A method to quantify mechanobiologic forces during zebrafish cardiac development using 4-D light sheet imaging and...

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.