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Light-sheet Fluorescence Microscopy to Capture 4-Dimensional Images of the Effects of Modulating Shear Stress on the Developing Zebrafish Heart
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A method to quantify mechanobiologic forces during zebrafish cardiac development using 4-D light sheet imaging and

Vijay Vedula1, Juhyun Lee2, Hao Xu3

  • 1Department of Pediatrics (Cardiology), Stanford University, Stanford, California, United States of America.

Plos Computational Biology
|October 31, 2017
PubMed
Summary

This study introduces a computational framework to quantify mechanical forces in developing zebrafish hearts, revealing how blood flow influences cardiac development and trabeculation. Findings suggest oscillatory forces regulate this crucial process.

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Area of Science:

  • Cardiovascular Biology
  • Biophysics
  • Developmental Biology

Background:

  • Cardiac development and trabeculation are influenced by blood flow and mechanical forces.
  • The precise mechanisms of mechanotransduction in the developing heart are not fully understood.
  • Quantifying mechanical forces in the embryonic heart presents significant technical challenges.

Purpose of the Study:

  • To develop and validate a novel computational framework for simulating cardiac hemodynamics in developing zebrafish embryos.
  • To extract time-dependent mechanical stimuli data from these simulations.
  • To investigate the role of hemodynamic forces in cardiac trabeculation.

Main Methods:

  • Coupling 4-D light sheet imaging with a stabilized finite element flow solver.
  • Utilizing deformable image registration for efficient ventricular segmentation across cardiac phases.
  • Solving Navier-Stokes equations within a moving wall domain to quantify ventricular hemodynamics.

Main Results:

  • The computational framework successfully simulated hemodynamics in wild-type and genetically modified zebrafish embryos.
  • Elevated wall shear stress (WSS) was observed in wild-type and AG1478-treated fish compared to gata1aMO and wea mutants.
  • High oscillatory shear index (OSI) in trabecular grooves suggests oscillatory forces regulate cardiac trabeculation.

Conclusions:

  • The developed computational framework provides a robust method for quantifying mechanical forces in the developing heart.
  • Hemodynamic forces, particularly oscillatory shear stress, play a significant role in cardiac trabeculation.
  • This framework has broad applicability for future studies on cardiac development and mechanotransduction.