Optical method for in-vivo, non-invasive imaging of neurovascular coupling in the retina

用于视网膜神经血管耦合体内非侵入性成像的光学方法

• 批准号: RGPIN-2020-06308
• 负责人: Bizheva, Kostadinka
• 金额: $ 2.99万
• 依托单位: University of Waterloo
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=717988
• 关键词: Optical; method; vivo; non; invasive

Motivation Potentially blinding retinal diseases such as Age-related Macular Degeneration and Glaucoma, alter the retinal structure, function (physiology and metabolism) and blood flow. Functional and blood flow changes in the retina occur at the early stages of the disease and can be both temporary and potentially reversible. Therefore, developing a technology that can image and quantify these changes in-vivo and non-invasively, can improve significantly the early diagnostics of blinding retinal diseases and aid the development of novel treatments. Optical Coherence Tomography (OCT) is the most advanced imaging modality for in-vivo, non-invasive, high resolution imaging of the retinal structure and blood flow. However, currently, retinal function is assessed clinically with Electroretinography (ERG), which is an invasive electrical measurement modality that requires placement of an electrode on the front surface of the eye. ERG has very low spatial resolution, as it integrates the functional response of many different types of retinal neurons over a wide volume of the retina. The main goal of the proposed research program is to develop a novel, non-invasive optical method, based on OCT, for in-vivo, non-invasive probing of retina function at cellular level (functional OCT or fOCT). Short Term Objectives 1) Develop fOCT technology with sufficient spatial resolution to image in-vivo individual retinal neurons and sufficient temporal resolution to probe fast physiological and metabolic changes in the retina associated with visual stimulation. 2) Validate the fOCT technology by conducting proof-of-concept studies in animals and humans. 3) Develop a theoretical model of light interaction with retinal tissue that can help explain the functional changes in retinal neurons measured with fOCT. Significance Potentially blinding retinal diseases affect a large portion of Canada's aging population and amount to billions of dollars in direct costs to the Canadian Health Care system. Since fOCT allows for simultaneous imaging of the retinal structure, blood low and function, clinical use of fOCT can reduce the overall time for patient examination, the number of clinical personnel required for imaging the patients and processing of the imaging data, as well as the rental cost of clinical space (housing of one vs multiple imaging instruments). This strategy may result in significant reduction of the direct cost for retinal exams to the Canadian Health Care system. In a broader context, the ability to simultaneously visualize and correlate retinal morphology, blood flow, physiology and metabolism, can directly address many important fundamental questions in vision research such as neurovascular coupling in the healthy and diseased retina. The technological development in the proposed program has strong potential for generation of novel intellectual property, and for commercialization of the novel fOCT system for vision research and vision health care.

动机 潜在致盲性视网膜疾病，如视网膜相关性黄斑变性和青光眼，改变视网膜结构、功能（生理和代谢）和血流。视网膜中的功能和血流变化发生在疾病的早期阶段，并且可以是暂时的和潜在可逆的。因此，开发一种可以在体内和非侵入性地对这些变化进行成像和量化的技术，可以显着改善致盲性视网膜疾病的早期诊断，并有助于开发新的治疗方法。 光学相干断层扫描（OCT）是用于视网膜结构和血流的体内、非侵入性、高分辨率成像的最先进的成像模式。然而，目前，视网膜功能在临床上用视网膜电图（ERG）评估，这是一种侵入性电测量模式，需要在眼睛的前表面上放置电极。ERG具有非常低的空间分辨率，因为它整合了许多不同类型的视网膜神经元在视网膜的广泛体积上的功能反应。 拟议的研究计划的主要目标是开发一种新的，非侵入性的光学方法，OCT的基础上，在体内，非侵入性探测视网膜功能在细胞水平（功能OCT或fOCT）。 短期目标 1)开发具有足够空间分辨率的fOCT技术，以成像体内单个视网膜神经元，并具有足够的时间分辨率，以探测与视觉刺激相关的视网膜中的快速生理和代谢变化。 2)通过在动物和人类中进行概念验证研究来验证fOCT技术。 3)开发光与视网膜组织相互作用的理论模型，以帮助解释fOCT测量的视网膜神经元功能变化。 意义 潜在的致盲性视网膜疾病影响了加拿大老龄人口的很大一部分，并给加拿大医疗保健系统带来了数十亿美元的直接成本。由于fOCT允许同时对视网膜结构、血液流动和功能进行成像，因此fOCT的临床使用可以减少患者检查的总时间、对患者进行成像和处理成像数据所需的临床人员数量以及临床空间的租赁成本（容纳一台与多台成像仪器）。这一战略可能会导致显着降低视网膜检查的直接成本，加拿大医疗保健系统。 在更广泛的背景下，同时可视化和关联视网膜形态，血流，生理和代谢的能力，可以直接解决视觉研究中的许多重要的基本问题，如健康和患病视网膜中的神经血管耦合。 拟议计划中的技术开发具有产生新知识产权的强大潜力，并将新型fOCT系统商业化用于视觉研究和视觉保健。