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.