Optical Coherence Tomography (OCT) is an imaging technique that uses near infra-red light to non-invasively form cross-sectional images of specimens, in a similar way to ultrasound and RADAR. A number of research groups have used OCT to study natural and artificial carious lesions and to some extent erosive lesions. For this, a variety of in vitro models have been used. However, the exact mechanism by which these demineralised enamel lesions affect the OCT measurements is not fully understood. This remains a barrier to its adoption as both an analytical laboratory tool and a widespread technique in clinical dentistry. Therefore, the aim of this thesis was to develop an understanding of how different demineralised enamel lesions manifest in OCT measurements. This is necessary for the technique to become useful as an in vivo clinical measurement and imaging system. Consequently, this study was carried out in a controlled laboratory environment for which a novel specimen holder was designed. This mitigated against specimen movement and maintained specimen hydration, which can be a source of uncertainty in the measurements. A custom-built OCT microscope was used for this work, which enabled automation of experiments and continuous time-lapse OCT imaging over time periods of hours to several days. This enabled bovine enamel demineralisation dynamics to be captured during in vitro caries and erosion formation. The stability of the system also enabled direct comparison between the OCT measurements of the optical properties of different demineralisation models. To achieve these measurements, the OCT system was carefully characterised and compared to established profilometry measurements. Interestingly, this revealed that the experimental protocol used to obtain lesions for profilometry was not to be representative of the lesions formed and measured by OCT. This is an important point when interpreting OCT data in light of other techniques. A novel method of analysis was developed that uses longitudinal OCT image correlation to quantify early stage surface softening during erosion. By using OCT volumetric data, this technique was able to measure sub-resolution changes at the specimen surface. Early results also indicate sensitivity to remineralisation. This thesis shows that OCT is sensitive to different demineralisation models produced and measured under controlled conditions. New method of handling the data can observe changes not previously seen in OCT. However, further work is still required to understand the underlying physical changes that lead to this sensitivity in OCT.

With current needs to better understand the interaction between atrial tissue microstructure and atrial fibrillation dynamics, micrometer scale imaging with optical coherence tomography has significant potential to provide further insight on arrhythmia mechanisms and improve treatment guidance. However, optical coherence tomography imaging of cardiac tissue in humans is largely unexplored, and the ability of optical coherence tomography to identify the structural substrate of atrial fibrillation has not yet been investigated. Therefore, the objective of this thesis was to develop an optical coherence tomography imaging atlas of the human heart, study the utility of optical coherence tomography in providing useful features of human left atrial tissues, and develop a framework for optical coherence tomography-informed cardiac modeling that could be used to probe dynamics between electrophysiology and tissue structure. Human left atrial tissues were comprehensively imaged by optical coherence tomography for the first time, providing an imaging atlas that can guide identification of left atrial tissue features from optical coherence tomography imaging. Optical coherence tomography image features corresponding to myofiber and collagen fiber orientation, adipose tissue, endocardial thickness and composition, and venous media were established. Varying collagen fiber distributions in the myocardial sleeves were identified within the pulmonary veins. A scheme for mapping optical coherence tomography data of dissected left atrial tissues to a three-dimensional, anatomical model of the human left atrium was also developed, enabling the mapping of distributions of imaged adipose tissue and fiber orientation to the whole left atrial geometry. These results inform future applications of structural substrate mapping in the human left atrium using optical coherence tomography-integrated catheters, as well as potential directions of ex vivo optical coherence tomography atrial imaging studies. Additionally, we developed a workflow for creating optical mapping models of atrial tissue as informed by optical coherence tomography. Tissue geometry, fiber orientation, ablation lesion geometry, and heterogeneous tissue types were extracted from optical coherence tomography images and incorporated into tissue-specific meshes. Electrophysiological propagation was simulated and combined with photon scattering simulations to evaluate the influence of tissue-specific structure on electrical and optical mapping signals. Through tissue-specific modeling of myofiber orientation, ablation lesions, and heterogeneous tissue types, the influence of myofiber orientation on transmural activation, the relationship between fluorescent signals and lesion geometry, and the blurring of optical mapping signals in the presence of heterogeneous tissue types were investigated. By providing a comprehensive optical coherence tomography image database of the human left atrium and a workflow for developing optical coherence tomography-informed cardiac tissue models, this work establishes the foundation for utilizing optical coherence tomography to improve the structural substrate characterization of atrial fibrillation. Future developments include analysis of optical coherence tomography imaged tissue structure with respect to clinical presentation, development of automated processing to better leverage the large amount of imaging data, enhancements and validation of the modeling scheme, and in vivo evaluation of the left atrial structural substrate through optical coherence tomography-integrated catheters

Papilledema is a particular type of optic disc swelling caused by elevated intracranial pressure. By observing the visible features from fundus images or direct funduscopic examination, a typical method of assessing papilledema (i.e., the six-stage Fris\'en grading system) is qualitative and frequently suffers from low reproducibility. Compared to fundus images, spectral-domain optical coherence tomography (SD-OCT) is a relatively new imaging technique and enables the cross-sectional information of the retina to be acquired. Using SD-OCT images, quantitative measurements like evaluating the retinal volume or depth are intuitively more robust than the traditional qualitative approach to evaluate papilledema. Also, multiple studies suggest that the deformation of the peripapillary retinal pigment epithelium and/or Bruch's membrane (pRPE/BM) may reflect the intracranial pressure change. In other words, modeling/quantifying the pRPE/BM shape can potentially be another indicator of papilledema. However, when the optic disc is severely swollen, the retinal structure is dramatically deformed and often causes the commercial SD-OCT devices to fail to segment the retinal layers. Without appropriate layer segmentation, all the retinal measurements are not reliable. To solve the current issue of inconsistently assessing papilledema severity, a comprehensive machine-learning framework is proposed in this doctoral work to achieve the goal by accomplishing following four aims. First, robust approaches are developed to automatically segment the retinal layers in 2D and 3D SD-OCT images, even though the optic discs can be severely swollen. Second, the semi- and fully automated methodologies are designed to segment the pRPE/BM opening under the swollen inner retina in these SD-OCT images. Third, the pRPE/BM shape models are constructed using both 2D and 3D SD-OCT images, and then the 2D/3D pRPE/BM shape measures are computed. Finally, based on the previously segmented retinal layers, eight OCT 2D/3D global/local measurements of retinal structure are reliably computed. Considering both the 2D/3D pRPE/BM shape measures and these eight OCT features as an input set, a machine-learning framework using the random forest technique is proposed to compute a papilledema severity score (PSS) on a continuous scale. The newly proposed PSS is expected to be an alternative to the traditional qualitative method to provide a more objective measurement of assessing papilledema severity.

Acquiring the motions of the inner ear sensory tissues provides insight to how the cochlea works. For this purpose, Spectral Domain Optical Coherence Tomography (SDOCT) is an ideal tool as it has a penetration depth of several millimeters. SDOCT can not only image inside the cochlear partition, but also measure the sample structures’ simultaneous displacements. We customized a commercial Spectral Domain Optical Coherence Tomography system for such functions and detailed the software and hardware steps so this powerful system could be more accessible to auditory researchers. The cochlea is surrounded by bones and tissues, and damage to it would make it passive. For this reason, cochlear vibrometry measuring locations have been limited to either the basal or apical regions. That is why I fabricated a two-dimensional scanning SDOCT-based probe, to access more cochlear locations through a small hand-drilled hole. What is exciting about the probe is that an electrode can be attached to its side to acquire spatially and temporally coincident voltage and displacement data. This would help us better understand the cochlear mechano-electrical feedback process. Lastly, I investigated how the SDPM-reported displacement could be influenced by its neighboring signals and demonstrated this signal competition phenomenon experimentally and theoretically.

The purpose of this project is to develop a retinal imaging system suitable for routine examination or screening of mouse models that acquires fundus and Optical Coherence Tomography (OCT) images. The imaging system is composed of a digital camera with an objective for biomicroscopic examination of the fundus, an OCT interferometer, an OCT beam delivery system designed for the mouse eye, and a mouse positioning stage. The image acquisition is controlled with software that displays the fundus and OCT images in real-time, and allows the user to control the position of the OCT beam spot on the fundus image display. The system was used to image healthy mice and a mouse model of glaucoma. Fundus images and OCT scans were successfully acquired in both eyes of all mice with eyes that had clear optics. The study demonstrates the feasibility of acquiring simultaneous fundus and OCT images of the mouse retina, by a single operator, in a manner suitable for rapid evaluation of mouse models of retinal disease.

Measuring the Mueller matrix with optical coherence tomography (OCT) makes it possible to acquire the complete polarization properties of scattering media with three-dimensional spatial resolution. We first proved that the measured degree-of-polarization (DOP) of the backscattered light by OCT remains unity-a conclusion that validated the use of Jones calculus in OCT. A multi-channel Mueller-matrix OCT system was then built to measure the Jones-matrix, which can be transformed into a Mueller matrix, images of scattering biological tissues accurately with single depth scan. We showed that when diattenuation is negligible, the round-trip Jones matrix represents a linear retarder, which is the foundation of conventional PS-OCT, and can be calculated with a single incident polarization state although the one-way Jones matrix generally represents an elliptical retarder; otherwise, two incident polarization states are needed. We discovered the transpose symmetry in the roundtrip Jones matrix, which is critical for eliminating the arbitrary phase difference between the two measured Jones vectors corresponding to the two incident polarization states to yield the correct Jones matrix. We investigated the various contrast mechanisms provided by Mueller-matrix OCT. Our OCT system for the first time offers simultaneously comprehensive polarization contrast mechanisms including the amplitude of birefringence, the orientation of birefringence, and the diattenuation in addition to the polarization-independent intensity contrast, all of which can be extracted from the measured Jones or the equivalent Mueller matrix. The experimental results obtained from rat skin samples, show that Mueller OCT provides complementary structural and functional information on biological samples and reveal that polarization contrast is more sensitive to thermal degeneration of biological tissues than amplitude-based contrast. Finally, an optical-fiber-based multi-channel Mueller-matrix OCT was built and a new rigorous algorithm was developed to retrieve the calibrated polarization properties of a sample. For the first time to our knowledge, fiber-based polarization-sensitive OCT was dynamically calibrated to eliminate the polarization distortion caused by the single-mode optical fiber in the sample arm, thereby overcoming a key technical impediment to the application of optical fibers in this technology.

This project initiated with the aim for improving the ultrahigh resolution optical coherence tomography (UHR-OCT) system performance by considering the limitations to the axial OCT resolution for in vivo imaging of human and animal retina. To this end, a computational model was developed to simulate the effect of wavelength-dependant water absorption on the detected spectral shape of the broad-bandwidth light source used in UHR-OCT at 1060nm wavelength region, which effectively determines the axial OCT resolution in the retina. For experimental verification of the computational model, a custom built light source with a re-shaped spectrum (Superlum Inc.) was interfaced to the state-of-the-art UHR-OCT system. About 30% improvement of the axial OCT resolution in the rat retina and ~12% improvement of the axial OCT resolution in the human retina was achieved compared to the case of the almost Gaussian shaped spectrum of the standard, commercially available SLD. Although water absorption in the 1060nm spectral region strongly affects the sample beam, selecting a suitable light source with specific spectral shape can compensate for the undesired water absorption effect and thus result in significantly improved axial resolution in in vivo OCT retinal images. To demonstrate the advantages of the state-of-the-art OCT technology for non invasive retinal imaging, an established animal model of outer retina degeneration (sodium iodate (NaIO3)-induced retina degeneration) was employed for longitudinal monitoring of the degeneration and investigation of possible early and dynamic signs of damage undetected by other imaging modalities. The long-term (up to 3 months) and short-term (up to 12 hours) effect of sodium iodate toxicity on the layered structure of retina was monitored longitudinally and in vivo for the first time using OCT. An initial acute swelling of the retina, followed by progressive disruption and degeneration of outer retina was observed as a result of sodium iodate-induced damage. Changes in the thickness and optical reflectivity of individual retinal layers were extracted from the OCT images to quantify the changes occurring at different stages of the disease model. Results from this project present the theoretical and practical limits to the highest axial OCT resolution achievable for retina imaging in the 1060nm spectral range both in small animals and humans, and provided a framework for future development of novel light sources. Furthermore, UHR-OCT imaging was shown to be an effective and valuable modality for in vivo, non invasive investigation of retina degenerative disease.

Abstract Both in the closed and open eye state the superior limbus is covered by the upper lid. This region is of physiological interest and clinical importance because in chronic hypoxia, neovascularization of the cornea commonly occurs here. The limbal region in general is additionally of importance as the stem cells which are the source of the new corneal cells are located in the epithelium of the limbus and these are vital for normal functioning and are affected under certain adverse conditions. Purpose: In this experiment I examined corneal morphology in the limbal area and in particular under the upper lid in order to primarily examine the variation in the corneal limbal epithelial and total thickness as well as epithelial and endothelial cell density. Methods: I measured 30 eyes OD/OS (chosen randomly) of thirty healthy subjects aged from 18 to 55 years in the first study and twelve participants in the second study, with refractive error ≤ ±4 D and astigmatism ≤ 2 D. The thickness and cell density of five positions: superior, inferior, temporal, nasal limbal and central cornea was determined with optical coherence tomography (OCT) and confocal microscopy. At least three scans of each position were taken in both studies with OCT. At least 40 of 100 adjacent sagittal scans of each image were measured using OCT software program. In the confocal study, image J software was used to determine cell densities. Results: The epithelial and corneal limbal thickness were significantly thicker than the epithelial and central corneal thickness (p<0.05). The limbal, inferior cornea is thinner than the three other positions and the temporal region of the cornea is the thickest both in epithelial and total cornea. Epithelial cell density was significantly lower in the superior cornea than the four other positions. There was no significant difference in the endothelial cell density. Conclusions: Using OCT with high resolution and cross-sectional imaging capability and confocal microscope with high magnification, I found that the limbal cornea is significantly thicker than the central cornea both in total and in epithelial thickness. In the limbus, one might expect the superior cornea (under the lid) to be thickest (because of the expected hypoxia) whereas I found the temporal cornea was thickest. The epithelial cell density was lower in the superior cornea but there was no significant difference in cell densities in the endothelium. Further morphological investigation is of interest.

Abstract Both in the closed and open eye state the superior limbus is covered by the upper lid. This region is of physiological interest and clinical importance because in chronic hypoxia, neovascularization of the cornea commonly occurs here. The limbal region in general is additionally of importance as the stem cells which are the source of the new corneal cells are located in the epithelium of the limbus and these are vital for normal functioning and are affected under certain adverse conditions. Purpose: In this experiment I examined corneal morphology in the limbal area and in particular under the upper lid in order to primarily examine the variation in the corneal limbal epithelial and total thickness as well as epithelial and endothelial cell density. Methods: I measured 30 eyes OD/OS (chosen randomly) of thirty healthy subjects aged from 18 to 55 years in the first study and twelve participants in the second study, with refractive error ≤ ±4 D and astigmatism ≤ 2 D. The thickness and cell density of five positions: superior, inferior, temporal, nasal limbal and central cornea was determined with optical coherence tomography (OCT) and confocal microscopy. At least three scans of each position were taken in both studies with OCT. At least 40 of 100 adjacent sagittal scans of each image were measured using OCT software program. In the confocal study, image J software was used to determine cell densities. Results: The epithelial and corneal limbal thickness were significantly thicker than the epithelial and central corneal thickness (p<0.05). The limbal, inferior cornea is thinner than the three other positions and the temporal region of the cornea is the thickest both in epithelial and total cornea. Epithelial cell density was significantly lower in the superior cornea than the four other positions. There was no significant difference in the endothelial cell density. Conclusions: Using OCT with high resolution and cross-sectional imaging capability and confocal microscope with high magnification, I found that the limbal cornea is significantly thicker than the central cornea both in total and in epithelial thickness. In the limbus, one might expect the superior cornea (under the lid) to be thickest (because of the expected hypoxia) whereas I found the temporal cornea was thickest. The epithelial cell density was lower in the superior cornea but there was no significant difference in cell densities in the endothelium. Further morphological investigation is of interest.

Recently, with the escalating demands for optical communications, the need for bandwidth in optical communication network has increased. The technology breakthrough indry fiber fabrication opens the possibility for fiber bandwidth form 1.3 to 1.6 £gm. Cr4+:YAG double-clad crystal fiber (DCF) grown by the co-drawing laser-heated pedestal growth method has a strong spontaneous emission spectum form 1.3 to 1.6 £gm. Such fiber is therefore, eminently suitable for optical coherence tomography (OCT), broadband optical amplifier, amplifier spontaneous emission (ASE) light source, and tunable solid-state laser applications. In this thesis, multilayer dielectric thin films were directly deposited by E-gun coating onto the end faces of the Cr4+:YAG DCF. To improve the thin-film quality, to increase transmittance of laser output, and to design for the high power laser. For broadband optical amplifier in dual-pump and double-pass scheme, a 3.0-dB gross gain, a 3.0-dB insertion loss, and a 0-dB net gain at 1.4-£gm signal wavelength have been successfully developed with HR coating onto one of the Cr4+:YAG DCF end faces. In addition, we have successfully developed the Cr4+:YAG DCF laser by direct HR coatings onto fiber end faces and increase transmittance of laser output. A record-low threshold of 31.2 mW with a slope efficiency of 7.5% was achieved at room temperature.