Thesis (Ph.D.)--Virginia Commonwealth University, 2009. / Prepared for: Dept. of Health and Human Performance. Title from title-page of electronic thesis. Includes bibliographical references.

Thesis (Ph. D.)--University of Minnesota, 1970. / Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 159-170).

Thesis (M.S.)--Worcester Polytechnic Institute. / Keywords: oxygen consumption; PET; blood flow. Includes bibliographical references (p. 58-61).

Blood flow and its payload of molecular oxygen are two parameters of most physiological interest. Systemic tissue health is routinely gauged through measurements of vitals and oxygen saturation to estimate the state of these physiological parameters. We design, develop, and deploy optical imaging systems for examining perfusion and oxygenation at the local tissue level and apply these techniques for elucidating the normal and pathological processes associated with neurovascular disease. Specifically, we develop and validate the ability to use Multi-Exposure Speckle Imaging (MESI) to estimate microvascular flow dynamics in rodents over acute and chronic periods. Next, we pose significant optimizations to improve the efficacy of the widefield imaging technique for adoption by bench-side and clinical perfusion studies. We also introduce re-interpretations of the underlying physics to advance the theory that quantifies motion from the imaged speckle patterns. Finally, the technique is deployed for chronic monitoring of cortical flow dynamics before after focal ischemia of the motor cortex as part of a behavioral study in rodents. At the microscale, we develop and validate Two Photon Phosphorescence Lifetime Microscopy (2PLM) to examine dissolved oxygen concentration in microvasculature in three dimensions. We examine the technique’s ability for functional mapping of the rodent cortical microvascular network by quantifying the partial pressure of oxygen (pO₂) before and after occlusion of critical arterioles. Automation of acquisitions and processing for robust oxygen mapping within the micro-vascular network are developed and evaluated. The in vivo results are presented in light of those from studies utilizing more invasive mapping electrodes to provide independent corroboration of the observed neurovascular oxygen distributions. The technique is deployed for examining high resolution functional and structural remodeling after focal cerebral ischemia. / text

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The arterioles of the cat sartorius muscle dilate when arterial pressure is reduced. It has been suggested that this dilation is due to a decrease in blood flow which in turn decreases oxygen delivery and increases tissue production of vasodilator substances. The latter diffuse into the vicinity of the arterioles and cause vascular relaxation. This vascular dilation acts to maintain blood flow through the tissue near the control level at a time when perfusion pressure is reduced. This phenomenon, called autoregulation of blood flow, has been observed in most organs of the body. In the following experiments, we attempted to test the hypothesis that a fall in the oxygen level of the tissue is responsible for blood flow autoregulation. We did this by studying the response of cat sartorius arterioles to arterial pressure reduction under conditions where the muscle was supplied with oxygen from the environment in addition to that normally supplied by the blood. Tissue PO₂ was altered by placing the isolated, auto-perfused cat sartorius muscle in contact with silicone fluid equilibrated with a 0% to 20% oxygen gas mixture. As oxygen tension in the bathing fluid was increased, the preponderant response was a decrease in arteriolar diameter, blood velocity and arteriolar volume flow. To illustrate, 8% of the arterioles constricted by an average of 10% and 18% when the muscle was exposed to oxygen tensions of 66 and 132 mmHg, respectively. When blood flow autoregulation was investigated, it was found that elevated oxygen tension in the bathing fluid abolished any significant arteriolar dilation or flow autoregulation in the majority of arterioles studied. In addition, the elevated oxygen environment caused complete cessation of blood flow in many of the smaller arterioles (< 15μ in diameter). The results of this study strongly suggest that the O₂ level of the tissue is an important determinant in local blood flow regulation.

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