IMAGING OPTIC NERVE FUNCTION AND PATHOLOGY

 描述（由申请人提供）：NEI的既定目标是再生眼睛和视觉系统中的神经元和神经连接，需要开发能够在眼睛和大脑之间重建神经连接时对神经连接进行非侵入性成像的模式。在概念验证研究中，我们介绍了两种有前途的技术，扩散基谱成像（DBSI）和扩散功能磁共振成像（扩散fMRI），用于可视化视神经原位的病理和功能。在目前的提案中，我们将联合收割机这些技术，提供一种新的，基于扩散MRI的方法，以评估视神经解剖，功能和病理同时在小鼠和人类受试者。我们将通过监测青光眼和视神经炎轴突损伤的进展和/或消退来验证这种方法。为了与NEI的总体愿望保持一致，我们的长期目标是利用这种方法来非侵入性地评估视神经中再生轴突的结构和功能。本研究的目的有三：（1）建立视神经损伤小鼠模型，将视神经损伤程度与视神经轴突数目、视神经功能之间的关系定量化，将视神经损伤程度与视神经轴突数目、视神经功能与视神经功能之间的关系定量化;（2）进行体内实验和计算机计算（调整从组织学获得的结构信息），以确定针对DBSI和弥散fMRI两者优化的弥散时间，从而区分限制性各向同性（远离 轴突）和各向异性（邻近轴突）扩散;和（3）开发和优化体内人视神经扩散MRI方案和视觉刺激范例，其可以同时可视化青光眼和视神经炎患者的视神经解剖、功能和病理。完成后，我们将建立一种新的成像方法，同时评估视神经解剖，功能和病理，允许详细的视神经病变的病理生理学调查。

 DESCRIPTION (provided by applicant): The stated aspirational goal of the NEI, to Regenerate Neurons and Neural Connections in the Eye and Visual System, requires the development of modalities capable of non-invasively imaging neural connections as they are reestablished between the eye and the brain. In proof-of-concept studies we have introduced two promising techniques, diffusion basis spectrum imaging (DBSI) and diffusion functional magnetic resonance imaging (diffusion fMRI) for visualizing the pathology and function of the optic nerve in situ. In the current proposal, we will combine these technologies to deliver a new, diffusion MRI-based method to assess optic nerve anatomy, function and pathology simultaneously in both mice and human subjects. We will validate this approach by monitoring the progression and/or regression of axonal damage in glaucoma and optic neuritis. In keeping with the overall aspirations of the NEI, our long-term goal is to utilize this methodology to assess, non- invasively, the structure and function of regenerating axons in the optic nerve. Three specific aims will be pursued: (1) To quantify the relationships between diffusion MRI signals, axon number and visual function in an optic nerve crush mouse model, correlating DBSI with histological counts of axon number and diffusion fMRI with visual acuity; (2) To perform in vivo experiments and in silico computation (adapting structural information obtained from histology) on the optic nerve crush mouse model to identify a diffusion time optimized for both DBSI and diffusion fMRI and thus distinguish the contribution of restricted isotropic (distant from the axons) and anisotropic (adjacent to the axons) diffusion; and (3) To develop and optimize in vivo human optic nerve diffusion MRI protocol and visual stimulation paradigm that can simultaneously visualize optic nerve anatomy, function and pathology in glaucoma and optic neuritis patients. At completion, we will have established a novel imaging method to simultaneously assess optic nerve anatomy, function, and pathology allowing a detailed pathophysiological investigation of optic neuropathies.