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Combined Photoacoustic and Doppler Ultrasound Imaging for Tissue Oxygen Consumption Estimation

  • Author / Creator
    Jiang, Yan
  • Oxygen is the substrate that cells use in the greatest quantity and upon which aerobic metabolism and cell integrity depend. Continuous and sufficient supply of oxygen is necessary to maintain normal cellular aerobic metabolism. Failure of oxygen supply to meet metabolic needs is a common feature of many tissue dysfunctions and diseases. Therefore, the ability to estimate metabolic rate of tissue oxygen consumption (MRO2) is important for diagnosis and therapy of many diseases related to metabolism functions. Currently, techniques to obtain MRO2 are limited. None of the single modalities has good performance both at blood flow and oxygenation measurements. Therefore, the long-term goal of our research is to develop a multi-modality imaging technique combining photoacoustic and Doppler ultrasound methods for non-invasive MRO2 estimation in vivo in animal and human subjects. Photoacoustic imaging provides high spatial resolution and high sensitivity in blood oxygenation estimation due to high physiologically specific optical absorption contrast. Doppler ultrasound is capable of imaging a wide range of flow velocities by choosing appropriate ultrasonic transducer and Doppler pulse-repetition-rate. The combination of these two imaging modalities has the potential to better visualize and estimate MRO2 for many research and clinical applications. In this dissertation, we propose MRO2 estimation using combined multi-wavelength photoacoustic microscopy and high-frequency (>20MHz) Doppler ultrasound. We aim to devise flow phantom experiments to validate the capabilities of our technique for MRO2 estimation, and further demonstrate the feasibility of cerebral MRO2 estimation in brain auto-regulation study in vivo in a pre-clinical animal model. Work conducted in this dissertation can be described in three sections. First, we developed a combined photoacoustic and high-frequency power Doppler ultrasound imaging system for blood volume detection, which is important for flow estimation. We presented a quantitative and objective comparison on blood volume detection using flow phantoms with various combinations of vessel size, flow velocity and optical wavelength. Second, we upgraded our system to introduce blood oxygen saturation estimation using multi-wavelength photoacoustic method, and color Doppler ultrasound for flow velocity estimation. We experimentally demonstrated the feasibility to image local blood oxygen flux of a single vessel by double-ink phantom studies, and in vitro sheep blood phantom studies. Third, we pushed forward our research to pre-clinical domain, and first demonstrated the cerebral MRO2 estimation in vivo by combining the measurements of arterial and venous oxygen saturation, and flow rate of internal jugular vein on a Sprague Dawley rat model. In this study, the physiological conditions of the animal were controlled from hypoxia to mild hyperoxia, to study the hypothesis of brain metabolic auto-regulation mechanisms. This research may have significant applicability in other tissues and has the potential for clinical translation in the future.

  • Subjects / Keywords
  • Graduation date
    Fall 2019
  • Type of Item
    Thesis
  • Degree
    Doctor of Philosophy
  • DOI
    https://doi.org/10.7939/r3-r8jc-s897
  • License
    Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.