Physics and Astronomy

Permanent URI for this collectionhttps://uwspace.uwaterloo.ca/handle/10012/9949

This is the collection for the University of Waterloo's Department of Physics and Astronomy.

Research outputs are organized by type (eg. Master Thesis, Article, Conference Paper).

Waterloo faculty, students, and staff can contact us or visit the UWSpace guide to learn more about depositing their research.

Browse

Now showing 1 - 7 of 7

Morphological and Multifractal Analyses of Retinal Amyloid Deposits for Staging in Alzheimer's Disease
(University of Waterloo, 2020-02-12) Neathway, Peter Andrew Charles; Campbell, Melanie
Dementia is a neurodegenerative condition that leads to loss of cognitive ability, typically in older adults. Alzheimer's disease (AD) is the most common cause of dementia and affects millions of people worldwide. The prominence and impact of AD is expected to intensify in the near future, especially in Canada, as the world's population continues to age. Current treatments for AD can delay symptoms, but there is no cure that has been made available to the general population. Detection of AD has been at the forefront of the medical sciences for decades but still involves expensive and inaccessible procedures. Dr. Campbell's group has shown that amyloid deposits, a hallmark of AD in the brain, also occur in the retina, in quantities correlated with brain pathology. The optical accessibility of the retina makes it a strong candidate for future diagnostic methods. In preparation for the implementation of a live-eye imaging device, our group has continued to seek new means for extracting information related to said deposits that could be of diagnostic interest. This thesis includes a description of the three-dimensional morphological features of amyloid deposits found in the retina, with proposed explanations for said features. Most deposits appear to be very flat, like sheets in the en face plane, and bear little resemblance to the typical isotropic deposits found in the brain. This thesis applied complexity and texture analysis to differentiate between key categories of amyloid deposits in human retinas. Texture analysis and polarization signals were both different on average for deposits in different layers of the retina, deposits from subjects with different likelihoods of AD, and deposits from subjects with AD from those with other pathologies. Tests were performed to assess the resilience of these methods to various resolutions (using both digital resampling and different magnifications in the imaging apparatuses) and orientations. Further analysis considered deposit texture as a function of depth in three-dimensional image volumes and found that texture appears to be somewhat continuous, to an extent that may be useful for the live-eye imaging application.
Mueller Matrix Confocal Scanning Laser Polarimetry and Optimal Conditions for Improved Image Quality
(University of Waterloo, 2021-01-26) Zangoulos, Julia; Campbell, Melanie
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.
Optical aberrations and cone photoreceptor sampling during normal emmetropization and emmetropization to imposed defocus
(University of Waterloo, 2018-04-23) Ke, Mengyuan; Campbell, Melanie
The eye grows in a coordinated fashion during normal emmetropization which results in an image close to being in focus on the retina for distance vision. Myopia results from the failure of normal emmetropization. Myopia increases the risk factors of a range of ocular diseases, such as retinal detachment, and is a leading cause of blindness. In addition, a rapidly increasing myopia rate has been reported in the last decade which requires more research into its mechanisms. Furthermore, understanding the mechanisms underlying normal emmetropization may lead to interventions that limit or prevent myopia. Instead of emmetropia, which equates with zero refractive error, a small nonzero refractive error following emmetropization has been reported in children, chicks and monkeys. Chicks are a popular animal model in which to study refractive development. When defocusing lenses are placed in front of the eye, the rate of eye growth changes to compensate the amount of defocus similar to normal emmetropization. Optical aberrations, which degrade the image quality of the eye, and cone photoreceptor sampling are important in studying the control of emmetropization. The right eyes of chicks were raised with positive (+10D) or negative (-15D) lenses while left eyes grew normally. Image quality degraded by optical aberrations and defocus was studied and compared to cone photoreceptor sampling in goggled eyes with the different lenses, and in control eyes. An image quality metric, equivalent blur, used here is a simpler calculation than other metrics calculated from point spread functions but still gives a good approximation of the radial extent of point spread function. Adaptive optics (AO) allows the longitudinal measurement of cone densities in vivo. The change of angular photoreceptor spacing with age in chick, measured and calculated from AO, was not affected by inducing either positive or negative defocus blurs. Thus, age changes in cone angular photoreceptor spacing do not appear to be influenced by optical blur. This spacing is compared for the first time to the extent of the optical blur on the retina. The minimum optically resolvable separation of two points (given by the Rayleigh criterion) achieved near the endpoint of refractive development matches the Shannon sampling resolution, given by the cone photoreceptor matrix. In turn, the minimum resolvable separation of two points is equal to the radius of the optical blur. The optical blur plateaus at the value which matches the limit of cone sampling. This may mean that the blur is no vi longer “visible” to the cones. This in turn may explain the nonzero refractive error found in chicks and possibly in monkeys and human. As previously found, astigmatism, particular oblique astigmatism increases in the eyes goggled with -15D lenses. At the time of and following the plateauing of optical blur, the presence of astigmatism generates a difference in the orientation of the PSF as the refraction varies in the goggled eyes goggled with positive or negative lenses over a short time period (with measured accommodation) and in control eyes with modeled accommodation. This orientation change can be resolved by the cone photoreceptors indicating that oblique astigmatism may provide a cue to the sign of defocus in goggled eyes and possibly in control eyes as well.
Polarimetric and birefringence analysis of presumed amyloid-beta deposits in the retina in association with Alzheimer's disease
(University of Waterloo, 2018-09-26) Jin, Tao; Campbell, Melanie
Alzheimer's disease is a neurodegenerative disease which leads to symptoms such as loss of memory and other neurological dysfunctions, ultimately leading to death. Two key hallmarks of Alzheimer's disease are abnormally folded Amyloid-beta and tau proteins in the brain. Currently, the diagnosis of Alzheimer's disease is only confirmed by finding these hallmarks in the brain after death. Two of the methods that reach a probable diagnosis of Alzheimer's disease are positron emission tomography and cerebral spinal fluid analyses. However, both methods are invasive as positron emission tomography uses radiation and dyes, and examination of cerebral spinal fluid requires invasive extraction from the patients' body. Fortunately, amyloid deposits, which presumed to contain Amyloid-beta, have been found in the retina. In vivo imaging of amyloid deposits using curcumin staining has been shown in AD patients receiving oral curcumin for several days. Since the retina can be directly imaged through the pupil and polarimetry does not require a dye, a noninvasive method of diagnosis could combine polarimetry and a retinal imaging device. In this thesis, one of the key polarimetric properties of amyloid deposits, linear birefringence, was studied. The linear birefringence was computed by using the combination of Mueller Matrix Polarimetry for linear retardance and Confocal Laser Scanning Microscopy for thickness. These measurements were conducted in retinal deposits as well as a matched number of pure Amyloid-beta deposits with similar thickness grown on glass slides. Between the two types of deposits, there was no significant difference shown in linear birefringence fitted to the linear regions of the retardance versus thickness plot. Both types of amyloid deposits show similar trends at high thickness where linear retardance plateaus and then decreases with increasing thickness, giving low birefringence value at high thickness. This result suggests that the retinal deposits are composed primarily of amyloid-beta and that there is only short range order of the fibrils in the retinal deposits. The birefringence of retinal deposits is also higher than the background retinal nerve fiber layer and the senile plaques in the brain measured to date. These senile plaques are higher in thickness than the retinal deposits and have birefringence values similar to the low birefringence values of pure Amyloid-beta deposits of high thickness. The high birefringence of the retinal deposits demonstrates the feasibility of in vivo imaging of retinal amyloid deposits using a patented label free method. In order to calculate the retardance used here to infer the birefringence measurements and in future clinical applications, the Mueller matrix computed from the acquired images needs to be decomposed. However, for a large image, the decomposition may take a long time. Hence, an accelerated implementation of the polar decomposition was developed and used in this thesis. By implementing the accelerated decomposition on a graphic processing unit, the speed of decomposition is more than 15 times faster than the original calculation before acceleration. For computing the birefringence of amyloid deposits, image segmentation was conducted to separate them from the surrounding retina. Automatic segmentation methods including Otsu's method, K-means clustering, Gaussian mixture model, and Markov random field were tested. Gaussian mixture model and Markov random field showed the highest success rate while both Otsu's method and K-means clustering performed poorly. It is thus recommended to use either Gaussian mixture model (faster) or Markov random field (slightly more accurate) to segment images of amyloid deposits. The results reported in this thesis show polarization properties of amyloid deposits, such as strong birefringence values, which are useful in identifying these deposits in the retina. Coupled with fast decomposition and automatic segmentation of the deposits in the image, an efficient, noninvasive diagnostic method may be established in living eyes in the future.
Predicting the thioflavin fluorescence of retinal amyloid deposits in association with Alzheimer’s disease and differentiating amyloid protein from alpha-syn
(University of Waterloo, 2020-09-02) Qiu, Yunyi; Campbell, Melanie
Alzheimer’s disease (AD) is a neurodegenerative disease and the most common cause of dementia. According to the World Health Organization (WHO) in 2019, dementia affects around 50 million people worldwide and this number is still going to increase by 10 million every year. Currently, some treatments can delay the symptoms but no effective cure is available for AD. Part of the reason is that the current definitive diagnosis of AD can only occur after patients’ death, by finding two hallmarks, amyloid-β (Aβ) plaques and tau proteins, in patients’ brains. Although the early confirmation of amyloid in the brain can be achieved by using positron emission tomography (PET) or analyzing cerebral spinal fluid (CSF), both of them are invasive to human health, PET also involves expensive procedures. Fortunately, the over-accumulation of one hallmark Aβ has also been found in the retinas of AD patients, which Dr. Campbell’s group has shown is naturally birefringent under polarized light. Considering the optical accessibility of the retina, our group has proposed that polarimetry imaging device could be a strong candidate as an early diagnostic method for AD. The presumed retinal amyloid deposits have been detected by our Mueller matrix polarimetry method ex vivo. Since thioflavin fluorescence is a biomarker for amyloid, we stained the retinal deposits with thioflavin dye and then imaged using fluorescence microscopy to determine the existence of a thioflavin fluorescence signal. To avoid the use of a dye in future in vivo live eye imaging, this thesis presents a method to predict the existence of thioflavin fluorescence of retinal deposits from their interactions with polarized light by combining polarimetry and machine learning. Three machine learning algorithms have been trained and tested, two oversampling methods have been applied to solve the problem of the low number of non-fluorescence deposits as polarimetry detects amyloid with high accuracy. The results suggest that the fluorescent retinal deposits can be differentiated from non-fluorescence deposits with high accuracy, and two polarimetric properties appear have high importance in predicting thioflavin fluorescence. To ensure that the source of fluorescence is amyloid-β protein, the second research project in this thesis aims to differentiate pure amyloid-β protein deposits from another protein alpha-synuclein, which contains a β-sheet structure and amyloid-like fibrils thus also show positivity in thioflavin fluorescence. A powerful convolutional neural network model (CNN) -the residual neural network, also known as Resnet, has been applied to differentiate the polarization images of pure Aβ-42 protein deposits, which is the amyloid that most relevant for AD, from the alpha-synuclein pure protein. The performance of CNNs trained by images of different polarimetric properties is compared with the machine learning algorithm used before. The CNN models, which directly take the images of the polarimetric properties as input, have outperformed the machine learning algorithms tested in differentiating Aβ-42 and alpha-synuclein protein deposits.The results reported here may be useful to assist in the label-free detection of these two types of retinal amyloid deposits in live-eye imaging.
Proposed Methods For Measuring and Interpreting Mueller Matrices in In Vivo Retinal Polarimetry
(University of Waterloo, 2020-12-23) Esau, Steven Kenneth; Campbell, Melanie
Mueller matrix polarimetry is the examination of how a sample transforms the polarization state of light. This requires probing the sample with input light of a variety of generated polarization states and analyzing the resulting output states, using a total of at least sixteen irradiance measurements. This allows one to calculate the Mueller matrix, which provides insight into the microstructure of the sample. In imaging applications this can yield additional contrast between different types of materials. Examination of the human retina has the potential to reveal not only ocular conditions, but also neurological disorders due to the fact that the retina is made up of neural tissue. Deposits of amyloid-beta in the brain are a standard biomarker for Alzheimer's disease. Similar deposits have been identified in the retina. By studying ex vivo human retinae, members of Campbell Labs have shown that these deposits can be imaged label-free using Mueller matrix polarimetry, and that their number correlates with the severity of Alzheimer's disease as assessed using brain pathology post-mortem. Imaging these deposits in the living eye using in vivo retinal polarimetry could provide an affordable and noninvasive biomarker for Alzheimer's disease, aiding in diagnosis. This thesis uses a "double pass model" to describe in vivo retinal polarimetry: it is assumed that light passes through the ocular tissue (i.e. the cornea, lens, and upper layers of the retina) before reflecting within the retina, and traversing polarimetrically similar tissue in the opposite direction. This model implies a particular mathematical structure for the Mueller matrix in in vivo retinal polarimetry. This thesis proposes ways in which this mathematical structure can be used advantageously when measuring and interpreting double pass Mueller matrices. While other authors have used the double pass model for in vivo retinal polarimetry, it is believed that this thesis is the first work to examine its implications without also making assumptions about the polarimetric properties of the ocular tissue. Following other authors, this thesis first describes the reciprocity theorem which relates a Mueller matrix for opposite paths through a sample, and uses it to apply the double pass model to Mueller matrices. It is shown that double pass Mueller matrices have fewer degrees of freedom than ordinary Mueller matrices. This allows double pass Mueller matrices to be calculated from as few as ten irradiance measurements. Several designs are developed for the generating and analyzing branches of a polarimeter, capable of measuring double pass Mueller matrices in ten measurements while being optimized for the best possible error performance. These are found using a novel extension of standard polarimeter optimization techniques that allows them to take into account the aforementioned restrictions on double pass Mueller matrices. These designs could be used to improve the speed of an in vivo retinal polarimeter used for Alzheimer's disease diagnosis, reducing patient discomfort and eye movement during the measurement. Next, the double pass Mueller matrix is compared to the corresponding single pass Mueller matrix for transmission once through the ocular tissue. New methods are found to calculate possible single pass polarimetric properties from the double pass Mueller matrix. This may provide additional insight into the microstructure of the sample and yield results that are more similar to the transmission properties of retinal amyloid deposits previously measured ex vivo. This thesis proposes new methods for measuring and interpreting Mueller matrices measured in in vivo retinal polarimetry assuming the double pass model. These methods could be applied in order to improve a future instrument for Alzheimer's disease diagnosis through observation of retinal amyloid deposits.
Wavefront assessment and correction of the rat eye for two photon excitation therapies
(University of Waterloo, 2016-08-31) Andrews, Ian; Campbell, Melanie
Photodynamic therapy (PDT) is a treatment in which light excites a photosensitive drug to produce oxygen radicals that kills nearby cells. Today, PDT’s is most commonly used application is for the destruction of cancerous tumor cells in humans, however it can also be used to treat the eye disease, age-related macular degeneration (AMD). One-photon excitation PDT treatment of AMD has not been found to successfully improve vision quality due to the revascularization in the retina which occurs post-treatment. Two-photon excitation (TPE) has been explored as an alternative because it may prevent revascularization of the retina post-treatment and provides more precise treatment localization. The rat eye has been selected as the optical model for testing TPE of a photosensitive drug, however the rat eye suffers from poor tear film quality and large optical aberrations requiring adaptive optics to improve retinal image quality and the probability of TPE. In vivo testing of the excitation of a photosensitive drug via TPE is an important step towards successful treatment of AMD in the human eye. In this thesis, the design of an adaptive optics scanning laser ophthalmoscope for two photon light delivery is outlined, retinal images and wavefront error correction of the rat eye using a Xinetics 37-channel deformable mirror are presented. The extension of a schematic rat eye model to include a contact lens and tear lens predicts improved image quality at the retina for a larger pupil size. During the course of this project, changes in refractive error and retinal image quality while using different contact lenses were observed. Based on the model and experimental observations, the use of rigid contact lenses was shown to improve retinal image quality of the rat eye and therefore the probability of TPE in the rat eye, prior to the use of adaptive optics.

Browse

Browsing Physics and Astronomy by Author "Campbell, Melanie"