Scattering angle resolved optical coherence tomography for early retinal detection of Alzheimer’s disease in a murine model

Alzheimer’s disease (AD), a debilitating neurodegenerative disease, is becoming more prevalent with an aging population. Early detection of AD is critical to extending healthy lives, but current techniques for AD detection are invasive and cost-prohibitive. The retina is embryonically derived from the forebrain and, with recent mounting evidence that it may reveal markers of brain injury, is considered a “window to the brain.” Early neurodegenerative changes in the brain are likely to be observed in the retina—synaptic failure and shifts in mitochondrial dynamics. Optical imaging techniques could hold the key to non-invasive early detection of AD in the retina since these disruptions may be observed with light. In particular, optical coherence tomography (OCT) retinal imaging offers 3D images of retinal neurons, but the resolution of clinical OCT systems is not fine enough to observe disruptions in the sub-cellular space. Scattering angle resolved (SAR-) OCT, a new method introduced in this work, aims to access sub-resolution scattering properties which could expose fundamental changes in the neurons associated with AD. In this dissertation, a custom SAR-OCT system and new image processing protocols are designed and constructed for murine retinal imaging. Then, three in-vivo studies are conducted using the imaging system to demonstrate its potential use in disease detection. In the first study, which establishes fundamental measures provided by SAR OCT, the imaging system discerns native scattering differences between retinal layers and regions in healthy mice. In the second study, significant scattering angle shifts are observed in ischemic retinas. Finally, a cross-sectional study compares a transgenic murine model of AD (3xTg-AD) with age-matched wild type controls. By examining the distribution of scattering angles detected by the SAR-OCT system, significant differences are observed in the earliest ages of the diseased mice compared the control mice. In the final chapter, limitations of these studies as well as the imaging and image processing protocols are examined, and recommendations are made for future studies to leverage SAR-OCT for early detection of AD or other neurodegenerative diseases