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Longitudinal Live Imaging Derived 5D Hemodynamics and Dynamic Tissue Strains Across Outflow Tract Morphogenesis

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2025-09-05
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Abstract

The cardiac outflow tract (OFT) undergoes complex remodeling and extensive morphogenesis within the early developmental stages to divide into the aortic and pulmonary great vessels, and form the semilunar valves. Malformation of the OFT is involved in about 30% of congenital heart defects (CHDs), which affect nearly 1% of newborns per year in the US. Over the past decade, fluid and mechanical forces are recognized as biomechanical stimuli for cardiac development, and hemodynamic perturbations have emerged as an appealing alternative cause of OFT CHDs. While live imaging techniques and computational fluid dynamics (CFD) simulations have been widely employed for hemodynamics investigations, the hemodynamics and tissue dynamics in a morphing cardiac OFT are still poorly understood. Thus, the focus of this thesis is to quantify the hemodynamic and dynamic tissue strains during cardiogenesis in a five-dimensional (5D) manner from Hamburger-Hamilton (HH) stage 21 to HH27, an important period of OFT remodeling and valve formation. The dynamic anatomies of the OFT were first reconstructed based on longitudinal high-frequency ultrasound imaging. 4D moving-domain CFD simulations based on the geometric reconstruction showed that the WSS in the distal portion of the OFT significantly increased from HH21 to HH27. Maximum WSSs were generally found at the OFT cushions. Moreover, the proximal portion of the OFT was found to undergo significantly larger strains than the distal portion (Chapter 2). Next, the growth strains from HH21 to HH24 were separated and investigated in a beating OFT by simulating cardiac morphogenesis in finite element models. The distal portion was found to undergo significantly higher growth strains, and their directions were in line with the blood flow (Chapter 3). Overall, this study has made significant advancements in understanding hemodynamics and tissue dynamics in cardiac OFT development and remodeling. Our computational modeling showed great potential for identifying biomechanical stimuli in cardiac remodeling, which may provide new insights into how mechanical forces lead to downstream morphology phenomena during cardiac development and contribute to the investigation of CHD pathogenesis.

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112 pages

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2023-08

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Butcher, Jonathan

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Esmaily Moghadam, Mahdi

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Mechanical Engineering

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M.S., Mechanical Engineering

Degree Level

Master of Science

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dissertation or thesis

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