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.