Cohort-based multiscale analysis of hemodynamic-driven growth and remodeling of the embryonic pharyngeal arch arteries
Cohort-based multiscale analysis of hemodynamic-driven growth and remodeling of the embryonic pharyngeal arch arteries
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DOI：
10.1242/dev.162578
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发表时间：
2018-10-01
期刊：
影响因子：
4.6
通讯作者：
Vignon-Clementel, Irene E.
中科院分区：
文献类型：
--
作者：
Lindsey, Stephanie E.;Butcher, Jonathan T.;Vignon-Clementel, Irene E.
原始咽弓动脉（PAA）网络进入心外大血管的生长和重塑知之甚少，但却是临床严重畸形的主要来源。不间断的血流是正常PAA发展所必需的，但血流动力学和重塑之间的具体关系在很大程度上仍然未知。面对这一挑战是阻碍了常见的还原主义分析形态单一的理想化模型，实际上结构形态差异很大。定量技术工具，允许跟踪形态和血流动力学变化的人口为基础的设置是必不可少的，以推进我们的理解形态发生。在这里，我们已经开发了一种方法管道，从高分辨率纳米计算机断层扫描成像和实时成像流量测量多尺度脉动计算模型。我们结合联合收割机的实验为基础的计算模型的多个PAA，以量化血液动力学的力量，在快速变形汉堡汉密尔顿（HH）阶段HH 18，HH 24和HH 26胚胎。我们确定局部形态变化沿着的PAA和它们的关联与特定的血流动力学变化。群体水平的机械形态变异性分析是一种强有力的策略，用于识别阶段特异性区域的良好和不良耐受的形态和/或血流动力学变异，可能会保护或启动心血管畸形。
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.