The objective of this study is to apply digital image processing (DIP) techniques to optical coherence tomography (OCT) images and develop computer-based non-subjective quantitative analysis, which can be used as diagnostic aids in early detection of dental caries. This study first compares speckle reduction effects on raw OCT image data by implementing spatial-domain and transform-domain speckle filtering. Then region-based contour search and global thresholding techniques examine digital OCT images with possible lesions to identify and highlight the presence of features indicating early stage dental caries. The outputs of these processes, which explore the combination of image restoration and segmentation, can be used to distinguish lesion from normal tissue and determine the characteristics prior to, during, and following treatments. The combination of image processing and analysis techniques in this thesis shows potential of detecting early stage caries lesion successfully.

Obtaining higher depth of imaging is an important goal in Optical Coherence Tomography (OCT) systems. One of the main factors that affect the depth of OCT imaging is the presence of noise. That’s why the study of noise statistics is an important problem. In the first part of this thesis we obtain an empirical estimate of the second order statistics of noise by using a sequence of Time domain (TD) OCT images. These estimates confirm the non-stationary nature of noise in TD-OCT. In the second part of the thesis these estimates are used to design a depth-dependent matched filter to maximize the Signal-to-Noise Ratio (SNR) and increase the Contrast-to-Noise Ratio (CNR) in TD-OCT. By applying our filter to TD-OCT images of both vascular rabbit tissue and a human tooth, both SNR and CNR were increased and a higher imaging depth was achieved.

This project initiated with the aim for improving the ultrahigh resolution optical coherence tomography (UHR-OCT) system performance by considering the limitations to the axial OCT resolution for in vivo imaging of human and animal retina. To this end, a computational model was developed to simulate the effect of wavelength-dependant water absorption on the detected spectral shape of the broad-bandwidth light source used in UHR-OCT at 1060nm wavelength region, which effectively determines the axial OCT resolution in the retina. For experimental verification of the computational model, a custom built light source with a re-shaped spectrum (Superlum Inc.) was interfaced to the state-of-the-art UHR-OCT system. About 30% improvement of the axial OCT resolution in the rat retina and ~12% improvement of the axial OCT resolution in the human retina was achieved compared to the case of the almost Gaussian shaped spectrum of the standard, commercially available SLD. Although water absorption in the 1060nm spectral region strongly affects the sample beam, selecting a suitable light source with specific spectral shape can compensate for the undesired water absorption effect and thus result in significantly improved axial resolution in in vivo OCT retinal images. To demonstrate the advantages of the state-of-the-art OCT technology for non invasive retinal imaging, an established animal model of outer retina degeneration (sodium iodate (NaIO3)-induced retina degeneration) was employed for longitudinal monitoring of the degeneration and investigation of possible early and dynamic signs of damage undetected by other imaging modalities. The long-term (up to 3 months) and short-term (up to 12 hours) effect of sodium iodate toxicity on the layered structure of retina was monitored longitudinally and in vivo for the first time using OCT. An initial acute swelling of the retina, followed by progressive disruption and degeneration of outer retina was observed as a result of sodium iodate-induced damage. Changes in the thickness and optical reflectivity of individual retinal layers were extracted from the OCT images to quantify the changes occurring at different stages of the disease model. Results from this project present the theoretical and practical limits to the highest axial OCT resolution achievable for retina imaging in the 1060nm spectral range both in small animals and humans, and provided a framework for future development of novel light sources. Furthermore, UHR-OCT imaging was shown to be an effective and valuable modality for in vivo, non invasive investigation of retina degenerative disease.

People with Down’s syndrome (DS) are known to experience premature ageing and have a high propensity for clinical diagnosis of dementia due to Alzheimer’s disease (AD). In DS there is a unique and natural model of over-expression of amyloid-beta (Aβ) protein, the accumulation of which is proposed to be the central early event in the pathogenesis of AD. In DS, AD neuropathology is universally seen in the brain from the fourth decade. Identifying biomarkers are essential to the evaluation of future treatment trials. The retina has been shown to experience changes in patients with AD, such as retinal thinning, compared to age-matched controls. As an extension of the brain, the retina can be quickly and non-invasively imaged and may provide a proxy measure of brain changes in AD. Using optical coherence tomography (OCT), cross-sectional retinal examinations were completed in 50 people with DS aged 18 years and over. Comparisons between retinal thickness of the DS and control groups were examined, as well as the effect of age on thickness in both groups. For the DS group, further investigations were made into the relationships between retinal thickness and (i) cognitive performance, (ii) diagnosis of dementia, (iii) cortical thickness and, (iv) presence of Aβ binding in the brain. Contrary to expectations, people with DS had thicker retina compared to age-matched controls. In addition, normal age-related retinal thinning was not seen in the DS group. People with DS have a life-long overproduction of Aβ, deposits of which have been previously imaged in the retina. Aβ may be responsible both directly, through physical mass, and indirectly through inflammation as a response to Aβ, for increased retinal thickness in people with DS. Consequently, retinal thickness in DS may be a proxy measure of Aβ deposition in the retina. As part of a collaborative study, brain Aβ binding was measured using positron emission tomography neuroimaging in a subset of the DS group. Individuals with positive Pittsburgh compound [11C]-PIB (PIB) binding to Aβ displayed a trend towards having thinner retina than those with negative PIB binding. These results indicate that a shift towards thinning retina in people DS may reflect changes in brain pathology. Future studies are discussed which aim to investigate Aβ and Aβ driven pathology in the retina.

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