Mueller Matrix Confocal Scanning Laser Polarimetry and Optimal Conditions for Improved Image Quality

Abstract

Alzheimer's disease (AD), a fatal neurodegenerative disorder, is the most common form of senile dementia. Five hundred thousand Canadians are living with dementia, a number predicted to double by 2030. Currently, the most definitive diagnosis of AD must be conducted after death due to the lack of both specific methods for detecting neurodegenerative disorders, and broadly accessible methods for screening preclinical symptoms. The disease is now known to manifest in the eye, an optically accessible structure, and so AD can be diagnosed if amyloid- β deposits are identified in the neural retina. Extensive research by Campbell labs has determined the intrinsic polarization properties of presumed amyloid- β deposits, and developed a novel Mueller-Matrix (MM) polarimetric tool that can image these deposits in ex-vivo retinas. Dr. Campbell's research group has shown MM polarization imaging to be a promising non-invasive, label-free diagnostic tool that provides improved image contrast and a higher signal-to-noise ratio (SNR) than conventional retinal imaging systems. Further, Dr. Campbell's group has found that amyloid- β deposits correlate well with brain pathology, making this imaging modality a strong candidate for an AD diagnostic method.

The research group is now working on a prototype live-eye MM imaging device, and this thesis contributes to this goal. The commercial market for ocular imaging technologies is highly competitive, and therefore defining design requirements that will place the MM polarimeter at a competitive position is important. The research presented in this thesis has taken into account these requirements to design an MM scanning laser polarimeter by integrating polarization optics with a donated scanning laser opthalmoscope (SLO). The polarization optics were selected based on the need for fast, repeatable and accurate polarization modulation, and to ensure a compact cost-effective product. The optimal setup of the polarization unit was identified and designed as a custom made linear holder with four quarter-waveplates placed at different orientations. This method eliminated rotation related errors, increasing the accuracy and repeatability of the polarization modulation unit.

Ocular performance and retinal imaging quality decrease during normal aging, which has important implications in the design of retina imaging instruments for the aging population. Furthermore, since optical resolution due to diffraction becomes better with increasing pupil size, whereas that due to aberrations becomes worse, the optimal pupil size for best lateral resolution as a function of age had to be determined. Eye models incorporating monochromatic aberrations of individual eyes were designed in Code V to determine optimal imaging parameters for retinal instruments targeting the older population. The optimal pupil size for best lateral resolution obtained from the encircled energy metric, in adults 58-70, was found to be 2.73 mm ± 0.402 mm, providing a lateral resolution of 4.48 μm ± 0.654 μm (𝜆 = 550 nm). The optimal pupil size for best lateral resolution, in adults 20-32, was found to be 3.09 mm ± 0.488 mm, providing a lateral resolution of 3.95 μm ± 0.6 μm (𝜆 = 550 nm). The optimal pupil size was found to be statistical significant with age. Further, regression analysis indicated that optimal pupil size as a function of higher order wavefront error gave an exponential t (R² = 0.75). These findings when implemented can enable high resolution retinal imaging without the use of adaptive optics. In addition, the optimal pupil size for best lateral resolution for an 830 nm imaging wavelength, in adults 58-70, was found to be 3.13 mm ± 0.486 mm, providing a lateral resolution of 5.9 μm ± 0.848 μm. It was also determined that in the presence of high aberrations at large pupil sizes, higher wavelengths do not introduce additional aberrations than in lower wavelengths.

In-vivo imaging of the human retina is a unique optical process because the retina is not directly accessible, so imaging must be done by detecting the double-pass reflection. Modalities for imaging the human retina using this approach have existed for many years and are constantly improving. Two specific optical setups, optimized for imaging amyloid-β deposits in older adults, are designed and presented in this thesis. The retinal image quality of the MM polarimeter using an SLO setup with a small entrance pupil was almost solely affected by the aberrations and diffraction of light leaving the eye in the second-pass, making it a single-pass method. In addition, the MM polarimeter with a conventional SLO setup with a large exit beam, which uses an optimal entrance pupil size and the whole exit pupil, was also found to be a single-pass modality. Thus, in this second con figuration, image quality depends only on the first-pass. Optimal pupil and pinhole sizes for 830 nm light were implemented in the optical design of both setups for the development of a system designed to image retinal amyloid- β deposits in older adults as a diagnostic tool for AD.

In summary, an MM confocal scanning opthalmoscope was designed and optimized for imaging the retinal amyloid- β deposits in older adults.