Luận án tiến sĩ: Dispersion trong hệ thống chụp ảnh quang học y sinh

Copyright by Sanghoon Oh 2006 The Dissertation Committee for Sanghoon Oh Certifies that this is the approved version of the following dissertation: Dispersion in Biomedical Optical Imaging Systems Committee: Thomas E. Grady Rylander III Baxter Womack Michael Becker Massoud Motamedi Dispersion in Biomedical Optical Imaging Systems by Sanghoon Oh, B. Dissertation Presented to the Faculty of the Graduate School of The University of Texas at Austin in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy The University of Texas at Austin May 2006 UMI Number: 3244926 UMI Microform 3244926 Copyright 2007 by ProQuest Information and Learning Company. All rights reserved.

This microform edition is protected against unauthorized copying under Title 17, United States Code. ProQuest Information and Learning Company 300 North Zeeb Road P. Box 1346 Ann Arbor, MI 48106-1346 Dedication To my family: Wife Mijung, Daughter Suah,Minah Father Jemmo Oh, Mother Soonhyung Choi, and Brother Minyoung Oh. Acknowledgements There are numerous people whom I would like to thank for helping me to finish my graduate life.

First of all, I would like to express my special appreciation to my supervisor, Dr. Milner, for guiding and training me as a research scholar. I thank him also for his patient and gracious research help. He has shared not only his innovative research ideas but also Christian faith to encourage me to have a peaceful mind.

I have had a really long journey of Ph. work to reach my goal, and he has been the man who points the most righteous direction to the next destination. Many thank to Dr. Michael Becker and Dr.

Baxter Womack for giving me many opportunities to have a teaching assistantship of EE464 and for always treating me as a member of their families; they have been my best teaching mentors. I thank particularly Dr. H Grady Rylander III and Dr. Massoud Motamedi for sharing valuable ideas and discussions.

I want to show gratitude to Mrs. Vicki Stratton for her supporting work including her expertise in administration; she has been a skillful nanny of the biomedical optics laboratory. I want to thank Dr. Rebecca Richards-Kortum for initiating my interest in biophotonics research and providing support for my Masters Degree work.

It would have been impossible to finish my Ph. work without collaborations of lab members and friends; Chris, Nate, Jesung, Roberto, Jordan, Junghwan, Jihoon, Wook, Bo, Jaesook, Gracy, Jeehyun, Hoya, and Eunha. I have had valuable discussions with v them and gotten instant feedbacks from them. They have afforded critical suggestions based on their practical and professional experiences.

Moreover, I have had plenty of joyful time with them. I thank my neighbors and church members for their friendship and prayer for me and my family. I would like to thank my father, mother, grand mother, and brother for their devoted love and endless mental support. 아버지 어머니 박사 마칠 수 있도록 잘 성장하게 해 주심에 정말 감사합니다.

Also, there are two precious ladies to thank, my daughters Suah and Minah who make me smile happily at all times. In addition, I would like to extend my special thanks to my wife, Mijung, for her heartful love and support. She is the suitable helper of my life, and I will never forget her help and prayer throughout my entire life, which makes me a good daddy of adorable daughters and a righteous man in our societies. vi Dispersion in Biomedical Optical Imaging Systems Publication No._____________ Sanghoon Oh, Ph.

The University of Texas at Austin, 2006 Supervisor: Thomas E. Milner Dispersion caused by the refractive index variation over a spectral range is an important characteristic to identify the structure and composition of materials. This research reports on work to obtain dispersion information using both time and spectral domain optical coherence tomography. To process time-frequency data, a non-uniform Fourier transformation is applied to remove the resolved non-uniform frequency sampling.

Analysis of the spectral phase function in the optical frequency domain is applied to measure the dispersion. First, this research experimented with water (H2O) to measure dispersion. The measured dispersion of water is compared with known data to confirm the methodology. Second, the concentration of a glucose solution was estimated by analyzing the spectral phase function.

The result showed that this method can provide an ability to measure glucose concentration with high sensitivity 0. In conclusion, this method can be implemented to monitor sample constituents and to compensate for material dispersion. vii Table of Contents LIST OF FIGURES. xi CHAPTER 1: INTRODUCTION.

Background and Motivation.7 CHAPTER 2: DISPERSION CONTROL SYSTEM FOR OPTICAL COHERENCE TOMOGRAPHY: FEASIBILITY STUDY. Computing group delay. Numerical Calculation of Coherence Function affected by Dispersion. Measurement of Group Delay caused by Water.26 CHAPTER 3: METHOD TO CALIBRATE SPATIAL LIGHT MODULATOR (SLM) USING DIFFERENTIAL PHASE OPTICAL COHERENCE TOMOGRAPHY (DPOCT).

Spatial Light Modulator (SLM). Differential Phase Optical Coherence Tomography (DPOCT).46 CHAPTER 4: A FIBER-BASED COMMON-PATH SPECTRAL INTERFEROMETER FOR MEASUREMENT OF HIGHER-ORDER REFRACTIVE INDEX AND DISPERSION. Spectral Phase Analysis. Measurement of Dispersion.

Measurement of Glucose Concentration. Non-Uniform Fourier Transformation. Multitaper Spectral Analysis. Spectral Interference Analysis.

Optical Path Length Estimation.81 CHAPTER 5: SUMMARY AND CONCLUSIONS. Summary of Dissertation.88 ix CHAPTER 6: FUTURE WORK – OPTICAL IMAGING AND CHARACTERIZATION OF CANCER CELLS USING SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY FOR EARLY CANCER DIAGNOSIS. The First Mode: Spatially Multiplexed Swept Source Optical Coherence Tomography. The second mode: Spectroscopic Optical Coherence Tomography.

Expected Results and Discussion.116 x List of Figures Figure 1. An illustration of time-domain OCT system. Procedures to compute group delay. Refractive index of water; real part (upper) and imaginary part (lower).

Diagram of dispersion controller. Optical experimental setup; interferometer with dispersion controller. Red dotted line: sample path, blue dotted line: reference path. Block diagram of dispersion control system.

(a) top: phase data of dispersed and non-dispersed coherence function in frequency domain, (b) middle: phase shift is difference between the two data in (a), and (c) bottom: wrapped phase shift data for SLM. A graph of phase shift variation versus sample depth from simulation result. Phase shift versus wavelength (experimental data). Experimental system; L: lens, M: mirror, M-G: mirror mounted on Galvanometer, G: grating, C: collimator with FC/APC optical connector, W: Wollaston Prism, D: photodetector, Seg: segment, ADC: analog to digital converter, RSDL: rapid scanning delay line, small squares and numbers above represent spliced locations and angles.

A detailed view of sample path with light trace; L: Triplet lens, W: Wollaston prism, OL: microscope objective lens, E: extraordinary axis, O: ordinary axis, f: focal length of the triplet lens, θ: diverged angle (2˚), 4-f geometry with two lenses and two Wollaston prisms. SLM consists of a controller and a liquid crystal window. A graph of the electro-optical response of the SLM liquid crystal. Data is a double pass, mean of 10 liquid crystal cells.

Range of levels (0 to 4095) with respect to electric input voltage (0 to 10 V). Standard deviation of 10 liquid crystal cells. Fiber-based common-path spectral interferometer using a frequency swept laser source. 1, 2, and 3: port number, C: collimator, R: reference plate, WC: a water filled sample chamber.

Experimental system: common-path spectral interferometer. C: collimator, L: plano-convex lens, SC: sample chamber, and ADC: analog-to-digital converter. Interference fringes in path length difference domain. Sample path layout is given in inserted box.

1, 2, A, B, C, and D are labels for each surface. 2/A, 2/B, 2/C, and 2/D are labels for interference fringes corresponding to mixing of reflections from the two surfaces. Incident light propagates from left to right. Detailed diagram of interferometer sample path.

ϕα (ν ) and ϕβ (ν ) represent the spectral phase functions of 2/C and 2/B interference fringes, respectively. l a , l g , and l s are physical path length in air, glass, and water; na , ng , and ns are refractive indices of air, glass, and water, respectively. The blue lines indicate light input while red are reflected light. Detailed diagram of interferometer sample path.

ϕ1/ C (ν ) and ϕ1/ B (ν ) represent the spectral phase functions generated from 1/C and 1/B interference fringes, respectively. l r , l a , l g , and l s are physical path lengths in lens, air, glass, and sample; nr , na , ng , and ns are refractive indices of lens, air, glass, and sample, respectively. Thick blue lines indicate light input while red thin lines are reflected light. Interference fringe intensity versus optical path length computed from Lomb-Scargle periodogram analysis.

This data provides the depth-scanned information of the optical construction of the sample chamber. Experimentally measured spectral phase variation. Mean of 20 experimental measurements (solid) and 5th order polynomial curve fitting of the mean (dashed). Spectral phase variation of refractive index of water estimated by numerical calculation using published water refractive index (solid), 5th order polynomial curve fitting (dashed).

Comparision of the two results; 5th order polynomial curve fits of experimental result (dashed) and numerical calculation (solid).995, Normalized mean square error = 0. Glucose concentration measurement for 0-5 mM in 1 mM increments (a) and 0-50 mM in 5 mM increments (b). Each error-bar represents the standard deviation of 20 measurements. Illustration of SMSS-OCT principle: multiplexing excessively long depth scan (a) into a laterally adjacent B-scans (b).

L: maximum scan depth, ∆L: longitudinal resolution, ∆d: lateral resolution, a: scan depth, d: lateral scan range. System diagram of SMSS-OCT imaging system. BS: beam splitter, C: collimator, M: mirror, M-G: mirror on the galvanometer, L: lens, and ADC: analog to digital converter. SMSS-OCT image of microscope cover slide; glass, 100µm thickness, n=1.

Second mode; spectroscopic OCT. C: collimator, R: reference glass plate, M-G: mirror on the galvanometer, L: lens, and ADC: analog to digital converter. High-order spectral phase variation of water (H2O).97 xiii Chapter 1: Introduction 1. BACKGROUND AND MOTIVATION 1.

Optical Imaging Biophotonics is rapidly developing and widely utilized in biological and medical research. Optical imaging and optical spectroscopy are two major research areas. Optical coherence tomography (OCT) was introduced by James Fujimoto in 1991 and is a highly sensitive interferometric method measuring light reflection from a target sample [1. OCT is a promising modality to improve the quality of biomedical imaging [1.

Development of spectrally broad-band laser sources has pushed OCT resolution to a few micrometers that is sufficient to resolve and image cross-sectional subcellular structures of tissue samples in vivo. In terms of measurement domains, OCT can be categorized into two types; time- domain and spectral domain OCT. Time-domain OCT was introduced first and requires a mechanically moving component for changing the optical path length of light in a reference path in order to process a depth scan. Spectral domain OCT was introduced later and does not require mechanical scanning.

Spectral-domain OCT needs either a frequency swept laser source or a spectrometer in the detection path of the interferometer. 1 According to reported research, spectral domain OCT provides better sensitivity of up to 30 dB over time domain OCT [1.1 illustrates basic layout of a time-domain OCT system. The system consists of a Michelson type interferometer and utilizes a broadband light source, a beam splitter, a reference reflector, a sample, and a photodetector. The broadband laser source enters the interferometer, and light is split into reference and the sample paths by the beam splitter.

Light reflected from the both paths recombine at the beam splitter and interfere. Half of the interfering light is detected at the photodetector. Detected photon number spectral density ( nD ) at the photodetector is Reference path Sample path Broadband Laser ∆l = C ⋅ ∆ τ Detector Figure 1. An illustration of time-domain OCT system 2 ⎡ 2 ⎛ 4πν∆l ⎞⎤ nD = η a0 (ν ) ⎢ s + r + 2 s r cos ⎜ + (φs − φr ) ⎟ ⎥ 2 (1.