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

潜在致盲性视网膜疾病，如年龄相关性黄斑变性和青光眼，会改变视网膜的结构、功能（生理和代谢）和血流。视网膜的功能和血流变化发生在疾病的早期阶段，可能是暂时的，也可能是可逆的。因此，开发一种能够在体内和无创地对这些变化进行成像和量化的技术，可以显著提高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）是最先进的视网膜结构和血流的活体、非侵入性、高分辨率成像方式。然而，目前，视网膜功能在临床上是通过视网膜电图（ERG）来评估的，这是一种侵入性的电测量方式，需要在眼睛的前表面放置电极。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上的大体积的功能反应。提出的研究计划的主要目标是开发一种基于OCT的新型无创光学方法，用于在细胞水平上进行视网膜功能的活体无创探测（功能性OCT或fOCT）。1)开发具有足够空间分辨率的fct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，以探测视网膜与视觉刺激相关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fct技术。3)建立光与视网膜组织相互作用的理论模型，有助于解释用fct测量的视网膜神经元的功能变化。潜在的致盲性视网膜疾病影响了加拿大很大一部分老龄化人口，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、血流和功能进行成像，因此临床使用fOCT可以减少患者检查的总体时间，减少对患者进行成像和处理成像数据所需的临床人员数量，以及减少临床空间的租金成本（一台或多台成像仪器的住房）。这一策略可以显著降低加拿大医疗保健系统视网膜检查的直接成本。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基础问题，如健康和病变视网膜中的神经血管耦合。该计划的技术发展具有强大的潜力，可以产生新的知识产权，并将用于视觉研究和视觉保健的新型fct系统商业化。

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.