| dc.description.abstract |
<p>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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