christopher Toepfer
Markus B Sikkel
Alexander R Lyon
Ken MacLeod
Mike A Ferenczi
author_facet Valentina Caorsi
Christopher Toepfer
Markus B Sikkel
Alexander R Lyon
Ken MacLeod
Mike A Ferenczi
author_sort Valentina Caorsi
collection DOAJ
description Many cardiac diseases have been associated with increased fibrosis and changes in the organization of fibrillar collagen. The degree of fibrosis is routinely analyzed with invasive histological and immunohistochemical methods, giving a limited and qualitative understanding of the tissue's morphological adaptation to disease. Our aim is to quantitatively evaluate the increase in fibrosis by three-dimensional imaging of the collagen network in the myocardium using the non-linear optical microscopy techniques Two-Photon Excitation microscopy (TPE) and Second Harmonic signal Generation (SHG). No sample staining is needed because numerous endogenous fluorophores are excited by a two-photon mechanism and highly non-centrosymmetric structures such as collagen generate strong second harmonic signals. We propose for the first time a 3D quantitative analysis to carefully evaluate the increased fibrosis in tissue from a rat model of heart failure post myocardial infarction. We show how to measure changes in fibrosis from the backward SHG (B(SHG)) alone, as only backward-propagating SHG is accessible for true in vivo applications. A 5-fold increase in collagen I fibrosis is detected in the remote surviving myocardium measured 20 weeks after infarction. The spatial distribution is also shown to change markedly, providing insight into the morphology of disease progression.
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institution Kabale University
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publishDate 2013-01-01
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spelling doaj-art-7d0d2bf49b5c4f0b9c722b91b9a53daa2025-08-20T03:26:47ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0182e5613610.1371/journal.pone.0056136Non-linear optical microscopy sheds light on cardiovascular disease.Valentina CaorsiChristopher ToepferMarkus B SikkelAlexander R LyonKen MacLeodMike A FerencziMany cardiac diseases have been associated with increased fibrosis and changes in the organization of fibrillar collagen. The degree of fibrosis is routinely analyzed with invasive histological and immunohistochemical methods, giving a limited and qualitative understanding of the tissue's morphological adaptation to disease. Our aim is to quantitatively evaluate the increase in fibrosis by three-dimensional imaging of the collagen network in the myocardium using the non-linear optical microscopy techniques Two-Photon Excitation microscopy (TPE) and Second Harmonic signal Generation (SHG). No sample staining is needed because numerous endogenous fluorophores are excited by a two-photon mechanism and highly non-centrosymmetric structures such as collagen generate strong second harmonic signals. We propose for the first time a 3D quantitative analysis to carefully evaluate the increased fibrosis in tissue from a rat model of heart failure post myocardial infarction. We show how to measure changes in fibrosis from the backward SHG (B(SHG)) alone, as only backward-propagating SHG is accessible for true in vivo applications. A 5-fold increase in collagen I fibrosis is detected in the remote surviving myocardium measured 20 weeks after infarction. The spatial distribution is also shown to change markedly, providing insight into the morphology of disease progression.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0056136&type=printable
spellingShingle Valentina Caorsi
Christopher Toepfer
Markus B Sikkel
Alexander R Lyon
Ken MacLeod
Mike A Ferenczi
Non-linear optical microscopy sheds light on cardiovascular disease.
PLoS ONE
title Non-linear optical microscopy sheds light on cardiovascular disease.
title_full Non-linear optical microscopy sheds light on cardiovascular disease.
title_fullStr Non-linear optical microscopy sheds light on cardiovascular disease.
title_full_unstemmed Non-linear optical microscopy sheds light on cardiovascular disease.
title_short Non-linear optical microscopy sheds light on cardiovascular disease.
title_sort non linear optical microscopy sheds light on cardiovascular disease
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0056136&type=printable
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