Development of Low-cost Imaging Tools for Screening of Retinal Biomarkers in Alzheimer’s Disease
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Alzheimer’s disease (AD) is a neurodegenerative disease currently affecting 5.8 million Americans and more than 50 million people worldwide. It is a progressive disease that destroys cognitive functions, leading to dementia. With increasing life-expectancy, important efforts have been made to clinically diagnose this age-related disease. However, definitive diagnosis of AD has been challenging, especially at an early stage, as there is a lack of quantifiable changes. Recently, many researchers have shown retinal changes as an extension of the brain pathology, leading to a window to study AD using fast and high-resolution retinal imaging tools. This dissertation will be focused on the development of low-cost imaging tools aimed to extract retinal biomarkers for AD. Specifically, the use of optical coherence tomography (OCT) and angle-resolved low-coherence interferometry (a/LCI) will be described, with steps leading to a combined optical system for retinal imaging in humans. OCT has already been established as the gold standard in ophthalmology due to its excellent axial resolution and high sensitivity. Similar to OCT, a/LCI is another interferometric technique that provides depth resolution. Previous work has supported the ability of a/LCI to retrieve depth-resolved light scattering measurements of nuclear morphology in dysplastic tissue. The use of OCT as image guidance for a/LCI can strengthen the technique, providing sample orientation as well as retinal layer segmentation to pinpoint a/LCI measurements. The dissertation starts with the development and clinical application of a low-cost OCT system. Despite the prevalence of OCT, its high-cost nature has limited its access to large eye centers and away from low-resource settings. Clinical feasibility of a complete low-cost OCT system will be evaluated, and its imaging performance compared to a commercial system. System design will be discussed, followed by a comprehensive image processing pipeline to characterize image quality for subsequent low-cost systems. The subsequent portions outline studies using a/LCI and the extraction of light scattering parameters in an AD mouse model. A benchtop co-registered system using a/LCI guided by OCT allowed measurements of depth-resolved light scattering measurements in an AD mouse retina model. Resulting parameters serve as unique quantification of AD tissue structure with potential to be translated to future human studies. A scanning mechanism for 2D a/LCI is also presented, which also allowed for the characterization of a/LCI sensitivity to anisotropic scattering that is often present in the complex retinal tissue. The last portion discusses the development of a second-generation low-cost OCT system which will be integrated in a combined imaging system for eventual AD studies in human patients. Several technical improvements are shown to facilitate clinical retinal imaging at the point-of-care. A characterization of this system in a small clinical study will illustrate the system’s capability to screen AD patients, and to serve as a morphological image guide for a clinical a/LCI system. Finally, a discussion of how the low-cost OCT system can be integrated to a multimodal imaging system for AD human retinal biomarker extraction will be provided.
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