Terahertz Spectroscopic Characterization and Imaging for Biomedical Applications

.............................................................................................................................. ii Dedication ........................................................................................................................... v Acknowledgments.............................................................................................................. vi Vita ................................................................................................................................... viii List of Tables .................................................................................................................... xv List of Figures .................................................................................................................. xvi Chapter 1: Introduction ...................................................................................................... 1 1.1 THz Waves and Their Applications in Spectroscopy and Imaging ..................... 2 1.2 THz Spectroscopic Imaging in a Bio-medical Tool ............................................. 5 1.3 Major Contributions of the Dissertation .............................................................. 9 1.4 Dissertation Overview ........................................................................................ 11 Chapter 2: Fundamentals of THz Spectroscopy ............................................................... 14 2.1 Generation and Detection Schemes of THz Signal ............................................ 15 2.1.1 Photoconductive Antenna ........................................................................... 15 2.1.2 Photomixing ................................................................................................ 18 2.1.3 Schottky Diode Frequency Multiplier Chain .............................................. 20 xii 2.2 Post-processing of Raw THz Spectroscopy ....................................................... 22 2.2.1 Time Domain Spectrometer ........................................................................ 23 2.2.2 Continuous Wave Spectrometer ................................................................. 28 2.3 Comparison of State-of-the-art THz Spectroscopic Systems ............................. 32 2.4 Validation of THz Spectroscopy ........................................................................ 34 Chapter 3: Spectroscopic Characterization of Bio-chemicals and Fresh Biological Tissues in the THz Band ................................................................................................................ 37 3.1 Unique Vibrational Absorption of Bio-chemicals ............................................. 38 3.2 Hydration Effect on Molecular Compound in THz Band .................................. 39 3.3 THz Hydration Sensitivity in Fresh Biological Tissues ..................................... 42 3.4 THz Spectroscopy and Imaging of Fresh Human Organ Tissues ...................... 45 Chapter 4: THz Imaging for Detection and Margin Assessment of Human Malignant Tumors .............................................................................................................................. 49 4.1 Susceptibility of Experimental Setup to THz Spectroscopic Imaging of Hydrated Tissues ........................................................................................................................... 50 4.2 Sample Preparation and Experimental Setup for Formalin-fixed and Paraffinembedded (FFPE) Tissue .............................................................................................. 56 4.3 THz Image and Optical Properties of Malignant Tissues for Endoscopic Sensing Application .................................................................................................................... 58 4.3.1 Lung Cancer: Neural Endocrine Carcinoma ............................................... 60 xiii 4.3.2 Small Intestine Cancer: Gastrointestinal Stromal Tumor (GIST)............... 62 4.4 Image Processing for Contrast Enhancement..................................................... 65 4.4.1 Image Contrast Enhancement ..................................................................... 66 4.4.2 Uniform Background Illumination ............................................................. 69 4.5 THz Polarimetric Sensor for Cancer Margin Identification ............................... 72 Chapter 5: THz Macromolecular Response from Abnormal Nervous System: Brain Tissue exhibiting Alzheimer’s Disease ............................................................................. 85 5.1 Background on Alzheimer’s Disease ................................................................. 86 5.2 Sample Preparation and Experimental Setup ..................................................... 88 5.3 THz Spectroscopic Imaging of Human Brain Tissue for Alzheimer’s Detection.. ............................................................................................................................ 91 5.3.1 THz Imaging of Alzheimer’s and Healthy Control Tissues ....................... 92 5.3.2 Origin of Prominent THz Image Contrast between White and Gray Matters in Alzheimer’s Tissue ................................................................................................ 95 5.3.3 Case Study of Alzheimer’s Tissues in THz Imaging .................................. 98 5.4 Full-EM Simulation of the Simplified Model for White Matter Disorder ....... 102 Chapter 6: Conclusion..................................................................................................... 108 6.1 Summary of this Work ..................................................................................... 108 6.2 Future Work ..................................................................................................... 110