Automated Hemodynamic Analysis in Microvessels by mu-Particle Image Velocimetry

描述(申请人提供)：这项研究的主要科学目标是开发必要的分析工具和进行必要的实验，以阐明血流动力学直接或间接影响心血管生理学正常和病理现象的机械和化学机制。我们预计最终会受到这一雄心勃勃的研究目标影响的大量此类现象的例子广泛涉及从内皮细胞机械转导和血管生成到炎症和动脉粥样硬化的各个领域。我们最近开发并验证了一套全面的新型分析工具的准确性，我们统称为显微粘度计，它以前所未有的准确性和细节提供了活体单个微血管内流动状态的全场视图。然而，为了应用显微粘度计来解决微动脉和动脉中的基本问题，我们必须将分析推广到非定常流型。由于这种分析增加了时间维度，因此需要大约十倍的数据，我们还必须开发新的方法来提取这种数据，因为乏味和艰苦的手动方法是不切实际的。因此，我们建议(1)开发自动颗粒跟踪和管壁检测工具，以分析示踪剂流动的视频显微图像，并将这些工具整合到一个集成的实时系统中，用于台式显微粘度计分析；(2)将该系统推广到大范围血管直径的非定常流动状态。一旦开发出来，我们建议应用这套强大的工具来测试血液的非牛顿本构行为的显著表现是否出现在主要动脉中，就像它们在微血管中一样，以及这种行为是否是施加在血管壁上的剪应力的基本决定因素。有了这些工具，我们准备彻底解决血流动力学中的这些和许多其他长期存在的不确定性，这些不确定性对与血管内皮细胞相关的生理和病理生理过程具有广泛的影响。

DESCRIPTION (provided by applicant): The driving scientific objective of this research is to develop analytical tools and conduct experiments necessary to elucidate mechanical and chemical mechanisms by which hemodynamics directly or indirectly influences normal and pathologic phenomena in cardiovascular physiology. The numerous examples of such phenomena that we expect would ultimately be impacted by this ambitious research objective extend broadly across fields ranging from endothelial-cell mechanotransduction and angio- genesis to inflammation and atherosclerosis. We have recently developed and verified the accuracy of a comprehensive set of novel analytical tools, which we collectively refer to as microviscometry, that provides a full-field view of the flow regime in individual microvessels in vivo with an accuracy and detail that is unprecedented in microvascular research. In order to apply microviscometry to address fundamental questions in arterioles and arteries, however, we must generalize the analysis to unsteady flow regimes. Since such an analysis adds the dimension of time, and consequently requires approximately ten-fold more data, we must also develop new methods for extracting such data since a tedious and painstaking manual approach is impractical. We therefore propose (1) to develop automatic particle- tracking and vessel-wall-detection tools to analyze video microscopic images of tracer-laden flows and to incorporate these tools into an integrated real-time system for benchtop microviscometric analysis and (2) to generalize this system to unsteady flow regimes across a broad range of vessel diameters. Once developed, we propose to apply this robust suite of tools to test whether significant manifestations of the non-Newtonian constitutive behavior of blood arise in the major arteries, as they do in microvessels, and whether such behavior is a fundamental determinant of the shear stress exerted on the vessel wall. With these tools, we are poised to definitively resolve these and many other long-standing uncertainties in hemodynamics that have broad-reaching implications for physiological and pathophysiological processes associated with the vascular endothelium.