Cardiovascular disease is one of the leading causes of the mortality in the western world. Many imaging modalities have been used to diagnose cardiovascular diseases. However, each has different forms of noise and artifacts that make the medical image analysis field important and challenging. This thesis is concerned with developing fully automatic segmentation methods for cross-sectional coronary arterial imaging in particular, intra-vascular ultrasound and optical coherence tomography, by incorporating prior and tracking information without any user intervention, to effectively overcome various image artifacts and occlusions. Combinatorial optimisation methods are proposed to solve the segmentation problem in polynomial time. A node-weighted directed graph is constructed so that the vessel border delineation is considered as computing a minimum closed set. A set of complementary edge and texture features is extracted. Single and double interface segmentation methods are introduced. Novel optimisation of the boundary energy function is proposed based on a supervised classification method. Shape prior model is incorporated into the segmentation framework based on global and local information through the energy function design and graph construction. A combination of cross-sectional segmentation and longitudinal tracking is proposed using the Kalman filter and the hidden Markov model. The border is parameterised using the radial basis functions. The Kalman filter is used to adapt the inter-frame constraints between every two consecutive frames to obtain coherent temporal segmentation. An HMM-based border tracking method is also proposed in which the emission probability is derived from both the classification-based cost function and the shape prior model. The optimal sequence of the hidden states is computed using the Viterbi algorithm. Both qualitative and quantitative results on thousands of images show superior performance of the proposed methods compared to a number of state-of-the-art segmentation methods.

Abstract This thesis presents an effective optical method for measuring liquid sorption into paper. From the two tested methods, based on a streak-camera and optical coherence tomography (OCT), the last-mentioned proved very promising for investigating dynamical paper-liquid interactions as spatially and temporally dependent processes. The streak-camera measurements were performed to explore the relationship between paper properties and light migration in dry and refractive index matched paper in general. Based on streak-camera measurements, a novel procedure for determining the average refractive index of cellulose fibre tissue was also presented here. In addition, the streak camera method lent itself to paper porosity determination. Results of the performed OCT measurements proved that liquids cannot penetrate into paper before filling the pores and pits of the paper surface. As a liquid penetrated into paper, the border between the wetted and dry area could be investigated in the depth direction. The liquid penetration velocity seemed to be slower at the beginning and end of the process. Liquid absorption into paper fibres could be investigated concurrently. For the first time, the location and moment of structural changes in paper could be determined during wetting, and the effect of three different coexistent subprocesses related to paper wetting could be detected. OCT only fell short of detecting the effect of liquid migration along fibres. Despite the limitations of the utilized method (resolution, probing depth and depth scanning rate), the obtained OCT measurement results are very promising for the development of an effective paper wetting measurement device for industrial applications. Even if this thesis focused on paper wetting, it is reasonable to assert that the presented ideas and obtained results have more general value in terms of explaining liquid penetration into porous structures and offer an alternative method of evaluating that process.

This thesis forms part of an ongoing long-term project to investigate the suitability of Doppler optical coherence tomography (OCT) as a measurement tool to investigate skin thickness and blood flow in patients with systemic sclerosis. There is a discussion of the characterisation of an electro-optic phase modulator for use in a Doppler OCT imaging system which is being built for the purpose of clinical studies. In addition to this the development of software for the same system is described. The work includes a comparison of two methods of obtaining Doppler information that were tested with the system; a phase resolved method and a correlation mapping method. Initial structural and Doppler images obtained using the system are presented. In addition to this the development of semi-automated software to measure skin thickness from both OCT and high frequency ultrasound images is discussed. The results of a study, for which this software was developed, into skin thickness measurements using both techniques in both patients with systemic sclerosis and healthy controls are presented. Both OCT and high frequency ultrasound were able to measure a statistically significant difference in epidermal thickness at multiple locations on the body. Finally, the modification of a freely available Monte Carlo simulation for light propagation in multi-layered tissue (MCML) to enable the simulation of structural and Doppler OCT images is covered. The simulation was able to extract the magnitude of the simulated flow accurately to within an order of magnitude, and after a simple filter was applied to eliminate fluctuations in the data the structure of the Doppler image closely matched what was modelled.

Optical Coherence Tomography (OCT) is a medical imaging technique which distinguishes itself by acquiring microscopic resolution images in-vivo at millimeter scale fields of view. The resulting in images are not only high-resolution, but often multi-dimensional to capture 3-D biological structures or temporal processes. The nature of multi-dimensional data presents a unique set of challenges to the OCT user that include acquiring, storing, and handling very large datasets, visualizing and understanding the data, and processing and analyzing the data. In this dissertation, three of these challenges are explored in depth: sub-resolution temporal analysis, 3-D modeling of fiber structures, and compressed sensing of large, multi-dimensional datasets. Exploration of these problems is followed by proposed solutions and demonstrations which rely on tools from multiple research areas including digital image filtering, image de-noising, and sparse representation theory. Combining approaches from these fields, advanced solutions were developed to produce new and groundbreaking results. High-resolution video data showing cilia motion in unprecedented detail and scale was produced. An image processing method was used to create the first 3-D fiber model of uterine tissue from OCT images. Finally, a compressed sensing approach was developed which we show to guarantee high accuracy image recovery of more complicated, clinically relevant, samples than had been previously demonstrated. The culmination of these methods represents a step forward in OCT image analysis, showing that these cutting edge tools can also be applied to OCT data and in the future be employed in a clinical setting.

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京都大学 / 新制・課程博士 / 博士(医学) / 甲第24498号 / 医博第4940号 / 新制||医||1064(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 中本 裕士, 教授 森本 尚樹, 教授 大森 孝一 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Optical Coherence Tomography (OCT) is a novel optical imaging technique that has assumed significant importance in bio-medical imaging in the last two decades because it is non-invasive and provides accurate, high resolution images of three dimensional cross-sections of body tissue, exceeding the capabilities of the current predominant imaging technique –ultrasound. In this thesis, high resolution OCT is investigated for in vivo detection of abnormal skin pathology for the early diagnosis of cancer. The technology presented is based on a dynamic focusing microscopic imaging probe conceived for skin imaging and the detection of abnormalities in the epithelium. A novel method for dynamic focusing in the biological sample using liquid crystal (LC) lens technology to obtain three dimensional images with invariant resolution throughout the cross-section and depth of the sample is presented and discussed. Two different skin probe configurations that incorporate dynamic focusing with LC lenses, one involving a reflective microscope objective sub-system, and the other involving an all-refractive immersion microscope objective sub-system are investigated. In order to ensure high resolution imaging, a low coherence broadband source, namely a femtosecond mode-locked Ti: sapphire laser centered at a wavelength of approximately 800nm is used to illuminate the sample. An in-depth description and analysis of the optical design and predicted performance of the two microscope objectives designed for dynamic three dimensional imaging at 5ìm resolution for the chosen broadband spectrum is presented.

Microvasculature can be found in almost every part of the human body, including the internal organs. Importantly, abnormal changes in microvasculature are usually related to pathological development of the tissue cells. Monitoring of changes in blood flow properties in microvasculature, therefore, provides useful diagnostic information about pathological conditions in biological tissues as exemplified in glaucoma, diabetes, age related macular degeneration, port wine stains, burn-depth, and potentially skin cancer. However, the capillary network is typically only one cell in wall thickness with 5 to 10 microns in diameter and located in the dermis region of skin. Therefore, a non-invasive flow imaging technique that is capable of depth sectioning at high resolution and high speed is demanded. Optical coherence tomography (OCT), particularly after its advancement in frequency domain OCT (FD-OCT), is a promising tool for non-invasive high speed, high resolution, and high sensitivity depth-resolved imaging of biological tissues. Over the last ten years, numerous efforts have been paid to develop OCTbased flow imaging techniques. An important effort is the development of phase-resolved Doppler OCT (PR-DOCT). Phase-resolved Doppler imaging using FD-OCT is particularly of interest because of the direct access to the phase information of the depth profile signal. Furthermore, the high speed capability of FD-OCT is promising for real time flow monitoring as well as 3D flow segmentation applications. However, several challenges need to be addressed; 1) Flow in biological samples exhibits a wide dynamic range of flow velocity caused by, for example, the iv variation in the flow angles, flow diameters, and functionalities. However, the improvement in imaging speed of FD-OCT comes at the expense of a reduction in sensitivity to slow flow information and hence a reduction in detectable velocity range; 2) A structural ambiguity socalled 'mirror image' in FD-OCT prohibits the use of maximum sensitivity and imaging depth range; 3) The requirement of high lateral resolution to resolve capillary vessels requires the use of an imaging optics with high numerical aperture (NA) that leads to a reduction in depth of focus (DOF) and hence the imaging depth range (i.e. less than 100 microns) unless dynamic focusing is performed. Nevertheless, intrinsic to the mechanism of FD-OCT, dynamic focusing is not possible. In this dissertation, the implementation of PR-DOCT in a high speed swept-source based FD-OCT is investigated and optimized. An acquisition scheme as well as a processing algorithm that effectively extends the detectable velocity dynamic range of the PR-DOCT is presented. The proposed technique increased the overall detectable velocity dynamic range of PR-DOCT by about five times of that achieved by the conventional method. Furthermore, a novel technique of mirror image removal called ‘Dual-Detection FD-OCT’ (DD-FD-OCT) is presented. One of the advantages of DD-FD-OCT to Doppler imaging is that the full-range signal is achieved without manipulation of the phase relation between consecutive axial lines. Hence the full-range DD-FDOCT is fully applicable to phase-resolved Doppler detection without a reduction in detectable velocity dynamic range as normally encountered in other full-range techniques. In addition, PRDOCT can utilize the maximum SNR provided by the full-range capability. This capability is particularly useful for imaging of blood flow that locates deep below the sample surface, such as v blood flow at deep posterior human eye and blood vessels network in the dermis region of human skin. Beside high speed and functional imaging capability, another key parameter that will open path for optical diagnostics using OCT technology is high resolution imaging (i.e. in a regime of a few microns or sub-micron). Even though the lateral resolution of OCT can be independently improved by opening the NA of the imaging optics, the high lateral resolution is maintained only over a short range as limited by the depth of focus that varies inversely and quadratically with NA. Recently developed by our group, ‘Gabor-Domain Optical Coherence Microscopy’ (GD-OCM) is a novel imaging technique capable for invariant resolution of about 2-3 m over a 2 mm cubic field-of-view. This dissertation details the imaging protocol as well as the automatic data fusion method of GD-OCM developed to render an in-focus high-resolution image throughout the imaging depth of the sample in real time. For the application of absolute flow measurement as an example, the precise information about flow angle is required. GDOCM provides more precise interpretation of the tissue structures over a large field-of-view, which is necessary for accurate mapping of the flow structure and hence is promising for diagnostic applications particularly when combined with Doppler imaging. Potentially, the ability to perform high resolution OCT imaging inside the human body is useful for many diagnostic applications, such as providing an accurate map for biopsy, guiding surgical and other treatments, monitoring the functional state and/or the post-operative recovery process of internal organs, plaque detection in arteries, and early detection of cancers in the gastrointestinal tract. Endoscopic OCT utilizes a special miniature probe in the sample arm to vi access tubular organs inside the human body, such as the cardiovascular system, the lung, the gastrointestinal tract, the urinary tract, and the breast duct. We present an optical design of a dynamic focus endoscopic probe that is capable of about 4 to 6 m lateral resolution over a large working distance (i.e. up to 5 mm from the distal end of the probe). The dynamic focus capability allows integration of the endoscopic probe to GD-OCM imaging to achieve high resolution endoscopic tomograms. We envision the future of this developing technology as a solution to high resolution, minimally invasive, depth-resolved imaging of not only structure but also the microvasculature of in vivo biological tissues that will be useful for many clinical applications, such as dermatology, ophthalmology, endoscopy, and cardiology. The technology is also useful for animal study applications, such as the monitoring of an embryo’s heart for the development of animal models and monitoring of changes in blood circulation in response to external stimulus in small animal brains.

<p>Asymmetric multiple quantum wells (AMQWs) can provide broad and flat gain spectra. Broadly tunable diode lasers can be realized with AMQW active regions and without the need for antireflection coatings on cleaved facets.</p> <p> This thesis reports the application of AMQW broadly tunable lasers with uncoated facets for Fourier domain and synthesized optical coherence tomography (OCT). A depth resolution of 13 μm in air was obtained with a test bed OCT system that used diffractive optical elements, short external cavities, and AMQW InGaAsP/InP broadly tunable lasers as the light sources for the Fourier domain and the synthesized OCT measurements. The centre wavelengths of the broadly tunable sources were 1550 nm and the tunable ranges were ≤ 117 nm.</p> <p>The features of broad and flat gain spectra of AMQWs also make AMQWs ideal candidates for broad spectral width superluminescent diodes (SLDs). 1300 nm AMQW InGaAsP/InP SLDs were designed and fabricated for application to time domain OCT. For the design of the active region, it was found by simulation of gain and the comparison of two growths that the transition carrier density (TCD) has to be reasonably high to achieve high power SLDs. A transfer matrix method was used to solve for the modes of planar optical waveguides with arbitrary layers and the thicknesses of these layers were optimized with a Marquardt nonlinear fitting method. With the optimization of the optical waveguide and with AMQWs with high TCDs, the output power of SLDs could reach 2 mW with > 90 nm spectral width. It is shown by time domain OCT measurements that the depth resolution of the OCT measurements could reach 7.85 μmin air with double section SLDs.</p> <p>Two dimensional OCT images of a glass cover slip were built with the imageSC function in Matlab™. Image enhancement with blind/not-blind deconvolution was performed based on the measured point spread function (PSF) of the OCT setup. A Richardson-Lucy algorithm was used as the blind deconvolution method and a not-blind version of a Jansson-Van Cittert method was used.</p> / Thesis / Doctor of Philosophy (PhD)

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