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  • Quantitative Photoacoustic Imaging

    by

    Peng Shao

    A thesis submitted in partial fulfillment of the requirements for the degree of

    Doctor of Philosophy

    in

    Biomedical Engineering

    Department of Electrical and Computer Engineering

    University of Alberta

    © Peng Shao, 2014

  • ii

    Abstract

    Tumor angiogenesis is the cancer-induced chaotic proliferation of blood vessel

    structure penetrating into surrounding cancerous tissue. Effective micro-

    vasculature imaging method is urgently desired for both fundamental biological and

    clinical studies. However, this is a challenging task, as existing standard imaging

    techniques are limited by factors such as poor resolution, high cost, necessity of

    using imaging contrast agent and invasiveness. Photoacoustic (PA) imaging, as a

    non-ionizing modality, has drawn significant interest due to the promise it holds for

    high-resolution, noninvasiveness and its capability to reveal functional information

    based on intrinsic optical contrast.

    The ultimate goal of this dissertation is to further previous work on quantitative

    photoacoustic imaging, specifically, to contribute to quantitative imaging of tumor

    angiogenesis and anti-angiogenetic therapy. The work presented in this dissertation

    can be divided into three parts. In the first part, we focus on quantitative

    photoacoutic tomography (qPAT) for deep tissue imaging. We developed a series of

    algorithms that are able to quantify deep tissue photoacoustic imaging. We

    demonstrated by simulations that spatial distributions of optical properties, namely

    optical absorption and scattering, as well as the Grüneisen parameter can be

  • iii

    faithfully reconstructed with our reconstruction algorithms. In the second part, we

    focused on developing new imaging platforms for quantitative photoacoustic

    microscopy (PAM) imaging for superficial imaging depths. We successfully

    included fluorescently-labeled molecular context in optical-resolution PAM (OR-

    PAM) imaging by our integrated micro-endoscopy system that is able to

    simultaneously accomplish fluorescence and OR-PAM imaging. With our fast,

    wide field-of-view OR-PAM imaging technique, we significantly reduced the data

    acquisition time of conventional OR-PAM systems to a clinically realistic level. In

    the third part, experimental work is presented for quantitative imaging of

    vasculature variations and oxygen depletions due to photodynamic therapy with an

    acoustic-resolution PAM (AR-PAM) system we developed.

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    Preface

    Chapter 3 of this dissertations has been published as P. Shao, B. Cox and R. J. Zemp,

    Estimating Optical Absorption, Scattering, and Grueneisen Distributions with

    Multiple-Illumination Photoacoustic Tomography, Appl. Opt., 50(19), 3145-3154,

    2011. I was responsible for algorithm development, simulation design,

    programming (data collection) as well as manuscript composition. B. Cox assisted

    with some of the data collection and contributed to manuscript edits. R. J. Zemp

    was the supervisory author and was involved with concept formation and

    manuscript composition.

    Chapter 4 of this dissertation has been published as P. Shao T. J. Harrison and

    R. J. Zemp, Iterative algorithm for multiple-illumination photoacoustic tomography

    (MIPAT) using ultrasound channel data, Biomed. Opt. Express, 3(12), 3240-3249,

    2012. I was responsible for the algorithm development, simulation design,

    programming (data collection) as well as manuscript composition. T. J. Harrison

    contributed to simulation design and manuscript edits. R. J. Zemp was the

    supervisory author and was involved with concept formation and manuscript

    composition.

    Chapter 6 of this dissertation has been published as P. Shao, W. Shi, P. Hajireza

    and R. J. Zemp, Integrated micro-endoscopy system for simultaneous fluorescence

  • v

    and optical-resolution photoacoustic imaging, J. Biomed. Opt., 17(7), 076024, 2012.

    I was the lead of the project, responsible for experiment design, data collection and

    manuscript composition. W. Shi contributed to experiments. P. Hajireza contributed

    to experiment design. R. J. Zemp was the supervisory author and was involved with

    concept formation and manuscript composition.

    Chapter 7 of this dissertation has been published as P. Shao, W. Shi, R. K. Chee,

    and R. J. Zemp, Mosaic Acquisition and Processing for Optical-Resolution

    Photoacoustic Microscopy, J. Biomed. Opt., 17(8), 070503, 2012. I was the lead of

    the project, responsible for experiment design, data collection and manuscript

    composition. W. Shi contributed to experiments. R. K. W. Chee contributed to

    software design and realization. R. J. Zemp was the supervisory author and was

    involved with concept formation and manuscript composition.

    Chapter 8 of this dissertation forms part of collaboration led by Dr. Ronald B.

    Moore, with Dr. Roger J. Zemp. Dr. Moore assisted with concept formation and

    experiment design. I conducted the study and manuscript composition. Dr. Roger J.

    Zemp was the supervisory author and was involved with experiment design,

    concept formation and manuscript composition.

    In vivo experiments procedures involving animals described in Chapter 6, 7

    and 8 in this dissertation followed follow the laboratory animal protocol approved

    by the University of Alberta Animal Use and Care Committee.

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    Acknowledgements

    First and foremost, I would like to express my sincere gratitude to my supervisor,

    Dr. Roger J. Zemp for his encouragement, patience, guidance and support during

    my doctoral program. I have been grateful that he took me as a graduate student

    and offered me the chance to work on exciting research projects, by which I built

    up my confidence to pursue a research career.

    My sincere thanks to my supervisory committee members, Dr. Robert

    Fedosejevs and Dr. Mrinal Mandal, our collaborator Dr. Ronald Moore from

    Faculty of Medicine, and Dr. Mauricio Sacchi from the Physics Department. I have

    been lucky to have the chance to learn from, and work with these excellent

    professors during my stay at the University of Alberta. Their scholarship and

    professionalism impressed me and set up role models for me to follow in my future

    career.

    Many thanks to the colleagues in my lab and my friends at the University of

    Alberta, for your support and companionship!

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    Contents

    1. Introduction 1

    1.1 The need for micro-vasculature imaging ··································· 1

    1.2 Photoacoustic imaging ························································ 1

    1.3 Problem statement and motivation ·········································· 2

    1.4 Major contribution of this dissertation ····································· 4

    1.5 Organization of this dissertation············································· 9

    2. Background 8

    2.1 Tumor angiogenesis and anti-angiogenetic therapy ···················· 17

    2.2 Photodynamic therapy ····················································· 18

    2.3 Micro-vasculature imaging ··············································· 19

    2.4 Photoacoustic imaging ···················································· 20

    2.5 Challenges of photoacoustic techniques ································ 29

    3. Estimating Optical Absorption, Scattering, and Grüneisen

    Distributions with Multiple-illumination Photoacoustic Tomography

    (MI-PAT) 47

    3.1 Introduction ·································································· 47

    3.2 Theory ········································································· 52

    3.2.1 Problem of absorption-scattering non-uniqueness ·············· 53

    3.2.2 Multiple-illumination locations as a potential remedy for

    absorption-scattering non-uniqueness ·························· 55

    3.2.3 Multiple-optical-source photoacoustic reconstruction

    methodology for absorption and scattering perturbations in a

    known turbid backgrond ·········································· 55

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    3.2.4 Recovery of the spatially varying Grüneisenp parameter ···· 61

    3.3 Computational reconstruction ············································ 61

    3.4 Discussion ········

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