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University Microfilms International A Bell & Howell Information Company 300 North Zeeb Road, Ann Arbor, Ml 48106-1346 USA 313/761-4700 800/521-0600 Order Number 9002012 Laser-tissue interactions in the arterial wall Roberts, Cynthia Jane, Ph.D. The Ohio State University, 1989 Copyright ©1989 by RobertB, Cynthia Jane. All rights reserved. UMI 300 N.ZeebRd. Ann Arbor, MI 48106 Laser-Tissue Interactions in the Arterial Wall A Dissertation Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of the Ohio State University by Cynthia Roberts, M.S.E.E., B.S.N. £ jfc # Jfc # The Ohio State University 1989 Dissertation Committee: Approved by: Professor J. F. Cornhill Professor R. L. Hamlin () Adviser Biomedical Engineering Professor H. Hsu Center Copyright by Cynthia Jane Roberts 1989 ACKNOWLEDGEMENTS I wish to express my great respect and appreciation to my advisor and mentor, Dr. J. Fredrick Cornhill. His confidence in my abilities, his intellectual guidance, and the resources he provided for my research made this work possible. I also thank the other members of my dissertation committee, Dr. Hsiung Hsu and Dr. Robert Hamlin, for their insight and interest in my work. I would like to acknowledge my use of the image processing and computing facilities of the Laboratory of Vascular Diseases. My sincere gratitude goes to Ed Herderick, System Manager, who was always willing to give generously of his time and technical expertise in the many invaluable discussions we had. My thanks also go to Shu-Fen Chang and Liz Field for modifying the specialized image processing software which allowed my images to be analyzed, and to John Meimer for his assistance with the experimental work. I would like to acknowledge the allocation of resources on the Cray X-MP by the Ohio Supercomputer Center, in support of the theoretical portion of this study. My deepest appreciation is for my husband, Robert H. Small, whose faith in me is the backbone of all my accomplishments. I wish to thank him and my family for the constant encouragement and the strength they provide. VITA November 22, 1958 ...................................Born —■ Chicago, Illinois 1979 B.S. in Nursing, The University of Iowa Iowa City, Iowa 1980-1983 ...................................................... Registered Nurse, The University of Iowa Hospitals and Clinics 1986 M.S., Electrical Engineering The Ohio State University PUBLICATIONS Hsiung Hsu, Clifford Shang, and Cynthia Roberts. Soliton Phase Conjuga­ tion in Four-Wave Nonlinear Interactions. In Proceedings of the A'F International Conference on Quantum Electronics, 1987. Cynthia Jane Roberts. Large Signal Characteristics of Phase Conjugation with Variable Split Pumps in Degenerate Four-Wave Mixing. Master’s Thesis, The Ohio State University, 1986. Cynthia Roberts and Hsiung Hsu. Generalized Large Signal Theory of Phase Conjugation in Four-Wave Interactions. In Proceedings of the 14th Congress of the International Commission for Optics, 1987. FIELDS OF STUDY Major Field: Biomedical Engineering Studies in Atherosclerosis Professor J. Fredrick Cornhill Studies in Cardiovascular Phsysiology Professor Robert Hamlin Studies in Nonlinear Optics Professor Hsiung Hsu TABLE OF CONTENTS ACKNOWLEDGEMENTS ii V IT A iii LIST OF FIGURES vii LIST OF TABLES xv I. Introduction 1 1.1 Accepted Treatment Modalities for Atherosclerotic HeartDisease: 2 1.2 Emerging Technologies for the Treatment of Atherosclerosis: . 3 1.3 Direct Laser Angioplasty ..................................................................... 5 II. Direct Laser Angioplasty: Review of Current Literature 6 2.1 Introduction ............................................................................................. 6 2.2 Feasibility of Laser Angioplasty ....................................................... 7 2.3 Laser-Tissue Interaction ..................................................................... 15 2.3.1 Tissue Response to Light ......................................................... 16 2.3.2 Thermal/Mechanical Mechanisms ........................................... 17 2.3.3 Ablative Photodecomposition and theExcimer Laser . 21 2.3.4 Debris and Photoproduct F o rm a tio n .................................... 25 2.3.5 Effects of Pulse Duration and Laser F luence ...................... 30 2.3.6 Lasing M e d iu m ............................................................................. 35 iv 2.3.7 Wavelength-Dependent Tissue Absorption ......................... 38 2.3.8 Preferential Energy Absorption: Selective Ablation . 42 2.3.9 Exogenous A g e n ts ....................................................................... 46 2.3.10 Photoemission Properties ......................................................... 52 2.4 Conclusions drawn From Current Literature ................................... 58 2.4.1 Optimal Lasing Parameters, Tissue Properties ............... 60 2.4.2 Areas of Further Study ............................................................ 63 2.4.3 Additional Considerations ......................................................... 68 III. Experimental Materials and Methods 69 3.1 Tissue Preparation ................................................................................... 69 3.2 Laser In ju ry .................................................................................................. 69 3.3 Histology ..................................................................................................... 70 3.4 Image P rocessing ....................................................................................... 71 3.5 A n aly sis ........................................................................................................ 75 IV. Experimental Results 79 4.1 Isolating the Effects of Power, Exposure, and E n e rg y .................. 80 4.2 Comparison of Normal and Atherosclerotic Tissue Injuries . 95 4.3 C onclusions ................................................................................................. 97 4.4 Sources of E rro r .......................................................................................... 100 V. Model of Light Absoprtion, Heat Conduction, and Ablation in Laser-Irradiated Tissue 101 5.1 Development of the Model ..................................................................... 102 5.1.1 Forms of the Source Term .......................................................... 107 5.2 Implementation of the M o d e l .............................................................. 112 v 5.3 Validation of the M odel .......................................................................... 117 5.4 Model Predictions and Comparison to Experimental Results . 118 5.4.1 Onset of Ablation ........................................................................ 121 5.4.2 Constant E n e rg y ........................................................................... 123 5.4.3 Constant Pow er ............................................................................... 126 5.4.4 Constant Pulse D uration ............................................................. 127 5.4.5 Time Evolution of Injury ......................................................... 129 5.4.6 Constant vs. Variable Thermal P ro p erties .......................... 129 5.5 Discussion and Conclusions ................................................................... 134 5.5.1 Implications for Laser A n g io p lasty ....................................... 138 VI. Arqas of Further Study 139 APPENDICES 145 A. Number of Iterations for Accuracy Data 146 B. Simulation Data for Constant Energy 154 C. Simulation Data for Constant Power 167 D. Simulation Data for Constant Pulse Duration 172 E. Fortran Program for the Simulation of Light Absorption and Heat Conduction in Arterial Tissue using Finite-Difference Methods 189 References 207 vi t LIST OF FIGURES 1 Relationship between laser burn dimensions and total laser energy in swine aorta under CW