Glaucoma is a leading cause of irreversible vision loss globally, and demands early and accurate diagnosis. OCT has become a key investigative technique in glaucoma, and, although it provides invaluable clinical support, detection of early glaucoma remains imperfect. Recent OCT developments enabled direct assessment of retinal nerve fibre bundle (RNFB) reflectance in en face OCT images. The technique has considerable potential in the assessment of glaucoma, yet it has limited clinical usability due to an incomplete understanding of RNFB features in healthy and glaucoma eyes and the lack of accepted methods to identify reflectance defects. This thesis aimed to better understand characteristics of RNFB reflectance in en face OCT imaging and to develop objective methods to extract defects in this domain. Structural and functional measures of glaucoma changes were collected in eyes with established glaucoma and age-similar controls. Results showed that the healthy configuration of RNFB varies across the retina and between different eyes. We developed a method for automated and objective examination of reflectivity changes in en face images. This method considers individual anatomy and varying RNFB configuration, and found more abnormalities than previous approaches. Measures of en face reflectance and conventional retinal nerve fibre layer thickness were strongly related. The agreement between changes of reflectance and visual function was moderate-to-good, and both testing domains presented concordant abnormalities in all tested eyes. Following further minimisation of artefacts in en face images, direct use of reflectance analysis or its combination with perimetry appear viable and with significant potential for clinical examination of glaucoma.

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This thesis presents a three-dimensional computed tomography (3D-CT) analysis of craniofacial morphology and growth changes in Malaysian Malay subjects. A large number of CT scans (n=205) from birth to adulthood were gathered for this purpose. CT scans were obtained using a GE Lightspeed Plus Scanner. Craniofacial morphology has been analysed based on cephalometric landmarks located in three-dimensions, using specially-designed computer software. The main aims were to produce new 3D normative reference data for selected craniofacial variables in Malaysian Malays and to study growth changes in different craniofacial regions. The specific areas of investigation included: 1. Construction of craniofacial growth references (in tabular and graphical formats) for Malaysian Malays; 2. Quantitative analysis of growth changes in the craniofacial complex using linear and angular measurements derived from landmark data; 3. Comparison of craniofacial measurements between males and females to determine the extent of sexual dimorphism; 4. Quantitative analysis of the nature and extent of directional asymmetry of selected craniofacial regions; 5. Comparisons of selected variables with published data from other ethnic groups. Craniofacial morphology and growth changes were analysed using 3D osseous landmarks. A computer program, PERSONA, was used to locate and analyse the three-dimensional cephalometric landmarks. The accuracy of landmark location was assessed using double determinations. Selected measurements were derived from the landmark data to describe the morphology of different craniofacial regions, e.g. facial skeleton, cranial base and cranial vault. Normative reference data for a large number of variables covering the skull, cranial base and face at selected age categories for males and females were constructed. These data were presented in tables and scatter plots of variables against age. From the normative data collected, patterns of growth changes of different craniofacial regions in three-dimensions were also investigated. Generally, each craniofacial region showed a unique growth pattern as observed from differential growth patterns. All measurements showed size increase from infancy to adulthood. Periods of increased size differences were also noted for most variables in all regions that corresponded to the timing of mid- and adolescent growth spurts. These extensive normative reference data, specific for age categories and sexes, provide normal references against which the craniofacial morphology of individuals with craniofacial abnormalities can be compared. Clinical applications of this quantitative approach to the craniofacial skeleton should facilitate the management of craniofacial abnormalities. Following the construction of normative data and description of growth changes for different craniofacial regions, intra-populational differences were studied. This included analysis of sexual dimorphism of the craniofacial structures and an investigation of asymmetry between paired left and right measurements. Sexual dimorphism was observed for linear variables in this study. Differences in size between males and females were not very obvious during infancy as only a few variables showed significant differences. The number of variables that showed sexual dimorphism in size increased from infancy to adulthood. Sexual dimorphism in the craniofacial region was most evident during adulthood with 46% of variables displaying significant differences between the sexes. During infancy, only 3% of the variables showed significant size differences between the sexes, increasing to 7% during childhood. Magnitudes of sexual dimorphism were calculated to highlight the pattern of dimorphism in different craniofacial regions and across different ages. A small degree of directional asymmetry was noted in all of the craniofacial regions investigated. Asymmetry analysis revealed that the cranial base, face and mandible tended to be larger on the right side than the left. Other regions exhibited asymmetry but without any clear trend in direction. Asymmetry percentages were also calculated to enable the patterns and magnitudes of asymmetry in different craniofacial regions to be compared. Generally, the amount of asymmetry exhibited in the craniofacial structures for Malaysian Malays was small. Having established that differences existed within the Malay sample, craniofacial data for Malays were compared with published data for two Caucasian populations. This analysis revealed that differences exist in craniofacial morphology between different ethnic groups. Some of the differences can be discerned from childhood but many variables only display differences during adulthood. Craniofacial structures tended to be smaller in Malays than in Caucasians. The intent of this investigation has been to provide clinicians with normative values of measurements that will be useful in diagnosis, treatment planning and post-operative care of patients with craniofacial abnormalities. Important treatment goals include producing balanced cranial and facial form to approximate that of unaffected people and also improving the quality of life of patients. Therefore, it is important for clinicians to be able to recognise the nature and extent of normal variation in craniofacial structures and also appreciate the growth changes that may occur over time, before investigating these changes in patients with craniofacial abnormalities. Comparisons of measurements of affected patients with well-characterised referent data can facilitate diagnosis and overall patient management. Moreover, quantification based on three-dimensional data provides new insights into craniofacial growth changes and morphology compared with conventional 2D approaches. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1280892 / Thesis (Ph.D.) -- Dental School, 2007.

La microscopie non linéaire a transformé le domaine de la neurobiologie depuis les années 1990, en permettant d'acquérir des images tridimensionnelles de tissus épais avec une résolution subcellulaire. Cependant, les profondeurs d'imagerie accessibles sont limitées à quelques centaines de micromètres dans des tissus diffusants tels que le tissu cérébral. Au cours des dernières années, plusieurs stratégies ont été développées pour dépasser cette limitation de profondeur et accéder à de plus grands volumes de tissu. Ces avancées récentes ont jusqu'à présent été limitées en terme de modes de contrastes accessibles, et ont souvent été réduites à des approches monochromes. Ce travail de thèse vise à développer des techniques d'imagerie non linéaires de grands volumes et de grande profondeur dotées de diverses possibilités de contrastes, indispensables pour l'étude de tissus complexes tels que le tissu cérébral. Dans un premier chapitre, nous présentons les difficultés associées à l'imagerie de grand volume de tissu cérébral, avec une emphase particulière sur les puissantes stratégies de marquages génétiques dont l'usage à jusqu'à présent été limité à des faibles étendues. Ensuite, nous introduisons la microscopie Chrom-SMP (chromatic serial multiphoton), une méthode développée au cours de cette thèse et consistant à combiner l’excitation deux-photon multicouleurs par mélange de fréquences avec une technique d'histologie automatisée (i.e découpe sériée) pour accéder à plusieurs contrastes non linéaires à travers de grands volumes de tissus ex vivo, allant de plusieurs mm3 à des cerveaux entiers, avec une résolution micrométrique et un coalignement intrinsèque des canaux spectraux. Dans un troisième chapitre, nous explorons le potentiel de cette nouvelle approche pour la neurobiologie. En particulier, nous démontrons l'histologie multicouleur de plusieurs mm3 de tissu "Brainbow" avec une résolution constante dans l’ensemble du volume imagé. Nous illustrons le potentiel de notre approche à travers l'analyse de la morphologie, des interactions et du lignage des astrocytes du cortex cérébral de souris. Nous explorons également l’apport du Chrom-SMP pour le suivi multiplexé de projections neuronales marquées par des traceurs de couleurs distinctes sur de grandes distances. Enfin, nous présentons dans un quatrième chapitre le développement de la microscopie à trois photons multimodale, approche permettant d’augmenter la profondeur d’imagerie sur tissus vivants. / Multiphoton microscopy has transformed neurobiology since the 1990s by enabling 3D imaging of thick tissues at subcellular resolution. However the depths provided by multiphoton microscopy are limited to a few hundreds of micrometers inside scattering tissues such as the brain. In the recent years, several strategies have emerged to overcome this depth limitation and to access larger volumes of tissue. Although these novel approaches are transforming brain imaging, they currently lack efficient multicolor and multicontrast modalities. This work aims at developing large-scale and deep-tissue multiphoton imaging modalities with augmented contrast capabilities. In a first chapter, we present the challenges of high-content large-volume brain imaging, with a particular emphasis on powerful multicolor labeling strategies which have so far been restricted to limited scales. We then introduce chromatic serial multiphoton (Chrom-SMP) microscopy, a method which combines automated histology with multicolor two-photon excitation through wavelength-mixing to access multiple nonlinear contrasts across large volumes, from several mm3 to whole brains, with submicron resolution and intrinsic channel registration. In a third chapter, we explore the potential of this novel approach to open novel experimental paradigms in neurobiological studies. In particular, we demonstrate multicolor volumetric histology of several mm3 of Brainbow-labeled tissues with preserved diffraction-limited resolution and illustrate the strengths of this method through color-based tridimensional analysis of astrocyte morphology, interactions and lineage in the mouse cerebral cortex. We further illustrate the potential of the method through multiplexed whole-brain mapping of axonal projections labeled with distinct tracers. Finally, we develop multimodal three-photon microscopy as a method to access larger depths in live settings.