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...

Full description

Bibliographic Details
Main Authors: Lyon, Alexander R., Ferenczi, Mike A., Sikkel, Markus B., Caorsi, Valentina, Toepfer, Christopher, MacLeod, Ken
Other Authors: Talkachova, Alena
Format: Journal Article
Language:English
Published: 2014
Subjects:
Online Access:https://hdl.handle.net/10356/100293
http://hdl.handle.net/10220/18448
_version_ 1811686099706183680
author Lyon, Alexander R.
Ferenczi, Mike A.
Sikkel, Markus B.
Caorsi, Valentina
Toepfer, Christopher
MacLeod, Ken
author2 Talkachova, Alena
author_facet Talkachova, Alena
Lyon, Alexander R.
Ferenczi, Mike A.
Sikkel, Markus B.
Caorsi, Valentina
Toepfer, Christopher
MacLeod, Ken
author_sort Lyon, Alexander R.
collection NTU
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 (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.
first_indexed 2024-10-01T04:55:02Z
format Journal Article
id ntu-10356/100293
institution Nanyang Technological University
language English
last_indexed 2024-10-01T04:55:02Z
publishDate 2014
record_format dspace
spelling ntu-10356/1002932022-02-16T16:31:06Z Non-linear optical microscopy sheds light on cardiovascular disease Lyon, Alexander R. Ferenczi, Mike A. Sikkel, Markus B. Caorsi, Valentina Toepfer, Christopher MacLeod, Ken Talkachova, Alena Lee Kong Chian School of Medicine (LKCMedicine) Medicine 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. Published version 2014-01-13T02:08:07Z 2019-12-06T20:19:52Z 2014-01-13T02:08:07Z 2019-12-06T20:19:52Z 2013 2013 Journal Article Caorsi, V., Toepfer, C., Sikkel, M. B., Lyon, A. R., MacLeod, K., & Ferenczi, M. A. (2013). Non-Linear Optical Microscopy Sheds Light on Cardiovascular Disease. PLoS ONE, 8(2), e56136-. 1932-6203 https://hdl.handle.net/10356/100293 http://hdl.handle.net/10220/18448 10.1371/journal.pone.0056136 23409139 en PLoS ONE © 2013 The Authors. This paper was published in PLoS ONE and is made available as an electronic reprint (preprint) with permission of the authors. The paper can be found at the following official DOI: [http://dx.doi.org/10.1371/journal.pone.0056136]. One print or electronic copy may be made for personal use only. Systematic or multiple reproduction, distribution to multiple locations via electronic or other means, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper is prohibited and is subject to penalties under law. application/pdf
spellingShingle Medicine
Lyon, Alexander R.
Ferenczi, Mike A.
Sikkel, Markus B.
Caorsi, Valentina
Toepfer, Christopher
MacLeod, Ken
Non-linear optical microscopy sheds light on cardiovascular disease
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
topic Medicine
url https://hdl.handle.net/10356/100293
http://hdl.handle.net/10220/18448
work_keys_str_mv AT lyonalexanderr nonlinearopticalmicroscopyshedslightoncardiovasculardisease
AT ferenczimikea nonlinearopticalmicroscopyshedslightoncardiovasculardisease
AT sikkelmarkusb nonlinearopticalmicroscopyshedslightoncardiovasculardisease
AT caorsivalentina nonlinearopticalmicroscopyshedslightoncardiovasculardisease
AT toepferchristopher nonlinearopticalmicroscopyshedslightoncardiovasculardisease
AT macleodken nonlinearopticalmicroscopyshedslightoncardiovasculardisease