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Characterization of Cardiac Tissue Using Optical Coherence Tomography

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Characterization of Cardiac Tissue Using Optical Coherence Tomography CHARACTERIZATION OF CARDIAC TISSUE USING OPTICAL COHERENCE TOMOGRAPHY by CHRISTINE P. FLEMING Submitted in partial fulfillment of the requirements For the degree of Doctor of Philosophy Dissertation Adviser: Dr. Andrew M. Rollins Department of Biomedical Engineering CASE WESTERN RESERVE UNIVERSITY May, 2010 CASE WESTERN RESERVE UNIVERSITY SCHOOL OF GRADUATE STUDIES We hereby approve the thesis/dissertation of Christine P. Fleming candidate for the PhD degree *. (signed) _______________________________________________ Andrew Rollins (chair of the committee) ________________________________________________ Igor Efimov ________________________________________________ David Rosenbaum ________________________________________________ Kenneth Singer ________________________________________________ Xin Yu (date) _______________________ *We also certify that written approval has been obtained for any proprietary material contained therein. Table of Contents Acknowledgements ........................................................................................................................ 17 List of Abbreviations ...................................................................................................................... 18 Abstract .......................................................................................................................................... 21 Chapter 1: Background and Significance ....................................................................................... 24 1.1. Catheter Ablation for the Treatment of Cardiac Arrhythmia ......................................... 24 1.2. Radiofrequency Ablation (RFA) .................................................................................... 26 1.2.1. Monitoring and Guidance of RFA ......................................................................... 30 1.2.2. Animal Models for Ablation ................................................................................... 31 1.2.3. Fiber Orientation ................................................................................................... 31 1.3. Optical Coherence Tomography .................................................................................... 33 1.3.1. Time Domain Optical Coherence Tomography ...................................................... 36 1.3.2. Fourier Domain Optical Coherence Tomography .................................................. 38 1.3.3. Polarization Sensitive OCT ..................................................................................... 43 1.3.4. OCT Catheter Probes ............................................................................................. 44 1.3.5. OCT Imaging of the Cardiovascular System ......................................................... 45 1.3.6. Image analysis ........................................................................................................ 47 1.4. Objective ........................................................................................................................ 50 Chapter 2: Characterization of Arrhythmogenic Substrates Using Optical Coherence Tomography ....................................................................................................................................................... 52 2. ................................................................................................................................................ 52 2.1. Introduction .................................................................................................................... 52 2.2. Two dimensional fiber orientation algorithm ................................................................ 54 2.2.1. Results ........................................................................................................................ 58 2.2.2. Healed Myocardial Infarction .................................................................................... 60 2.2.3. High Resolution Imaging ........................................................................................... 63 2.3. Analysis of an Optical Mapping Inverse Model ............................................................ 66 2.4. Discussion ...................................................................................................................... 76 2.5. Conclusion ..................................................................................................................... 78 Chapter 3: Characterization of ablation lesions using optical coherence tomography .................. 79 3 3. ................................................................................................................................................ 79 3.1. Introduction .................................................................................................................... 79 3.1.1. Radiofrequency Ablation ....................................................................................... 79 3.1.2. Monitoring Radiofrequency Ablation Therapy ...................................................... 80 3.2. Methods ......................................................................................................................... 82 3.2.1. Feasibility Testing .................................................................................................. 82 3.2.2. In vitro ablation protocol........................................................................................ 89 3.2.3. Optical Coherence Tomography Imaging .............................................................. 91 3.2.4. Validation ............................................................................................................... 92 3.2.5. Image Analysis ....................................................................................................... 92 3.3. Results ............................................................................................................................ 96 3.3.1. Tissue Classification .............................................................................................. 97 3.3.2. Visualization of Overtreatment ............................................................................ 104 3.4. Discussion .................................................................................................................... 106 3.5. Conclusion ................................................................................................................... 111 Chapter 4: Toward Guidance of Epicardial Radiofrequency Ablation Therapy using Optical Coherence Tomography ............................................................................................................... 112 4. .............................................................................................................................................. 112 4.1. Introduction .................................................................................................................. 112 4.1.1. Epicardial Ablation .............................................................................................. 112 4.1.2. Pre-procedural imaging ........................................................................................ 113 4.1.3. Optical Coherence Tomography .......................................................................... 114 4.2. Methods ....................................................................................................................... 116 4.2.1. Sample Preparation .............................................................................................. 116 4.2.2. Imaging Protocol .................................................................................................. 117 4.2.3. Validation ............................................................................................................. 119 4.3. Results .......................................................................................................................... 119 4.3.1. Discussion ............................................................................................................ 127 4.3.1.1. Substrate Characterization ............................................................................... 128 4.3.1.2. Real time Guidance .......................................................................................... 129 4.3.1.3. Future Work ..................................................................................................... 130 4.3.2. Conclusion ........................................................................................................... 131 4 Chapter 5: Real-time Monitoring of Cardiac Radiofrequency Ablation Lesion Formation using an Optical Coherence Tomography Forward Imaging Catheter ....................................................... 132 5. .............................................................................................................................................. 132 5.1. Introduction .................................................................................................................. 132 5.2. Methods ....................................................................................................................... 134 5.2.1. Feasibility Testing ................................................................................................ 134 5.2.4. Real Time Monitoring of Ablation Lesion Formation ......................................... 144 5.2.5.
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