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DANA-DISSERTATION-2016.Pdf Copyright by Nicholas Pacheco Dana 2016 The Dissertation Committee for Nicholas Pacheco Dana Certifies that this is the approved version of the following dissertation: Photoacoustic Image Guidance and Tissue Characterization in Cardiovascular Applications Committee: Laura Suggs, Supervisor Stanislav Emelianov, Co-Supervisor Andrew Dunn James Tunnell Richard Bouchard Photoacoustic Image Guidance and Tissue Characterization in Cardiovascular Applications by Nicholas Pacheco Dana, B.S.; M.S.E. Dissertation Presented to the Faculty of the Graduate School of The University of Texas at Austin in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy The University of Texas at Austin December 2016 Acknowledgements When work such as this comes to fruition, it is impossible acknowledge everyone who has made a worthy contribution. Still, the generosity of a several people stand out and deserve recognition. I’d like to thank the colleagues I’ve worked with in the various ultrasound and biomaterials labs incarnations. Your support and assistance, as well as your patience and tolerance of my incoherent mumblings in our shared workspace, cannot be overstated. I’d also like to thank Tera Sherrard and Marissa Canales, whose friendship and diligence allowed this work to continue. I’d like to thank Dr. Jason Cook, who has often been my unofficial mentor as I’ve stumbled along. I wish to thank Joshua Gray and Trevor Mitcham, for their help with work done far afield. For the inelegant composition before you, I’d like to thank Timothy Sowers, who has been a terrific boon composing this work. Of course, I owe much to my committee members, Dr. Andrew Dunn and Dr. James Tunnell, for their tutelage and insight over the years. For Dr. Richard Bouchard, much thanks is owed as an early mentor of mine. To my advisors, Dr. Laura Suggs and Dr. Stanislav Emelianov, innumerable accolades are due. Their insight, gentleness, guidance and thoughtful mentorship have been gifts that cannot be adequately repaid. Lastly, I wish to thank my many friends and loved ones, both present and absent. Heather’s unending love and patience is forever an inspiration to me. The fidelity of my brother, Terry, and my sister, Sherry, of which I am undeserving and grateful. And lastly, for my son, Nathaniel, in whose hands I lay my legacy. May this work serve as a testimony your collective contributions. Thank you. iv PHOTOACOUSTIC IMAGE GUIDANCE AND TISSUE CHARACTERIZATION IN CARDIOVASCULAR APPLICATIONS Nicholas Pacheco Dana, Ph. D. The University of Texas at Austin, 2016 Supervisor: Laura Suggs Co-Supervisor: Stanislav Emelianov Collectively, cardiovascular diseases continue to be the leading cause of death, across nations and across decades. Improved diagnostic imaging methods offer promise to alleviate the morbidity associated with these diseases. Photoacoustic (PA) imaging is one such method, poised to make a significant impact on cardiovascular imaging, both as a research tool, as well as a clinical imaging modality. Offering the potential of molecular imaging in real-time, PA methods have been demonstrated in proof-of-concept studies tracking myocyte calcium dynamics. These results open the door to non-invasive longitudinal assessment of cardiac electrophysiological function, with implications for drug and contrast agent development. PA image guidance has also been extended to the characterization of cardiac radiofrequency ablation lesions. This method has been demonstrated to utilize endogenous chromophore changes resulting from ablation for the generation of depth-resolved tissue characterization maps, capable of assessing lesion extent. The technique has been subsequently validated by assessing high-intensity focused ultrasound ablation lesions in myocardium, with the hope for offering thermographic capabilities as well. While PA imaging offers such promise in cardiac ablation procedures, it is also in the process of clinical translation for image guidance and v characterization in coronary artery disease applications. Research has shown, using Monte Carlo optical modeling, that using a simple dual-wavelength PA imaging technique has great potential for successful visualization of atherosclerotic plaques across multiple tissue types and at clinically relevant multiple millimeters of depth. Collectively these results offer a suite of PA imaging tools with the potential for molecular and thermographic imaging across a broad range of cardiovascular applications. vi Table of Contents PHOTOACOUSTIC IMAGE GUIDANCE AND TISSUE CHARACTERIZATION IN CARDIOVASCULAR APPLICATIONS ............................................................... V List of Tables ....................................................................................................... xiv List of Figures ........................................................................................................xv Chapter 1: Introduction To Photoacoustic Imaging For Cardiovascular Applications .........................................................................................................................1 1.1 Introduction ...............................................................................................1 1.2 Physics of Photoacoustics .........................................................................2 1.2.1 Optical Transport in Tissue ...........................................................2 1.2.1.1 Simplification of the Radiative Transport Equation .........4 1.2.2 Derivation of tissue-heating function............................................4 1.2.2.1 Heating and Pressure-Velocity Relationship ....................5 1.2.3 Photoacoustic Equation .................................................................6 1.2.3.1 Thermal Confinement .......................................................6 1.2.3.2 Stress Confinement ...........................................................7 1.2.4 Photoacoustic Imaging Data .........................................................8 1.2.4.1 Molecular Imaging ............................................................9 1.2.4.2 Thermosensitive Photoacoustic Response ......................10 1.3 Photoacoustic Imaging Techniques ........................................................12 1.3.1 Photoacoustic Contrast Agents ...................................................12 1.3.1.1 Hemoglobin Imaging ......................................................13 1.3.1.2 Plasmonic Nanoparticle Agents ......................................13 1.3.1.3 Non-plasmonic Nanoparticle Agents ..............................15 1.3.1.4 Dye-based Contrast Agents .............................................16 1.3.2 Tomographic and illumination methods .....................................17 1.3.2.1 Single-element solutions .................................................18 1.3.2.2 One-dimensional Array Transducers ..............................19 vii 1.3.3 Photoacoustic Microscopy Methods ...........................................20 1.3.4 Spectroscopic and Multiplex Photoacoustic Methods ................21 1.3.5 Multimodal Photoacoustic Imaging ............................................23 1.3.5.1 Combined Photoacoustic-Ultrasound Imaging ...............23 1.4 Cardiovascular Applications of Photoacoustic Imaging .........................23 1.4.1 Overview of Cardiac Arrhythmia ...............................................24 1.4.1.1 Atrial Fibrillation ............................................................27 1.4.1.2 Current State of Atrial Fibrillation Treatment ................28 1.4.2 Image Guidance for Cardiac Arrhythmia Procedures .................28 1.4.2.1 Visualization of Myocyte Depolarization .......................29 1.4.2.2 Tissue Characterization for Guided Cardiac Ablation Procedures ..........................................................................30 1.4.2.3 Thermographic Visualization for Ablation Temperature Monitoring .........................................................................30 1.4.3 Overview of Coronary Heart Disease .........................................31 1.4.3.1 Summary of Coronary Heart Disease .............................31 1.4.3.2 Current Treatment Practices ...........................................32 1.4.4 Intravascular Photoacoustic Imaging ..........................................33 1.4.4.1 Spectroscopic Photoacoustic Tissue Characterization ....34 1.4.4.2 Thermal Intravascular Photoacoustic Imaging ...............36 1.4.4.3 Modeling of Light Transport for Photoacoustic Imaging36 1.5 Overview of Research Goals ..................................................................38 1.5.1 Image Guidance of Arrhythmia Treatment Goals ......................38 1.5.1.1 Visualization of Myocyte Depolarization and Cardiac Electric Potential ................................................................38 1.5.1.2 Toward Tissue Characterization of Cardiac Ablation Lesions ............................................................................................39 1.5.2 Image Guidance of Coronary Heart Disease ..............................40 1.5.2.1 Model-based Optimization of Intravascular Photoacoustic Imaging ..............................................................................40 1.5.3 Summary of Research Goals .......................................................41 1.6 References ...............................................................................................41 viii Chapter 2: In Vitro Photoacoustic Sensing Of Calcium Dynamics With Arsenazo III .......................................................................................................................52
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