Changes in Hemodynamics by Time-Lapse Microscopy during Embryonic Development

心血管系统通过重塑脉管系统来适应生理需要。 血管重塑涉及新血管的形成（称为血管生成）和现有血管直径的变化（称为动脉生成）。 血管重塑是重要的治疗靶点。当血管变得闭塞时，例如在中风或心脏病发作期间发生时，血管网络必须经历血管重塑以恢复血流。 血管重塑最重要的线索之一是血流本身。 血流在血管壁上产生一种称为壁切应力的机械力，血管壁的细胞可以感受到壁切应力。 本研究的目的是研究血管壁切应力对血管生成和动脉生成的影响。 我们建议使用鸟类胚胎作为我们的模型。 当血液在胚胎中开始流动时，血管通过血管生成和动脉生成进行显著的重塑。 胚胎的优点是它是一个简单得多的系统，此外，我们可以使用显微镜载物台上的胚胎培养来实时成像流体动力学和血管变化。 因此，我们将在显微镜下培养胚胎，观察血管增殖、血管细胞迁移、血管直径变化和新血管发芽与壁面切应力的关系。 我们还将使用计算技术来更详细地分析重塑过程中存在的流动模式。 谁是根据这项研究计划培训的学生将开发先进的流体动力学知识，以及学习在体内成像技术，是非常抢手。

The cardiovascular system adapts to physiological needs by remodeling the vasculature. Vascular remodeling involves both the formation of new blood vessels, called angiogenesis, and changes in diameter of existing blood vessels, called arteriogenesis. Vascular remodeling is an important therapeutic target. When a blood vessel becomes occluded, such as occurs during a stroke or a heart attack, the network of blood vessels must undergo vascular remodeling in order to restore blood flow. One of the most important cues for vascular remodeling is the blood flow itself. Blood flow creates a mechanical force on the vessel wall called wall shear stress and the cells that line the blood vessel wall can sense wall shear stress. This aim of this proposal is to study the effect of wall shear stress on angiogenesis and arteriogenesis. We propose using the avian embryo as our model. When blood flow starts in the embryo, the blood vessels undergoes significant remodeling both by angiogenesis and by arteriogenesis. The advantage of the embryo is that it is much simpler system and furthermore, we can image both the fluid dynamics and the changes in the blood vessels in real-time using embryo culture on a microscope stage. We will therefore culture embryos on a microscope stage and look at vascular proliferation, migration of vascular cells, changes in vessel diameter and the sprouting of new vessels in relationship to the amount of wall shear stress present. We will also uses computational techniques to analyse the flow patterns that are present during remodeling in more detail. The students who are trained under this research program will develop advanced knowledge of fluid dynamics as well as learning in vivo imaging techniques that are highly sought after.