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Detection and Modeling of Radiation Induced Effects in Tissues by Dielectric Spectroscopy Dorin A

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Detection and Modeling of Radiation Induced Effects in Tissues by Dielectric Spectroscopy Dorin A Old Dominion University ODU Digital Commons Physics Theses & Dissertations Physics Winter 2000 Detection and Modeling of Radiation Induced Effects in Tissues by Dielectric Spectroscopy Dorin A. Todor Old Dominion University Follow this and additional works at: https://digitalcommons.odu.edu/physics_etds Part of the Biophysics Commons, and the Radiation Medicine Commons Recommended Citation Todor, Dorin A.. "Detection and Modeling of Radiation Induced Effects in Tissues by Dielectric Spectroscopy" (2000). Doctor of Philosophy (PhD), dissertation, Physics, Old Dominion University, DOI: 10.25777/42wg-ap17 https://digitalcommons.odu.edu/physics_etds/88 This Dissertation is brought to you for free and open access by the Physics at ODU Digital Commons. It has been accepted for inclusion in Physics Theses & Dissertations by an authorized administrator of ODU Digital Commons. For more information, please contact [email protected]. DETECTION AND MODELING OF RADIATION INDUCED EFFECTS IN TISSUES BY DIELECTRIC SPECTROSCOPY by Dorin A. Todor B.S., June 1985, University of Bucharest, Romania A Dissertation Submitted to the Faculty of Old Dominion University in Partial Fulfillment of the Requirement for the Degree of DOCTOR OF PHILOSOPHY PHYSICS OLD DOMINION UNIVERSITY December 2000 Gary E. Copeland (Director) Gafl E. Dodge (Member) Raymond K. Wu (Member) Charles E. Hyde-yright Qfember) Linda L. Vahala (Member) Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. UMI Number. 9999654 UMI’ UMI Microform 9999654 Copyright 2001 by Bell & Howell Information and Learning Company. All rights reserved. This microform edition is protected against unauthorized copying under Title 17, United States Code. Bell & Howell Information and Learning Company 300 North Zeeb Road P.O. Box 1346 Ann Arbor, Ml 48106-1346 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. ABSTRACT DETECTION AND MODELING OF RADIATION INDUCED EFFECTS IN TISSUES BY DIELECTRIC SPECTROSCOPY Dorin A. Todor Old Dominion University, 1999 Director: Dr. Gary E. Copeland The work presented here is applied physics research in the field of radiation treatment. We address the development of a new and innovative method, in vivo and possibly non- invasive, for tumor and healthy tissues control during and after the radiation treatment. The radiation treatment is delivered in an almost standardized manner for particular classes of tumors. The large variance in the individual radiosensitivity of healthy tissues and tumors often leads to local recurrence of neoplastic growth and/or distant metastatic disease which often remains untreated. The method is based on the measurement and analysis of electrical impedance data in the frequency domain from 50 mHz to I MHz. The dielectric signature of the tissue carries information about the integrity of the plasma membrane, as well as about the tissue micro-architecture. We present dielectric models for biological materials and correlate their parameters with the subtle changes characterizing oncosis or apoptosis occurring as result of radiation or excision. Five tissue types (blood, kidney, liver, lung and heart) were studied and specific impedance models were created for each of them. Based on these models, analysis of freshly excised tissue and radiation-induced effects in excised tissue was carried out and model parameters extracted. The data we present shows correlation between known mechanisms of cellular death and the delivery of radiation, thus making possible a quantification of the individual response. Further work will be needed in order to correlate early impedance changes with late tissue changes characterizing the side effects of the radiotherapy. Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. This thesis is dedicated to my family. Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. ACKNOWLEDGMENTS It was a real privilege to have worked with so many amazing people in the last five years. I am very thankful to all and each of you for the great gifts I received, whether knowledge, or support, leadership, friendship, generosity or any of their linear combinations. It is customary to express gratitude to the thesis committee members. 1 was extremely fortunate to have had in my committee members so much more than what they are supposed to be: I had mentors and collaborators and friends. Gail Dodge was a constant presence in my work, somebody ready to answer any question, to critically review articles, proposals, letters and to always come with a fresh, sharp and thorough view, with tactful suggestions that made my thinking and writing evolve. Her cleverness, focus, and efficiency, together with immeasurable generosity and kindness made her not only a remarkable professor but also a great friend. I am particularly grateful to Raymond Wu, from Virginia Beach General Hospital and Eastern Virginia Medical School. Without his altruism, none of our experiments would have been possible. I learned a great deal from him; he is a dedicated and meticulous scientist and his advice and mentoring, played an important role in my choice to pursue medical physics. Charles Hyde-Wright was one of the very first with which I discussed my idea of using impedance spectroscopy in radiation therapy. His natural curiosity and DaVincian thinking were both guides and tests of my work. In a great extent, my work involved biology and radiation biology. I was privileged to have in Frank Lattanzio from Eastern Virginia Medical School not only an expert that can talk a physicist’s language but also, through his experience and suggestions, an active contributor to what our work became. My gratitude goes also to Linda Vahala for accepting to review my thesis and for her promptness. I would like to thank my advisor, Gary Copeland for his willingness to supervise a research somehow peculiar for a regular physics department Not only did he take a chance that few others would have taken, but he was a constant and subtle presence that only an experienced professor can be. His expertise, sagacity and steady assistance made my work possible. Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. V A good friend, a patient and cultivated interlocutor, Anca Dobrian from EVMS, not only made possible our experiments by making available the tissues we used, but brought new and interesting ideas from which I fully benefited. I cannot thank enough the people from the company whose generosity made our access to the state of the art equipment, possible. The late engineer Peeter Kark, who first visited the lab and assessed our plans, followed by Brad Barchus and Nigel Evans, are just few of the people from Solartron, Inc., which helped us. Thank you. Also many thanks to Charles Sukenik and Leposava Vuskovic, who, on all occasions, helped us with equipment and good advice. About four years ago, in an informal discussion with Jim Cox, the chair of our department, I expressed my desire to pursue medical physics research and he recommended that I contact Raymond Wu. The rest is history. I am very grateful, for Jim’s continuous guidance and visionary advice. Even though from far away, I received constant and knowledgeable support from Larisa Cheran (University of Toronto) and Vali Raicu (Kochi Medical School, Japan), to which I am thankful. A very special thanks goes to our special friends, Walt and Vickie Hooks, who not only acted as our extended, American family, but as a ceaseless source of moral support and generosity. Living abroad, rising children and getting adjusted to another culture (not to mention the many small problems, from cars to taxes) was infinitely easier with your help. I would also like to thank to Richard Wright for his assistance and good humor. Building parts for experiments, setting up the labs and fixing computers was almost a fun job having Dick always ready to help. I am thankful to my fellow graduate students, in particular to Laura Marcucci, George Brooks, Trey Truman, Nicolas Tregoures and Rama Balasubramanian, with which I shared good moments, exams and homework, as well as frustrations and gray days. A big multumesc mult (thank you very much) for everything you did, for being with me and for me whenever I needed it the most, goes to Luminita and my children Alina and Horia. Thank you for all the good days and successes we shared. Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. TABLE OF CONTENTS Page LIST OF TABLES................................................................................................................. viii LIST OF FIGURES...................................................................................................................ix Chapter I. INTRODUCTION..................................................................................................... I II. IONIZING RADIATION........................................................................................6 The interaction of radiation with matter ......................................................6 Biological effects of ionizing radiation ......................................................16 IU. DIELECTRIC PROPERTIES OF MATTER.....................................................27 Dielectric properties, a practical definition ................................................27
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