Automated Hemodynamic Analysis in Microvessels by mu-Particle Image Velocimetry

描述（由申请人提供）：本研究的主要科学目标是开发分析工具并进行必要的实验，以阐明血液动力学直接或间接影响心血管生理正常和病理现象的机械和化学机制。我们预计，这一雄心勃勃的研究目标将最终影响到从内皮细胞机械转导和血管生成到炎症和动脉粥样硬化等广泛领域的许多此类现象。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，我们统称为微粘度计，它提供了体内单个微血管流动状态的全方位视图，其准确性和细节在微血管研究中是前所未有的。然而，为了应用微粘度学来解决小动脉和动脉的基本问题，我们必须将分析推广到非定常流动状态。由于这样的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些数据，因为繁琐而艰苦的手工方法是不切实际的。因此，我们建议(1)开发自动颗粒跟踪和容器壁检测工具，以分析含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，用于台式微粘度分析；(2)将该系统推广到广泛的容器直径范围内的非定常流场。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质行为的显著表现是否出现在大动脉中，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切应力的基本决定因素。有了这些工具，我们准备明确地解决这些和许多其他长期存在的血流动力学不确定性，这些不确定性对与血管内皮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.