Diabetes is a rapidly growing disease with 415 million affected adults worldwide. The pancreatic endocrine cells, most importantly the insulin producing β-cells, play an important role in regulating blood glucose homeostasis. Type 1 diabetes (T1D) is characterized by the inability of the pancreas to secrete sufficient amounts of insulin due to autoimmune destruction of insulin producing β-cells. Type 2 diabetes (T2D) on the other hand is characterized by defects in insulin secretion and insulin sensitivity. Alterations in the β-cell mass (BCM) and/or function play a major role in the development and progression of the disease. Understanding BCM dynamics in disease models is therefore a key aspect for better interpretation of research results. In this thesis, we have used optical projection tomography (OPT) as a tool to evaluate a non-invasive imaging modality for β-cell scoring and to study disease dynamics in frequently used animal models for T1D and T2D. The possibility to monitor BCM in vivo would radically improve our competence in studying the pathogenesis of diabetes and in therapeutic interventions. Single photon emission computed tomography (SPECT) is a widely used technique that has become a promising approach to monitor changes in BCM in vivo. A key issue for using this approach is to evaluate the β-cell specificity and read out of the utilized radiotracers. This is most commonly performed by conventional stereological approaches, which rely on the extrapolation of 2D data. We developed a protocol for SPECT-OPT multimodal imaging that enables rapid and accurate cross evaluation of SPECT based assessments of BCM. While histological determination of islet spatial distribution was challenging, SPECT and OPT revealed similar distribution patterns of the radiotracer 111In-exendin-3 and insulin positive β-cell volumes respectively between different pancreatic lobes, both visually and quantitatively. We propose SPECT-OPT multimodal imaging as an accurate and better approach for validating the performance of β-cell radiotracers. The leptin deficient ob/ob mouse is a widely used model for studies of metabolic disturbances leading to T2D, including obesity and insulin resistance. By OPT imaging we created the first 3D-spatial and quantitative account of BCM distribution in this model. We observed a previously unreported degree of cystic lesions in hypertrophic islets, that were occupied by red blood cells (RBCs) and/or fibrin mesh. We propose that these lesions are formed by a mechanism involving the extravasation of RBCs/plasma due to increased blood flow and islet vessel instability. Further, our data indicate that the primary lobular compartments of the ob/ob pancreas have different potentials for expanding their β-cell population. Unawareness of these characteristics of β-cell expansion in ob/ob mice presented in this study may significantly influence ex vivo and in vivo assessments of this model in studies of β-cell adaptation and function. The tomographic data, on which this study was based, will be made publically available as a resource to the research community for the planning and interpretation of research involving this model. There are limited studies on early metabolic and functional changes of BCM in the settings of T1D. In order to assess initial metabolic alterations in BCM before the onset of diabetes, we characterized congenic diabetes prone Bio-breeding (BB) DR.lyp/lyp rats, a widely used model for T1D diabetes. We observed lower acute insulin response, reduced islet blood flow and a significant reduction in the BCM of small and medium sized islets at a very early stage (40 days), i.e. before insulitis and development of diabetes. Underlying changes in islet function may be a previously unrecognized factor of importance in the development of T1D.

A região da articulação temporomandibular (ATM) possui uma limitação na obtenção de imagens pela radiografia convencional. A tomografia computadorizada é o exame mais indicado pela alta especificidade e sensibilidade, para o diagnóstico, planejamento cirúrgico e tratamento das lesões ósseas. O objetivo deste trabalho consiste na avaliação de lesões ósseas simuladas na cabeça da mandíbula pela tomografia computadorizada. Foram utilizadas 15 mandíbulas secas, onde foram criadas lesões esféricas, com o auxílio de brocas esféricas cirúrgicas de uso odontológico com tamanhos variados (nº 1, 3, 6) na cabeça da mandíbula. As lesões foram avaliadas por meio da TC multislice (64 canais), por 2 examinadores independentemente, em 02 ocasiões distintas, utilizando 2 protocolos: axial, coronal, sagital e imagens parassagitais para visualização dos pólos (anterior, lateral, posterior, medial, superior). Posteriormente, as imagens foram comparadas com as lesões presentes na mandíbula seca (Padrão Ouro) avaliando o grau de especificidade e sensibilidade da TC. Estatística de Kappa, teste de validade e teste do Qui-Quadrado foram utilizados como métodos estatísticos. Como resultados observaram a vantagem da associação dos cortes axial, coronal e sagital com cortes parassagitais para detecção de lesões na região de cabeça de mandíbula. Para determinada localização de lesões nos pólos, os tipos de protocolos não apresentaram diferenças significativas em relação as porcentagens de concordância. Os protocolos para visualização da região de cabeça da mandíbula foram estabelecidos no intuito de melhorar a visualização da presença de alterações de cada pólo da cabeça da mandíbula. No que se refere aos pólos avaliados pelos cortes parassagitais houve melhor visualização no pólo anterior e posterior no sentido látero medial. Nos pólos superior, medial e lateral foram mais bem visualizados no sentido ântero-posterior. / There are limitations for image acquisition using conventional radiography of the temporomandibular joint (ATM) region. Computerized tomography (CT) scan is a better option due to its higher specificity and sensitivity for diagnosis, surgical planning and treatment of bone injuries. The purpose of this study is to evaluate simulated bone injuries of the head of the jaw by CT scan. Spherical lesions were created in the head of 15 dry jaws with dentist drills (sizes 1, 3, and 6). Lesions were evaluated using the CT multislice (64 bits) by 2 examiners independently, in 2 different occasions, using 2 protocols: axial, coronal, and sagittal and parasagittal images for head of the mandible visualization (anterior, lateral, posterior, medial, and superior). Images were compared with the dry jaw (gold standard) regarding the presence of injuries, evaluating the degree of specificity and sensitivity of the CT. Kappa statistics, validity tests, and chi-square tests were used as statistical methods. As a result, we observed the advantage of the association of axial, coronal and sagittal slices with parasagittal slices for detection of lesions in the region of mandibles head. For some lesions localized in polar regions, protocols did not show statistically significant differences regarding the proportion of agreement. Protocols for visualization were created to improve the visualization of lesions in each polar region of the jaws head. Regarding parassagittal slices, there was better lateromedial visualization of the anterior and posterior poles and better anteroposterior visualization of superior, medial, and lateral poles.

Orientador: Mateus Borba Cardoso / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Física Gleb Wataghin / Made available in DSpace on 2018-09-05T14:11:53Z (GMT). No. of bitstreams: 1 Vescovi_RafaelFerreiraDaCosta_D.pdf: 72387058 bytes, checksum: 728a9ca57a44975a0fbb2f766a7bbd5c (MD5) Previous issue date: 2017 / Resumo: Esta tese apresentará uma introdução a imagens de raios-x e como adquirir e processar imagens usando linhas de luz síncrotron. Apresentará os desafios matemáticos e técnicos para reconstruir amostras em três dimensões usando a reconstrução de Tomografia Computadorizada, uma técnica conhecida como CT. Esta técnica tem seu campo de visão limitado ao tamanho da câmera e ao tamanho da iluminação. Uma técnica para ampliar esse campo de visão vai ser apresentada e os desafios técnicos envolvidos para que isso aconteça. Um \textit{pipeline} é proposto e todos os algoritmos necessários foram empacotados em um pacote python chamado Tomosaic. A abordagem baseia-se em adquirir tomogramas parciais em posiçoes pré definidas e depois mesclar os dados em um novo conjunto de dados. Duas maneiras possíveis são apresentadas para essa mescla, uma no domínio das projeções e uma no domínio dos sinogramas. Experimentos iniciais serão então usadas para mostrar que o método proposto funciona com computadores normais. A técnica será aplicada mais tarde para pesquisar a anatomia de cérebros de camundongo completos. Um estudo será apresentado de como obter informação em diferentes escalas do cérebro completo do rato utilizando raios-x / Abstract: This thesis will present an introduction to x-ray images and how to acquire and thread images using synchrotron beamlines. It will present the mathematical and technical challenges to reconstruct samples in three dimensions using Computed Tomography reconstruction, a technique known as CT. This technique has a field of view bounded to the camera size and the illumination size. A technique to extended this field of view is going to be presented and the technical challenges involved in order for that to happen will be described. A pipeline is proposed and all the necessary algorithms are contained into a python packaged called Tomosaic. The approach relies on acquired partial tomogram data in a defined grid and later merging the data into a new dataset. Two possible ways are presented in order to that: in the projection domain, and in the sinogram domain. Initial experiments will then be used to show that the pipeline works with normal computers. The technique will be later applied to survey the whole anatomy of whole mouse brains. A study will be shown of how to get the complete range of scales of the mouse brain using x-ray tomography at different resolutions / Doutorado / Física / Doutor em Ciências / 163304/2013-0 / 1247445/2013, 1456912/2014 / CNPQ / CAPES

The problem of reconstructing an image from a set of tomographic data is not new, nor is it lacking attention. However there is still a distinct gap between the mathematicians and the experimental scientists working in the computed tomography (CT) imaging community. One of the aims in this thesis is to bridge this gap with mathematical reconstruction algorithms and analysis approaches applied to practical CT problems. The thesis begins with an extensive analysis for assessing the suitability of reconstruction algorithms for a given problem. The paper presented examines the idea of extracting physical information from a reconstructed sample and comparing against the known sample characteristics to determine the accuracy of a reconstructed volume. Various test cases are studied, which are relevant to both mathematicians and experimental scientists. These include the variance in quality of reconstructed volume as the dose is reduced or the implementation of the level set evolution method, used as part of a simultaneous reconstruction and segmentation technique. The work shows that the assessment of physical attributes results in more accurate conclusions. Furthermore, this approach allows for further analysis into interesting questions in CT. This theme is continued throughout the thesis. Recent results in compressive sensing (CS) gained attention in the CT community as they indicate the possibility of obtaining an accurate reconstruction of a sparse image from severely limited or reduced amount of measured data. Literature produced so far has not shown that CS directly guarantees a successful recovery in X-ray CT, and it is still unclear under which conditions a successful sparsity regularized reconstruction can be achieved. The work presented in the thesis aims to answer this question in a practical setting, and seeks to establish a direct connection between the success of sparsity regularization methods and the sparsity level of the image, which is similar to CS. Using this connection, one can determine the sufficient amount of measurements to collect from just the sparsity of an image. A link was found in a previous study using simulated data, and the work is repeated here with experimental data, where the sparsity level of the scanned object varies. The preliminary work presented here verifies the results from simulated data, showing an "almost-linear" relationship between the sparsity of the image and the sufficient amount of data for a successful sparsity regularized reconstruction. Several unexplained artefacts are noted in the literature as the `partial volume', the 'exponential edge gradient' or the 'penumbra' effect, with no clear explanation for their cause, or established techniques to remove them. The work presented in this paper shows that these artefacts are due to a non-linearity in the measured data, which comes from either the set up of the system, the scattering of rays or the dependency of linear attenuation on wavelength in the polychromatic case. However, even in monochromatic CT systems, the non-linearity effect can be detected. The paper shows that in some cases, the non-linearity effect is too large to ignore, and the reconstruction problem should be adapted to solve a non-linear problem. We derive this non-linear problem and solve it using a numerical optimization technique for both simulatedand real, gamma-ray data. When compared to reconstructions obtained using the standard linear model, the non-linear reconstructed images show clear improvements in that the non-linear effect is largely eliminated. The thesis is finished with a highlight article in the special issue of Solid Earth, named "Pore-scale tomography & imaging - applications, techniques and recommended practice". The paper presents a major technical advancement in a dynamic 3D CT data acquisition, where the latest hardware and optimal data acquisition plan are applied and as a result, ultra fast 3D volume acquisition was made possible. The experiment comprised of fast, free-falling water-saline drops traveling through a pack of rock grains with varying porosities. The imaging work was enhanced by the use of iterative methods and physical quantification analysis performed. The data acquisition and imaging work is the first in the field to capture a free falling drop and the imaging work clearly shows the fluid interaction with speed, gravity and more importantly, the inter- and intra-grain fluid transfers.

Although the current OCT imaging system was designed to examine the retinal structures, a novel application in imaging the anterior chamber angle was studied in section 3.7. OCT was demonstrated to be clinically useful for visualization of the different patterns of angle configurations in different forms of angle closure glaucoma. / In section 3.5, RNFL measurement by OCT was cross-validated by another nerve fiber analyzer, scanning laser polarimetry (SLP). While both OCT and SLP demonstrated comparable diagnostic performance for glaucoma detection and high correlation in the respective RNFL measurements, OCT was found to provide a closer estimation of RNFL thickness with reference to the reported histological measurements. In section 3.6, the structural-functional relationship between RNFL thickness and visual sensitivity was evaluated and compared between OCT and SLP. The relationships were found to be dependent on the choice of the perimetry scale, the type of RNFL measuring devices and the characteristics of the studied subjects. It was concluded that regression analysis of the structural-functional profile could provide important information in the assessment of the trend and pattern of glaucoma progression. / In summary, optical coherence tomography was shown to be useful in the diagnosis of glaucoma and in the evaluation of the trend and pattern of disease progression. / Objectives. The research project was designed to investigate the applications of optical coherence tomography in the assessment of glaucoma. The goals are to identify sensitive and specific anatomic markers, and analytical method for detection of glaucomatous changes, to evaluate the intricate structural-functional relationships in glaucoma with regression analysis and to assess the potential application of optical coherence tomography imaging system in visualization of the anterior chamber angle with a view to obtain OCT data to help understanding the pathophysiology of different forms of angle-closure glaucoma. / Sections 3.1 to 3.3 were designed to identify the most sensitive and specific diagnostic marker(s) for glaucoma detection. Peripapillary retinal nerve fiber layer (RNFL), macular thickness, optic nerve head parameters measured with different reference planes, and a novel anatomic marker - macular nerve fiber layer were investigated. The averaged peripapillary RNFL thickness measured with a high resolution scan (512 scan point) was found to have the best discriminating power for detection of glaucoma. It also has the strongest correlation with visual function. To examine if utilization of the complete data profile of peripapillary RNFL could further improve diagnostic sensitivity, a novel approach with the use of neural network trained to recognize RNFL pattern was studied in section 3.4. It was concluded that neural network analysis could enhance the diagnostic performance for glaucoma detection. / Summary. Glaucoma is a progressive optic neuropathy characterized by the loss of retinal ganglion cells resulting in constriction of visual field and loss of vision as the disease progresses. Since structural damage in glaucoma occurs well before any detectable loss in visual function, clinical examination of the optic nerve head and its nerve fiber layer is crucial in establishing the diagnosis, monitoring the progression and initiating treatment before irreversible damage takes place. The present research project is composed of 7 coherent studies (sections 3.1 to 3.7), aiming to investigate the clinical applications of optical coherence tomography (OCT), an advanced imaging device for detailed examination of optic nerve head and nerve fiber layer, in the assessment of glaucoma. / Leung Kai-shun. / "June 2006." / Adviser: Chi Pui Pang. / Source: Dissertation Abstracts International, Volume: 67-11, Section: B, page: 6323. / Thesis (M.D.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (p. 212-227). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / School code: 1307.

Lorentz TEM observations of magnetic nanoparticles contain information on the magnetic and electrostatic potentials of the sample. These potentials can be extracted from the electron wave phase shift by separating electrostatic and magnetic phase shifts, followed by 3D tomographic reconstructions. In past, Vector Field Electron Tomography (VFET) was utilized to perform the reconstruction. However, VFET is based on a conventional tomography method called filtered back-projection (FBP). Consequently, the VFET approach tends to produce inconsistencies that are prominent along the edges of the sample. We propose a model-based iterative reconstruction (MBIR) approach to improve the reconstruction of magnetic vector potential, A(r). In the case of scalar tomography, the MBIR method is known to yield better reconstructions than the conventional FBP approach, due to the fact that MBIR can incorporate prior knowledge about the system to be reconstructed. For the same reason, we seek to use the MBIR approach to optimize vector field tomographic reconstructions via incorporation of prior knowledge. We combine a forward model for image formation in TEM experiments with a prior model to formulate the tomographic problem as a maximum a posteriori probability estimation problem (MAP). The MAP cost function is minimized iteratively to deduce the vector potential. A detailed study of reconstructions from simulated as well as experimental data sets is provided to establish the superiority of the MBIR approach over the VFET approach.

Yuen, Wing Ki. / "June 2008." / Thesis (M.Phil.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references (leaves 44-58). / Abstracts in English and Chinese, some text in appendix also in Chinese. / Acknowledgements --- p.2 / Abstract --- p.3 / Table of Contents --- p.5 / List of Tables --- p.8 / List of Figures --- p.9 / CHAPTER / Chapter 1. --- INTRODUCTION --- p.11 / Purpose of the Study --- p.12 / Hypotheses --- p.12 / Chapter 2. --- LITERATURE REVIEW --- p.13 / Chapter 3. --- METHODS --- p.17 / Study population --- p.17 / Aerobic Capacity of Apparently Healthy Hong Kong Population --- p.17 / Mr Os and Ms Os --- p.18 / Recruitment of subjects --- p.19 / Chapter (a) --- Relationship between age and vBMD for the Chinese population using pQCT --- p.19 / Chapter (b) --- Risk factors for vBMD in peripheral sites --- p.20 / Chapter (c) --- Performance of pQCT and DXA on fracture discrimination --- p.20 / Subject inclusion and exclusion criteria --- p.21 / Interview and questionnaire --- p.21 / Anthropometric measurements --- p.22 / Overall health and medication --- p.22 / Cigarette smoking and alcohol consumption --- p.23 / Grip strength --- p.23 / Physical activity --- p.23 / Walking speed --- p.23 / Assessment of fracture case --- p.24 / Incident fracture --- p.24 / Bone Mineral Measurements --- p.24 / pQCT measurement --- p.24 / DXA measurement --- p.25 / Statistical Analysis --- p.26 / Chapter 4. --- RESULTS --- p.27 / Chapter (a) --- Relationship between age and vBMD for the Chinese population using pQCT --- p.27 / Chapter (b) --- Risk factors for vBMD in peripheral sites --- p.29 / Lifestyle factors --- p.29 / Medical history and medications --- p.30 / Fracture history --- p.30 / Multivariate model --- p.30 / Chapter (c) --- Performance of pQCT and DXA on fracture discrimination --- p.31 / Chapter 5. --- DISCUSSION --- p.33 / Relationship between age and vBMD for the Chinese population using pQCT --- p.33 / Risk factors for vBMD in peripheral sites --- p.36 / Performance of pQCT and DXA on fracture discrimination --- p.39 / Limitations --- p.42 / Conclusion --- p.42 / Reference --- p.44 / Appendix --- p.84 / Chapter A) --- Informed Consent Form --- p.84 / Chapter B) --- Medical Record Consent Form --- p.86 / Chapter C) --- MrOs/ MsOs baseline Questionnaire --- p.87 / Chapter D) --- MrOs/ MsOs Physical Measurement Questionnaire --- p.111 / Chapter E) --- MrOs/ MsOs follow-up Questionnaire --- p.120

Glaucoma is characterized by progressive optic nerve head (ONH) deformation and retinal nerve fiber layer (RNFL) thinning but the relative sequence of ONH and RNFL changes in glaucoma remains largely uncertain. It has been proposed that structural damage of the optic nerve can often be detected before detectable functional loss. Therefore, investigating structural changes of the ONH and RNFL is of importance and relevance in the monitoring and management of glaucoma progression. Spectral domain optical coherence tomography (OCT), scanning laser polarimetry (SLP) and confocal scanning laser ophthalmoscopy (CSLO) are the three prevailing digital imaging technologies for measurement of RNFL thickness, RNFL retardance and ONH parameters, respectively. Although these instruments have been extensively investigated for detection of glaucomatous damage, less is known about their relative performance for detection of change in glaucoma progression. Although previous studies on non- human primates showed that disruption of the microtubule structure of the retinal ganglion cell axons detected by SLP as reduction of RNFL retardance, as well as ONH surface deformation detected by CSLO, could be detected prior to reduction of RNFL thickness measured with OCT, clinical data corroborating this observation are lacking. The sequence of change of RNFL thickness, RNFL retardance and ONH parameters has not been investigated in human glaucoma. / This research project aimed to investigate the performance of OCT, SLP and CLSO for change detection of RNFL and ONH damages, determine the relative sequence of change of RNFL retardance and RNFL thickness and ONH deformation, and evaluate if ocular biomechanical properties, measured as corneal hysteresis by the ocular response analyzer (ORA, Reichert Inc.), influence the detection of ONH and RNFL progression in glaucoma patients. We hypothesized that ONH deformation and loss of RNFL retardance could be detected before detectable RNFL thinning and that the baseline corneal hysteresis would be a risk factor for ONH and RNFL damage in glaucoma. / In the first study, we analyzed 184 eyes of 116 patients with glaucoma and 43 normal eyes of 23 healthy individuals followed for a mean of 4.6 years. All subjects had RNFL retardance and RNFL thickness measurements obtained with GDx ECC (Carl Zeiss Meditec) and Cirrus HD-OCT (Carl Zeiss Meditec), respectively, at 4-month intervals. Progressive reduction of RNFL retardance and RNFL thickness were evaluated with Guided Progression Analysis (GPA, Carl Zeiss Meditec) with reference to the RNFL retardance change map and RNFL thickness change map, respectively. Twenty seven eyes of 26 patients showed progressive RNFL thinning whereas 8 eyes of 8 patients had RNFL retardance reduction in the latest follow-up visit. Seven eyes of 7 patients had progressive RNFL thinning and reduction of RNFL retardance detected by both instruments; all had progressive RNFL thinning evident before reduction of RNFL retardance and the mean lag time was 13.4 months (range: 4.0-37.6 months). The survival time of eyes detected with RNFL thinning was significantly shorter than the survival time of eyes detected with reduction of RNFL retardance (P=0.001). No eyes in the normal group showed progressive RNFL changes during follow-up. Collectively, we showed that at a comparable specificity (100%, 95% confidence interval: 96.3%-100%), progressive RNFL thinning was detected more often than progressive reduction of RNFL retardance and the former preceded the latter in eyes with both progressive RNFL thinning and reduction of RNFL retardance. / In the second study using a similar study design, we investigated the sequence of change of ONH surface depression detected by CSLO (HRT 3, Heidelberg Engineering) and RNFL thinning detected by OCT (Cirrus HD-OCT, Carl Zeiss Meditec) in 146 eyes of 90 glaucoma patients followed at approximately 4-month intervals for an average of 5.4 years. Significant ONH surface depression and RNFL thinning were defined with reference to Topographic Change Analysis (TCA, Heidelberg Engineering) and Guided Progression Analysis (GPA, Carl Zeiss Meditec), respectively. At a specificity of 94.3% (95% confidence interval: 86.2%-97.8%) for both RNFL thinning and ONH surface depression (determined in a normal group comprising 70 eyes from 35 normal subjects), 57 eyes (39.0%) had ONH surface depression, 46 eyes (31.5%) had RNFL thinning, and 23 eyes (15.8%) had both in the glaucoma group. Among these 23 eyes, 19 (82.6%) had ONH surface depression detected prior to RNFL thinning and the median lag time was 15.8 months (range, 4.0-40.8 months). Although only 7.0% of eyes (4/57) had RNFL thinning at the onset of ONH surface depression, 45.7% (21/46) had ONH surface depression at the onset of RNFL thinning. The survival time of eyes with ONH surface depression was significantly shorter than the survival time of eyes detected with RNFL thinning (P=0.002). With reference to the HRT TCA and OCT GPA, ONH surface depression occurred before RNFL thinning in a significant proportion of patients with glaucoma at a comparable specificity. / Of note, a significant proportion of eyes had ONH surface depression without any detectable progressive RNFL thinning in the second study, and vice versa. Investigating whether the risk factors for ONH surface depression and RNFL progression are different is therefore important. In the final study, we investigated if baseline corneal hysteresis is a risk factor for progressive ONH surface depression and RNFL thinning. Following the same cohort of 146 eyes of 90 glaucoma patients for an average of 6.8 years, we detected that 65 eyes (44.5%) had progressive ONH surface depression, 55 eyes (37.7%) had progressive RNFL thinning and 20 eyes (13.7%) had visual field progression (based on the EMGT criteria). After adjusting for ages, CCT, baseline diastolic IOP, average IOP during follow-up, baseline disc area and baseline MD in the cox proportional hazards model, baseline corneal hysteresis was significantly associated with ONH surface depression (HR=0.70, P=0.008), visual field progression (HR=0.56, P=0.019), but not with progressive RNFL thinning (HR=0.96, P=0.751). For each 1-mmHg decrease of baseline CH, the hazards for ONH surface depression and visual field progression increased by 30% and 44%, respectively. / In summary, at a comparable level of specificity, progressive ONH surface depression detected by CSLO could be observed prior to progressive RNFL thinning detected by OCT, which preceded identified reduction of RNFL retardance detected by SLP. For eyes with concomitant ONH surface depression, RNFL thinning and visual field progression, ONH surface depression always preceded visual field progression. Our finding indicates that a time window for therapeutic intervention may exist upon detection of ONH surface depression before irreversible RNFL and visual field loss and that measurement of CH would be useful to predict ONH surface depression and visual field progression. / Further studies are required to investigate the sequence of optic nerve head change and RNFL progression with the same instrument. Whether IOP lowering treatment initiated at the time of ONH deformation would be effective to prevent or slow down RNFL and visual field loss needs to be further investigated. A more reliable and accurate measure of the ocular biomechanical properties is necessary for evaluation of their contribution to glaucoma progression. / 青光眼是一種進展性視神經病變，其特徵為﹕視神經乳頭變形，神經纖維層（RNFL）的變薄以及相應的視野缺損。然而，青光眼結構性改變和功能性變化發生的相對順序仍不清楚。視神經結構性改變被認為要早於功能性改變的發生。因此，研究視乳頭的結構性改變具有重要意義，有助於早期診斷青光眼的進展及隨訪青光眼患者。目前主要用於RNFL厚度，RNFL阻滯性以及視乳頭參數的影像學掃描儀器為頻域OCT，鐳射偏振光掃描器（SLP）和共聚焦鐳射掃描眼底鏡（CSLO）。儘管這三種儀器已經廣泛用於青光眼損傷的檢測，但在青光眼患者結構性變化的應用並不常見。既往在非人靈長類動物的實驗中，通過破壞神經節細胞軸突中的微小管結構，從而發現RNFL的阻滯性以及視乳頭的變化要先於RNFL厚度變化的發生。然而在臨床研究中並未得到證實。同時，在青光眼患者中，RNFL厚度變化，RNFL阻滯減少以及視神經頭參數改變之間的先後順序並未得到證實。 / 本次實驗研究的目的在於探討OCT，SLP及CSLO在診斷青光眼病人RNFL及視乳頭進展的能力，確定RNFL厚度變化，RNFL阻滯性減少以及視神經頭參數改變之間的相對順序，以及評估眼反應分析儀（ORA）測得的角膜粘滯性（CH）是否影響視乳頭及RNFL厚度的進展。我們假設：視神經乳頭的變形，RNFL阻滯性的減少要先於RNFL厚度的變化，基線角膜粘滯性的測量會影響視乳頭及RNFL進展的檢測。116個青光眼病人的184隻眼以及23個正常對照的43隻眼被納入第一個研究中。所有受試物件均接受每4個月一次的OCT以及SLP RNFL的掃描，平均隨訪時間為4.6年。通過OCT及SLP中Guided Progression Analysis（GPA, Carl Zeiss Meditec）程式，一系列RNFL厚度及粘滯性圖被自動分析從而獲得RNFL厚度及粘滯性的變化結果。26個青光眼患者的27隻眼表現為RNFL厚度的進行性變薄，8個患者的8隻眼表現為RNFL粘滯性的減少。其中7個患者的7隻眼同時表現為RNFL厚度變薄及粘滯性的減少，所有這7隻眼的RNFL變薄的發生要早於RNFL粘滯性的減少，兩者間隔時間平均為13.4月（4.0-37.6月）。RNFL厚度變薄者的生存概率明顯小於RNFL粘滯性減少的青光眼患者（P=0.001）。隨訪中，我們未發現正常對照組中RNFL厚度變薄或者粘滯性改變者。總體說來，在同一特異性水準（100%），RNFL厚度的變化頻率高於粘滯性的改變，RNFL厚度的變薄要早於粘滯性減少的發生。 / 採用相同於第一個研究的研究方法，我們研究CSLO測得的視乳頭表面凹陷以及測得OCT的RNFL厚度變化發生的相對順序。90個青光眼患者的146隻眼以及35個正常對照物件的70隻眼被納入第二個研究中。所有受試物件均接受4個月一次的CSLO及OCT掃描從而獲得一系列的視神經頭表面的拓撲圖像以及RNFL厚度圖。CSLO TCA及OCT GPA程式自動對比基線及隨訪中所獲得的視神經頭表面的拓撲圖像以及RNFL厚度圖，從而獲得視乳頭表面凹陷及RFNL進展報告。平均隨訪5.4年後，CSLO及OCT在診斷視神經頭及RNFL進展的特異性為94.3%，57只青光眼患眼（39.0%）表現為顯著性視乳頭表面凹陷，46隻眼（31.5%）表現為RFNL厚度的進行性變薄，而23隻眼（15.8%）同時表現為視乳頭面凹陷和RFNL的進行性變薄。在這23只眼中，19隻眼（82.6%）變現為視乳頭表面凹陷先於RFNL厚度變薄的發生，間隔時間的中值為15.8個月（4.0-40.8月）。儘管在顯著性視乳頭表面凹陷發生時，僅有7.0%的患眼表現為RNFL厚度的變薄；但是，在RNFL厚度發生顯著性變薄時已有45.7%的患眼表現為視乳頭表面凹陷。視乳頭表面凹陷患眼的生存概率差於RNFL厚度變薄患眼（P=0.002）。在青光眼患者的隨訪中，CLSO TCA測得的視乳頭表面凹陷要早於OCT GPA測得的RNFL厚度的變化。 / 最後的一個研究目在於評估眼反應分析儀（ORA）測得的基線角膜粘滯性（CH）是否為視乳頭表面凹陷及RNFL厚度變薄的危險因素。平均隨訪同一人群即第二個研究中的90個青光眼患者的146眼6.8年，65隻眼（44.5%）被檢測出具有進行性視乳頭表面凹陷，55隻眼（37.7%）表現為進行性RNFL厚度的變薄，20隻眼（13.7%）表現為進行性視野的缺損（基於EMGT標準）。基線CH與視乳頭表面凹陷，視野進展間具有顯著性相關關係（HR=0.70，P=0.008及HR=0.56，P=0.019），但CH與進行性RNFL厚度變薄間並無顯著性相關關係（HR=0.96，P=0.751）。每1毫米汞柱基線CH的降低，發生視乳頭表面凹陷及視野缺損的危險性將增加30%及44%。CH的測量值與青光眼進展的危險性具有顯著相關關係。 / 總之，在具有可比性特異性水準下，CSLO檢測的進展性視乳頭表面凹陷的發生要先於OCT檢測的進行性RNFL厚度的變薄，後者的發生早於SLP測得的RNFL粘滯性的改變。對於同時有視乳頭表面凹陷，RNFL厚度變薄及RNFL粘滯性改變的青光眼患眼，視乳頭表面凹陷的發生要早於視野的進展。我們的實驗研究表明了在青光眼患者發生視乳頭表面凹陷時，治療的時間窗的存在有助於避免不可逆的RNFL缺失及視野的缺損。角膜粘滯性的測量對於預測視乳頭表面凹陷及視野進展具有重要意義。 / 展望未來的研究中，用同一種儀器進行視乳頭及神經纖維層的隨訪，從而得出相對的變化次序很有必要。研究在視乳頭或者神經纖維層發生變化時進行眼壓的干預是否能避免視功能的進一步損傷顯得尤為重要。用於測量角膜生物學特性的更為準確，可信度更高的儀器真正研發中，以及進一步探討角膜生物學特性與青光眼進展之間的關係。 / Xu, Guihua. / Thesis Ph.D. Chinese University of Hong Kong 2015. / Includes bibliographical references (leaves 116-145). / Abstracts also in Chinese. / Title from PDF title page (viewed on 18, October, 2016). / 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.

L'imagerie médicale remonte à la fin du XIXe siècle avec la découverte des rayons X par Röntgen. Depuis, de nombreuses modalités d'imagerie ont été développées, et sont aujourd'hui utilisées dans une large gamme d'indications cliniques. L'imagerie TEP (Tomographie par Émission de Positron) est une modalité fonctionnelle, quantitative et ayant une haute sensibilité, ce qui en fait une modalité de choix, notamment en cancérologie. Hélas, sa diffusion est freinée en comparaison avec le scanner ou l'imagerie par résonance magnétique, en raison de son coût notamment. C'est dans ce contexte que s'insère cette thèse, qui a pour objectif de montrer la faisabilité d'un imageur TEP ambulatoire dédié au suivi thérapeutique en cancérologie. À partir de développements instrumentaux originaux (localisation des gammas par division de lumière dans des barreaux scintillateurs, lecture à l'aide de Silicon PhotoMultiplier, géométrie compacte), ces travaux s'efforcent de baisser les coûts tout en restant compétitif en terme de performances. Dans un premier temps, une étude extensive de la division de lumière à travers toute une série de paramètres (longueur des barreaux scintillateurs, revêtement optique, matériau scintillateur, traitement des données) a été menée. Une résolution spatiale inférieure à 5 mm pour un barreau de 75 mm de LYSO emballé dans du teflon a notamment été obtenue. À partir de cette configuration, une première image a été reconstruite, à partir de deux modules en coïncidence, offrant une résolution spatiale de 5 mm pour un tel imageur. Enfin, toute une série de simulations a été menée, à partir des données expérimentales et avec une géométrie originale. En particulier, les performances ont été mesurées à partir du protocole NEMA, un standard permettant de comparer les performances à travers la littérature. Une résolution spatiale intrinsèque de l'ordre de 4 mm a été obtenue, soit meilleure que le marché actuel. La sensibilité de l'ordre de 2.5 cps/kBq est revanche relativement basse par rapport à l'existant, mais s'explique par un champ de vue axial restreint. Enfin, le potentiel en terme de quantification a été adressé, et est comparable au marché actuel. / Medical imaging first began at the end of the XIXth century with the discover of X-rays by Röntgen. Then, numerous imaging modalities have been developed and are used now for a wide range of cases. Positron Emission Tomography (PET) has a high sensitivity, is functional and quantitative, thus being of high interest in cancer monitoring. Nevertheless, PET is not as much spread in hospitals as magnetic resonance imaging and scanner. In this context, this work aims to prove the faisability of PET dedicated for cancer monitoring. Thanks to instrumental developments such as light sharing in scintillating crystals, use of Silicon Photomultipliers, and an original geometry, cost is expected to be reduced while having same performances as commercial devices. An extensive study of light sharing within scintillating barrels has been made, through many parameters (crystal length, coating, data analysis...). An intrinsic spatial resolution of 4 mm has been measured over a 75 mm long crystal of LYSO, coated with teflon. From such a configuration, a first image has been reconstructed using two modules in coincidence. A spatial resolution of 5 mm has been measured in the image. Finally, Monte Carlo simulations has been made with experimental data as input, in order to measure the performances of the final PET device. Thanks to NEMA standard protocol, performances has been measured and compared to other systems. A spatial resolution of 4 mm has been reached, for a sensitivity of 2.5 cps/kBq. Quantification problem has been assessed, providing results similar to existing devices.

The understanding of multiphase flow properties is essential for the exploitation of hydrocarbon reserves in a reservoir; these properties in turn are dependent on the geometric properties and connectivity of the pore space. The determination of the pore size distribution in carbonate reservoirs remains challenging; carbonates exhibit complex pore structures comprising length scales from nanometers to several centimeters. A major challenge to the accurate evaluation of these reservoirs is accounting for pore scale heterogeneity on multiple scales. This is the topic of this thesis. Conventionally, this micron scale information is achieved either by building stochastic models using 2D images or by combining log and laboratory data to classify pore types and their behaviour. None of these capture the true 3D connectivity vital for flow characterisation. We present here an approach to build realistic 3D network models across a range of scales to improve property estimation through employment of X-ray micro-Computed Tomography (μCT) and Focussed Ion Beam Tomography (FIBT). The submicron, or microporous, regions are delineated through a differential imaging technique undertaken on x-ray CT providing a qualitative description of microporosity. Various 3-Phase segmentation methods are then applied for quantitative characterisation of those regions utilising the attenuation coefficient values from the 3D tomographic images. X-ray micro-CT is resolution limited and can not resolve the detailed geometrical features of the submicron pores. FIB tomography is used to image the 3D pore structure of submicron pores down to a scale of tens of nanometers. We describe the experimental development and subsequent image processing including issues and difficulties resolved at various stages. The developed methodology is implemented on cores from producing wackstone and grainstone reservoirs. Pore network models are generated to characterise the 3D interconnectivity of pores. We perform the simulations of petrophysical properties (permeability and formation resistivity) directly on the submicron scale image data. Simulated drainage capillary pressure curves are matched with the experimental data. We also present some preliminary results for the integration of multiscale pore information to build dual-scale network models. The integration of multiscale data allows one to select appropriate effective medium theories to incorporate sub-micron structure into property calculations at macro scale giving a more realistic estimation of properties.