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: 9892006
• 负责人: XINCHENG YAO
• 金额: $ 35.29万
• 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 2023-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9892006
• 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：该项目旨在研究神经活动和神经活动之间的时空相互作用 视网膜血流动力学改变，探讨视网膜神经血管偶联的定量标测 由神经退行性疾病引起的缺陷。视网膜神经退行性疾病，如与年龄相关的 黄斑变性(AMD)、视网膜色素变性(RP)、糖尿病视网膜病变(DR)和青光眼 如果不能及时提供医疗干预，会造成严重的视力损失。作为中央神经系统的一部分 (CNS)，视网膜也是其他神经退行性疾病的靶点，如帕金森氏症和阿尔茨海默氏症 疾病是导致痴呆症的主要原因。这些神经退行性疾病的早期检测是 这对于更好地研究和制定预防战略至关重要。神经血管的功能成像 偶联缺陷有望及早发现神经退化。直接访问大脑以实现高分辨率 神经血管偶联缺陷的检查很困难。视网膜为高分辨率研究打开了一扇窗 神经血管偶联缺陷。该项目是探索三维(3D)的时空映射。 神经活动与血流动力学变化之间的相互作用。这个项目的第一个目标是完善我们的 现有的光谱域光学相干层析成像(OCT)，并扩展我们最近演示的扫描- 源并行OCT到多功能并行OCT(MF-P-OCT)仪器，将提供5微米空间 分辨率和5ms OCT音量速度。MF-P-OCT将实现刺激诱发神经的功能OCT 同时进行微血管活动和功能OCT血管成像(OCTA)。第二个目标 目的是研究视网膜变性rd10和APPswe/PSEN1dE9小鼠的视网膜神经血管缺陷。 外视网膜(光感受器)和内视网膜(神经节)分别最先变性。形态 OCT和OCTA特征，包括视网膜厚度、血管口径(BVC)、血管曲度(BVT)、 血管周长指数(VPI)和血管密度(BVD)将定量比较正常和 生病的老鼠。刺激性血管扩张、一过性血氧变化的综合分析 将用于深入了解正常和疾病患者毛细血管水平的血液/氧气消耗 视网膜。与神经活动相关的刺激诱发内源性光学信号(IOSS)的同时监测 (即神经-IOS)和血管反应(即血流动力学-IOS)将用于客观评价空间 以及视网膜中神经血管耦合相互作用的时间特征。成功的关键标准是 该项目是为了验证神经血管耦合缺陷(即，扭曲的刺激诱发的)的功能检测 毛细血管水平的血流动力学)，在出现可检测的形态异常之前(即， 神经元丢失和血管脱落)。该项目的成功将产生一个非侵入性的成像平台，用于 神经退行性变与血管功能关系的解析与客观评价 病理学，促进神经退行性疾病的早期发现和治疗发展。