Spectral Domain - Optical Coherence Tomography
FIBER BASED SPECTRAL DOMAIN OPTICALCOHERENCE TOMOGRAPHY: MECHANISMAND CLINICAL APPLICATIONSByLeo Renyuan ZhangCopyright Renyuan Zhang 2015A Thesis Submitted to the Faculty of theCOLLEGE OF OPTICAL SCIENCESIn Partial Fulfillment of the RequirementsFor the Degree ofMASTER OF SCIENCEIN OPTICAL SCIENCESTHE UNIVERSITY OF ARIZONA2015
FIBER BASED SPECTRAL DOMAIN OPTICALCOHERENCE TOMOGRAPHY: MECHANISMAND CLINICAL APPLICATIONSByLeo Renyuan ZhangCopyright Renyuan Zhang 2015Examination committee:Dr. Khanh KieuAssistant Professor of Optical Sciences, ChairmanDr. Robert A. NorwoodProfessor of Optical Sciences, Committee MemberDr. Leilei PengAssistant Professor of Optical Sciences , Committee Member
AbstractOptical Coherence Tomography (OCT) is a novel, non-invasive, micrometer-scalesolution tomography, which use coherent light to obtain cross-sectional images ofspecific samples, such as biological tissue. Spectral Domain Optical CoherenceTomography (SD-OCT) is the second generation of Optical Coherence Tomography. Incomparison to the first generation Time Domain Optical Coherence Tomography (TDOCT), SD-OCT is superior in terms of its capturing speed, signal to noise ratio, andsensitivity. The SD-OCT has been widely used in both clinical and research imaging.The primary goal of this research is to design and construct a Spectral Domain OpticalCoherence Tomography system which consists of a fiber-based imaging system and aline scan CCD-based high-speed spectrometer, and is capable of imaging and analyzingbiological tissue at a wavelength of 1040 nm. Additionally, a NI LabVIEW software forcontrolling, acquiring and signal processing is developed and implemented. An axialresolution of 16.9 micrometer is achieved, and 2-D greyscale images of varioussamples have been obtained from our SD-OCT system. The device was initiallycalibrated using a glass coverslip, and then tested on multiple biological samples,including the distal end of a human fingernail, onion peels, and pancreatic tissues. Ineach of these images, both tissue and cell structures were observed at depths of up to0.6 millimeter. The A-scan processing time is 8.445 millisecond. Our SD-OCT systemdemonstrates tremendous potential in becoming a vital imaging tool for clinicians andresearchers.1
ContentsAbstract . 1List of Figures . 4List of Tables . 5Chapter 1 Introduction. 61.1 Optical Coherence Tomography . 61.2 Development of current SD-OCT . 71.3. Structure of this report . 7Chapter 2 SD-OCT Mechanisms and Calculations . 92.1 SD-OCT principles . 92.2 Noise in the SD-OCT system . 132.3 SD-OCT system performance . 132.3.1 Resolution . 132.3.2 Image depth . 142.3.3 Signal-to-noise ratio . 152.4 Grating Design . 16Chapter 3 SD-OCT Setup and Data Acquisition . 193.1 SD-OCT System Setup. 193.2 SD-OCT Data Acquisition and Signal Processing . 203.2.1 Data Acquisition . 203.2.2 Signal Processing . 213.2.3 Calibration of Depth-axis . 223.2.4 Software . 223.3 Calibration of Sample and Reference Arms . 233.4 Calibration of the SD-OCT Spectrometer . 23Chapter 4 SD-OCT Imaging and Optimization . 264.1 Measurement of a Glass Cover Slip for calibration purpose . 264.2 Sample Imaging . 274.2.1 Imaging of human fingernail . 274.2.2 Imaging of Onion. 284.2.3 Imaging of pancreas . 294.3 Imaging Summary . 302
Chapter 5 Summary and Future Work . 31Reference . 323
List of FiguresFigure 1: Schematic diagram of Fercher's OCT system (RM stands for Reference Mirror,WL stands for white light, PA stands for pixel array) . 7Figure 2: SD-OCT configuration . 9Figure 3: Laser spectrum and typical interferogram of SD-OCT . 9Figure 4: Illustration of A-scan sample. 12Figure 5: Illustration of an A-scan resulting from Fourier transforming . 12Figure 6: Low NA and high NA Rayleigh range comparison . 14Figure 7: Grating design . 16Figure 8: OCT spectrometer design by Zemax . 17Figure 9: Footprint of the focusing beam . 18Figure 10: SD-OCT setup . 20Figure 11: Signal Processing Procedure . 21Figure 12: LabVIEW based SD-OCT system front panel . 22Figure 13: Sample arm and reference arm setup . 23Figure 14: OCT spectrometer setup . 24Figure 15: A-scan of a single cover slip . 26Figure 16: Human fingernail OCT image, two surfaces are clearly seen ((a) uppersurface and (b) bottom surface are the nail top and (a) bottom and (b) upper are thenail bottom) . 27Figure 17: OCT image of an onion peel ((a), total onion scanned, (b), onion peels, (c),onion cells level). 28Figure 18: OCT image of pancreas ((a), pancreas structure, (b), detailed image from (a)box) . 294
List of TablesTable 1: Experiment preparation . 19Table 2: Datasheet based on calculation of the components . 20Table 3: Experiment Datasheet . 305
Chapter 1 Introduction1.1 Optical Coherence TomographyTomography technology has been developed rapidly over the last 50 years. Amongmost tomography inventions, Computed Tomography (CT) and Magnetic ResonanceImaging (MRI) have already been applied in radiology and medical diagnosis toinvestigate anatomy and physiology.[1]Optical Coherence Tomography (OCT) is a relatively new technology whichdemonstrates better axial resolution (in comparison to other existing tomographytechnologies). Because of its micrometer resolution and millimeter penetration depth,OCT technology has been applied in biomedical imaging to produce high-resolutioncross-sectional images.There are three main types of OCT systems that have been introduced including theTime-Domain OCT (TD-OCT), the Spectrum-Domain OCT (SD-OCT) and the SweptSource OCT (SSOCT). The SD-OCT and SSOCT are newer technologies as they useFourier transform calculations in their analysis and operate at a faster rate than TDOCT.TD-OCT is characterized by mechanical scanning over the sample, which results in thescan rate being limited to approximately 1 kHz. In addition, due to the limitation ofcoherence optical path difference (OPD), the signal to noise ratio (SNR) is notcomparable to that of the SD-OCT system.SS-OCT has multiple advantages such as reduced noise, better SNR and heterodynedetection ability.[2] However, the SS-OCT system is realized in 1300 nm band in mostimplementations where suitable laser sources exist.[3] SS-OCT also requires a tunablehigh-speed swept source laser which is not simple to build. For other wavelengthranges, or preferred wavelengths, SS-OCT is not applicable. For example, 1040 nm lightis more suitable for retinal imaging.[4]In our design, the SD-OCT configuration is adopted. The SD-OCT system that wedeveloped consists of a high-speed spectrometer and a broad-band light source inorder to eliminate the disadvantages observed in TD-OCT. A 1040 nm amplifiedspontaneous emission (ASE) source with 120 nm FWHM bandwidth is implemented.6
1.2 Development of current SD-OCTSD-OCT was first performed by A. F. Fercher in 1995,[5] as shown in Figure 1. The centralwavelength for this system was at 780 nm, and the spectral bandwidth was only 3 nm.The detection component consisted of 1800 lines/mm diffraction gratings and320 288 pixels plane scan CCD. By performing a Fast Fourier Transform (FFT), Fercherwas able to obtain the depth image of the sample. Therefore, the one-dimensionaldepth scan was applied to corneal thickness measurement.Figure 1. Schematic diagram of Fercher's OCT system(RM stands for Reference Mirror, WL stands for white light, PA stands for pixel array)In 1998, G. Häusler used a "Spectral Radar" system to achieve in vivo measurement ofhuman skin surface morphology; additionally, he quantitatively verified that skinsamples containing melanomas backscatter at a higher intensity than normal skinsamples.[ 6 ] The system consisted of a super luminescent diode (SLD), which wascharacterized by a central wavelength of 840 nm, a FWHM spectral bandwidth of 20nm, and an output power of 1.7 mW. Moreover, the system’s A-scan rate was around10 Hz and the axial resolution was measured to be 35 µm. The dynamic range couldreach up to 79 dB.In 2002, M. Wojtkowski applied the SD-OCT system to image the human retina for thefirst time.[7] This system consisted of a source with central wavelength of 810 nm, aFWHM spectral bandwidth of 20 nm, and an output power of 2 mW. The detectionarm consisted of 1800 lines diffraction gratings and 16-bit plane scan CCD. The lateraland axial resolutions were measured to be 30 µm and 15 µm, respectively.Furthermore, the A-scan rate was 50 Hz and the dynamic range was 67 dB.The ultra-high resolution SD-OCT developed next. Degeneration and regeneration ofphotoreceptors in the adult zebrafish retina have been studied by Weber et al. at anaxial resolution of 3.2 µm in 2012.[8]1.3. Structure of this reportWe will first discuss the design, mechanism and methodology of the OCT system. Insection 1.1, we have briefly outlined the differences between Time-Domain Optical7
Coherence Tomography (TD-OCT), Spectral-Domain Optical Coherence Tomography(SD-OCT) and Swept-Source Optical Coherence Tomography (SS-OCT). Additionally, wehave discussed the reasons as to why SD-OCT was chosen as the method for imagingin our system. In later chapters, the imaging contrast mechanism will be discussed indetail with calculations and derivations of important parameters.In addition, the optical setup and a LabVIEW-based acquisition, detection and signalprocessing software is designed and implemented. The optical setup is fully calculatedand carefully aligned with kinematic mounts and translation stages. The signalprocessing procedure for acquiring 2-D data sets will be studied. Additionally, analgorithm performed to increase the signal-to-noise (SNR) ratio is discussed.Furthermore, imaging and optimization are performed during this research, and areshown in the analysis of botanic and biological tissue. In addition, the optimization forthe spectrum and measurement, as well as the actual data (ex. axial resolution, imagedepth, etc.) are also discussed.8
Chapter 2 SD-OCT Mechanisms and Calculations2.1 SD-OCT principlesFigure 2. SD-OCT configurationFrom Figure 2, we can see the SD-OCT system’s configuration. SD-OCT system is basedon the interferometry of the sample arm and the reference arm beam. The signal isdirected into the 2 x 2 coupler and then subsequently analyzed by the OCTspectrometer. The spectrometer consists of a collimator, a transparent or reflectivegrating, a focusing lens, and the CCD camera. We have also added an attenuating filterin order to prevent reaching the saturation level of the CCD. The line scan CCD willacquire the A-scan data and then the computer can convert the signal by Fast FourierTransform to develop a depth B-scan image. We will describe the data acquisitionmethods in Chapter 3.Figure 3. Laser spectrum and typical interferogram of SD-OCTFigure 3 provides the ASE optical spectrum and a typical interferogram analyzed by anoptical spectrum analyzer (OSA). The ASE source we use is centered at 1040 nm as1040 nm is superior at biological and ophthalmological imaging. In order to analyze9
specific samples, it is essential to understand the basic math governing the imagingformation.SD-OCT, as well as TD-OCT, has two working arms: the source and the detection arms.From the source arm, we have the incident light electric field:Equation 1𝐸𝑖 𝑆(𝑘, 𝑤)𝑒 (𝑤𝑡 𝑘𝑧)Assuming the sample is made from multiple layers, and that reflection is discrete, wehave:Equation 2𝑁𝑟𝑆 (𝑧𝑆 ) 𝑟𝑆𝑛 𝛿(𝑧𝑆 𝑧𝑆𝑛 )𝑛 1The following equation describes the electric field of the light reflected from thesample arm:Equation 3𝐸𝑆 𝐸𝑖 2[𝑟𝑆 (𝑧𝑆) 𝑒 𝑖2𝑘𝑧𝑆] 𝑁𝐸𝑖 𝑟𝑆𝑛 𝑒 2𝑖𝑘𝑧𝑆𝑛 2 𝑛 1This equation represents the electric field of the light reflected from the reference arm:Equation 4𝐸𝑅 𝐸𝑖𝑟𝑅 𝑒 𝑖2𝑘𝑧𝑅 2Set z 0 at the coupler, and the detector’s current could be calculated as:Equation 5𝐼𝐷 (𝑘, 𝑤) 𝜌 𝐸𝑅 𝐸𝑆 2 2𝑁2𝜌𝑆(𝑘, 𝑤)𝑆(𝑘, 𝑤) 𝑟𝑅 𝑒 𝑖(2𝑘𝑧𝑅 𝑤𝑡) 𝑟𝑆𝑛 𝑒 𝑖(2𝑘𝑧𝑆𝑛 𝑤𝑡) 2 2 2𝑛 1Eliminate the 𝑤 term,Equation 6𝐼𝐷 𝜌[𝑆(𝑘)(𝑅𝑅 𝑅𝑆1 𝑅𝑆2 𝑅𝑆3 )] 4𝑁𝜌[𝑆(𝑘) 𝑅𝑅 𝑅𝑆𝑛 (𝑒 𝑖2𝑘(𝑧𝑅 𝑧𝑆𝑛) 𝑒 𝑖2𝑘(𝑧𝑅 𝑧𝑆𝑛) )] 4𝑛 1𝑁𝜌[𝑆(𝑘) 𝑅𝑆𝑛 𝑅𝑆𝑚 (𝑒 𝑖2𝑘(𝑧𝑆𝑛 𝑧𝑆𝑚) 𝑒 𝑖2𝑘(𝑧𝑆𝑛 𝑧𝑆𝑚) )]4𝑛 𝑚 1In this equation, there are three terms contributed to the total intensity signal: the DCterm, the cross-correlation terms (CC terms) and the auto-correlation terms (AC terms).10
These terms are all important in any OCT system, as every OCT system consists of theseterms and each term contributes to a different signal shape. The DC term is derivedfrom the sample reflectivity and reference reflectivity. The CC terms are generated bythe sample optical path difference (OPD), which is defined by the accumulation of theinterference of the sample and reference signals. Additionally, the AC terms aregenerated because of the accumulation of the interference of the different sampleoptical paths.As the 𝐼𝐷 is dependent on 𝑘, it is necessary to perform the Fourier transform to getthe depth signal. For an arbitrary cosine function, we get the following:𝐹𝑇 1cos(𝑘𝑧0 ) [𝛿(𝑧 𝑧0 ) 𝛿(𝑧 𝑧0 )]2After applying Fourier Transform on 𝐼𝐷 , we will get:Equation 7𝐼𝐷 𝜌[𝛾(𝑘)(𝑅𝑅 𝑅𝑆1 𝑅𝑆2 𝑅𝑆3 )] 8𝑁𝜌{𝛾(𝑘) 𝑅𝑅 𝑅𝑆𝑛 𝛿[𝑧 2(𝑧𝑅 𝑧𝑆𝑛 )]} 4𝑛 1𝑁𝜌{𝛾(𝑘) 𝑅𝑆𝑛 𝑅𝑆𝑚 𝛿[𝑧 2(𝑧𝑆𝑛 𝑧𝑆𝑚 )]}4𝑛 𝑚 1Simplify the equation,Equation 8𝜌[𝛾(𝑘)(𝑅𝑅 𝑅𝑆1 𝑅𝑆2 𝑅𝑆3 )] 8𝐼𝐷 𝑁𝜌 𝑅𝑅 𝑅𝑆𝑛 {𝛾[2(𝑧𝑅 𝑧𝑆𝑛 )] 𝛾[ 2(𝑧𝑅 𝑧𝑆𝑛 )]} 4𝑛 1𝑁𝜌{ 𝑅𝑆𝑛 𝑅𝑆𝑚 {𝛾[2(𝑧𝑅 𝑧𝑆𝑛 )] 𝛾[ 2(𝑧𝑅 𝑧𝑆𝑛 )]}4𝑛 𝑚 1This is the calculation of intensity in depth of the SD-OCT system. The 𝑅𝑅 𝑅𝑆1 𝑅𝑆2 𝑅𝑆3 terms are DC terms. The 𝑅𝑅 𝑅𝑆𝑛 terms represent the interferenceof the reference and sample and they are related to the cross-correlation terms. Sincethe 𝑅𝑆𝑛 is relatively low compared to the reference reflectivity, a large 𝑅𝑅 isnecessary in order to obtain the accurate coherence image. Moreover, the two termswithin a single CC term are symmetric and only half of the image needs to be shownafter FFT. The 𝑅𝑆𝑛 𝑅𝑆𝑚 terms are related to auto-correlation terms and they arerelatively small when compared to the other two terms.11
The results from Equation 8 for the example of discrete sample reflectors can be seenin Figure 4 and Figure 5. Figure 4 shows the illustration of an A-scan signal. We can seethat the 𝑆(𝑘) is referred to as the source envelope and that the signal reflects cosinefringes. These fringes represent the interference of the sample and reference signals.Additionally, from the FFT of the raw A-scan data shown in Figure 5 (which refers tothe intensity A-scan data), the different terms are able to be distinguished by FFT. Thecross-correlation terms are discrete and reflect the reflected signals from the differentdepths of the sample. The B-scan image can be analyzed by merging multiple A-scandata by moving the Z/F stage.Figure 4. Illustration of A-scan sampleFigure 5. Illustration of an A-scan resulting from Fourier transformingFurthermore, for multiple reflectors, the cross-correlation components in k space aresuperposition of fringes.[ 9 ] The super-positional cosine fringes will contribute todifferent peaks (distinguished with different depth difference). The analysis ofspectrum may later be discussed through signal processing in Chapter 3.In this paper, the A-scan refers to the coherence signal in the lateral direction. Asopposed to in TD-OCT systems, the axial coherence signal is not needed to obtain theB-scan data in SD-OCT.12
2.2 Noise in the SD-OCT systemFrom Equation 8, the sample information obtained by the Fourier transform is not onlyaccompanied with the sample image, but also with correlated noise samples from theDC and AC terms. The AC and DC terms are located in the vicinity of zero optical pathlocation, and the AC terms are related to the intensity of the sample. For highlyscattering samples such as biological tissue, the autocorrelation terms are relativeweak. 𝑧
Tomography (SD-OCT) is the second generation of Optical Coherence Tomography. In comparison to the first generation Time Domain Optical Coherence Tomography (TD-OCT), SD-OCT is superior in terms of its capturing speed, signal to noise ratio, and sensitivity. The SD-OCT has been widely used in both clinical and research imaging.
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