Cohort-based multiscale analysis of hemodynamic-driven growth and remodeling of the embryonic pharyngeal arch arteries
Related Experiment Video
Updated: Feb 3, 2026
Visualization and Analysis of Pharyngeal Arch Arteries using Whole-mount Immunohistochemistry and 3D Reconstruction
Published on: March 31, 2020
Stephanie E Lindsey1, Jonathan T Butcher2, Irene E Vignon-Clementel3,4
1Nancy E. and Peter C. Meinig School of Biomedical Engineering, Ithaca, NY 14850, USA.
Insights
Normal development of great vessels from the primitive pharyngeal arch artery (PAA) network requires specific blood flow. This study quantifies hemodynamic forces and morphological variations in developing PAAs, identifying critical factors for cardiovascular malformations.
Area of Science:
- Developmental biology
- Cardiovascular science
- Biomedical engineering
Background:
- The development of the primitive pharyngeal arch artery (PAA) network into great vessels is crucial but poorly understood.
- Cardiovascular malformations often arise from disruptions in this process.
- The precise relationship between blood flow (hemodynamics) and structural changes (remodeling) during PAA development is largely unknown.
Purpose of the Study:
- To develop and apply quantitative methods to analyze morphological and hemodynamic changes in the PAA network.
- To investigate the association between local morphological variations and specific hemodynamic forces during embryonic development.
- To identify regions of variability that may predispose to or protect against cardiovascular malformations.
Main Methods:
- A methodological pipeline combining high-resolution nano-computed tomography imaging and live-imaging flow measurements.
- Development of multiscale pulsatile computational models based on experimental data.
- Quantification of hemodynamic forces in PAAs from Hamburger Hamilton (HH) stages HH18, HH24, and HH26 embryos.
Main Results:
- Identification of local morphological variations along the PAAs.
- Correlation of these variations with specific changes in hemodynamic forces.
- Demonstration of population-level mechano-morphogenic variability analysis as a strategy to understand morphogenesis.
Conclusions:
- Specific hemodynamic forces are associated with morphological variations in developing PAAs.
- This variability can influence the initiation or prevention of cardiovascular malformations.
- Population-based analysis of mechano-morphogenesis is essential for understanding embryonic cardiovascular development.
Abstract:
Growth and remodeling of the primitive pharyngeal arch artery (PAA) network into the extracardiac great vessels is poorly understood but a major source of clinically serious malformations. Undisrupted blood flow is required for normal PAA development, yet specific relationships between hemodynamics and remodeling remain largely unknown. Meeting this challenge is hindered by the common reductionist analysis of morphology to single idealized models, where in fact structural morphology varies substantially. Quantitative technical tools that allow tracking of morphological and hemodynamic changes in a population-based setting are essential to advancing our understanding of morphogenesis. Here, we have developed a methodological pipeline from high-resolution nano-computed tomography imaging and live-imaging flow measurements to multiscale pulsatile computational models. We combine experimental-based computational models of multiple PAAs to quantify hemodynamic forces in the rapidly morphing Hamburger Hamilton (HH) stage HH18, HH24 and HH26 embryos. We identify local morphological variation along the PAAs and their association with specific hemodynamic changes. Population-level mechano-morphogenic variability analysis is a powerful strategy for identifying stage-specific regions of well and poorly tolerated morphological and/or hemodynamic variation that may protect or initiate cardiovascular malformations.
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