Quantification of Myocyte Disarray in Human Cardiac Tissue

Proper three-dimensional (3D)-cardiomyocyte orientation is important for an effective tension production in cardiac muscle. Cardiac diseases can cause severe remodeling processes in the heart, such as cellular misalignment, that can affect both the electrical and mechanical functions of the organ. T...

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Autores principales: Francesco Giardini, Erica Lazzeri, Giulia Vitale, Cecilia Ferrantini, Irene Costantini, Francesco S. Pavone, Corrado Poggesi, Leonardo Bocchi, Leonardo Sacconi
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Publicado: Frontiers Media S.A. 2021
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Acceso en línea:https://doaj.org/article/45e7f98f680e4abbb1bfc477a0996276
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spelling oai:doaj.org-article:45e7f98f680e4abbb1bfc477a09962762021-11-16T05:07:49ZQuantification of Myocyte Disarray in Human Cardiac Tissue1664-042X10.3389/fphys.2021.750364https://doaj.org/article/45e7f98f680e4abbb1bfc477a09962762021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphys.2021.750364/fullhttps://doaj.org/toc/1664-042XProper three-dimensional (3D)-cardiomyocyte orientation is important for an effective tension production in cardiac muscle. Cardiac diseases can cause severe remodeling processes in the heart, such as cellular misalignment, that can affect both the electrical and mechanical functions of the organ. To date, a proven methodology to map and quantify myocytes disarray in massive samples is missing. In this study, we present an experimental pipeline to reconstruct and analyze the 3D cardiomyocyte architecture in massive samples. We employed tissue clearing, staining, and advanced microscopy techniques to detect sarcomeres in relatively large human myocardial strips with micrometric resolution. Z-bands periodicity was exploited in a frequency analysis approach to extract the 3D myofilament orientation, providing an orientation map used to characterize the tissue organization at different spatial scales. As a proof-of-principle, we applied the proposed method to healthy and pathologically remodeled human cardiac tissue strips. Preliminary results suggest the reliability of the method: strips from a healthy donor are characterized by a well-organized tissue, where the local disarray is log-normally distributed and slightly depends on the spatial scale of analysis; on the contrary, pathological strips show pronounced tissue disorganization, characterized by local disarray significantly dependent on the spatial scale of analysis. A virtual sample generator is developed to link this multi-scale disarray analysis with the underlying cellular architecture. This approach allowed us to quantitatively assess tissue organization in terms of 3D myocyte angular dispersion and may pave the way for developing novel predictive models based on structural data at cellular resolution.Francesco GiardiniErica LazzeriGiulia VitaleCecilia FerrantiniCecilia FerrantiniIrene CostantiniIrene CostantiniIrene CostantiniFrancesco S. PavoneFrancesco S. PavoneFrancesco S. PavoneCorrado PoggesiLeonardo BocchiLeonardo BocchiLeonardo SacconiLeonardo SacconiLeonardo SacconiFrontiers Media S.A.article3D cardiomyocyte orientation3D FFTcytoarchitecture reconstructiondisarray quantificationtissue modelingPhysiologyQP1-981ENFrontiers in Physiology, Vol 12 (2021)
institution DOAJ
collection DOAJ
language EN
topic 3D cardiomyocyte orientation
3D FFT
cytoarchitecture reconstruction
disarray quantification
tissue modeling
Physiology
QP1-981
spellingShingle 3D cardiomyocyte orientation
3D FFT
cytoarchitecture reconstruction
disarray quantification
tissue modeling
Physiology
QP1-981
Francesco Giardini
Erica Lazzeri
Giulia Vitale
Cecilia Ferrantini
Cecilia Ferrantini
Irene Costantini
Irene Costantini
Irene Costantini
Francesco S. Pavone
Francesco S. Pavone
Francesco S. Pavone
Corrado Poggesi
Leonardo Bocchi
Leonardo Bocchi
Leonardo Sacconi
Leonardo Sacconi
Leonardo Sacconi
Quantification of Myocyte Disarray in Human Cardiac Tissue
description Proper three-dimensional (3D)-cardiomyocyte orientation is important for an effective tension production in cardiac muscle. Cardiac diseases can cause severe remodeling processes in the heart, such as cellular misalignment, that can affect both the electrical and mechanical functions of the organ. To date, a proven methodology to map and quantify myocytes disarray in massive samples is missing. In this study, we present an experimental pipeline to reconstruct and analyze the 3D cardiomyocyte architecture in massive samples. We employed tissue clearing, staining, and advanced microscopy techniques to detect sarcomeres in relatively large human myocardial strips with micrometric resolution. Z-bands periodicity was exploited in a frequency analysis approach to extract the 3D myofilament orientation, providing an orientation map used to characterize the tissue organization at different spatial scales. As a proof-of-principle, we applied the proposed method to healthy and pathologically remodeled human cardiac tissue strips. Preliminary results suggest the reliability of the method: strips from a healthy donor are characterized by a well-organized tissue, where the local disarray is log-normally distributed and slightly depends on the spatial scale of analysis; on the contrary, pathological strips show pronounced tissue disorganization, characterized by local disarray significantly dependent on the spatial scale of analysis. A virtual sample generator is developed to link this multi-scale disarray analysis with the underlying cellular architecture. This approach allowed us to quantitatively assess tissue organization in terms of 3D myocyte angular dispersion and may pave the way for developing novel predictive models based on structural data at cellular resolution.
format article
author Francesco Giardini
Erica Lazzeri
Giulia Vitale
Cecilia Ferrantini
Cecilia Ferrantini
Irene Costantini
Irene Costantini
Irene Costantini
Francesco S. Pavone
Francesco S. Pavone
Francesco S. Pavone
Corrado Poggesi
Leonardo Bocchi
Leonardo Bocchi
Leonardo Sacconi
Leonardo Sacconi
Leonardo Sacconi
author_facet Francesco Giardini
Erica Lazzeri
Giulia Vitale
Cecilia Ferrantini
Cecilia Ferrantini
Irene Costantini
Irene Costantini
Irene Costantini
Francesco S. Pavone
Francesco S. Pavone
Francesco S. Pavone
Corrado Poggesi
Leonardo Bocchi
Leonardo Bocchi
Leonardo Sacconi
Leonardo Sacconi
Leonardo Sacconi
author_sort Francesco Giardini
title Quantification of Myocyte Disarray in Human Cardiac Tissue
title_short Quantification of Myocyte Disarray in Human Cardiac Tissue
title_full Quantification of Myocyte Disarray in Human Cardiac Tissue
title_fullStr Quantification of Myocyte Disarray in Human Cardiac Tissue
title_full_unstemmed Quantification of Myocyte Disarray in Human Cardiac Tissue
title_sort quantification of myocyte disarray in human cardiac tissue
publisher Frontiers Media S.A.
publishDate 2021
url https://doaj.org/article/45e7f98f680e4abbb1bfc477a0996276
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