<p>Optical coherence tomography (OCT) is a non-invasive imaging modality that uses low coherence interferometry to generate three-dimensional datasets of a sample's structure. OCT has found tremendous clinical applications in imaging the retina and has demonstrated great utility in the diagnosis of various retinal diseases. However, such diagnoses rely upon the ability to observe abnormalities in the structure of the retina caused by pathology. By the time an ocular disease has progressed to the point of affecting the morphology of the retina, irreversible vision loss in the eye may already occur. Changes in the functionality of the tissue often precede changes to the structure. Thus, if imaging methods are developed to provide additional functional information about the behavior and response of the retinal tissue and vasculature, earlier treatment for disease may be prescribed, thus preserving vision for the patient. </p><p>Within the last decade, significant technological advances in OCT systems have enabled high-speed and high sensitivity image acquisition using either spectral domain OCT (SDOCT) or swept-source OCT (SSOCT) configurations. Such systems use Fourier processing to extract structural information of a sample from interferometric principles. But such systems also have access to the optical phase information, which allows for functional analysis of sample dynamics. This dissertation details the development and application of methods using both intensity and phase information as a tool for studying interesting biological phenomena. The goal of this work is an extension of techniques to image the vasculature in the retina and enhance the clinical utility of OCT.</p><p>I first outline basic theory necessary for understanding the principles of OCT. I then describe OCT phase imaging in cellular applications as a demonstration of the ability of OCT to provide functional information on biological dynamics. Phase imaging methods suffer from an artifact known as phase wrapping, and I have developed a software technique to overcome this problem in OCT, thus extending its usefulness in providing quantitative information. I characterize the limitations in measuring moving scatterers with Doppler OCT in both SDOCT and SSOCT system. I also show the ability to image the vasculature in the retina using variance imaging with a high-speed retinal imaging system and software based methods to correct for patient motion and create a widefield mosaic in an automated manner. Finally, future directions for this work are discussed.</p> / Dissertation

<p>Optical coherence tomography (OCT) is a noninvasive three-dimensional interferometric imaging technique capable of achieving micrometer scale resolution. It is now a standard of care in ophthalmology, where it is used to improve the accuracy of early diagnosis, to better understand the source of pathophysiology, and to monitor disease progression and response to therapy. In particular, retinal imaging has been the most prevalent clinical application of OCT, but researchers and companies alike are developing OCT systems for cardiology, dermatology, dentistry, and many other medical and industrial applications. </p><p>Adaptive optics (AO) is a technique used to reduce monochromatic aberrations in optical instruments. It is used in astronomical telescopes, laser communications, high-power lasers, retinal imaging, optical fabrication and microscopy to improve system performance. Scanning laser ophthalmoscopy (SLO) is a noninvasive confocal imaging technique that produces high contrast two-dimensional retinal images. AO is combined with SLO (AOSLO) to compensate for the wavefront distortions caused by the optics of the eye, providing the ability to visualize the living retina with cellular resolution. AOSLO has shown great promise to advance the understanding of the etiology of retinal diseases on a cellular level.</p><p>Broadly, we endeavor to enhance the vision outcome of ophthalmic patients through improved diagnostics and personalized therapy. Toward this end, the objective of the work presented herein was the development of advanced techniques for increasing the imaging speed, reducing the form factor, and broadening the versatility of OCT and AOSLO. Despite our focus on applications in ophthalmology, the techniques developed could be applied to other medical and industrial applications. In this dissertation, a technique to quadruple the imaging speed of OCT was developed. This technique was demonstrated by imaging the retinas of healthy human subjects. A handheld, dual depth OCT system was developed. This system enabled sequential imaging of the anterior segment and retina of human eyes. Finally, handheld SLO/OCT systems were developed, culminating in the design of a handheld AOSLO system. This system has the potential to provide cellular level imaging of the human retina, resolving even the most densely packed foveal cones.</p> / Dissertation

Colorectal cancer (CRC) remains the second deadliest cancer in the United States, despite steady reduction in mortality rate over the last three decades. Colonoscopy is the gold-standard screening modality with high sensitivity and specificity to mature polyps. However, the miss rate for small (<5 mm) lesions is estimated to be as high as 26%. Because the five-year survival rate for CRC detected at the local stage is 90%, there is a clear need for a screening procedure that is sensitive to these small lesions. Optical coherence tomography (OCT) has become a major biomedical imaging modality since its invention in 1991. As the optical analog to ultrasound, OCT provides information in both lateral and depth dimensions with resolution < 10 µm and an imaging depth of about 1.5 mm in scattering tissue. In this dissertation, I describe my efforts to develop new uses of OCT for improved early detection of adenoma in the azoxymethane mouse model of CRC. In recent years, commercial OCT systems have reached imaging speeds sufficiently high for in vivo volumeric imaging while laterally sampling the tissue at the Nyquist limit. First, I describe the design of a miniature endoscope and the integration of this probe with a commercial OCT system. Then I describe the development of two OCT imaging methods, one structural and one functional, that could be used for future work in diagnostic or therapeutic studies. The structural method produces en face images of the colon surface showing the colonic crypts, the first such demonstration of crypt visualization in the mouse. Changes in the crypt pattern are correlated with adenoma and are one of the earliest morphological changes. The functional method uses a Doppler OCT algorithm and image processing to detect the colon microvasculature. This technique can be used for vessel counting and blood flow measurements. Angiogenesis occurs at the beginning of tumorigenesis, and the tumor-originated arterioles are incapable of regular vasodilation. This Doppler OCT technique could potentially detect tumors at the earliest stages by measuring the change in local blood flow velocity in response to vasodilatory stimuli.

The optical design for a dual modality endoscope based on piezo scanning fiber technology is presented including a novel technique to combine forward-viewing navigation and side viewing OCT. Potential applications include navigating body lumens such as the fallopian tube, biliary ducts and cardiovascular system. A custom cover plate provides a rotationally symmetric double reflection of the OCT beam to deviate and focus the OCT beam out the side of the endoscope for cross-sectional imaging of the tubal lumen. Considerations in the choice of the scanning fiber are explored and a new technique to increase the divergence angle of the scanning fiber to improve system performance is presented. Resolution and the necessary scanning density requirements to achieve Nyquist sampling of the full image are considered. The novel optical design lays the groundwork for a new approach integrating side-viewing OCT into multimodality endoscopes for small lumen imaging.

As lesões vasculares estão entre as anormalidades congênitas e neonatais mais comuns. Cerca de 60% estão localizadas na região da cabeça e pescoço. A identificação e a classificação adequadas de cada tipo de lesão, tem um impacto direto no diagnóstico e, no tratamento destes pacientes. A técnica de Tomografia por Coerência Óptica (Optical coherence tomography: OCT) obtém imagens em alta resolução, geradas em tempo real que permitem visualizar de forma não invasiva, estruturas celulares e extracelulares, com uma resolução espacial da ordem de 10&mu;m, que é 20 vezes maior que a de um ultrassom, aproximando-se do nível histológico convencional, razão pela qual é considerada biópsia óptica. Com o objetivo de fornecer imagens que possibilitassem avaliar as diferenças na arquitetura dos vasos em diferentes tipos de lesões localizadas, no tecido cutâneo e na mucosa, em regiões da cabeça e pescoço, foram tomadas imagens de lesões de 27 pacientes usando um sistema de OCT com Doppler (1325nm). Os resultados deste estudo clínico comprovaram a viabilidade da OCT permitindo distinguir entre a pele normal e a pele com lesão. Na má-formação capilar, os vasos sanguíneos tiveram diâmetro médio de 114\\&mu;m &plusmn; 92&mu;m e apresentaram uma profundidade média de 304 &mu;m &plusmn; 99 &mu;m. Os hemangiomas apresentaram vasos sanguíneos com diâmetro médio de 39&mu;m &plusmn; 19 &mu;m e profundidade média de 298 &mu;m &plusmn; 133 &mu;m. Nas lesões diagnosticadas pelo clínico como Hemangioma da mucosa labial, medimos diâmetro médio dos vasos de 45&mu;m &plusmn; 16 &mu;m com profundidade média de 520,5&mu;m &plusmn; 189,5&mu;m. Na má-formação linfática de lábio, os vasos sanguíneos apresentaram diâmetro médio de 157,5&mu;m &plusmn; 90&mu;m e, uma profundidade média 695&mu;m &plusmn; 136&mu;m. Na má-formação vascular de lábio, os vasos sanguíneos apresentaram diâmetro médio de 128&mu;m&plusmn;63&mu;m e, uma profundidade média 689 &mu;m &plusmn; 217&mu;m. Com estas informações obtidas das imagens de OCT indicando fluxo, foi possível avaliar diferenças peculiares da lesão de cada paciente, promovendo o diagnóstico diferencial das lesões vasculares da superfície tecidual da pele e mucosa oral. / Vascular lesions are among the most common congenital and neonatal abnormalities. About 60% are in the head and neck region. The proper identification and classification of each type of lesion has a direct impact on the diagnosis and consequently on the treatment of these patients. The Optical Coherence Tomography (OCT) technique obtains high resolution, real time generated images that allow non-invasive visualization of bio tissue structures with a spatial resolution of the order of 10&mu;m, which is 20 times greater than that of an ultrasound, approaching the conventional histological level. That is why it is considered an optical biopsy. In this thesis, images of lesions from 27 patients were obtained using a Doppler OCT system operating at 1325nm, with the purpose of providing images that allowed to evaluate the differences in the architecture of the vessels in different types of lesions located in the cutaneous and mucosa tissue in head and neck regions. The results of this clinical study proved the viability of OCT to distinguish between normal skin and lesioned skin. In vascular malformation, the blood vessels had an average diameter of 114 &mu;m &plusmn; 92 &mu;m and had a mean depth of 304,3 &mu;m &plusmn; 99 &mu;m. The skin hemangiomas had blood vessels with a mean diameter of 38,6 &mu;m &plusmn; 19 &mu;m and a mean depth of 297,8 &mu;m &plusmn; 132 &mu;m. In the lesions clinically diagnosed as oral mucosa hemangioma (lips), the mean vessel diameter was 45 &mu;m &plusmn; 16 &mu;m and a mean depth of 520,5 &mu;m &plusmn; 189,5 &mu;m. In lip lymphatic malformation, the blood vessels had a mean diameter of 157,5 &mu;m &plusmn; 90 &mu;m and a mean depth of 695 &mu;m &plusmn; 136 &mu;m. In lip vascular malformation, the blood vessels had a mean diameter of 128 &mu;m &plusmn; 63 &mu;m and a mean depth of 689 &mu;m &plusmn; 217 &mu;m. With this information obtained from the Doppler OCT images indicating flow, it was possible to evaluate peculiar differences of the lesion of each patient, promoting the differential diagnosis of vascular lesions of the tissue surface of the skin and oral mucosa.

A detecção de lesões cariosas nos estágios iniciais possibilita a escolha de tratamentos baseados na preservação da estrutura dental. Dessa forma, a utilização de exames capazes de diagnosticar precocemente essas lesões, como a Tomografia por Coerência Óptica (OCT Optical Coherence Tomography) é adequada. Assim, o objetivo do trabalho foi avaliar a capacidade da OCT em quantificar os estágios de desmineralização do esmalte durante o desenvolvimento de lesões simuladas de cárie, tendo como padrão de referência o teste de microdureza seccional. Foram utilizados 53 dentes terceiros molares hígidos, os quais tiveram as coroas seccionadas para obtenção de 210 amostras. Para avaliar as possíveis alterações sofridas por cada amostra, essas foram examinadas através da técnica de OCT no início do experimento e novamente examinadas após o término do período de ciclagem estabelecido para cada grupo, utilizando os coeficientes de atenuação óptica total e o cálculo de área em gráficos de intensidade de sinal de OCT, como parâmetros de análise. Posteriormente, as amostras foram submetidas a testes de microdureza seccional. A diferença entre os coeficientes de atenuação óptica obtidos antes e depois da ciclagem de pH apresentou elevado grau de correlação com os resultados de microdureza seccional. Por meio da análise das áreas provenientes de gráficos de intensidade de sinal de OCT e microdureza Knoop, ambos em função da profundidade, foi observada relação de linearidade entre os resultados e elevada correlação entre as técnicas avaliadas (&rho; = 0,99). De acordo com os resultados, a técnica de OCT foi capaz de detectar diferentes graus de desmineralização do esmalte dental humano em lesões simuladas de cárie. / The detection of carious lesions in early stages enables treatment choose based on dental structure preservation. This way, the utilization of exams capable of early diagnosis of these lesions, like OCT (Optical Coherence Tomography), is appropriate. Therefore, the objective of this work was to assess the capability of OCT in quantifying the enamel demineralization stages during the development of simulated caries lesions, having as reference standard the sectional microhardness test. There were used 53 sound third molars, which had their crowns sectioned to obtain 210 samples. To assess possible changes in each sample, these were examined by the OCT technique in the beginning of the experiment and again in the end of the cycling period established to each group, using the total optical attenuation coefficient and the area calculations using OCT signal intensity as analysis parameters. After that, the samples were submitted to sectional microhardness test. The difference between optical attenuation coefficients taken before and after the pH cycling, showed a high level of correlation with the microhardness results. Through areas analysis of OCT signal intensity and Knoop microhardness against depth, it was observed linearity relation between results and high correlation among assessed techniques (&rho;=0,99). According to the results, the OCT technique was capable of detecting different degrees of demineralization of the human enamel in carious simulated lesions.

Introdução: O tratamento do buraco macular idiopático ainda é acompanhado de incertezas em relação ao seu prognóstico. Ao longo dos últimos anos, têm sido utilizados o tempo de história, o tamanho e a acuidade visual pré-operatória dos buracos como critérios de orientação quanto ao resultado visual final. O aspecto final da parte mais externa da retina foveal tem merecido especial atenção em relatos recentes. Neste trabalho, avaliou-se, por meio da tomografia de coerência óptica, a integridade da camada de fotorreceptores, correlacionando o seu aspecto final com a acuidade visual obtida em casos de buraco macular idiopático, fechados cirurgicamente. Métodos: Pacientes operados com sucesso e com seguimento mínimo de 12 meses foram submetidos à avaliação oftalmológica completa incluindo a medida da acuidade visual final em escala logMar, biomicroscopia de mácula, oftalmoscopia indireta e angiofluoresceinografia. Colheram-se dados sobre idade, sexo, raça, tempo de história e tamanho do buraco além da acuidade visual pré-operatória. Para a classificação das lesões, utilizaram-se os critérios definidos por Gass. Imagens tomográficas da camada correspondente aos fotorreceptores da retina na região foveal foram criteriosamente obtidas através da tomografia de coerência óptica. Uma avaliação qualitativa desta camada foi realizada por examinador experiente, de forma mascarada, com os pacientes então classificados em três grupos (1, 2 e 3), em ordem crescente de integridade. Resultados: Foram incluídos no estudo 39 olhos de 37 pacientes, sendo eles 22 mulheres (59,5%) e 15 homens (40,5%). A idade média foi de 68,2 anos variando entre 51 e 83 anos. O tempo de seguimento pós-operatório médio foi de 38,5 meses. Entre todos os olhos estudados, 12 foram incluídos no grupo 1 (menor integridade); sete, no grupo 2 e vinte, no grupo 3. Na comparação entre os grupos 1 e 3, a acuidade visual final melhorou em ambos; porém, com maior intensidade no grupo 3 (p<0,001). O tamanho pré-operatório do buraco e o tempo de história da doença não impactaram significativamente o resultado visual final (p=0,223 e p=0,559, respectivamente). A acuidade visual pré-operatória média foi maior no grupo 3 que no grupo 1 (p=0,012). Conclusões: Os dados obtidos através deste estudo sugerem correlação entre uma maior integridade da camada dos fotorreceptores e um melhor resultado visual de longo prazo, em pacientes com buraco macular idiopático, operados com sucesso. Embora a visão tenha melhorado em todos os grupos, a melhora foi significativamente maior no grupo 3 que no grupo 1. Em relação ao tamanho pré-operatório da lesão e o tempo de história da doença, não se observou impacto significativo no resultado. Uma melhor acuidade visual inicial pré-operatória pode influenciar positivamente a acuidade visual final. / Purpose: To evaluate the integrity of the retina photoreceptor layer as determined by optical coherence tomography and its relationship with final visual outcome in successfully closed idiopathic macular holes. Methods: Successfully operated patients with a minimal follow-up of 12 months, underwent complete ophthalmic exam involving post-operative best corrected visual acuity using logMar scale, macula biomicroscopy and indirect ophthalmoscopy and fluorescein angiography. Complete epidemiologic data was collected as well as time duration, pre-op visual acuity, and size and Gass classification of the holes. Optical coherence tomography images of the layer corresponding to the transition between inner and outer segments of the photoreceptors were meticulously generated using commercially available Stratus OCT (OCT3). Qualitative analysis of this layer was carried out, in a masked fashion, by a certified and well experienced examiner. Based on increasing integrity showed in the images, patients were then distributed in 3 groups: 1, 2 and 3. Group 1 integrity from 1 to 33%, group 2 from 34 to 66%, and group 3 from 67 to 100%. Results: A total of 39 eyes of 37 patients were included in the study. Among all patients, 12 were included in group 1, 7 in group 3 and 20 in group 3. There were 22 female (59,5%) and 15 male (40,5%). Mean age was 68.2 years varying from 51 to 83 years of age. Mean post-op follow-up time was 38.5 months. When comparing groups 1 and 3, best corrected final visual acuity improved in both groups but dramatically in group 3 (better integrity) (p<0.001). Pre-operative size and time duration of the hole did not correlate with better visual acuity (p=0.223 and p=0.559 respectively). Mean pre-op visual acuity was better in group 3 than in group 1 (p=0.012). Conclusion: Data obtained in our study indicate that there is a strong correlation between better integrity of the photoreceptor layer, as determined by optical coherence tomography, and a more successful final, long term, visual acuity in patients with idiopathic macular hole successfully operated. Although final visual acuity has improved in all groups, there was statistical difference between groups 1 and 3. Pre-operative size and time duration of the hole did not have impact on final visual acuity. Better pre-op visual acuity may have an effect on final outcome.

A Tomografia por Coerência Óptica (OCT) baseia-se na propriedade de retroespalhamento dos meios para construir imagens tomográficas do interior das amostras. De maneira similar, a técnica LIDAR (Light Detection and Range) faz uso desta propriedade para determinar as características da atmosfera, em especial o coeficiente de extinção do sinal. Explorar esta similaridade permitiu aplicar métodos de inversão utilizados na técnica LIDAR às imagens OCT, permitindo construir imagens de coeficiente de extinção, resultado inédito até o momento. Este trabalho teve o objetivo de estudar, propor, desenvolver e implementar algoritmos de métodos de inversão do sinal OCT para determinação do coeficiente de extinção em função da profundidade. Foram utilizados três métodos de inversão, da inclinação, do ponto de contorno e da profundidade óptica, com implementação em ambiente LABView&reg; . Estudo dos erros associados aos métodos de inversão foi realizado e, amostras reais (homogêneas e estratificadas) foram utilizadas para análises em uma e duas dimensões. As imagens de coeficiente de extinção obtidas pelo método da profundidade óptica claramente foram capazes de diferenciar o ar da amostra. As imagens foram estudadas empregando PCA e análise de clusters que avaliou a robustez da técnica em determinar o valor do coeficiente de extinção da amostra. Além disso, o método da profundidade óptica proposto foi empregado para estudar a hipótese de que existe correlação entre o coeficiente de extinção do sinal e a desmineralização de esmalte dental durante o processo cariogênico. Com a aplicação desta metodologia foi possível observar a variação do coeficiente de extinção em função da profundidade e sua correlação com a variação da microdureza, além de mostrar que em camadas mais profundas o valor do coeficiente de extinção valor tende ao de um dente sadio, comportando-se da mesma maneira que a microdureza do dente. / Optical Coherence Tomography (OCT) is based on the media backscatering properties in order to obtain tomographic images. In a similar way, LIDAR (Light Detection and Range) technique uses these properties to determine atmospheric characteristics, specially the signal extinction coeficient. Exploring this similarity allowed the application of signal inversion methods to the OCT images, allowing to construct images based in the extinction coeficient, original result until now. The goal of this work was to study, propose, develop and implement algorithms based on OCT signal inversion methodologies with the aim of determine the extinction coeficient as a function of depth. Three inversion methods were used and implemented in LABView&reg; : slope, boundary point and optical depth. Associated errors were studied and real samples (homogeneous and stratified) were used for two and three dimension analysis. The extinction coeficient images obtained from the optical depth method were capable to diferentiate air from the sample. The images were studied applying PCA and cluster analysis that established the methodology strength in determining the sample´s extinction coefficient value. Moreover, the optical depth methodology was applied to study the hipothesis that there is some correlation between signal extinction coeficient and the enamel teeth demineralization during a cariogenic process. By applying this methodology, it was possible to observe the variation of the extinction coefficient as depth function and its correlation with microhardness variation, showing that in deeper layers its values tends to a healthy tooth values, behaving as the same way that the microhardness.

青光眼作為一種慢性進展性視神經病變，已經成為世界眼科病變中導致不可逆盲的首要原因。青光眼的早期診斷和治療對於降低疾病進展的風險至關重要。光學相干斷層掃描（OCT）可以提供在體視網膜橫斷面的視圖，從而實現了對視網膜神經纖維層（RNFL）改變的客觀測量，這些改變已經被證明了與青光眼引起的視神經損害相關，並已成為診斷青光眼的重要參考依據。 / 頻域OCT是最新一代的光學相干斷層掃描，它具有比時域OCT更快的掃描速度和更高的圖像解析度，因此，頻域OCT可以提供更可靠的RNFL厚度測量和RNFL缺損評估。本文的研究目的在於評估頻域OCT對RNFL厚度的重測再現性，以及探討影響RNFL厚度測量的因素，這些因素包括（1）影像平均法的應用，（2）RNFL分層錯誤，和（3）視網膜血管的影響。此外，由於RNFL攝影是一個評估青光眼RNFL缺損的臨床參考標準，我們還將其對RNFL缺損的測量與頻域OCT的RNFL厚度偏差圖所作出的測量進行了比較。 / 首先，為了評估頻域OCT對RNFL厚度測量的重測再現性，15名正常人和15名青光眼患者連續四周每週均接受一次OCT掃描。正常組和青光眼組的RNFL厚度再現性係數分別為4.77-12.65微米和4.53-16.66微米，由於組內相關性係數均大於0.773，說明頻域OCT所作出的RNFL厚度測量是具備可重複性的。 / 其次，通過分析54隻眼（25名正常志願者和29名青光眼患者）的RNFL厚度測量值，本文對圖像平均法的應用是否會影響RNFL厚度的測量這一問題進行了探討。分析中，每一隻眼均接受了3次OCT掃描，3次掃描的圖像分別使用2、8、和16張連續的圖像進行影像平均。結果顯示，除了青光眼組的鼻下象限RNFL厚度測量值之外（P=0.036），不同的圖像幀數並不會對兩組的總體和其它各象限的RNFL厚度測量值產生顯著的影響（P≥0.055）。雖然圖像平均法的應用對RNFL厚度測量的影響並不顯著，但是視網膜血管和RNFL分層錯誤對青光眼,尤其是對RNFL非常薄的晚期青光眼患者的RNFL厚度測量有影響。結論來自對60個正常人，66個輕至中度青光眼（MD≥-6 dB）患者和54個嚴重青光眼（MD<-6 dB）患者的共180張OCT圖像的分析。視網膜血管相對於平均RNFL厚度的比例均值在正常組，輕至中度青光眼組，和嚴重青光眼組分別為11.2±2.3，12.6±2.5，和16.6±3.9。在人為調整了RNFL界限以糾正RNFL分層錯誤的前後，總體RNFL厚度的差異範圍在正常組為-3.0-2.5微米，輕至中度青光眼組為-2.5-5.0微米，嚴重青光眼組為-11.0-9.5微米組。 / 最後，通過對41名青光眼患者的51隻眼的RNFL缺損面積，位置，和覆蓋角度進行測量，本文將頻域OCT作出的測量結果和共焦鐳射掃描檢眼鏡（CSLO）RNFL反射影像圖的測量結果進行了比較，結果顯示：OCT不但可以檢測到所有出現在CSLO的RNFL反射影像圖上的RNFL缺損，更重要的是，OCT還可以檢測出額外的並未在RNFL反射影像圖上出現的RNFL缺損。 / 總之，頻域OCT是一種可提供高再現性RNFL厚度測量的影像方法。對青光眼,尤其是晚期青光眼的RNFL厚度測量值的詮釋，應當考慮到視網膜血管和RNFL分層錯誤的影響。OCT具備對RNFL缺損進行多維度量化（包括厚度，面積，位置，和覆蓋角度）的能力，在青光眼RNFL改變的檢測和監測方面，相對于傳統的RNFL攝影，OCT無疑是更有效的選擇。 / Glaucoma, a chronic progressive optic neuropathy, is the leading cause of irreversible blindness in the world. An early diagnosis and treatment of glaucoma is vital to reduce the risk of disease progression. Providing a cross-sectional view of the retina in vivo, optical coherence tomography (OCT) can objectively measure the changes of retinal nerve fiber layer (RNFL), which has been shown to be of relevance and importance in detecting glaucomatous damage of the optic nerve. / The latest generation of OCT, the spectral-domain OCT, has a faster scan speed and a higher image resolution compared to the time-domain OCT. It is expected that the spectral-domain OCT would allow a more reliable measurement of the RNFL thickness and assessment of RNFL defects. The objectives of this research project were to examine the test-retest reproducibility of spectral-domain OCT RNFL measurement and investigate factors including (1) image averaging, (2) segmentation failure, and (3) contribution of retinal blood vessels that might affect the measurement of RNFL thickness. As RNFL photography is a reference standard to evaluate RNFL defects in glaucoma, we also evaluated whether RNFL defects measured in the spectral-domain OCT RNFL thickness map would be comparable to those detected in RNFL photographs. / To evaluate the test-retest reproducibility of RNFL measurements obtained by the spectral-domain OCT, 15 normal individuals and 15 glaucoma patients were followed and imaged weekly for 4 consecutively weeks. The reproducibility coefficients of RNFL thicknesses ranged between 4.53 and 16.66 μm for the normal group, and 4.77 and 12.65 μm for the glaucoma group. The intraclass correlation coefficients were all above 0.773, indicating RNFL measurement with spectral-domain OCT was reproducible. / We then investigated if multiple-image averaging would influence the measurement of RNFL thickness. A total of 54 eyes from 25 normal volunteers and 29 glaucoma patients with RNFL images captured and averaged with 2, 8, and 16 consecutive image frames were analyzed. For both groups, there were no significant differences in global or sectoral RNFL thicknesses among the image series averaged with different number of image frames (all with P≥0.055) except for the inferonasal sector in the glaucoma group (P=0.036). Although the impact of image averaging on RNFL measurement was insignificant, the presence of retinal blood vessels and segmentation errors were influential on the measurement, particularly in advanced glaucoma patients when the RNFL was thin. Analyzing a total of 180 eyes from 60 normal individuals, 66 mild to moderate (MD≥-6 dB) and 54 advanced (MD<-6 dB) glaucoma patients, the mean proportion of retinal blood vessels relative to the average RNFL thickness was 11.2±2.3%, 12.6±2.5% and 16.6±3.9%, respectively. After correcting the segmentation errors by manually refining the RNFL boundaries, the differences in average RNFL thickness ranged from -3.0 to 2.5 m in the normal, -2.5 to 5.0 m in the mild to moderate glaucoma and -11.0 to 9.5 m in the advanced glaucoma groups. / Finally, we compared the area, the angular location, and the angular width of RNFL defects from 51 eyes of 41 glaucoma patients measured with the spectral-domain OCT and RNFL reflectance images obtained by a confocal scanning laser ophthalmoscope (CSLO). OCT was able to detect areas of RNFL abnormalities in all eyes with RNFL defects which were evident in the CSLO RNFL reflectance images. More important, OCT could identify additional RNFL thinning not apparent in RNFL reflectance images. / In summary, spectral-domain OCT could offer an effective approach in measuring RNFL with high reproducibility. Interpretation of RNFL measurement should take the contribution of the retinal blood vessels and segmentation errors into consideration, particularly in advanced glaucoma when the RNFL is thin. With the ability to quantify multiple dimensions of RNFL defects (thickness, area, angular location, and angular width), OCT could provide a useful alternative to detect and monitor RNFL changes in glaucoma. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Ye, Cong. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2012. / Includes bibliographical references (leaves 117-130). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese. / ABSTRACT --- p.i / 摘要 (ABSTRACT IN CHINESE) --- p.v / DEDICATION --- p.viii / ACKNOWLEDGEMENT --- p.ix / TABLE OF CONTENTS --- p.x / PUBLICATIONS --- p.xiv / ABBREVIATIONS --- p.xvi / Chapter CHAPTER 1: --- INTRODUCTION --- p.1 / Chapter 1.1 --- Glaucoma --- p.2 / Definition of Glaucoma --- p.2 / Epidemiology of Glaucoma --- p.3 / Pathogenesis of Glaucoma --- p.4 / Diagnosis of Glaucoma --- p.7 / Chapter 1.2 --- Retinal Nerve Fiber Layer --- p.13 / Anatomy of Retinal Nerve Fiber Layer --- p.13 / Visualization of Retinal Nerve Fiber Layer --- p.14 / Retinal Nerve Fiber Layer Defect in Glaucoma --- p.16 / Significance of Detecting Retinal Nerve Fiber Layer Defect in Glaucoma --- p.18 / Chapter 1.3 --- Optical Coherence Tomography --- p.20 / Principle of Optical Coherence Tomography --- p.20 / Retinal Nerve Fiber Layer Imaging with OCT --- p.21 / Optic Nerve Head Imaging with OCT --- p.27 / Advantages and Disadvantages of Optical Coherence Tomography --- p.29 / Chapter 1.4 --- Research Objectives --- p.30 / Chapter CHAPTER 2: --- GENERAL MATERIALS AND METHODS --- p.32 / Chapter 2.1 --- Subject Enrollments --- p.33 / Chapter 2.2 --- Clinical Ophthalmic Examination --- p.34 / Chapter 2.3 --- Visual Field Examination --- p.35 / Definition of Normal and Glaucoma Groups --- p.35 / Chapter 2.4 --- Optical Coherence Tomography Imaging --- p.37 / Cirrus HD-OCT Imaging --- p.37 / Spectralis OCT Imaging --- p.37 / Chapter 2.5 --- Statistical Analysis --- p.39 / Chapter CHAPTER 3: --- RETINAL NERVE FIBER LAYER IMAGING WITH SPECTRAL-DOMAIN OPTICAL COHERENCE TOMOGRAPHY --- p.40 / Chapter 3.1 --- Reproducibility and Agreement of Retinal Nerve Fiber Layer Measurement --- p.41 / Introduction and Study Objectives --- p.41 / Methods --- p.42 / Results --- p.45 / Discussion --- p.47 / Tables and Figures --- p.51 / Chapter 3.2 --- Effect of Multiple B-scans Averaging on Retinal Nerve Fiber Layer Measurement --- p.58 / Introduction and Study Objectives --- p.58 / Methods --- p.59 / Results --- p.61 / Discussion --- p.62 / Tables and Figures --- p.67 / Chapter 3.3 --- Impact of Blood Vessels and Segmentation Failure on Retinal Nerve Fiber Layer Measurement --- p.73 / Introduction and Study Objectives --- p.73 / Methods --- p.75 / Results --- p.78 / Discussion --- p.80 / Tables and Figures --- p.84 / Chapter 3.4 --- Agreement of Localized Retinal Nerve Fiber Layer Defect Assessment with Confocal Scanning Laser Ophthalmoscopy --- p.95 / Introduction and Study Objectives --- p.95 / Methods --- p.97 / Results --- p.101 / Discussion --- p.103 / Tables and Figures --- p.108 / Chapter CHAPTER 4: --- GENERAL CONCLUSIONS --- p.115 / REFERENCES --- p.117

Cette thèse porte sur la segmentation et la caractérisation des artères coronaires et des endoprothèses (stent) en imagerie de Tomographie par Cohérence Optique (OCT). L’OCT est une imagerie de très haute résolution qui permet d’apprécier des structures fines comme la couche intimale de la paroi vasculaire et les mailles du stent (struts). L’objectif de cette thèse est de proposer des outils logiciels autorisant l’analyse automatique d’un examen avec un temps d’exécution compatible avec une utilisation peropératoire. Ces travaux font suite à la thèse de Dubuisson en OCT, qui avait proposé un premier formalisme pour la segmentation de la lumière et la détection des struts pour les stents métalliques. Nous avons revisité la chaine de traitement pour ces deux problèmes et proposé une méthode préliminaire de détection de stents en polymère biorésorbable. Une modélisation surfacique du stent a permis d’estimer une série d’indices cliniques à partir des diamètres, surfaces et volumes mesurés sur chaque coupe ou sur l’ensemble de l’examen. L’apposition du stent par rapport à la paroi est également mesurée et visualisée en 3D avec une échelle de couleurs intuitive. La lumière artérielle est délimitée à l’aide d’un algorithme de recherche de plus court chemin de type Fast Marching. Son originalité est d’exploiter l’image sous la forme hélicoïdale native de l’acquisition. Pour la détection du stent métallique, les maxima locaux de l’image suivis d’une zone d’ombre ont été détectés et caractérisés par un vecteur d’attributs calculés dans leur voisinage (valeur relative du maximum, pente en niveau de gris, symétrie...). Les pics correspondant à des struts ont été discriminés du speckle environnant par une étape de régression logistique avec un apprentissage à partir d’une vérité terrain construite par un expert. Une probabilité d’appartenance des pics aux struts est construite à partir de la combinaison des attributs obtenue. L’originalité de la méthode réside en la fusion des probabilités des éléments proches avant d’appliquer un critère de décision lui aussi déterminé à partir de la vérité terrain. La méthode a été évaluée sur une base de données de 14 examens complets, à la fois au niveau des pixels et des struts détectés. Nous avons également validé de façon exhaustive une méthode de recalage non rigide d’images OCT exploitant des amers appariés par un expert sur les examens source et cible. L’objectif de ce recalage est de pouvoir comparer les examens coupe à coupe et les indices calculés aux mêmes positions à des temps d’acquisition différents. La fiabilité du modèle de déformation a été évaluée sur un corpus de quarante-quatre paires d’examens OCT à partir d’une technique de validation croisée par Leave-One-Out. / This thesis deals with the segmentation and characterization of coronary arteries and stents in Optical Coherence Tomography (OCT) imaging. OCT is a very high resolution imaging that can appreciate fine structures such as the intimal layer of the vascular wall and stitches (struts). The objective of this thesis is to propose software tools allowing the automatic analysis of an examination with a runtime compatible with an intraoperative use. This work follows Dubuisson's thesis in OCT, which proposed a first formalism for light segmentation and strut detection for metal stents. We revisited the treatment chain for these two problems and proposed a preliminary method for detecting bioabsorbable polymer stents. Surface modeling of the stent made it possible to estimate a series of clinical indices from the diameters, surfaces and volumes measured on each section or on the entire examination. Applying the stent to the wall is also measured and visualized in 3D with an intuitive color scale. The arterial lumen is delineated using a Fast Marching short path search algorithm. Its originality is to exploit the image in the native helical form of the acquisition. For the detection of the metallic stent, the local maxima of the image followed by a shadow zone have been detected and characterized by a vector of attributes calculated in their neighborhood (relative value of the maximum, slope in gray level, symmetry ...). Peaks corresponding to struts were discriminated from the surrounding speckle by a logistic regression step with learning from a field truth constructed by an expert. A probability of belonging to the peaks to struts is constructed from the combination of attributes obtained. The originality of the method lies in the fusion of the probabilities of the close elements before applying a decision criterion also determined from the ground truth. The method was evaluated on a database of 14 complete examinations, both at the level of pixels and struts detected. We have also extensively validated a method of non-rigid registration of OCT images using bitters matched by an expert on the source and target exams. The objective of this registration is to be able to compare cut-to-cut examinations and indices calculated at the same positions at different acquisition times. The reliability of the strain model was evaluated on a corpus of forty-four pairs of OCT exams from a Leave-One-Out cross validation technique.