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A method to quantify mechanobiologic forces during zebrafish cardiac development using 4-D light sheet imaging and computational modeling
Blood flow and mechanical forces in the ventricle are implicated in cardiac development and trabeculation. However, the mechanisms of mechanotransduction remain elusive. This is due in part to the challenges associated with accurately quantifying mechanical forces in the developing heart. We present...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5679653/ https://www.ncbi.nlm.nih.gov/pubmed/29084212 http://dx.doi.org/10.1371/journal.pcbi.1005828 |
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author | Vedula, Vijay Lee, Juhyun Xu, Hao Kuo, C.-C. Jay Hsiai, Tzung K. Marsden, Alison L. |
author_facet | Vedula, Vijay Lee, Juhyun Xu, Hao Kuo, C.-C. Jay Hsiai, Tzung K. Marsden, Alison L. |
author_sort | Vedula, Vijay |
collection | PubMed |
description | Blood flow and mechanical forces in the ventricle are implicated in cardiac development and trabeculation. However, the mechanisms of mechanotransduction remain elusive. This is due in part to the challenges associated with accurately quantifying mechanical forces in the developing heart. We present a novel computational framework to simulate cardiac hemodynamics in developing zebrafish embryos by coupling 4-D light sheet imaging with a stabilized finite element flow solver, and extract time-dependent mechanical stimuli data. We employ deformable image registration methods to segment the motion of the ventricle from high resolution 4-D light sheet image data. This results in a robust and efficient workflow, as segmentation need only be performed at one cardiac phase, while wall position in the other cardiac phases is found by image registration. Ventricular hemodynamics are then quantified by numerically solving the Navier-Stokes equations in the moving wall domain with our validated flow solver. We demonstrate the applicability of the workflow in wild type zebrafish and three treated fish types that disrupt trabeculation: (a) chemical treatment using AG1478, an ErbB2 signaling inhibitor that inhibits proliferation and differentiation of cardiac trabeculation; (b) injection of gata1a morpholino oligomer (gata1aMO) suppressing hematopoiesis and resulting in attenuated trabeculation; (c) weak-atrium(m58) mutant (wea) with inhibited atrial contraction leading to a highly undeveloped ventricle and poor cardiac function. Our simulations reveal elevated wall shear stress (WSS) in wild type and AG1478 compared to gata1aMO and wea. High oscillatory shear index (OSI) in the grooves between trabeculae, compared to lower values on the ridges, in the wild type suggest oscillatory forces as a possible regulatory mechanism of cardiac trabeculation development. The framework has broad applicability for future cardiac developmental studies focused on quantitatively investigating the role of hemodynamic forces and mechanotransduction during morphogenesis. |
format | Online Article Text |
id | pubmed-5679653 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-56796532017-11-18 A method to quantify mechanobiologic forces during zebrafish cardiac development using 4-D light sheet imaging and computational modeling Vedula, Vijay Lee, Juhyun Xu, Hao Kuo, C.-C. Jay Hsiai, Tzung K. Marsden, Alison L. PLoS Comput Biol Research Article Blood flow and mechanical forces in the ventricle are implicated in cardiac development and trabeculation. However, the mechanisms of mechanotransduction remain elusive. This is due in part to the challenges associated with accurately quantifying mechanical forces in the developing heart. We present a novel computational framework to simulate cardiac hemodynamics in developing zebrafish embryos by coupling 4-D light sheet imaging with a stabilized finite element flow solver, and extract time-dependent mechanical stimuli data. We employ deformable image registration methods to segment the motion of the ventricle from high resolution 4-D light sheet image data. This results in a robust and efficient workflow, as segmentation need only be performed at one cardiac phase, while wall position in the other cardiac phases is found by image registration. Ventricular hemodynamics are then quantified by numerically solving the Navier-Stokes equations in the moving wall domain with our validated flow solver. We demonstrate the applicability of the workflow in wild type zebrafish and three treated fish types that disrupt trabeculation: (a) chemical treatment using AG1478, an ErbB2 signaling inhibitor that inhibits proliferation and differentiation of cardiac trabeculation; (b) injection of gata1a morpholino oligomer (gata1aMO) suppressing hematopoiesis and resulting in attenuated trabeculation; (c) weak-atrium(m58) mutant (wea) with inhibited atrial contraction leading to a highly undeveloped ventricle and poor cardiac function. Our simulations reveal elevated wall shear stress (WSS) in wild type and AG1478 compared to gata1aMO and wea. High oscillatory shear index (OSI) in the grooves between trabeculae, compared to lower values on the ridges, in the wild type suggest oscillatory forces as a possible regulatory mechanism of cardiac trabeculation development. The framework has broad applicability for future cardiac developmental studies focused on quantitatively investigating the role of hemodynamic forces and mechanotransduction during morphogenesis. Public Library of Science 2017-10-30 /pmc/articles/PMC5679653/ /pubmed/29084212 http://dx.doi.org/10.1371/journal.pcbi.1005828 Text en © 2017 Vedula et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Vedula, Vijay Lee, Juhyun Xu, Hao Kuo, C.-C. Jay Hsiai, Tzung K. Marsden, Alison L. A method to quantify mechanobiologic forces during zebrafish cardiac development using 4-D light sheet imaging and computational modeling |
title | A method to quantify mechanobiologic forces during zebrafish cardiac development using 4-D light sheet imaging and computational modeling |
title_full | A method to quantify mechanobiologic forces during zebrafish cardiac development using 4-D light sheet imaging and computational modeling |
title_fullStr | A method to quantify mechanobiologic forces during zebrafish cardiac development using 4-D light sheet imaging and computational modeling |
title_full_unstemmed | A method to quantify mechanobiologic forces during zebrafish cardiac development using 4-D light sheet imaging and computational modeling |
title_short | A method to quantify mechanobiologic forces during zebrafish cardiac development using 4-D light sheet imaging and computational modeling |
title_sort | method to quantify mechanobiologic forces during zebrafish cardiac development using 4-d light sheet imaging and computational modeling |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5679653/ https://www.ncbi.nlm.nih.gov/pubmed/29084212 http://dx.doi.org/10.1371/journal.pcbi.1005828 |
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