The changes in the human crystalline lens shape and its internal structure during accommodation and with aging are a fundamental component of the dynamic mechanism of accommodation and presbyopia, the loss of near vision with age. A better understanding of the crystalline lens changes during accommodation will help in developing new treatments to correct for presbyopia. The goal of this dissertation is to design and develop an imaging system to study the dynamic changes in lens shape during accommodative response. An imaging system based on spectral domain optical coherence tomography (SD-OCT) was developed with long axial range, high axial and lateral resolution and high speed for in vivo imaging the anterior segment along its entire length at video-rate. A slit-lamp mounted optical delivery scanning device for the extended depth SD-OCT system was developed. The delivery system was combined with a custom made unit that provides accommodation and disaccommodation step stimuli. A method to correct for the distortions of the OCT images was also developed that provides corrected two dimensional biometric data at different accommodative states.

The main objective of this thesis is to investigate the intrinsic optical signals (IOSs) with an ultra-high resolution optical coherence tomography system (UHROCT). In order to study the retinal IOSs evoked by visible light, an UHROCT and an Electroretinogram (ERG) system was combined. An animal model (chicken retina) based on its retinal avascularity and cone dominance, was selected. Imaging the chicken retina with OCT resulted in high contrast, high resolution (~3μm axial and ~5 μm lateral resolution) 2D and 3D volumetric tomograms, in which all retina layers were clearly distinguishable. Using the combined UHROCT and ERG system to image IOSs from the chicken retina exposed to visible light (7ms green flash) resulted in highly reproducible IOS recordings from all retinal layers for the first time. All inner retinal layers showed an initial increase and subsequently a decrease in the intensity of the backreflected imaging light within the first 100 ms after the onset of the stimulus. Outer segments of the photoreceptors also showed a decrease in the backreflected imaging light within 100 ms after the onset of the flash. All retinal layers showed a strong decrease in the backreflected light within 150 to 175 ms after the onset of the flash. Imaging the pupil dynamics of the chicken with a modified combined UHROCT and ERG system showed that part of the strong negative IOSs observed in all retinal layers resulted from the vignetting of the imaging beam due to the light induced pupil constriction. Thorough analysis of the pupil dynamics acquired with UHROCT showed a time dependent effect of the anesthesia agent on pupil constriction. Further experiments to investigate an anesthesia effects on retinal function showed significant changes in ERG components. Statistical analysis showed that Isoflurane anesthesia severely affects the inner retinal response. In conclusion, it was hypothesized that the fast IOSs within ~50-100 ms after the onset of the visual stimulus originated from the neuronal tissue in the retina and are related to tissue optical property changes as a result of the electrical signal propagation in the light activated retina. Longer term decreases in backreflected light are likely due to pupil changes.

Thesis (Ph. D.)--Ohio State University, 2008. / Title from first page of PDF file. Includes bibliographical references (p. 219-230).

Thesis (Ph. D.)--Duke University, 2008. / Includes bibliographical references.

Optical Coherence Tomography (OCT) is a catheter‐based imaging method that employs near‐infrared light to produce high‐resolution cross sectional intravascular images. Α new segmentation technique is implemented for automatic lumen area extraction and stent strut detection in intravascular OCT images for the purpose of quantitative analysis of neointimal hyperplasia (NIH). Also a graphical user interface (GUI) is designed based on the employed algorithm. Methods: Four clinical dataset of frequency‐domain OCT scans of the human femoral artery were analysed. First, a segmentation method based on Fuzzy C Means (FCM) clustering and Wavelet Transform (WT) was applied towards inner luminal contour extraction. Subsequently, stent strut positions were detected by utilizing metrics derived from the local maxima of the wavelet transform into the FCM membership function. Results: The inner lumen contour and the position of stent strut were extracted with very high accuracy. Compared with manual segmentation by an expert physician, the automatic segmentation had an average overlap value of 0.917 ± 0.065 for all OCT images included in the study. Also the proposed method and all automatic segmentation algorithms utilised in this thesis such as k‐means, FCM, MRF – ICM and MRF – Metropolis were compared by means of mean distance difference in mm and processing time in sec with the physician’s manual assessments.. The strut detection procedure successfully identified 9.57 ± 0.5 struts for each OCT image. Conclusions: A new fast and robust automatic segmentation technique combining FCM and WT for lumen border extraction and strut detection in intravascular OCT images was designed and implemented. The proposed algorithm may be employed for automated quantitative morphological analysis of in‐stent neointimal hyperplasia. / Η τομογραφία οπτικής συνοχής (OCT) είναι μια απεικονιστική μέθοδος βασισμένη στον καθετηριασμό και χρησιμοποίει υπέρυθρο φως για να παράγει ένδo‐αγγειακές εικόνες – εγκάρσιας τομής με υψηλή ανάλυση. Σε αυτήν την διατριβή, μια νέα τεχνική τμηματοποίησης υλοποιήθηκε για την αυτόματη εξαγωγή της περιοχής του αυλού καθώς και για την ανίχνευση των «strut» στις ένδo‐ αγγειακές OCT εικόνες με σκοπό την ποσοτική ανάλυση της υπερπλασίας. Επίσης ένα εύκολο στην χρήση περιβάλλον γραφικών για καθημερινή κλινική χρήση σχεδιάστηκε με τον υλοποιημένο αλγόριθμο. Μέθοδοι: Τέσσερις OCT κλινικές εξετάσεις πεδίου‐συχνότητας της ανθρώπινης μηριαίας αρτηρίας αναλύθηκαν. H προτεινόμενη μέθοδος τμηματοποίησης για την εξαγωγή του εσωτερικού περιγράμματος αυλού, είναι βασισμένη στον Fuzzy CMeans (FCM) clustering και τον μετασχηματισμό κυματιδίου. Στη συνέχεια, οι θέσεις των «strut» εντοπίστηκαν χρησιμοποιώντας διάφορες τοπικές παραμέτρους που προέρχονται από τα τοπικά μέγιστα του μετασχηματισμού κυματιδίων εντός της FCM συνάρτησης. Αποτελέσματα: Το εσωτερικό περίγραμμα αυλού και η θέση των «strut» εξήχθηκαν με πολύ μεγάλη ακρίβεια. Σε σύγκριση με την ποσοτική αξιολόγηση από έναν ειδικό ιατρό, η αυτόματη τμηματοποίηση είχε μέση τιμή επικάλυψης 0,917±0,065 για όλες τις OCT εικόνες που περιλαμβάνονται στη μελέτη. Επίσης, έγινε σύγκριση με τους k‐means, FCM, ICM και Μetropolis αυτόματους αλγόριθμους τμηματοποίησης για εξαγωγή του εσωτερικού περιγράμματος αυλού και επέδειξε υψηλής ακρίβειας αποτελέσματα στον μικρότερο δυνατό χρόνο επεξεργασίας. Η διαδικασία ανίχνευσης «strut» προσδιόρισε επιτυχώς 9.57± 0,5 «strut» για κάθε OCT εικόνα. Συμπεράσματα: Μια νέα αποτελεσματική και γρήγορη αυτόματη τεχνική τμηματοποίησης που συνδυάζει FCM και WT για την εξαγωγή των ορίων του αυλού και την ανίχνευση των «strut» στις ένδο‐αγγειακές εικόνες OCT σχεδιάστηκε και υλοποιήθηκε. Ο προτεινόμενος αλγόριθμος μπορεί να χρησιμοποιηθεί για την αυτοματοποιημένη ποσοτική μορφολογική ανάλυση της υπερπλασίας.

Basic science and early clinical trial evidence suggest the safe diuretic drug amiloride, may exert a neuroprotective effect in multiple sclerosis (MS) through blockade of the acid sensing ion channel. Neuroprotective treatments are a key unmet need in multiple sclerosis. Optic neuritis (ON) is a discrete CNS inflammatory event leading to neuro-axonal injury in the optic nerve and retina. The optic nerve is part of the visual system, one of the most functionally and structurally eloquent systems in the central nervous system, which affords a number of unique modalities to assess neurodegeneration and neuroprotection. The visual system can be classified into two parts, the anterior and posterior visual systems, which are defined by the lateral geniculate nucleus, where the two components synapse. The extent of neurodegeneration following ON in the anterior visual system can be imaged in vivo through scanning laser polarimetry (GDx) and optical coherence tomography (OCT). The posterior visual system can be imaged by quantitative and functional magnetic resonance imaging (MRI) of the brain, giving insights into white matter structural integrity and cortical plasticity over time. Combining these modalities in a longitudinal study, allows assessment of the impact of neurodegeneration in the anterior visual system on neurodegeneration downstream in the posterior visual system and on changes in functional connectivity over time in the visual cortex. Furthermore, in the clinical trial setting the neuroprotective effect of any intervention both on direct anterior neurodegeneration and downstream processes can be assessed. The functional relevance of changes in all of these biomarkers can be tested through a number of visual measures, including low contrast visual acuity. In MS, the contribution of transsynaptic neurodegeneration to the global neuronal loss experienced by patients is an area of incomplete understanding. In addition, the role of the visual cortex, through neuroplasticity, in aiding visual recovery from optic neuritis, is unclear. To address these issues, this thesis reports the results of the first clinical trial of amiloride in ON, and shows that despite the pre- and early clinical evidence of neuroprotection of amiloride, no neuroprotective benefit was found. It goes on to explore reasons for this lack of effect including the finding of early retinal neurodegeneration in ON, and the need for early recruitment windows in the future. From there, it makes a detailed assessment of the longitudinal changes in retinal OCT for 12 months following ON, including a novel finding of the temporal evolution of inner nuclear layer swelling, previously reported only cross-sectionally. Next, for the first time macular retinal neurodegeneration is shown to influence diffusion tensor MRI derived measures of white matter integrity in the optic radiations, indicating transsynaptic neurodegeneration. Finally, longitudinal changes in resting state functional connectivity following ON are found in the visual system for the first time. The interaction between this cortical functional, retinal neurodegeneration and visual recovery is probed.

The utilisation of near-infrared Raman spectroscopy for the discrimination of cancers and pre-cancers from normal tissue in the acro-digestive tract has been evaluated. A commercially available Raman microspectrometer has been modified to provide optimum throughput, sensitivity and fluorescence suppression for epithelial tissue measurements. Laser excitation at 830nm was demonstrated to be optimum. High quality (SN ratio 15-20) NIR-Raman spectra have been acquired from oesophageal and laryngeal tissues in time scales under 30 seconds. Pathological groupings covering the full range of normal and neoplastic tissues in the organs of interest have been studied. Both fresh (snap frozen) and formalin fixed tissue samples were investigated, firstly to indicate whether tissue-types can be distinguished in vivo and secondly to demonstrate the use of Raman spectroscopy as a tool for classification in the pathology lab. Results using multivariate statistical techniques to distinguish between spectra from specimens exhibiting different tissue pathologies have been extremely promising. Cross-validation of the spectral predictive models has shown that three groups of larynx tissue can be separated with sensitivities and specificities of between 86 and 90% and 87 and 95% respectively. Oesophageal prediction models have demonstrated sensitivities and specificities of 84 to 97% and 93 to 98% respectively for a three-group consensus model and 73 to 100% and 92 to 100% for an eight-group consensus model. Epithelial tissues including stomach, tonsil, endometrium, bladder and prostate have been studied to identify further tissues where Raman spectroscopy may be employed for detection of disease. Spectra were similar to those obtained from oesophagus and larynx, although sufficiently different for distinct discriminant models to be required. This work has demonstrated the generic nature of Raman spectroscopy for the detection and classification of cancers and pre-cancerous lesions in many tissues. The evidence provided by this study indicates that utilisation of Raman spectroscopy for non-invasive detection and classification of disease is a distinct possibility. Potential difficulties in the transferability from in vitro to in vivo have been evaluated and no significant barriers have been observed. However, further in vivo probe development and optimisation will be required before 'optical biopsy' with Raman spectroscopy can become a reality.

Este estudo teve como objetivo avaliar a adaptação marginal em restaurações classe II em dentina e esmalte dental utilizando um sistema adesivo universal de acordo com três técnicas diferentes de aplicação: Autocondicionante, condicionamento seletivo e condicionamento total, através do sistema de tomografia por coerência óptica (OCT), antes e após ao envelhecimento por termociclagem (TC). Preparos classe II foram confeccionados nas paredes mesial e distal, em 30 molares hígidos humanos, com término da cavidade em esmalte e em dentina. Todos os espécimenes foram restaurados (adesivo Single Bond Universal e resina composta Filtek Z350 XT) nas três técnicas de aplicação. Os dentes foram distribuídos aleatoriamente em três grupos (n=10), sendo um para cada técnica de aplicação adesiva: Grupo I: autocondicionante, Grupo II: condicionamento seletivo e Grupo III: condicionamento total; em seguida os grupos foram avaliados antes e depois a termociclagem pelo sistema de tomografia por coerência ótica. De posse dos corpos de prova devidamente restaurados, partimos para os procedimentos de termociclagem (1000 ciclos de 1 minuto com intervalo de 30 segundos) e a avaliação pelo sistema de Tomografia por Coerência Óptica. Em seguida, as amostras foram examinadas por meio de imagens geradas pelo OCT e os dados foram submetidos ao teste estatístico não-paramétricos de Kruskal-Wallis e Dunn (p<0.05). Foi observada diferença estatisticamente significante da adaptação marginal entre os grupos com término em esmalte (p= 0.0073); para os grupos com término em dentina, não foi observada diferença estatisticamente significante na adaptação marginal (p=0.2063). Conclui-se que o OCT foi, então, capaz de diagnosticar a microinfiltração marginal nas restaurações em cavidades classe II. Existe deterioração das margens e alteração de padrão de infiltração marginal com as diferentes técnicas adesivas dos preparos classe II restauradas com resina em esmalte. Atribui-se à termociclagem a falha de vedamento marginal observada nos espécimes após em esmalte. / This study aimed to evaluate the marginal adaptation of Class II restorations in enamel and dentin using a universal adhesive according to three different application techniques: self-etching, selective packaging and selective conditioning through the system optical coherence tomography (OCT) before and after aging thermocycling (TC). Class II preparations were made in the mesial and distal surfaces in 30 healthy human molars, with completion in enamel and dentin. All samples were restored ( composite Filtek Z350 XT resin Universal Single Bond) in three application techniques. The teeth were randomized into three groups (n = 10), one for each adhesive application technique: Group I: etching, Group II: engraved selective and Group III: Engraving the total; then the groups were assessed before and after thermal cycling through the system optical coherence tomography (OCT). With properly restored specimens, we went to the procedures of thermal cycles (1000 cycles of one minute at intervals of 30 seconds) and evaluation system through optical coherence tomography. Then the samples were examined by OCT-generated images and data were subjected to a non-parametric statistical test Kruskal-Wallis and Dunn (p <0.05). Was observed found statistically significant difference in marginal adaptation between the groups ended in tooth enamel (p = 0.0073); for groups with completion in dental dentin, there was no statistically significant difference in marginal adaptation (p = 0.2063). It is concluded that the OCT was then able to diagnose the microleakage in restorations in class II cavities. There are margins deterioration and changes in microleakage standard with different adhesive techniques of class II preparations restored with resin enamel. Assigns to the thermal cycling the marginal sealing failure observed in specimens in enamel.

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.

Orientador: Vital Paulino Costa / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-23T16:05:44Z (GMT). No. of bitstreams: 1 Silva_FabricioReis_M.pdf: 2953091 bytes, checksum: 5a1660d55c27fcad4aeb1be8cceeb33f (MD5) Previous issue date: 2013 / Resumo: Objetivo: Avaliar a sensibilidade e especificidade dos classificadores de aprendizagem de máquina no diagnóstico de glaucoma usando dados do Spectral Domain OCT (SD-OCT) e perimetria automatizada acromática (PAA). Desenho do estudo: Estudo transversal observacional. Método: Sessenta e dois pacientes com glaucoma e 48 indivíduos normais foram incluídos. Todos os pacientes foram submetidos a exame oftalmológico completo, PAA (24-2 SITA; Humphrey Field Analyzer II, Carl Zeiss Meditec, Inc., Dublin, CA) e exame de imagem da camada de fibras nervosas utilizando SD-OCT (Cirrus HD-OCT; Carl Zeiss Meditec Inc., Dublin, California). Curvas ROC (Receiver Operating Characteristic) foram obtidas para todos os parâmetros do SD-OCT e índices globais da perimetria acromática (MD, PSD, GHT). Subsequentemente, os seguintes classificadores de aprendizagem de máquina (CAMs) foram testados usando parâmetros do OCT e PAA: Bagging (BAG), Naive-Bayes (NB), Multilayer Perceptron (MLP), Radial Basis Function (RBF), Random Forest (RAN), Ensemble Selection (ENS), Classification Tree (CTREE), Ada Boost M1(ADA), Support Vector Machine Linear (SVML) e Support Vector Machine Gaussian (SVMG). Áreas abaixo da curva ROC (aROC) obtidas com os parâmetros isolados do campo visual (CV) e OCT foram comparados com os CAMs usando dados combinados do OCT e CV. Resultados: A média de idade foi de 57,0 ± 9,2 anos para os indivíduos normais e 59,9 ± 9,0 anos para os pacientes glaucomatosos (p=0,103). As médias dos valores do Mean Deviation (MD) foram -4,1 ± 2,4 dB para glaucomatosos e -1,5 ± 1,6 dB para indivíduos normais (p<0,001). Os parâmetros do SD-OCT com maiores aROCs foram: quadrante inferior (aROC=0,813) e espessura média (aROC=0,807). O melhor parâmetro do CV foi PSD (aROC=0,915). Combinando os dados do OCT e do CV, aROCs dos CAMs variaram entre 0,777 (CTREE) e 0,946 (RAN). A maior aROC dos CAMs OCT+CV, obtida com RAN (0,946) foi significativamente maior que o melhor parâmetro do OCT (p=0,003), mas não houve diferença estatisticamente significante com o melhor parâmetro do CV (p=0,37). Conclusão: Os classificadores de aprendizagem de máquina treinados com dados do OCT e CV podem discriminar entre olhos normais e glaucomatosos com sucesso. A combinação das medidas do OCT e CV melhoraram a acurácia diagnóstica comparados aos parâmetros do OCT / Abstract: Purpose: To evaluate the sensitivity and specificity of machine learning classifiers (MLCs) for glaucoma diagnosis using Spectral Domain OCT (SD-OCT) and standard automated perimetry (SAP). Design: Observational cross-sectional study. Population: Sixty two glaucoma patients and 48 healthy individuals were included. Methods: All patients underwent a complete ophthalmologic examination, SAP and retinal nerve fiber layer (RNFL) imaging with SD-OCT (Cirrus HD-OCT; Carl Zeiss Meditec Inc., Dublin, California). Receiver operating characteristic (ROC) curves were obtained for all SD-OCT parameters and some SAP parameters (MD, PSD, GHT). Subsequently, the following MLCs were tested using parameters from SD-OCT and SAP: Bagging (BAG), Naive-Bayes (NB), Multilayer Perceptron (MLP), Radial Basis Function (RBF), Random Forest (RAN), Ensemble Selection (ENS), Classification Tree (CTREE), Ada Boost M1 (ADA), Support Vector Machine Linear (SVML) and Support Vector Machine Gaussian (SVMG). Areas under the ROC (aROC) obtained with SAP and OCT parameters were compared with those obtained with MLCs using combined OCT+SAP data. Results: The mean age was 57.0 ± 9.2 years for healthy individuals and 59.9 ± 9.0 years for glaucoma patients (p=0.103). Mean Deviation (MD) values were -4.1 ± 2.4 dB for glaucoma patients and -1.5 ± 1.6 dB for healthy individuals (p<0.001). SD-OCT parameters with the greater aROCs were inferior quadrant (0.813) and average thickness (0.807). The best SAP parameter was PSD (aROC=0.915). Combining OCT and SAP data, MLCs'aROCs varied from 0.777(CTREE) to 0.946 (RAN). The best combined OCT+SAP aROC, obtained with RAN (0.946), was significantly larger than the best single OCT parameter (p=0.003), but was not significantly different from the aROC obtained with the best single SAP parameter (p=0.37). Conclusion: Machine learning classifiers trained with OCT and SAP data can successfully discriminate between healthy and glaucomatous eyes. The combination of OCT and SAP measurements improved the diagnostic accuracy compared with OCT data alone / Mestrado / Oftalmologia / Mestre em Ciências Médicas