Non-linear optical microscopy sheds light on cardiovascular disease
File(s)
Author(s)
Type
Journal Article
Abstract
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 (BSHG) 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.
Date Issued
2013-02-07
Date Acceptance
2013-01-05
Citation
PLoS ONE, 2013, 8 (2)
ISSN
1932-6203
Publisher
Public Library of Science (PLoS)
Journal / Book Title
PLoS ONE
Volume
8
Issue
2
Copyright Statement
© 2013 Caorsi et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Sponsor
British Heart Foundation
Biotechnology and Biological Sciences Research Council (BBSRC)
British Heart Foundation
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000315157200113&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Grant Number
FS/11/67/28954
BB/I019448/1
RG/11/20/29266
Subjects
Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
2ND-HARMONIC GENERATION
HEART-FAILURE
IN-VIVO
FIBROSIS
CARDIOMYOPATHY
TISSUES
FLUORESCENCE
FIBRILS
FIBERS
CORNEA
Publication Status
Published
Article Number
ARTN e56136