Functional tomography of neurovascular coupling interactions in healthy and diseased retinas

项目概述：本项目旨在研究神经活动与神经元活动之间的时空相互作用， 视网膜血流动力学变化，并探索视网膜神经血管耦合的定量绘图 由神经退行性疾病引起的缺陷。视网膜神经退行性疾病，例如与年龄相关的疾病 黄斑变性（AMD）、色素性视网膜炎（RP）、糖尿病性视网膜病变（DR）和青光眼，可产生 如果不能及时提供医疗干预，则会出现严重视力丧失。作为中央铁路系统的一部分 (CNS)视网膜也是其他神经退行性疾病的目标，如帕金森病和阿尔茨海默病 这些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。神经血管功能成像 偶联缺陷保证了神经变性的早期检测。直接进入大脑进行高分辨率 神经血管耦合缺陷的检查是困难的。视网膜为高分辨率研究打开了一扇窗 神经血管耦合缺陷的症状本项目旨在探索三维（3D）的时空映射 神经活动和血液动力学变化之间的相互作用。该项目的第一个目标是完善我们的 现有的谱域光学相干断层扫描（OCT），并扩展我们最近展示的扫描- 将源并行OCT转换为多功能并行OCT（MF-P-OCT）仪器，该仪器将提供5 µm空间 分辨率和5 ms OCT容积速度。MF-P-OCT将使刺激诱发的神经功能OCT 活动和功能性OCT血管造影（OCTA）的微血管反应。第二个目的 研究视网膜变性rd 10和APPswe/PSEN 1dE 9小鼠的视网膜神经血管缺陷， 其中外层视网膜（光感受器）和内层视网膜（神经节）分别首先退化。形态 OCT和OCTA特征，包括视网膜厚度、血管口径（BVC）、血管迂曲度（BVT）， 血管周长指数（VPI）和血管密度（BVD）将在正常和 患病的老鼠综合分析刺激诱发的血管舒张、瞬时血氧变化 将用于深入了解正常和患病时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的内在光信号（IOS）的同时监测 (i.e.,神经-IOS）和血管反应（即，血液动力学-IOS）将用于客观评价空间 和视网膜中神经血管耦合相互作用的时间特性。成功的关键标准 该项目是为了验证神经血管耦合缺陷的功能检测（即，畸变刺激诱发 毛细血管水平的血液动力学），在出现可检测的形态学异常（即， 神经元损失和血管脱落）。该项目的成功将产生一个非侵入性成像平台，用于高 神经退行性变与血管功能关系的客观评价 病理学，促进神经退行性疾病的早期发现和治疗发展。

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.