PURPOSE: This study aims to quantify the retinal vascular blood flow in eyes affected by unilateral central retinal vein occlusions (CRVO) or branch retinal vein occlusions (BRVO). We created and explored a new, unitless metric for the severity of these diseases: relative blood flow (RBF). We then contextualized RBF in terms of patient demographics, ocular presentation and other systemic conditions, as well as explored its efficacy as a predictor of future outcomes. METHODS: Data was collected from 20 control subjects and 32 patients with clinically diagnosed retinal vein occlusions (15 CRVO and 17 BRVO). Laser speckle flowgraphy was then used to quantify retinal vascular blood flow in terms of mean blur rate, a metric shown to be highly heterogeneous between patients but fairly consistent in intra-patient repeated measurements over time. After confirming this and establishing a strong correlation between a healthy patient’s two eyes, we used an RVO patient’s fellow eye as a nondiseased expectation and presented relative blood flow as the ratio between their diseased and healthy eye. We then correlated this data with demographic variables and disease characteristics from patients’ medical history. RESULTS: We found an average blood flow decrease of 26% in CRVO eyes relative to healthy eyes in the same patients and an average decrease of 7% in BRVO eyes. In CRVO, duration of occlusion, central macular thickness, intraocular pressure, diabetes, previous laser and injection treatments, and an injection within three months after blood flow measurement were significantly associated with relative blood flow. In BRVO, no demographic variables or disease characteristics were significantly associated with relative blood flow. CONCLUSIONS: Relative blood flow represents a promising new, consistent and informative metric for quantifying the severity of unilateral retinal vein occlusions. With both descriptive and predictive properties in eyes with CRVO, future work should explore its great potential.

京都大学 / 新制・課程博士 / 博士(医科学) / 甲第23610号 / 医科博第133号 / 新制||医科||9(附属図書館) / 京都大学大学院医学研究科医科学専攻 / (主査)教授 松田 道行, 教授 林 康紀, 教授 安達 泰治 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

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The main goal of the project was to compare how the Achilles tendon is affected while running with traditional shoes, minimalistic shoes and barefoot. Displacement and strain were calculated both for different shoes and for different foot strike patterns. The calculations were done with a speckle tracking algorithm and displacement was calculated for three different depths in the tendon: deep layer, mid layer and superficial layer. The goal was also to conduct this analysis after a review of the algorithm used. The review of the algorithm focused on the size of the region of interest, kernel size and frequency. Literature study showed that it is more common to use a smaller kernel size, but the same shape. The region of interest was chosen depending on the size of the tendon. Displacement and strain in the Achilles tendon was calculated for seven subjects and the result did not show any difference in amount of mean deformation due to different shoe types or foot strike patterns. It was a small sample group but the result indicated a difference in peak displacement between deep and superficial layer depending on different shoe types and foot strike patterns. The difference in peak displacement between deep and superficial layer was lowest when running barefoot, larger when running with minimalistic shoes and greatest when running with traditional shoes. This result was only achieved when running with rear foot strike pattern. When running with fore foot strike pattern the difference in peak displacement between layers did not change with different conditions. In all conditions the difference in peak displacement between the layers was greater when running with rear foot strike pattern than when running with front foot strike pattern. The deep layer displaced more than the superficial layer (p<0.01) for all conditions and foot strike patterns.

Highly coherent light, although beneficial in specific applications, suffers from the formation of speckles, resulting in poor imaging, lighting, and projection/display quality. Moreover, the long coherence length limits the resolution in interference based sensing. This has led to the emergence of edge-emitting semiconductor low coherence light sources (e.g., broadband lasers, superluminescent diodes, etc.), which have been used in display applications, optical coherence tomography, and random bit generation. However, edge emission prevents the ease of fabricating two-dimensional arrays. Conversely, vertical-cavity surface-emitting lasers (VCSELs) have recently been widely used in consumer electronics due to the unique advantages of surface emission. Nevertheless, they still suffer from issues caused by high coherence. The aim of this dissertation is to design low-coherence surface-emitting lasers to push simultaneous illumination and optical wireless communication (OWC) toward reliable implementation with higher speeds. To that end, we demonstrate, for the first time, the use of chaotic cavities to lower the coherence of VCSELs without increasing their emission area, which would lower their speed. Not only did the chaotic cavity result in doubling the number of modes (lowering the coherence) compared to conventional VCSELs, but it also resulted in an increase in the optical power of up to 60%. We also show that chaotic-cavity broad-area VCSELs can achieve significantly broader modulation bandwidths (up to 5 GHz) and higher data rates (up to 12.6 Gb/s) compared to other low-coherence light sources, while achieving a lower speckle contrast. We further report a novel technique of lowering the speckle contrast 2 by carefully designing the AC signal used for communication. We show that the apparent spatial coherence is dramatically decreased by inserting a short chirp signal between symbols. Using this method with a chaotic-cavity VCSEL, the number of apparent modes can be up to 450 modes, compared to 88 modes measured from a conventional broad-area VCSEL. The simplicity of implementing the reported design, which requires no additional fabrication steps, makes it a promising solution for applications that would benefit from the lower speckle density of the emitted light as well as those that rely on lower temporal coherence.

Cerebral blood flow (CBF) is a biomarker for brain health, facilitating the advancement of studies on brain states in both healthy and diseased individuals. While there are indirect approaches of CBF based on human physiology, there is a need for technology that measures CBF directly and continuously. Laser speckle contrast imaging (LSCI) is an optical modality that measures changes in CBF by analyzing the blurring of speckle patterns. LSCI has been extensively employed to obtain two-dimensional blood flow maps in thinned-skull mouse brains and has found diverse applications in studies involving the retina, skin, and strokes. However, the effectiveness of LSCI has been limited in animal models due to the lack of depth-sensitivity. Speckle contrast optical spectroscopy (SCOS), an extension of LSCI for non-invasive human brain studies, has recently been developed to probe dynamics in deeper tissue regions by increasing the source-detector separation. But the low photon flux detected from human brain limits the usability of SCOS for brain activation measurements. To address these limitations, this thesis focuses on advancements made in laser speckle technology for improved measure of blood flow in both animal and human brains. Firstly, analytical and numerical methods have been developed for an interferometric LSCI system, which employs a heterodyne detection scheme to enhance CBF within the coherence volume in small animals. Next, a dynamic speckle model (DSM) is created to simulate the temporal evolution of the speckle patterns. DSM has been utilized to quantify the impact of noise sources on speckle contrast, particularly relevant in human brain measurements utilizing SCOS where low photon counts is a norm. Finally, a fiber-based SCOS system with a long source-detector separation has been presented to perform human brain activation studies. Through experiments involving three healthy subjects performing a mental subtraction task, changes in brain activation have been observed. Importantly, the SCOS system has demonstrated an order of magnitude improvement in the signal-to-noise ratio compared to the state-of-the-art diffuse correlation spectroscopy system.These methods serve as valuable tools to augment existing LSCI systems and promoting the widespread adoption of SCOS in human brain activation studies thus contributing to the development of future non-invasive, continuous, and cost-effective blood flow monitoring devices.

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