Changes in Hemodynamics by Time-Lapse Microscopy during Embryonic Development

心血管系统通过重塑血管系统来适应生理需要。血管重塑包括新血管的形成，称为血管生成，以及现有血管直径的改变，称为动脉生成。血管重塑是重要的治疗靶点。当血管闭塞时，如中风或心脏病发作时，血管网络必须经历血管重塑才能恢复血液流动。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被称为壁剪切力的机械力，而排列在血管壁上的细胞可以感知壁剪切力。本研究的目的是研究壁面切应力对血管生成和动脉生成的影响。我们建议使用禽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都经历了显著的重塑。胚胎的优点是它的系统要简单得多，而且我们可以在显微镜舞台上使用胚胎培养来实时成像流体动力学和血管变化。因此，我们将在显微镜舞台上培养胚胎，观察血管增殖、血管细胞的迁移、血管直径的变化以及新血管的萌发与壁切应力的关系。我们还将使用计算技术来更详细地分析重建过程中出现的流动模式。根据这一研究计划接受培训的学生将发展高级流体动力学知识，并学习备受欢迎的体内成像技术。

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.