OPTICAL COHERENCE TOMOGRAPHY

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1 OPTICAL COHERENCE TOMOGRAPHY PRINCIPLES AND APPLICATIONS Mark E. Brezinski MD, PhD Slillllilifc P^^^fi ELSEVIER AMSTERDAM BOSTON HEIDELBERG. LONDON NEW YORK. OXFORD. PARIS. SAN DIEGO SAN FRANCISCO. SINGAPORE SYDNEY. TOKYO Academic Press is an imprint of Elsevier

2 CONTENTS About the Author v Preface xix Acknowledgments xxvii 1 SECTION I The Basics (math, waves, etc.) for the Nonphysical Scientist General Properties of Waves and Coordinates 1.2 Trigonometry Imaginary Numbers The Exponential e Infinite Series Differentiation Integration Differential Equations Vectors and Sealars Unit Vector Scalar and Vector Fields 18

3 VÜi CONTENTS 1.12 Matrices and Linear Algebra Waves Combining Waves of Two Wavelengths Fourier Series and Integrals Fourier Series Fourier Integral Dirac Delta Function Miscellaneous Basic Physics 27 References 28 Appendix Z- Light and Electromagnetic Waves General 32 Electromagnetic Spectrum 32 Vector Calculus Divergence Curl Gradient 35 Maxwell's Equations Faraday's Law Gauss's Law for Electrical Fields Gauss's Law for a Magnetic Field Ampere's Law 38 Polarization 39 Reflection 42 Refraction 44 Optical Components 45 Lens 45 Grin Lens 46 Optical Fiber 47 Energy Propagation 51 Doppler Shifts 51 References 51 Appendix Light in Matter Oscillating Dipole Moment 61 Dispersion 65 Absorption 65 Scattering 66 Summary 69 References 69

4 CONTENTS ix Interference, Coherence, Diffraction, and Transfer Functions Coherence and Interference Coherence Interferometry and the Michelson Interferometer Partial Coherence Using a Source with Continuous Frequencies Diffraction Huygens and Huygens-Fresnel Principle Fraunhofer and Fresnel Diffraction Diffraction Limited Convolution and Transfer Functions Transfer Function 88 References 91 Appendix SECTION II Optical Coherence Tomography Theory General Time Domain OCT (TD-OCT) Interferometry with a Monochromatic Source Low Coherence Interferometry with OCT Determination of Axial Resolution Transfer Function Dispersion Lateral Resolution Light Beam Paraxial Wave Equation Relationship between the Paraboloidal and Gaussian Wave The Gaussian Wave Properties of a Gaussian Wave Important Points of a Gaussian Beam Relevant to OCT Speckle Spectral Radar or Fourier Domain OCT (FD-OCT) Swept Source (SS-OCT) The Resolution 136 References 137 Bibliography 139 Appendix

5 CONTENTS Optoelectronics and Optical Components General 148 Sources Semiconductor Sources Femtosecond Lasers Doped Fiber Amplifiers Wavelength Scanning 150 Interfer ometer s 150 Delay Lines Galvonometer Retroreflector Piezoelectric Fiber Stretcher Gräting Based Delay Lines Rotating Elements 156 Detectors CCD 156 Detection Electronics TD-OCT FD-OCT A-D Conversion/Frame Grabbers 160 Light Delivery Devices Rotational Catheters/Guidewires Translational Devices Forward Imaging MEMS 164 References 165 Appendix Noise and System Performance with TD-OCT and SD-OCT Introduction Definitions Noise Overview Noise in CCD versus Photodiode A-D Conversion in SD-OCT and TD-OCT Embodiment and Theory TD-OCT SD-OCT Detector Array Signal Integration 188, SS-OCT Conclusion 191 References 193

6 CONTENTS XI 8 Polarization and Polarization Sensitive OCT General Polarization Properties of Tissue Collagen Single Detector PS-OCT SDPS-OCT Theoretical Model Simulations with Layered Birefringent Phantoms Varying Differential Group Index (Layer Birefringence) Different Intra-Layer Medium Varying Layer Concentration Periodical Rotation of Polarization State in Reference Arm Use of the Fast Fourier Transform SDPS-OCT of Human Tissue Dual Detector PS-OCT Measurement of the Stokes Vector, Mueller Matrix, and Poincare's Sphere 234 References 237 Appendix Adjuvant Techniques: Absorption Spectroscopy, Contrast Probes, Phase Contrast, Elastography, and Entangied Photons General Absorption Spectroscopy Absorption Intrinsic Absorption Dual Source Single Source Same Frequency (Spectroscopic OCT) Second Harmonie Generation OCT Dyes/Probes Elastography Basic Concepts Ultrasound Elastography OCT Elastography Limitations of the Elastography Techniques Differential Phase Measurements Embodiment Limitations Entangied Photons General Entangied States Generation Interference Experiments Ghost Imaging 267

7 XII CONTENTS Entanglement and OCT Conclusion 272 References 272 Doppler Optical Coherence Tomography Bin Liu PhD The Principle of Doppler OCT Doppler Shift and Laser Doppler Velocimetry Optical Signal Evolution in Doppler OCT Interferogram Detection in Doppler OCT Signal Processing in Doppler OCT Signal Processing in Time Domain Doppler OCT Signal Processing in Spectral Domain Doppler OCT Applications of Doppler OCT 298 References 300 Digital Image Processing Techniques for Speckle Reduction, Enhancement, and Segmentation of Optical Coherence Tomography (OCT) Images Jadwiga Rogowska PhD Introduction Speckle Reduction Techniques Mean, Median, and Hybrid Median Filters Adaptive Filtering Other Techniques Evaluation of Image Enhancement Results Image Segmentation Techniques Thresholding Region Growing Watershed Algorithm Edge-Based Segmentation Techniques Other Segmentation Techniques Summary 324 References 325 SECTION III Application of OCT to Clinical Imaging: Introduction Introduction 334

8 XIII 12.2 Areas Where OCT Shows Promise as a Clinical Imaging Device When Biopsy Cannot Be Performed Where Sampling Errors with Conventional Biopsy Are Likely Guiding Surgical and Microsurgical Procedures Three-Dimensional Reconstruction of In Vitro Pathology Factors That Influence Decisions on the Clinical Relevance of OCT OCT Imaging of Human Tissue Methods for Validating the Structure in OCT Images General »2 Histopathology Immunohistochemistry Enzymatic Assay High-Performance Liquid Chromatography Scanning Electron Microscopy Animal Models Justification of Need for Animals Justification for the Species Justification of the Total Number of Animals Drugs and Their Dosages Used for Anesthesia and Euthanasia Will the Animal Experience Discomfort and Is a Survival Model Utilized? Use of Experienced Personnel Registration Example Rat Protocol Statistical Analysis Role of Human Perception on Image Interpretation Conclusion 351 References 351 Other Technologies General Structural Imaging Confocal Microscopy High Frequency Ultrasound Magnetic Response Imaging Computer Tomography Light-Scattering Spectroscopy Spectroscopic Techniques Fluorescence Two-Photon Laser Scanning Microscopy Near Infrared Absorption Spectroscopy Raman Scattering 367 References 368

9 xiv Introduction to Clinical Research Design and Analysis Kelly Jenkins MD, PhD and Kimberlee Gauvreau ScD Elements of Study Design Choosing a Primary Research Question Descriptive versus Analytical Studies Threats to Validity Random Variability Bias Confounding Effect Modification Evaluating Threats to Validity Choice of Study Design Randomized, Blinded, Controlled Clinical Trials Other Study Designs Longitudinal Studies Cohort Studies Cross-Sectional Studies Case-Control Studies Nested Case-Control Studies Secondary Data Diagnostic Test Evaluation Elements of Data Analysis Types of Numerical Data Summarizing and Describing Data Variability in Data Making an Inference from Data Common Statistical Tests for Comparing Two Groups Power and Sample Size Evaluating Relationships among Continuous Measurements Multivariate Models 389 References 389 Appendix OCT in Cardiovascular Medicine General Acute Coronary Syndromes General Epidemiology Coronary Circulation Classification of Plaque 398 CONTENTS

10 Unstable Plaque Histopathology Triggers of Plaque Rupture Interventions Imaging Modalities OCT for Coronary Imaging Limitations Current State of Intravascular OCT Imaging Current OCT Markers for In Vivo Studies Potential Additional OCT Markers Technological Investigations Other Coronary Areas Stroke General Epidemiology Risk Factors Cerebral Circulation Carotid Plaque Imaging Approaches Treatment Pulmonary Hypertension Atrial Fibrillation Conclusion 445 References 446 OCT in the Musculoskeletal Disease Osteoarthritis General Cartilage Structure Osteoarthritis Cartilage Knee Anatomy Current Imaging Modalities Serum and Urine Markers Chondroprotection and Cartilage Repair In Vitro and In Vivo Human Data Current OA Animal Models Canine Anterior Cruciate Ligament Transection Model Rabbit Partial Medial Meniscectomy Rabbit ACLT Guinea Pigs Rats Mice Assessing Cartilage OA with OCT in the Rat 475

11 xvi 16.3 Tendon/Ligaments General Ligaments and Tendons OCT Imaging of Tendons and Ligaments Achilles Tendinopathy Shoulder Pain Other Potential Applications Conclusion 488 References 488 OCT in Oncology General Epidemiology of Cancer Need for a Diagnostic Imaging Technique Epithelium Esophageal Cancer General Adenocarcinoma of the Esophagus Squamous Cell Carcinoma Gastric Cancer Epidemiology Risk Factors Staging Diagnosis Bladder Cancer Epidemiology Staging Diagnosis Lung Cancer Epidemiology Risk Factors Histopathology Staging System Treatment Screening Sclerosing Cholangitis and Cholangiocarcinoma Epidemiology Diagnosis Cervical Cancer Epidemiology/Histology Staging Diagnosis Treatment 531

12 CONTENTS xvii 17.8 Other Potential Applications General Colon Cancer Postmenopausal Bleeding and Endometrial Carcinoma Breast Cancer Skin Cancer Oral and Pharyngeal Cancers Assessing Pathological Samples Conclusion 534 References 534 Appendix Other Applications and Conclusions General Dentistry General Anatomy and Histology Dental Caries Minimally Invasive Treatments Diagnosing Caries OCT and Dental Limitations Prostate Surgical Guidance General Benign Prostatic Hypertrophy Treatment OCT and BPH Nerve Repair General Repair Diagnostics OCT and Nerve Repair Vascular Repair General Vessel Re-anastomosis OCT and Arterial Repair Neurosurgery General Brain Tumors Imaging Brain Tumors OCT and Brain Tumor Resection 574

13 xviü CONTENTS 18.7 The Role of OCT in Assessing Subfertility General TheOviduct Oviduct Pathology Infertility Testing Treatment OCT and Imaging the Fallopian Tubes Conclusion 584 References 585 Index 591 Online companion site:

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