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

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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.