Aortic Arch Morphogenesis and Flow Modeling in the Chick Embryo

Aortic Arch Morphogenesis and Flow Modeling in the Chick Embryo
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鸡胚胎主动脉弓形态发生和血流建模

DOI:
10.1007/s10439-009-9682-5
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发表时间:
2009
影响因子:
3.8
通讯作者:
K. Pekkan
K. Pekkan
中科院分区:
工程技术2区
文献类型:
--
作者:
Yajuan Wang;O. Dur;M. J. Patrick;J. P. Tinney;K. Tobita;B. Keller;K. Pekkan

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在活跃的生物力学环境中,“未成熟对称胚胎主动脉弓”向“成熟和不对称主动脉弓”的形态发生涉及一系列微妙的细胞和组织迁移、增殖和重塑。患者和实验动物模型数据都支持生物力学力在弓发育过程中的重要作用。本研究的目的是量化在正常弓形态发生期间几何形状、血流和剪切应力模式(WSS)的变化。利用荧光染料注射、微ct、多普勒速度记录和脉冲计算流体动力学(CFD)技术,在汉堡-汉密尔顿(HH)发育阶段HH18和HH24建立了鸡胚主动脉弓的复合三维(3D)模型。将墨汁和荧光染料注入胚胎心室或心房,观察左、右主动脉弓形态和血流。通过聚合物铸型和微ct扫描获得了发育中的大血管的三维形态。通过20 MHz脉冲多普勒速度测量和文献资料获得入口主动脉弓血流和脑-下体血流分裂。据报道,单个拱直径在发育时间轴上有统计学意义的变化,并与CFD计算的WSS相关。CFD模拟量化了HH18和HH24期流出道通过主动脉弓的脉动血流分布。所有三个弓对的血流灌注与常见咽弓缺损进展的体内观察相关。早期胚胎主动脉弓复杂的空间WSS和速度分布在HH18和HH24阶段之间发生变化,与血流速度增加和解剖结构改变相一致。在最窄的弓径处,WSS值最高。通过改变入口气流的分布,可以模拟单个拱门内的流动和WSS的变化。因此,入口血流分布、三维主动脉囊和主动脉弓几何形状以及局部血管生物学对WSS空间变化的响应都可能是调节主动脉弓形态发生的重要因素。
Morphogenesis of the “immature symmetric embryonic aortic arches” into the “mature and asymmetric aortic arches” involves a delicate sequence of cell and tissue migration, proliferation, and remodeling within an active biomechanical environment. Both patient-derived and experimental animal model data support a significant role for biomechanical forces during arch development. The objective of the present study is to quantify changes in geometry, blood flow, and shear stress patterns (WSS) during a period of normal arch morphogenesis. Composite three-dimensional (3D) models of the chick embryo aortic arches were generated at the Hamburger–Hamilton (HH) developmental stages HH18 and HH24 using fluorescent dye injection, micro-CT, Doppler velocity recordings, and pulsatile subject-specific computational fluid dynamics (CFD). India ink and fluorescent dyes were injected into the embryonic ventricle or atrium to visualize right or left aortic arch morphologies and flows. 3D morphology of the developing great vessels was obtained from polymeric casting followed by micro-CT scan. Inlet aortic arch flow and cerebral-to-lower body flow split was obtained from 20 MHz pulsed Doppler velocity measurements and literature data. Statistically significant variations of the individual arch diameters along the developmental timeline are reported and correlated with WSS calculations from CFD. CFD simulations quantified pulsatile blood flow distribution from the outflow tract through the aortic arches at stages HH18 and HH24. Flow perfusion to all three arch pairs are correlated with the in vivo observations of common pharyngeal arch defect progression. The complex spatial WSS and velocity distributions in the early embryonic aortic arches shifted between stages HH18 and HH24, consistent with increased flow velocities and altered anatomy. The highest values for WSS were noted at sites of narrowest arch diameters. Altered flow and WSS within individual arches could be simulated using altered distributions of inlet flow streams. Thus, inlet flow stream distributions, 3D aortic sac and aortic arch geometries, and local vascular biologic responses to spatial variations in WSS are all likely to be important in the regulation of arch morphogenesis.
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