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Terahertz Spectroscopic Characterization and Imaging for Biomedical Applications

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2015, Doctor of Philosophy, Ohio State University, Electrical and Computer Engineering.
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. 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 optical properties associated with the corresponding tissue characteristics. To do so, we develop calibration techniques to take into account 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 freshly-excised tissue samples. We demonstrate that cancer margins can also be accurately characterized using the differences in tissue hydration. The study is 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 polarimetry 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 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. To support this hypothesis, we present full-wave electromagnetic simulations of a simplified axon model and compare the simulation data with THz 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 Alzheimer’s detection in early stage.
Kubilay Sertel (Advisor)
Fernando Teixeira (Committee Member)
Umit Catalyurek (Committee Member)
Niru Nahar (Committee Member)
157 p.

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Citations

  • Yeo, W. G. (2015). Terahertz Spectroscopic Characterization and Imaging for Biomedical Applications [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1430825935

    APA Style (7th edition)

  • Yeo, Woon Gi. Terahertz Spectroscopic Characterization and Imaging for Biomedical Applications. 2015. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1430825935.

    MLA Style (8th edition)

  • Yeo, Woon Gi. "Terahertz Spectroscopic Characterization and Imaging for Biomedical Applications." Doctoral dissertation, Ohio State University, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=osu1430825935

    Chicago Manual of Style (17th edition)