Οι εμποτισμένες με φάρμακα μεταλλικές ενδοπροθέσεις (DES) έχει αποδειχθεί ότι ελαχιστοποιούν την υπερπλασία του ενδοθηλίου των στεφανιαίων αγγείων. Η υπερπλαστική αντίδραση του ουροθηλίου είναι το πιο συχνή επιπλοκή της χρήσης των μεταλλικών ενδοπροθέσεων στον ουρητήρα. Στην παρούσα μελέτη αξιολογήσαμε τις εμποτισμένες με zotarolimus μεταλλικές ενδοπροθέσεις (ZES- Endeavor Resolute, Medtronics Inc, USA) στον ουρητήρα χοίρων και κουνελιών. Μέθοδος: Μία ZES and μία συνήθης μεταλλική ενδοπρόθεση (BMS) τοποθετήθηκαν στον κάθε ουρητήρα 10 χοίρων και 6 κουνελιών. Η τοποθετήση έγινε κυστεοσκοπικά. Αξονική τομογραφία (CT) έγινε για την αξιολόγηση των ουρητήρων του χοίρου και ενδοφλέβιος πυελογραφία (IVP) έγινε για τον ίδιο σκοπό στα κουνέλια. Το πρόγραμμα παρακολούθησης περιλάμβανε CT ή IVP κάθε εβδομάδα για τις επόμενες 4 εβδομάδες για τους χοίρους και 8 εβδομάδες για τα κουνέλια. Σπινθηρογραφήματα νεφρών πριν την τοποθέτηση των ενδοπροθέσεων και κατά την 3 εβδομάδα παρακολούθησης έλαβε χώρα σε όλα τα ζώα. Οπτική τομογραφία συνοχής (OCT) χρησιμοποιήθηκε για την εκτίμηση της κατάστασης του αυλού και τοιχώματος των ουρητήρων που έφεραν τις ενδοπροθέσεις. Ιστοπαθολογική εξέταση των ουρητήρων με τις ενδοπρόθεσεις έγινε με τα παρασκευάσματα να έχουν στερεοποιηθεί σε glycol-methacrylate ρητίνη. Αποτελέσματα: Υπερπλαστική αντίδραση διαπιστώθηκε και στους δύο τύπους ενδοπροθέσεων. Οι BMS ενδοπροθέσεις αποφράχτηκαν πλήρως σε 7 ουρητήρες χοίρων ενώ οι ουρητήρες των ιδίων ζώων που έφεραν ZES ενδοπρόθεση έφεραν υπερπλαστική αντίδραση αλλά δεν κατέληγαν σε απόφραξη. Δύο ουρητήρες κουνελιών με BMS ενδοπροθέσεις αποφράχτηκαν τελείως ενώ όλες οι ZES ενδοπροθέσεις δε συσχετίστηκαν με απόφραξη του ουρητήρα. Διαπιστώθηκε έκπτωση της λειτουργίας 7 νεφρών χοίρων και 2 κουνελιών που είχαν ουρητήρες με αποφραγμένες ενδοπροθέσεις. Η OCT έδειξε αυξημένη υπερπλαστική αντίδραση σε ουρητήρες που έφεραν BMS ενδοπρόθεση σε σχέση με ZES. Παρόλα αυτά, η ιστοπαθολογική εξέταση έδειξε υπερπλαστική αντίδραση παρούσα σε όλες τις ενδοπροθέσεις αλλά σημαντικά περισσότερη υπερπλαστική αντίδραση στις BMS ενδοπροθέσεις. Συμπέρασμα: Οι ZES ενδοπροθέσεις στους ουρητήρες χοίρων και κουνελιών δε συσχετίστηκαν με υπερπλαστική αντίδραση που οδηγούσε σε απόφραξη της ενδοπρόθεσης. Αυτές οι ενδοπροθέσεις συσχετίστηκαν με σημαντικά μικρότερη υπερπλαστική αντίδραση συγκριτικά με τις BMS ενδοπροθέσεις ενώ η φλεγμονώδης αντίδραση ήταν παρόμοια και στους δύο τύπους ενδοπροθέσεων. / Drug eluting stents (DES) proved to minimize neointimal hyperplasia in coronary vessels. Hyperplastic reaction is the most common unwelcome event related to the use of metal mesh stents in the ureter. We evaluated the effect of zotarolimus eluting stent (ZES- Endeavor Resolute, Medtronics Inc, USA) in porcine and rabbit ureter. Methods: A ZES and a bare metal stent (BMS) were inserted in each ureter of 10 pigs and 6 rabbits. The insertion was performed by retrograde approach. Computerized tomography (CT) was used for the evaluation of porcine ureters while intraoperative intravenous pyelography (IVP) for rabbit ureters. The follow-up included CT or IVP every week for the following 4 weeks for pigs and 8 weeks for rabbits. Renal scintigraphies were performed prior to stent insertion and during the 3rd week in all animals. Optical coherence tomography (OCT) has been used for the evaluation of the luminal and intraluminal condition of the stented ureters. Histopathologic examination of the stented ureters embedded in glycol-methacrylate was performed. Results: Hyperplastic reaction was present in both stent types. BMSs in 7 porcine ureters were completely obstructed while porcine ureters stented with ZES had hyperplastic tissue which did not result in obstruction. Two rabbit ureters stented by BMS were occluded while no ZES was associated with ureteral obstruction. The function of the 7 porcine renal units and the two rabbit units with obstructed stented ureter was compromised. The OCT revealed increased hyperplastic reaction in the ureters stented by BMSs in comparison to ZESs. Although, hyperplastic reaction was present in all cases, pathology examination revealed significantly more hyperplastic reaction in BMSs. Conclusion: ZESs in the pig and rabbit ureter were not related to hyperplastic reaction resulting in stent occlusion. These stents were related to significantly lower hyperplastic reaction in comparison to BMSs while inflammation rates were similar for both stent types.

The Shannon sampling framework is widely used for discrete representation of analog bandlimited signals, starting from samples taken at the Nyquist rate. In many practical applications, signals are not bandlimited. In order to accommodate such signals within the Shannon-Nyquist framework, one typically passes the signal through an anti-aliasing filter, which essentially performs bandlimiting. In applications such as RADAR, SONAR, ultrasound imaging, optical coherence to-mography, multiband signal communication, wideband spectrum sensing, etc., the signals to be sampled have a certain structure, which could manifest in one of the following forms: (i) sparsity or parsimony in a certain bases; (ii) shift-invariant representation; (iii) multi-band spectrum; (iv) finite rate of innovation property, etc.. By using such structure as a prior, one could devise efficient sampling strategies that operate at sub-Nyquist rates. In this Ph.D. thesis, we consider the problem of sampling and reconstruction of finite-rate-of-innovation (FRI) signals, which fall in one of the two classes: (i) Sum-of-weighted and time-shifted (SWTS) pulses; and (ii) Sum-of-weighted exponential (SWE). Finite-rate-of-innovation signals are not necessarily bandlimited, but they are specified by a finite number of free parameters per unit time interval. Hence, the FRI reconstruction problem could be solved by estimating the parameters starting from measurements on the signal. Typically, parameter estimation is done using high-resolution spectral estimation (HRSE) techniques such as the annihilating filter, matrix pencil method, estimation of signal parameter via rotational invariance technique (ESPRIT), etc.. The sampling issues include design of the sampling kernel and choice of the sampling grid structure. Following a frequency-domain reconstruction approach, we propose a novel technique to design compactly supported sampling kernels. The key idea is to cancel aliasing at certain set of uniformly spaced frequencies and make sure that the rest of the frequency response is specified such that the kernel follows the Paley-Wiener criterion for compactly supported functions. To assess the robustness in the presence of noise, we consider a particular class of the proposed kernel whose impulse response has the form of sum of modulated splines (SMS). In the presence of continuous-time and digital noise cases, we show that the reconstruction accuracy is improved by 5 to 25 dB by using the SMS kernel compared with the state-of-the-art compactly supported kernels. Apart from noise robustness, the SMS kernel also has polynomial-exponential reproducing property where the exponents are harmonically related. An interesting feature of the SMS kernel, in contrast with E-splines, is that its support is independent of the number of exponentials. In a typical SWTS signal reconstruction mechanism, first, the SWTS signal is trans formed to a SWE signal followed by uniform sampling, and then discrete-domain annihilation is applied for parameter estimation. In this thesis, we develop a continuous-time annihilation approach using the shift operator for estimating the parameters of SWE signals. Instead of using uniform sampling-based HRSE techniques, operator-based annihilation allows us to estimate parameters from structured non-uniform samples (SNS), and gives more accurate parameters estimates. On the application front, we first consider the problem of curve fitting and curve completion, specifically, ellipse fitting to uniform or non-uniform samples. In general, the ellipse fitting problem is solved by minimizing distance metrics such as the algebraic distance, geometric distance, etc.. It is known that when the samples are measured from an incomplete ellipse, such fitting techniques tend to estimate biased ellipse parameters and the estimated ellipses are relatively smaller than the ground truth. By taking into account the FRI property of an ellipse, we show how accurate ellipse fitting can be performed even to data measured from a partial ellipse. Our fitting technique first estimates the underlying sampling rate using annihilating filter and then carries out least-squares regression to estimate the ellipse parameters. The estimated ellipses have lesser bias compared with the state-of-the-art methods and the mean-squared error is lesser by about 2 to 10 dB. We show applications of ellipse fitting in iris images starting from partial edge contours. We found that the proposed method is able to localize iris/pupil more accurately compared with conventional methods. In a related application, we demonstrate curve completion to partial ellipses drawn on a touch-screen tablet. We also applied the FRI principle to imaging applications such as frequency-domain optical-coherence tomography (FDOCT) and nuclear magnetic resonance (NMR) spectroscopy. In these applications, the resolution is limited by the uncertainty principle, which, in turn, is limited by the number of measurements. By establishing the FRI property of the measurements, we show that one could attain super-resolved tomograms and NMR spectra by using the same or lesser number of samples compared with the classical Fourier-based techniques. In the case of FDOCT, by assuming a piecewise-constant refractive index of the specimen, we show that the measurements have SWE form. We show how super-resolved tomograms could be achieved using SNS-based reconstruction technique. To demonstrate clinical relevance, we consider FDOCT measurements obtained from the retinal pigment epithelium (RPE) and photoreceptor inner/outer segments (IS/OS) of the retina. We show that the proposed method is able to resolve the RPE and IS/OS layers by using only 40% of the available samples. In the context of NMR spectroscopy, the measured signal or free induction decay (FID) can be modelled as a SWE signal. Due to the exponential decay, the FIDs are non-stationary. Hence, one cannot directly apply autocorrelation-based methods such as ESPRIT. We develop DEESPRIT, a counterpart of ESPRIT for decaying exponentials. We consider FID measurements taken from amino acid mixture and show that the proposed method is able to resolve two closely spaced frequencies by using only 40% of the measurements. In summary, this thesis focuses on various aspects of sub-Nyquist sampling and demonstrates concrete applications to super-resolution imaging.

Retinal nerve fiber layer measurement in patients with Alzheimer's disease The current ophthalmologist's possibilities in diagnostics of Alzheimer's disease Alzheimer disease (AD) is the most common cause of dementia syndrome and mild cognitive impairment. To enroll the disease most securely there are used so called biomarkers using evidence of changed brain metabolism by pozitron emission tomography (PET) and in cerebrospinal fluid or the brain's structure magnetic resonance imaging (MRI). These methods are expensive, organisationally and temporally challenging and burdening for the patients. According to that reasons we are still seeking for alternative attitudes suitable for early diagnosis. The evaluation of thickness of retinal nerve fiber layer (RNFL) which is well accessible to examination through optical aparatus of the eye could be one of the options. The aim of our work was to present current knowledges about Alzheimer's disease targeting relations of Alzheimer's disease and an ophthalmological finding. In the next part of this paper we introduce the retinal nerve fiber layer measurement by optical coherence tomography (OCT) as a potential diagnostics method by screening of patients with Alzheimer's disease and to present our results measured in our cohort of patients. The studied cohort...

OBJETIVO: Avaliar a capacidade dos parâmetros do eletrorretinograma de padrão reverso de campo total e hemianópico em diferenciar olhos com atrofia em banda do nervo óptico e, a correlação entre as amplitudes do eletrorretinograma de padrão reverso, a espessura da camada de fibras nervosas da retina e macular obtidas pela tomografia de coerência óptica e a perda de campo visual nestes pacientes. MÉTODOS: Quarenta e um olhos de 41 pacientes com perda de campo visual temporal permanente por compressão do quiasma óptico e 41 controles normais foram submetidos ao eletrorretinograma de padrão reverso de estimulação de campo total e hemianópicos (temporal e nasal), a tomografia de coerência óptica, para avaliação das medidas da espessura da camada de fibras nervosas da retina e macular e, ao exame de campo visual, pela perimetria automatizada padrão. O desvio do normal da sensibilidade dos 18º centrais do campo visual foram expressos em decibéis e unidades 1/Lambert. As comparações foram feitas pelo teste t de Student. A correlação entre os parâmetros do campo visual central, do eletrorretinograma de padrão reverso e da tomografia de coerência óptica foi avaliada pela correlação de Pearson e análise de regressão linear. RESULTADOS: Os valores das amplitudes P50, N95, and P50+N95 do eletrorretinograma de padrão reverso de campo total, e de estimulação hemianópica e os valores das medidas da espessura macular e da camada de fibras nervosas da retina obtidas pela tomografia de coerência óptica foram significativamente menores nos olhos com atrofia em banda do que nos controles (P<0,001). Uma correlação significativa foi encontrada entre a perda de sensibilidade no campo visual central e as amplitudes do eletrorretinograma de padrão reverso de estimulação de campo total e nasal, mas não para o temporal. Uma correlação significativa positiva foi observada entre os parâmetros de perda de sensibilidade no campo visual e a maioria dos parâmetros da espessura da camada de fibras nervosas da retina e macular obtidas pela tomografia de coerência óptica. Nenhuma correlação significativa foi observada entre os parâmetros do eletrorretinograma de padrão reverso e a tomografia de coerência óptica, exceto para amplitude P50+N95 do eletrorretinograma de padrão reverso de estimulação de hemicampo nasal. Uma correlação significativa foi observada entre os parâmetros de espessura macular e da camada de fibras nervosas pela tomografia de coerência óptica, exceto entre a espessura da camada de fibras nervosas no segmento de 30º, correspondente as 9 horas do relógio e os parâmetros maculares. CONCLUSÕES: Os valores das amplitudes do eletrorretinograma de padrão reverso foram eficazes em diferenciar olhos com atrofia em banda do nervo óptico de controles normais. Em pacientes com atrofia em banda do nervo óptico, as amplitudes do eletrorretinograma de padrão reverso e medidas da espessura da camada de fibras nervosas da retina e macular correlacionaram de forma significativa com a perda de campo visual, mas não houve correlação entre eles. O eletrorretinograma de padrão reverso e a tomografia de coerência óptica detectaram a perda neural e ambos são métodos diagnósticos úteis na compreensão da correlação estrutura-função em pacientes com compressão do quiasma óptico / PURPOSE: To evaluate the ability of full-field and hemifield pattern electroretinogram parameters to differentiate between healthy eyes and eyes with band atrophy of the optic nerve and also to evaluate the relationship between pattern electroretinogram amplitude, macular and retinal nerve fiber layer thickness by optical coherence tomography, and visual field loss on standard automated perimetry in eyes with BA of optic nerve. METHODS: Forty-one eyes from 41 patients with permanent temporal visual field defects from chiasmal compression and 41 healthy subjects underwent transient fullfield and hemifield (temporal or nasal) stimulation pattern electroretinogram, standard automated perimetry and time domain- optical coherence tomography macular and retinal nerve fiber layer thickness measurements. Comparisons were made using Students t-test. Deviation from normal visual field sensitivity for the central 18° was expressed in dB and 1/Lambert units. Correlations between measurements were verified by Pearsons correlations and linear regression analysis. RESULTS: Full-field P50, N95, and P50+N95 amplitude values were significantly smaller in eyes with band atrophy than in control eyes (P<0.001). Nasal and temporal hemifield pattern electroretinogram studies revealed significant differences in N95 and P50+N95 amplitudes measurements. Pattern electroretinogram and optical coherence tomography measurements were significantly lower in eyes with temporal hemianopia than in normal eyes. A significant correlation was found between visual field sensitivity loss and full-field or nasal, but not temporal, hemifield pattern electroretinogram amplitude. Likewise a significant correlation was found between visual field sensitivity loss and most optical coherence tomography parameters. No significant correlation was observed between optical coherence tomography and pattern electroretinogram parameters, except for nasal hemifield amplitude. A significant correlation was observed between several macular and retinal nerve fiber layer thickness parameters. CONCLUSIONS: Transient pattern electroretinogram amplitude measurements were efficient at differentiating eyes with band atrophy and permanent visual field defects from normal controls. In patients with chiasmal compression, pattern electroretinogram amplitude and optical coherence tomography thickness measurements were significant related to visual field loss, but not to each other. Pattern electroretinogram and optical coherence tomography quantify neuronal loss differently, but both technologies are useful in understanding structure-function relationship in patients with chiasmal compression

A terapia fotodinâmica (PDT) é uma alternativa promissora de tratamento para lesões pré-cancerosas e para câncer de pele não-melanoma, como o carcinoma espinocelular, agressivo e potencialmente metastático. Visando melhorar a eficiência da terapia fotodinâmica de carcinoma espinocelular de pele, este estudo otimizou o tempo para início da terapia, avaliou a eficácia dos fotossensibilizadores ácido aminolevulínico (ALA- 20%) e o metil-ester aminolevulínico (MEALA-10%) e verificou o coeficiente de atenuação relativo à pele normal dos grupos experimentais, por meio de Tomografia por Coerência Óptica. Para a indução do tumor foi realizada a carcinogênese química (DMBA/TPA) por um período de 28 semanas. A espectroscopia de fluorescência foi utilizada para monitoração da emissão da molécula de protoporfirina IX, induzida pelo ALA e MEALA. A aquisição de dados a cada 30 minutos totalizando um período de 360 minutos, permitiu verificar a máxima incorporação de ALA e MEALA em 300 e 330 minutos após a aplicação, respectivamente. Após a otimização foi realizada a PDT, avaliação clínica, histopatológica e análise por OCT dos grupos experimentais, por meio das quais verificou-se maior eficiência do grupo tratado com MEALA. No período de 20 dias, o percentual de lesões com redução de área maior que 50%, foi de 33% na PDT com ALA e 83% para o MEALA. Os coeficientes de atenuação ópticos para os grupos com neoplasia foram maiores do que os do grupo controle. Os grupos tratados com PDT apresentaram valores de coeficiente de atenuação que se aproximam dos valores obtidos para a pele sadia, evidenciando a resposta ao tratamento. Entretanto para ambos os fotossensibilizadores utilizados, a PDT mostrou-se eficaz quando iniciada nos tempos determinados neste estudo, e a técnica de OCT mostrou-se uma potencial ferramenta na avaliação deste tratamento. / Photodynamic therapy (PDT) is a promising alternative for pre-cancerous lesions and non-melanoma skin cancer treatment as squamous cells carcinoma, which is aggressive and potentially metastatic. Aiming the improvement of photodynamic therapy efficiency for skin squamous cells carcinoma, this study has optimized the time to start the therapy, it also evaluated the effectiveness of the aminolevulinic acid (ALA-20%) and methyl-ester aminolevulinic (MEALA-10%) as photosensitizers as well as verified the optical attenuation coefficient relative to normal skin of the experimental groups by optical coherence tomography (OCT). A chemical carcinogenesis was performed (DMBA/TPA), by a period of 28 days. Fluorescence Spectroscopy was used to monitor the emission of protoporphyrin IX induced by ALA and MEALA. Signal acquisition was performed every 30 minutes for a total period of 360 minutes, showing a maximum incorporation of ALA and MEALA, 300 and 330 minutes after the application. PDT was conducted after the optimization of the irradiation time. Clinical and histopathologic evaluation and OCT analysis of the experimental groups showed higher efficiency of the MEALA-treated group. After 20 days of treatment, the percentage of lesions with area reduction greater than 50%, was 33% for the ALA group and 83% for the MEALA group. The optical attenuation coefficients for groups with cancer were higher than those in the control group. The groups treated with PDT presented attenuation coefficient values that are close to the values obtained for healthy skin, showing the positive response to the treatment. This study showed that PDT was effective for both photosensitizers when initiated at the times determined in this study, and OCT technique proved to be a potential tool in the assessment of this treatment.

A exposição crônica à radiação ultravioleta (UV) resulta no fotoenvelhecimento da pele humana. A fim de tratá-lo, a terapia fotodinâmica (TFD) - técnica que utiliza luz, um fotossensibilizador (FS) e oxigênio molecular - tem sido utilizada em ambientes clínicos, no entanto são escassas as investigações que revelam os achados histopatológicos desse tratamento na pele fotoenvelhecida. Com isso, o objetivo deste trabalho foi analisar experimentalmente os efeitos da TFD na pele fotoenvelhecida de camundongos por meio de técnicas ópticas e histológicas. Portanto, foram utilizados camundongos hairless (sem pelo) distribuídos aleatoriamente em diferentes grupos, tais como: Controle, animais de pele sadia envelhecida intrinsecamente, não irradiados com luz UV e não tratados; UV, animais irradiados com luz UV e não tratados; UV/Luz, animais irradiados com luz UV e tratados com fototerapia; UV/TFD, animais fotoenvelhecidos (irradiados com luz UV) e tratados com a TFD; e Controle/TFD, animais de pele sadia envelhecida intrinsecamente e tratados com TFD. A indução do fotoenvelhecimento foi realizada por diferentes fontes de luz contendo, principalmente, a banda espectral UV; para a TFD, foram utilizadas fontes de luz com comprimento de onda de 415, 630 e 635 nm (azul e vermelho) juntamente com o ácido 5-aminolevulínico (ALA), precursor do FS endógeno protoporfirina IX (PpIX). Para fazer o seguimento da TFD por técnicas ópticas, foram realizadas espectroscopia de fluorescência, imagem de fluorescência de campo amplo e tomografia por coerência óptica (OCT, do inglês optical coherence tomography). A avaliação histopatológica pós-TFD foi realizada com os corantes HE, Tricrômio de Masson (TM) e Verhoeff a fim de analisar a espessura da epiderme, o infiltrado inflamatório, o conteúdo de colágeno na derme e sua espessura e a qualidade das fibras elásticas. Como resultado, observouse aumento significativo da espessura da epiderme pela regeneração dos queratinócitos e deposição de novas fibras colágenas dérmicas apenas nos animais tratados com ALA-TFD, tanto irradiados quanto não-irradiados com luz UV (grupos UV/TFD e Controle/TFD, respectivamente). Assim, torna-se evidente que a TFD trata a pele fotoenvelhecida do camundongo hairless pelos achados histopatológicos e através das imagens de OCT. Com isso, este trabalho agrega informação às investigações clínicas a respeito da TFD no tratamento da pele fotoenvelhecida, atestando seu uso para o fotorrejuvenescimento cutâneo. / The chronic exposure to ultraviolet radiation (UVR) leads to photoaging of the human skin. As a treatment, the photodynamic therapy (PDT) which brings together light, a photosensitizer, and molecular oxygen has been extensively used on clinical trials; however, there are few studies that highlight the histopathologic findings regarding this technique on photoaged skin. Thus, the aim of this study was to analyze experimentally the effects of PDT on photoaged skin of hairless mice by means of optical and histopathologic assessments. For this, hairless mice were randomly allocated in different groups, such as: Control, animals with healthy aged skin, neither exposed to an UV lamp nor treated; UV, animals exposed to an UV lamp with no treatment; UV/Light, animals exposed to an UV lamp and treated just with light; UV/PDT, animals exposed to an UV lamp and treated with PDT; and Control/PDT, animals with healthy aged skin treated with PDT. The photoaging process was induced by different light sources, which had mainly the UV spectrum; for the PDT, light sources of different wavelengths (415, 630, 635 nm) were used (blue and red light sources) and the 5-aminolevulinic acid (ALA), PS precursor of the endogenous protoporphyrin IX (PpIX). In order to follow the PDT protocol up by means of optical techniques, we used fluorescence spectroscopy, fluorescence images and optical coherence tomography. The histopathologic assessment after the PDT procedure was performed with H&E, Massons Trichrome and Verhoeff stains for epidermal thickness, inflammatory infiltrate, dermal collagen content, dermal thickness, and quality of elastic fibers. As a result, it has been observed a significant epidermal thickening due to keratinocytes regeneration and newly formed dermal collagen fibers only on the groups treated with PDT-ALA (UV/PDT and Control/PDT groups). Therefore, it is evident that PDT treats the photoaged skin of hairless mice since histopatologic findings and OCT images have shown those morphology changes. In conclusion, this work add information to the clinical trials regarding the PDT as a reliable technique to treat photoaged skin, proving its use for the skin photorejuvenation.

O presente trabalho experimental, tem como objetivo avaliar \"in vitro\" possíveis falhas na cimentação de fragmentos cerâmicos sobre substrato de esmalte dentário previamente submetido ao clareamento dental e analisados pelo sistema de tomografia por coerência ótica. O ensaio experimental foi realizado in vitro, fazendo uso de trinta pré-molares superiores humanos. Cada elemento dental teve sua porção de esmalte vestibular aplainada por meio de disco de sílica na granulação 120, foram cimentados fragmentos cerâmicos retangulares de 1.5mm de espessura. Os dentes foram distribuídos aleatoriamente em 3 grupos de 10 dentes cada (n=10), Grupo 1: Fragmentos cimentados sem serem submetidos ao tratamento clareador; Grupo 2: Fragmentos cimentados 24 hrs. Após serem submetidos ao clareamento dental; Grupo 3: Fragmentos cimentados 7 dias após serem submetidos ao clareamento dental. Os espécimes foram transferidos para o sistema de tomografia por coerência óptica para seus respectivos monitoramentos após exposição ao agente clareador e cimentação da restauração indireta e ao final dos ensaios de envelhecimento artificial por termociclagem. A variável de resposta, falhas na interface esmalte e cimento resinoso, foi avaliada por escores (0,1 e 2) que representam em ordem crescente as falhas entre o substrato dental e a restauração indireta. Os valores obtidos foram analisados por meio de testes não paramétricos (Kruskal-Wallis e Wilcoxon). Os resultados constituíram de 60 escores de fendas referentes aos 3 grupos (G1;G2;G3) analisados imediatamente após a cimentação e após a termociclagem. A comparação entre os 3 grupos após termociclagem demonstrou haver diferença estatisticamente significante (p<0,0001) pela comparação dois a dois pelo teste complementar de Dunn e detectou-se que o G2 cimentado após 24 horas do clareamento apresentou mais fendas que G1 e G3. Com base nestes resultados e na metodologia utilizada pode-se concluir que, dentes submetidos ao tratamento clareador, o protocolo clinico de cimentação de restaurações cerâmicas indiretas, quando realizado 7 dias após o clareamento gerou menor quantidade de fendas na interface, propondo assim melhor qualidade na adaptação dente/restauração. / The present experimental study has the objective of evaluating in vitro possible failures in the cementation of ceramic fragments over dental enamel substrate previously submitted to dental bleaching and analyzed by optical coherence tomography system. The experimental trial was performed in vitro using thirty human maxillary premolars. Each dental element had have it\'s portion of vestibular enamel planed by a silic disk in granulation 120, ceramic fragments with a diameter of 1.5mm thickness were cemented. The teeth were randomly distributed in 3 groups of 10 teeth each (n = 10), Group 1: Bonded Veneer without being subjected to bleaching treatment Group 2: Bonded Veneer 24 hours after being submitted to dental bleaching Group 3: Bonded Veneer 7 days after being submitted to dental bleaching. The specimens were transferred to the optical coherence tomography system for their respective monitoring after being exposured to the whitening agent and cementation of the indirect restoration and at the end of the artificial aging tests by thermocycling. The variable of response, at faults in the interface enamel and resin cement, was evaluated by scores (0,1 and 2) that represent in increasing order the failures between dental substrate and indirect restoration. The values obtained were analyzed by non-parametric tests (Kruskal-Wallis and Wilcoxon). The results consisted of 60 gaps scores for the three groups (G1, G2, G3) analyzed immediately after bonding and after thermocycling. The comparison between the 3 groups after thermocycling, showed a statistically significant difference (p <0.0001) by the two-to-two comparison by Dunn\'s complementary test and it was detected that G2 after 24 hours of bleaching, showed more gaps than G1 and G3. Based on these results and the methodology used, it was concluded that, when teeth were submitted to the bleaching treatment, the clinical cementation protocol of indirect ceramic restorations, when performed 7 days after bleaching, generated fewer gaps at the interface, thus proposing a better quality in the relation Tooth / restoration.

OBJETIVO: Caracterizar morfologicamente e funcionalmente as alterações observadas no fundo de olho de pacientes com a doença de Vogt-Koyanagi- Harada (VKH) no estágio tardio. MÉTODOS: Estudo prospectivo, transversal, com inclusão de 36 pacientes com diagnóstico de doença de VKH no estágio tardio (definido como 6 meses ou mais após o início da doença) após obtenção do termo de consentimento livre e esclarecido. Fundo de olho (retinografia, RG) foi estratificado baseado em alterações difusas e focais assim como a função global da retina (eletroretinograma campo total, ERGct) segundo o método matemático de aglomeração (cluster). A concordância entre os dois métodos de estratificação foi estimada pelo teste kappa. Atividade clínica foi correlacionada com alterações indicativas de atividade de coróide pela angiografia com indocianina verde (AICV) (teste exato de Fisher). Alterações na integridade dos segmentos interno e externo de fotorreceptores (IS/OS) avaliada pela tomografia de coerência óptica espectral (OCT espectral) foram correlacionadas com a função macular (eletroretinograma multifocal, ERGmf) e acuidade visual (AV) (teste de Mann-Whitney). RESULTADOS: Houve concordância substancial entre os observadores em relação ao sistema analítico para estratificação fundoscópica proposto (kappa=0,78; intervalo de confiança 95%(IC95%)=0,63-0,93). Este sistema analítico também se correlacionou de maneira substancial com os achados do ERGct (kappa=0,68; IC 95% 0,52-1,07). Na avaliação com AICV, a proporção dos olhos com resultados compatíveis com atividade subclínica de coróide foi maior em pacientes com doença fundoscópica leve (12/13 olhos) se comparados exclusivamente com aqueles portadores de doença fundoscópica grave (11/19 olhos) (p=0,049). Os pacientes estratificados de acordo com as características fundoscópicas não diferiram de maneira substancial quanto aos aspectos clínicos. Atividade subclínica de coróide detectada pela AICV foi observada em 36 dos 51 olhos (72%). Atividade clínica (células na câmara anterior) foi observada em 21 dos 51 olhos (41%). Destes 76% (16/21) demonstravam sinais de atividade de coróide, ao passo que 5 de 21 olhos (24%) não os apresentavam. Dos pacientes com atividade clínica de doença e com AICV negativa, a maioria tinha doença grave (4/5 olhos) e nenhum tinha doença leve pela classificação fundoscópica. Quanto à função macular, as amplitudes e latências das ondas N1 e P1 diferiram dos controles (p<0,01). A junção IS/OS macular estava alterada em 17 de 42 olhos (40%) dos olhos. A AV foi diferente entre grupos estratificados de acordo com os resultados do ERGmf ( leve= 0,0 [20/20] e grave = 0,2 [20/32]; p<0,05) assim como entre os grupos estratificados pelo OCT espectral (IS/OS+ = 0,0 [20/20] e IS/OS-= 0,7 [20/100]; p<0,05). O grau de concordância entre estas estratégias foi baixo (K=0,17). CONCLUSÕES: O sistema analítico para achados fundoscópicos proposto teve alta reprodutibilidade e correlacionou-se com medidas objetivas de função retiniana (ERGct). A gravidade de doença estimada segundo a estratégia fundoscópica influencia a interpretação da AICV, sendo que pacientes com achados leves tendem a ter maior prevalência de atividade subclínica detectada pela AICV assim como pacientes graves apresentaram exame angiográfico negativo mesmo na vigência de atividade de segmento anterior. Os grupos estabelecidos com as estratégias funcional (ERGmf) e morfológica (OCT espectral) de análise macular diferiram significativamente em termos de acuidade visual, sendo que o ERGmf discerniu grupos com acuidades semelhantes. A concordância entre as duas técnicas de análise macular foi baixa devido à maior sensibilidade do ERGmf em detectar alterações. Estes dados sugerem que o dano funcional pode preceder e/ou ocorrer na ausência de alterações maculares detectáveis com o OCT espectral em pacientes no estágio tardio da doença de VKH / OBJECTIVES: To characterize the structural and functional derangements observed in eyes of patients with late-stage Vogt-Koyanagi-Harada (VKH) disease. METHODS: Cross sectional, prospective study including 36 patients diagnosed with late-stage VKH disease (defined as more than 6 months from disease`s onset) after obtainment of informed consent. Fundoscopy (retinography, RG) was stratified based on diffuse and focal findings as well as according to global retinal function (full-field electroretinogram, ffERG) applying cluster method of aggregation. The concordance between the two methods of stratification was estimated with the kappa test. Clinical disease activity was correlated with findings suggestive of subclinical choroidal activity on indocyanine green angiography (ICGA) (Fisher`s exact test). Disruption of photoreceptors inner and outer segments\' junction (IS/OS) evaluated using spectral optical coherence tomography (spectral OCT) was correlated with macular function (multifocal electroretinogram, mfERG) and best corrected visual acuity (BCVA)(Mann- Whitney test). RESULTS: Substantial interobserver concordance was detected with regard to the analytic system for fundus findings proposed (kappa=0.78; confidence interval 95%(CI95%); 0.63-0.93). This system also showed substantial correlation with ffERG findings (kappa=0.68; CI 95%; 0.52-1.07). Upon ICGA investigation, the proportion of eyes presenting signs of disease activity on ICGA was significantly greater among mild fundus cases (12/13) when compared exclusively with those presenting severe fundus disease (11/19) (p=0.049). The different severity categories based on fundoscopic evaluation did not differ in terms of clinical characteristics. Subclinical choroidal activity was observed in 36 of 51 eyes analyzed (72%). Clinical disease activity (cells in the anterior chamber) was observed in 21 of 51 eyes (41%). Most patients with clinical activity and negative ICGA examination (4/5) had severe disease and none had mild disease according to fundoscopic stratification. On macular evaluation, patients\' amplitudes and latencies of N1 and P1 waves differed from controls (p<0.01). Macular IS/OS junction was altered in 17 out of 42 eyes (40%). BCVA differed significantly between groups stratified according to both, mfERG (mild = 0.0 [20/20] and severe = 0.2 [20/32]; p<0.05) as well as spectral OCT (IS/OS+ = 0.0 [20/20] and IS/OS-= 0.7 [20/100]; p<0.05) assessment techniques. Concordance between these strategies of macular assessment was weak (K=0.17). CONCLUSIONS: The analytic system for fundus findings proposed herein demonstrated high reproducibility and substantial interobserver concordance with objective measures of retinal compromise (ffERG). The severity grading proposed influenced the interpretation of ICGA, as patients with mild disease had a greater proportion of positive findings while patients with severe disease presented negative ICGA in spite of anterior segment activity. Groups established according to both functional (mfERG) and morphological (spectral OCT) macular analysis strategies differed in terms of BCVA, although the mfERG distinguished groups with similar BCVA. The low concordance between the two strategies detected is attributable to the greater sensibility of the mfERG to detect alterations. These findings suggest that functional derangements may precede and/or occur in absence of alterations detectable with the spectral OCT in patients with late-stage VKH disease.

L’OCT plein champ est une technique d’imagerie permettant de faire de la microscopie des milieux diffusants à une profondeur donné à l’aide d’un système interférométrique. L’un des principaux objectifs qui ont motivé le développement de l’OCT plein champ ces dernières années a été de pouvoir fournir au chirurgien, durant les opérations des images similaires aux coupes histologiques mais en temps réel. Actuellement, les diagnostiques effectué à partir des images d’OCT plein champs donne de bon résultats, notamment dans le cas de certaine pathologie mammaire. Cependant, la différence majeure entre les coupes histologiques et les images d’OCT plein champs est qu’en OCT plein champ le contraste est uniquement un contraste morphologique et que dans certain cas, ce contraste seul ne suffit pas pour faire le diagnostic. Au cours des travaux de recherche décrits dans cette thèse nous nous sommes attachés à développer de nouvelles approches tomographiques, conduisant à de nouvelles formes de contraste susceptible d’enrichir les images d’OCT plein champ pour une meilleure qualité du diagnostic. Plus précisément, nous avons travaillé sur la détection optique et photo-thermique de nanoparticules d’or par OCT plein champ et la cartographie des propriétés mécaniques par trois méthodes dans le but de développer de nouveaux types de contrastes qui pourront permettre d’améliorer le diagnostic. / Full Field OCT (FF-OCT) is an imaging technic use to do microscopy inside scattering media at a given depth using an interferometric setup. One of the main objectives that motivated the development of FF-OCT was to provide during surgery to the surgeon images similar to histological slices but in real time. Currently, diagnostic made from FF-OCT images gives good results, especially in the case of some breast disease. However, the major difference between the histological and FF-OCT is that FF-OCT has only a morphological contrast and in some cases, this contrast is not enough to make the diagnosis. In the research described in this thesis we are committed to developing new tomographic approaches, leading to new forms of contrast may enhance images of FF- OCT for a better quality of diagnosis. Specifically, we worked on the optical and photothermal detection of gold nanoparticles by FF-OCT and the mechanical properties mapping by three methods in order to develop new types of contrasts that will help improve the diagnosis.

<p>The goal of my Ph.D. thesis is to enhance the visualization of the peripheral retina using wide-field optical coherence tomography (OCT) in a clinical setting.</p><p>OCT has gain widespread adoption in clinical ophthalmology due to its ability to visualize the diseases of the macula and central retina in three-dimensions, however, clinical OCT has a limited field-of-view of 300. There has been increasing interest to obtain high-resolution images outside of this narrow field-of-view, because three-dimensional imaging of the peripheral retina may prove to be important in the early detection of neurodegenerative diseases, such as Alzheimer's and dementia, and the monitoring of known ocular diseases, such as diabetic retinopathy, retinal vein occlusions, and choroid masses.</p><p>Before attempting to build a wide-field OCT system, we need to better understand the peripheral optics of the human eye. Shack-Hartmann wavefront sensors are commonly used tools for measuring the optical imperfections of the eye, but their acquisition speed is limited by their underlying camera hardware. The first aim of my thesis research is to create a fast method of ocular wavefront sensing such that we can measure the wavefront aberrations at numerous points across a wide visual field. In order to address aim one, we will develop a sparse Zernike reconstruction technique (SPARZER) that will enable Shack-Hartmann wavefront sensors to use as little as 1/10th of the data that would normally be required for an accurate wavefront reading. If less data needs to be acquired, then we can increase the speed at which wavefronts can be recorded.</p><p>For my second aim, we will create a sophisticated optical model that reproduces the measured aberrations of the human eye. If we know how the average eye's optics distort light, then we can engineer ophthalmic imaging systems that preemptively cancel inherent ocular aberrations. This invention will help the retinal imaging community to design systems that are capable of acquiring high resolution images across a wide visual field. The proposed model eye is also of interest to the field of vision science as it aids in the study of how anatomy affects visual performance in the peripheral retina.</p><p>Using the optical model from aim two, we will design and reduce to practice a clinical OCT system that is capable of imaging a large (800) field-of-view with enhanced visualization of the peripheral retina. A key aspect of this third and final aim is to make the imaging system compatible with standard clinical practices. To this end, we will incorporate sensorless adaptive optics in order to correct the inter- and intra- patient variability in ophthalmic aberrations. Sensorless adaptive optics will improve both the brightness (signal) and clarity (resolution) of features in the peripheral retina without affecting the size of the imaging system.</p><p>The proposed work should not only be a noteworthy contribution to the ophthalmic and engineering communities, but it should strengthen our existing collaborations with the Duke Eye Center by advancing their capability to diagnose pathologies of the peripheral retinal.</p> / Dissertation