Dhaliwal Khushmeet, Wong Alexander, Wright Tom, Bizheva Kostadinka
University of Waterloo, Department of Physics and Astronomy, Waterloo, Ontario, Canada.
University of Waterloo, Systems Design Engineering Department, Waterloo, Ontario, Canada.
Neurophotonics. 2025 Jul;12(3):035004. doi: 10.1117/1.NPh.12.3.035004. Epub 2025 Aug 9.
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 , 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.
在神经和神经退行性疾病的早期发展阶段，会在细胞水平上引起生物组织形态、生理和代谢的变化，以及局部血流的急性、短暂变化。开发能够同时对这些变化进行成像和量化，并研究神经组织中它们之间关系（神经血管耦合）的光学方法，可能会对深化我们对神经退行性变的理解产生深远影响。
我们的目标是开发一个光学成像平台，用于以高空间和时间分辨率对人视网膜中的神经血管耦合进行成像和表征。
开发了一种紧凑的、临床上可行的光学相干断层扫描技术，用于对人视网膜进行结构、功能和血管的同步成像，并与临床视网膜电图系统集成。开发了图像处理算法，以测量活体视网膜中视觉诱发的生理和血流变化，并探索健康人视网膜中的神经血管耦合。
通过光学相干断层扫描测量了大多数主要视网膜层（神经纤维层、丛状层、光感受器的内段和外段以及视网膜色素上皮）在4毫秒单白光闪光视觉刺激下的强度和光程长度变化。视觉刺激还导致局部血管中视网膜血流的快速短暂变化。这些变化的时间进程相似，其幅度与视觉刺激的强度成正比。
我们开发了一种光学成像模式，用于对活体人视网膜中的神经血管耦合进行无创探测，并在对健康受试者的初步研究中证明了其效用和临床潜力。这个成像平台可以作为一个有用的临床研究工具，用于研究潜在致盲的视网膜疾病，以及在视网膜中表现出来的神经退行性脑疾病，如阿尔茨海默病和帕金森病。
