Combined optical coherence tomography and electroretinography system for imaging neurovascular coupling in the human retina

During their early stages of development, neurological and neurodegenerative diseases cause changes to the biological tissue's morphology, physiology and metabolism at the cellular level, and acute, transient changes in the local blood flow. The development of optical methods that can image and quantify such changes simultaneously and investigate the relationship among them (neurovascular coupling) in neural tissues can have a profound effect on furthering our understanding of neurodegeneration. Our aim is to develop an optical imaging platform for imaging and characterization of neurovascular coupling in the human retina with high spatial and temporal resolutions. A compact, clinically viable optical coherence tomography technology was developed for in vivo, simultaneous structural, functional, and vascular imaging of the human retina and was integrated with a clinical electroretinography system. Image processing algorithms were developed to measure visually evoked physiological and blood flow changes in the living retina and explore neurovascular coupling in the healthy human retina. Both intensity and optical path length changes were measured with optical coherence tomography from most major retinal layers (nerve fiber layer, plexiform layers, inner and outer segments of the photoreceptors, and the retinal pigmented epithelium) in response to a visual stimulation with a 4-ms single white light flash. The visual stimulus also caused fast transient changes in the retinal blood flow in the local blood vessels. The time courses of these changes were similar, and their magnitude was proportional to the intensity of the visual stimulus. We have developed an optical imaging modality for non-invasive probing of neurovascular coupling in the living human retina and demonstrated its utility and clinical potential in a pilot study on healthy subjects. This imaging platform could serve as a useful clinical research tool for investigation of potentially blinding retinal diseases, as well as neurodegenerative brain diseases that are expressed in the retina such as Alzheimer's and Parkinson's diseases.