Functional tomography of neurovascular coupling interactions in healthy and diseased retinas

健康和患病视网膜神经血管耦合相互作用的功能断层扫描

• 批准号: 10334551
• 负责人: XINCHENG YAO
• 金额: $ 30.35万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10334551
• 关键词: 3-Dimensional; Advanced Development; Age related macular degeneration; Algorithms; Alzheimer' s Disease; Angiography; Appearance; Arteries; Blindness; Blood; Blood Vessels; Blood capillaries; Brain; Caliber; Characteristics; Cornea; Defect; Dementia; Detection; Development; Diabetic Retinopathy; Disease; Dropout; Early Diagnosis; Early treatment; Evaluation; Fostering; Functional Imaging; Functional disorder; Ganglion Cell Layer; Ganglionic Layer; Glaucoma; Health; Image; Intervention; Lighting; Medical; Methods; Monitor; Morphologic artifacts; Morphology; Mus; Nerve; Nerve Degeneration; Neurodegenerative Disorders; Nutrient; Ophthalmology; Optical Coherence Tomography; Optics; Oxygen; Oxygen Consumption; Oxygen saturation measurement; Parkinson Disease; Pathology; Phase; Photoreceptors; Prevention strategy; Resolution; Retina; Retinal Degeneration; Retinal Diseases; Retinal Ganglion Cells; Retinal Photoreceptors; Retinitis Pigmentosa; Scanning; Signal Transduction; Source; Speed; Stimulus; System; Thick; Thinness; Treatment Protocols; Vasodilation; Veins; adaptive optics; arteriole; density; digital; hemodynamics; imaging platform; indexing; instrument; neuron loss; neurovascular; neurovascular coupling; non-invasive imaging; relating to nervous system; response; retinal imaging; spatiotemporal; success; therapy development; tomography; two-dimensional; venule

Project summary: This project is to investigate spatiotemporal interactions between neural activities and hemodynamic changes in the retina, and to explore quantitative mapping of retinal neurovascular coupling defects caused by neurodegenerative diseases. Retinal neurodegenerative diseases, such as age-related macular degeneration (AMD), retinitis pigmentosa (RP), diabetic retinopathy (DR) and glaucoma, can produce severe vision losses if medical interventions cannot be provided promptly. As one part of the central never system (CNS), the retina is also targeted by other neurodegenerative diseases, such as Parkinson's and Alzheimer's diseases which are the major cause of dementia. Early detection of these neurodegenerative diseases is essential for better study and development of preventive strategies. Functional imaging of neurovascular coupling defects promises early detection of neurodegeneration. Direct access to the brain for high-resolution examination of neurovascular coupling defects is difficult. The retina opens a window for high-resolution study of neurovascular coupling defects. This project is to explore spatiotemporal mapping of three-dimensional (3D) interactions between neural activities and hemodynamic changes. The first aim of this project is to refine our existing spectral-domain optical coherence tomography (OCT), and to extend our recently demonstrated swept- source parallel OCT to a multi-functional parallel OCT (MF-P-OCT) instrument, which will provide 5 µm spatial resolution and 5 ms OCT volume speed. The MF-P-OCT will enable functional OCT of stimulus-evoked neural activities and functional OCT angiography (OCTA) of microvascular responses simultaneously. The second aim is to investigate retinal neurovascular defects in retinal degeneration rd10 and APPswe/PSEN1dE9 mice, in which outer retina (photoreceptor) and inner retina (ganglion) are degenerated first, respectively. Morphological OCT and OCTA features, including retinal thickness, blood vessel caliber (BVC), blood vessel tortuosity (BVT), vessel perimeter index (VPI), and blood vessel density (BVD) will be quantitatively compared in normal and diseased mice. Comprehensive analysis of stimulus-evoked vasodilation, transient blood and oxygen changes will be used for in-depth understanding of blood/oxygen consumption at the capillary level in normal and diseased retinas. Concurrent monitoring of stimulus-evoked intrinsic optical signals (IOSs) correlated with neural activity (i.e., neural-IOS) and vascular response (i.e., hemodynamic-IOS) will be used for objective evaluation of spatial and temporal characteristics of neurovascular coupling interactions in the retina. The key success criterion of this project is to verify functional detection of neurovascular coupling defects (i.e., distorted stimulus-evoked hemodynamics at capillary level), before the appearance of detectable morphological abnormalities (i.e., neuronal loss and vessel dropout). Success in this project will produce a noninvasive imaging platform for high- resolution and objective assessment of functional relationship between neural degeneration and vascular pathology, promoting early detection and therapy development of neurodegeneration diseases.

项目摘要：该项目是为了调查神经活动与 视网膜的血液动力学变化，并探索残留神经血管耦合的定量映射 由神经退行性疾病引起的缺陷。视网膜神经退行性疾病，例如与年龄有关 黄斑变性（AMD），色素性视网膜炎（RP），糖尿病性视网膜病（DR）和青光眼可以产生 如果无法及时提供医疗干预措施，则严重的视力损失。作为中央永不系统的一部分 （CNS），视网膜也受到其他神经退行性疾病的目标，例如帕金森氏症和阿尔茨海默氏症 疾病是痴呆症的主要原因。这些神经退行性疾病的早期发现是 更好的研究和制定预防策略至关重要。神经血管的功能成像 耦合缺陷有望早期检测神经变性。直接进入大脑高分辨率 检查神经血管耦合缺陷是困难的。视网膜为高分辨率研究打开了一个窗口 神经血管耦合缺陷。该项目是探索三维（3D）的空间时间映射 神经活动与血液动力学变化之间的相互作用。该项目的第一个目的是完善我们的 现有的光谱域光学相干断层扫描（OCT），为了扩展我们最近证明的扫荡 源与多功能平行OCT（MF-P-OCT）仪器平行，该仪器将提供5 µm空间 分辨率和5 ms OCT量速度。 MF-P-OCT将实现刺激诱发的中性的功能性OCT 简单的微血管反应的活性和功能性八个血管造影（OCTA）。第二个目标 是为了研究残留变性RD10和AppSwe/psen1de9小鼠的永久神经血管缺陷， 首先将视网膜外视网膜（感光受体）和内部视网膜（神经节）分别退化。形态学 OCT和OCTA特征，包括残留厚度，血管口径（BVC），血管曲折（BVT）， 血管周边指数（VPI）和血管密度（BVD）将在正常和 患病的老鼠。刺激诱发的血管舒张，瞬态血液和氧气变化的全面分析 将用于对毛细血管水平的血液/氧气消耗的深入了解正常和解散 视网膜。同时监测刺激引起的固有光信号（IOSS）与神经活动相关 （即神经os）和血管反应（即血液动力学 - ios）将用于空间的客观评估 视网膜中神经血管耦合相互作用的临时特征。关键成功标准 该项目旨在验证神经血管耦合缺陷的功能检测（即，被扭曲的刺激诱发 在出现可检测的形态异常之前（即 神经元损失和血管辍学）。该项目的成功将为高级产生一个无创的成像平台 神经变性与血管之间功能关系的分辨率和客观评估 病理学，促进神经退行性疾病的早期检测和治疗发展。