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Terahertz Spectroscopic Characterization and Imaging for Biomedical Applications

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Terahertz Spectroscopic Characterization and Imaging for Biomedical Applications Terahertz Spectroscopic Characterization and Imaging for Biomedical Applications DISSERTATION Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The Ohio State University By Woon-Gi Yeo, B.S., M.S. Graduate Program in Electrical and Computer Science The Ohio State University 2015 Dissertation Committee: Kubilay Sertel, Advisor Fernando Teixeira Ümit V. Ҫatalyürek Niru K. Nahar Copyright by Woon-Gi Yeo 2015 Abstract THz-frequency spectroscopic imaging has recently drawn increasing attention as a novel modality for bio-medical analysis of diseases and conditions of living tissues. More importantly, detection of cancerous tumors as well as necrotic tissue regions is being studied using THz waves with the aim of translating research studies into clinical practice. THz radiation provides unique sensing capabilities applicable to a variety of areas including non-destructive inspection, security screening, as well as bio-medical imaging. THz waves are safe (non-ionizing), and they can provide high-resolution with better specificity compared to X-rays. In addition, THz waves enable the spectroscopic analysis of organic molecules, since many of their rotational and vibrational resonances fall within the THz band. Perhaps more importantly, THz waves are extremely sensitive to the degree of sample hydration and this property has been utilized to differentiate cancerous tissue regions. However, previous studies on human tissue groups have been largely disconnected, with publications focusing on only limited tissue groups at a time. In addition, assessment of cancer margins to differentiate in-situ extent of disease has rarely been a major focus. As such, a more general in-depth study of the THz response of extended human tissue groups is much desired to demonstrate the potential of THz sensing as a clinical tool. ii In this work, we initially focus on a comprehensive experimental study of the THz response of major human tissue malignancies to investigate the efficacy of THz sensing as a clinical bio-medical tool. In particular, using the THz-band spectroscopic reflectivity and transmission properties of bulk and thin tissue samples, we characterize the material properties, such as index of refraction and material loss associated with the corresponding tissue characteristics. To do so, we develop accurate calibration techniques to take into account and eliminate experimental fixture effects. In addition, the specificity and sensitivity of the commercial time-domain THz spectroscopy system is quantified using bio-chemical compounds with known spectroscopic response. Subsequently, the sensitivity of THz waves to tissue hydration is quantified through several freshly-excised tissue samples. Based on this study, we demonstrate that cancer margins can also be accurately characterized using the differences in tissue hydration. The study is then expanded to include human lung and small intestine tissues with malignant regions. New image processing algorithms are developed to enhance THz image contrast and localization of malignant areas. Furthermore, a THz polarimetric sensing scheme is introduced to increase sensitivity of cancer margin identification and its performance is demonstrated through full-wave simulations. Finally, human brain tissues exhibiting Alzheimer’s disease are investigated to demonstrate the utility of THz imaging in Alzheimer’s detection. We quantify, for the first time, measurable differences in THz reflectivity of gray and white brain matter, leading to accurate post-mortem diagnosis of Alzheimer’s disease. Furthermore, we hypothesize that the reason for the reflectivity contrast is due to demyelination of axons. iii To support this hypothesis, we present full-wave electromagnetic simulations of a simplified axon model and compare the simulation data with THz reflectivity measurements. Although this initial study demonstrates the efficacy of THz sensing in Alzheimer’s detection, more case studies are needed to establish this finding as a viable clinical biomarker in the detection of Alzheimer’s disease in early stage. iv This is dedicated to my wife Hyosoon, lovely sons Ian & Ethan, parents Gonghyun & Okhee, and younger brother, Woonsung. v Acknowledgments This work could not have been completed without the heartfelt advice and the considerate support of many people around me. First and foremost, I would like to express the deepest gratitude to my advisor, Prof. Kubilay Sertel, and to my supervisor, Dr. Niru K. Nahar. Their continuous guidance, patience, and encouragement in study as well as in life throughout years are invaluable and are compelled sincere thanks of me. Considering how important it is to have a good advisor for Ph.D. study, I feel very fortunate that I have worked with such morally and professionally wonderful people like Prof. Sertel and Dr. Nahar. I would also like to thank my previous advisors, Prof. John L. Volakis and Prof. Robert Lee, for accepting me in the Ph.D. program and guiding me to be successful in early Ph.D. study. Without their supports, this work was not even started. In addition, I am grateful to Prof. Ümit V. Çatalyürek and Prof. Fernando L. Teixeira for serving on the committee for my Ph.D. candidacy exam and dissertation defense. They not only took time off from their busy schedule but also kindly guided me to complete this work. It has been a great experience to meet and become good friends with many colleagues at ElectroScience Laboratory (ESL). For their valuable discussion, motivation, and friendship, I really want to give special thanks to Dr. Georgios Trichopoulos, Dr. Yasir Karisan, Cosan Caglaran, Dr. William Moulder, Varittha Sanphuang, Dr. Elian vi Alwan, Dr. Nil Apaydin, Henry Vo, Rey Febo, Anas Abumunshar, Seckin Sahin, Syed An Nazmus. I would also like to thank both present and past Korean friends at ESL for their emotional support, valuable discussion, and the useful consultation of my past, present, and future plans: Hak-Su Moon, Seung-Ho Doo, Dr. Gil Young Lee, Dr. Chun- Sik Chae, Dr. James Park, Dr. Jun Seok Lee, Dr. Kuem Su Song, Dr. Joonshik Kim, Dr. Jae-Young Chung. Dr. Youngchel Kim, Jeonghwan Park, Dongyeop Na. In addition, I would like to acknowledge a favor of my friends out of ESL and the acquaintances who know through research projects: especially, Dr. Sangjo Choi, Dr. Jungsuek Oh, Dr. Wonbin Hong, Dr. Ogan Gurel, Richard Higgins, Scott Yano, Dr. Don Burdette, Dr. David Daughton, the late Dr. Gilbert E. Pacey, Dr. Phil Taday, Rebecca Goodall, Dr. Robert May, Dr. Ian Gregory, James McGilp. Finally, I would like to thank my family. The unconditional love and support of my parents and mother-in-law have been the greatest motivation during the graduate study. Most importantly, I would like to express the deepest gratitude to my wife, Hyosoon Kim, for the full material and emotional support. Just the mere existence of her has given me full healing in the graduate life. I also thank to my two sons, Ian Yeo and Ethan Yeo. You are all of my pleasures and hopes. I love you! vii Vita July 14, 1981 ..................................................Born – Namwon, Jeollabuk-do, Korea February, 2007 ...............................................B.E. Electronics, Telecommunication, and Computer Eng., Korea Aerospace University May, 2010 ......................................................M.S. Electrical Eng., University of Michigan August, 2014 ..................................................M.S. Electrical and Computer Eng., The Ohio State University 2010 to present ..............................................Graduate Research Associate, ElectroScience Laboratory, Department of Electrical and Computer Engineering, The Ohio State University Publications Journal Publications W.-G. Yeo, N. K. Nahar, and K. Sertel, “Far-IR Multi-Band Dual-Polarization Perfect Absorber for Wide-Incident Angles,” Microwave and Optical Technology Letter, 55(3), pp. 632-636, January 2013. viii V. Sanphuang, W.-G. Yeo, J. L. Volakis, and N. K. Nahar, “THz Transparent Metamaterials for Enhanced Spectroscopic and Imaging Measurement,” IEEE Transaction on Terahertz Science and Technology, 5(1), pp. 117-123, January 2015. W.-G. Yeo and N. K. Nahar, “Characterization of a THz CW spectrometer pumped at 1550nm,” Infrared Physics and Technology, vol. 71, pp. 70-76, July 2015. W.-G. Yeo, N. K. Nahar, C. L. Hitchcock, S. Park, O. Gurel, and K. Sertel, “THz Imaging of Human Lung and Small Intestine Tissues for Cancer Margin Assessment,” Submitted to IEEE Transaction on Terahertz Science and Technology. Conference Publications (selected) W.-G. Yeo, T.-Y. Seo, J. W. Lee, and C. S. Cho, “H-Plane Sectoral Filtering Horn Antenna in PCB Substrates Using Via Fences at Millimeter-Wave,” in European Microwave Conference (EuMC), Munich, Germany, October 2007. W.-G. Yeo, N. K. Nahar, R. Lee, and J. L. Volakis, “New frontiers for commercial applications of terahertz,” in IEEE National Aerospace and Electronics Conference (NAECON), Dayton, Ohio, USA, July 2011. W.-G. Yeo, N. K. Nahar, and J. L. Volakis, “Validation of CW THz Spectral Measurements,” in IEEE International Symposium on Antennas and Propagation and USNC-URSI National Radio Science Meeting, Chicago, Illinois, USA, July 2012. W.-G. Yeo, N. K. Nahar, and K. Sertel, “Dual-Band, Wide-Incident-Angle Absorber for Far-IR and THz Frequencies,” in IEEE National Aerospace and Electronics Conference (NAECON), Dayton, Ohio, USA, July 2012. W.-G. Yeo, V. Snaphuang, N. K. Nahar, and John L. Volakis,
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