In vivo Imaging of Light Induced Intrinsic Optical Signals in the Chicken Retina with a Combined Ultra-High Resolution Optical Coherence Tomography and Electroretinography System

The main objective of this thesis is to investigate the intrinsic optical signals (IOSs) with an ultra-high resolution optical coherence tomography system (UHROCT). In order to study the retinal IOSs evoked by visible light, an UHROCT and an Electroretinogram (ERG) system was combined. An animal model (chicken retina) based on its retinal avascularity and cone dominance, was selected. Imaging the chicken retina with OCT resulted in high contrast, high resolution (~3μm axial and ~5 μm lateral resolution) 2D and 3D volumetric tomograms, in which all retina layers were clearly distinguishable. Using the combined UHROCT and ERG system to image IOSs from the chicken retina exposed to visible light (7ms green flash) resulted in highly reproducible IOS recordings from all retinal layers for the first time. All inner retinal layers showed an initial increase and subsequently a decrease in the intensity of the backreflected imaging light within the first 100 ms after the onset of the stimulus. Outer segments of the photoreceptors also showed a decrease in the backreflected imaging light within 100 ms after the onset of the flash. All retinal layers showed a strong decrease in the backreflected light within 150 to 175 ms after the onset of the flash. Imaging the pupil dynamics of the chicken with a modified combined UHROCT and ERG system showed that part of the strong negative IOSs observed in all retinal layers resulted from the vignetting of the imaging beam due to the light induced pupil constriction. Thorough analysis of the pupil dynamics acquired with UHROCT showed a time dependent effect of the anesthesia agent on pupil constriction. Further experiments to investigate an anesthesia effects on retinal function showed significant changes in ERG components. Statistical analysis showed that Isoflurane anesthesia severely affects the inner retinal response. In conclusion, it was hypothesized that the fast IOSs within ~50-100 ms after the onset of the visual stimulus originated from the neuronal tissue in the retina and are related to tissue optical property changes as a result of the electrical signal propagation in the light activated retina. Longer term decreases in backreflected light are likely due to pupil changes

The value of measurement of macular carotenoid pigment optical densities and distributions in age-related macular degeneration and other retinal disorders

AbstractThere is increasing recognition that the optical and antioxidant properties of the xanthophyll carotenoids lutein and zeaxanthin play an important role in maintaining the health and function of the human macula. In this review article, we assess the value of non-invasive quantification of macular pigment levels and distributions to identify individuals potentially at risk for visual disability or catastrophic vision loss from age-related macular degeneration, and we consider the strengths and weaknesses of the diverse measurement methods currently available

Microsaccades in applied environments: Real-world applications of fixational eye movement measurements

Across a wide variety of research environments, the recording of microsaccades and other fixational eye movements has provided insight and solutions into practical problems. Here we review the literature on fixational eye movements—especially microsaccades—in applied and ecologically-valid scenarios. Recent technical advances allow noninvasive fixational eye movement recordings in real-world contexts, while observers perform a variety of tasks. Thus, fixational eye movement measures have been obtained in a host of real-world scenarios, such as in connection with driver fatigue, vestibular sensory deprivation in astronauts, and elite athletic training, among others. Here we present the state of the art in the practical applications of fixational eye movement research, examine its potential future uses, and discuss the benefits of including microsaccade measures in existing eye movement detection technologies. Current evidence supports the inclusion of fixational eye movement measures in real-world contexts, as part of the development of new or improved oculomotor assessment tools. The real-world applications of fixational eye movement measurements will only grow larger and wider as affordable high-speed and high-spatial resolution eye trackers become increasingly prevalent

Expanding the role of functional mri in rehabilitation research

Functional magnetic resonance imaging (fMRI) based on blood oxygenation level dependent (BOLD) contrast has become a universal methodology in functional neuroimaging. However, the BOLD signal consists of a mix of physiological parameters and has relatively poor reproducibility. As fMRI becomes a prominent research tool for rehabilitation studies involving repeated measures of the human brain, more quantitative and stable fMRI contrasts are needed. This dissertation enhances quantitative measures to complement BOLD fMRI. These additional markers, cerebral blood flow (CBF) and cerebral blood volume (CBV) (and hence cerebral metabolic rate of oxygen (CMRO₂) modeling) are more specific imaging markers of neuronal activity than BOLD. The first aim of this dissertation assesses feasibility of complementing BOLD with quantitative fMRI measures in subjects with central visual impairment. Second, image acquisition and analysis are developed to enhance quantitative fMRI by quantifying CBV while simultaneously acquiring CBF and BOLD images. This aim seeks to relax assumptions related to existing methods that are not suitable for patient populations. Finally, CBF acquisition using a low-cost local labeling coil, which improves image quality, is combined with simultaneous acquisition of two types of traditional BOLD contrast. The demonstrated enhancement of CBF, CBV and CMRO₂measures can lead to better characterization of pathophysiology and treatment effects.Ph.D.Committee Chair: Hu, Xiaoping; Committee Member: Benkeser, Paul; Committee Member: Keilholz, Shella; Committee Member: Sathian, Krish; Committee Member: Schuchard, Ronal

Photoaversion in inherited retinal diseases: clinical phenotypes, biological basis, and qualitative and quantitative assessment

Severe light sensitivity is a feature common to a range of ophthalmological and neurological diseases. In inherited retinal diseases (IRDs) particularly, this may be accompanied by significant visual disruption. These symptoms are extremely debilitating for affected individuals and have significant implications in terms of day-to-day activities. Underlying mechanisms remain to be fully elucidated. Currently, there are many assessments of photoaversion (PA), however, all have limitations, with quantitative measurement in particular needing further evaluation. To understand the complexities associated with photoaversion from different pathologies, qualitative and quantitative assessments of the light aversion response must be standardized. There is no treatment to date, and strategies to alleviate symptoms focus on light avoidance. With respect to IRDs, however, gene therapy is currently being investigated in clinical trials and promising and further treatments may be on the horizon. The better characterization of these symptoms is an important end point measure in IRD gene therapy trials

Ultrahigh Resolution Optical Coherence Tomography for Non-invasive Imaging of Outer Retina Degeneration in Rat Retina

This project initiated with the aim for improving the ultrahigh resolution optical coherence tomography (UHR-OCT) system performance by considering the limitations to the axial OCT resolution for in vivo imaging of human and animal retina. To this end, a computational model was developed to simulate the effect of wavelength-dependant water absorption on the detected spectral shape of the broad-bandwidth light source used in UHR-OCT at 1060nm wavelength region, which effectively determines the axial OCT resolution in the retina. For experimental verification of the computational model, a custom built light source with a re-shaped spectrum (Superlum Inc.) was interfaced to the state-of-the-art UHR-OCT system. About 30% improvement of the axial OCT resolution in the rat retina and ~12% improvement of the axial OCT resolution in the human retina was achieved compared to the case of the almost Gaussian shaped spectrum of the standard, commercially available SLD. Although water absorption in the 1060nm spectral region strongly affects the sample beam, selecting a suitable light source with specific spectral shape can compensate for the undesired water absorption effect and thus result in significantly improved axial resolution in in vivo OCT retinal images. To demonstrate the advantages of the state-of-the-art OCT technology for non invasive retinal imaging, an established animal model of outer retina degeneration (sodium iodate (NaIO3)-induced retina degeneration) was employed for longitudinal monitoring of the degeneration and investigation of possible early and dynamic signs of damage undetected by other imaging modalities. The long-term (up to 3 months) and short-term (up to 12 hours) effect of sodium iodate toxicity on the layered structure of retina was monitored longitudinally and in vivo for the first time using OCT. An initial acute swelling of the retina, followed by progressive disruption and degeneration of outer retina was observed as a result of sodium iodate-induced damage. Changes in the thickness and optical reflectivity of individual retinal layers were extracted from the OCT images to quantify the changes occurring at different stages of the disease model. Results from this project present the theoretical and practical limits to the highest axial OCT resolution achievable for retina imaging in the 1060nm spectral range both in small animals and humans, and provided a framework for future development of novel light sources. Furthermore, UHR-OCT imaging was shown to be an effective and valuable modality for in vivo, non invasive investigation of retina degenerative disease