Combined Low-Cost Balanced Detection Optical Coherence Tomography and Angle-Resolved Low Coherence Interferometry Towards Alzheimer’s Disease Screening

Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder for which early detection remains a major clinical challenge. Current diagnostic methods rely on invasive cerebrospinal fluid assays or costly neuroimaging techniques, limiting scalability for widespread screening. Separately, access to high-quality retinal imaging is constrained by the cost and infrastructure requirements of commercial optical coherence tomography (OCT) systems. This dissertation addresses these two distinct needs through the development of cost-conscious retinal imaging technology and the extension of retinal measurement beyond structural morphology toward microstructural analysis.The first aim was to develop and validate the third generation (Gen 3) low-cost spectral-domain OCT system incorporating digital balanced detection. A custom dual low-cost spectrometer configuration was implemented to improve image quality while maintaining reduced component cost. Clinical feasibility testing demonstrated stable retinal imaging performance and improved contrast-to-noise ratio (CNR) compared to prior low-cost generations. The second aim was to benchmark the Gen 3 low-cost OCT system against a commercially available OCT platform in a representative clinical setting. In matched-eye comparisons within the same patients, no statistically significant difference in CNR was detected between the low-cost OCT and commercial OCT systems. These findings demonstrate that high-quality structural retinal imaging can be achieved within a cost-conscious engineering framework. The third aim was to augment the OCT platform with a two-dimensional angle-resolved low-coherence interferometry (2D a/LCI) system to enable depth-resolved in vivo measurement of retinal microstructure. The combined OCT-a/LCI system provides structural localization through OCT and angular scattering analysis through a/LCI. Phantom validation confirmed sensitivity to scatterer size, surface self-similarity, and anisotropic orientation. The integrated system was subsequently used to perform the first in vivo feasibility study of human retinal a/LCI v measurements, demonstrating successful acquisition of depth-resolved angular scattering profiles from multiple retinal layers. Together, these contributions establish a scalable pathway for accessible retinal imaging and demonstrate the technical feasibility of multimodal structural and microstructural retinal assessment. This work provides an engineering and translational framework for expanding access to retinal diagnostics and for future exploration of non-invasive retinal biomarkers for Alzheimer’s disease.