A novel method for volumetric oxygen mapping in living retina

一种在活体视网膜中进行体积氧测绘的新方法

• 批准号: 10361407
• 负责人: Ji Yi
• 金额: $ 47.75万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-01 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10361407
• 关键词: 3-Dimensional; Address; Affect; Age related macular degeneration; American; Biochemistry; Blood Vessels; Blood capillaries; Blood flow; Cardiovascular system; Cell Respiration; Choroid; Consumption; Data; Data Set; Detection; Diabetic Retinopathy; Dyes; Eye; Fluorescence Angiography; Fundus; Future; Glaucoma; Goals; Human; Hypoxia; Image; Imaging Device; Imaging Techniques; Inhalation; Label; Lasers; Life; Light; Location; Machine Learning; Measurement; Measures; Mediating; Medicine; Metabolic; Methodology; Methods; Microscopy; Multimodal Imaging; Mus; Nobel Prize; Ophthalmoscopes; Ophthalmoscopy; Optical Coherence Tomography; Optics; Oxygen; Oxygen saturation measurement; Partial Pressure; Pathologic; Pathology; Photons; Physiology; Public Health; Resolution; Retina; Retinal Diseases; Role; Scanning; Signal Pathway; Signal Transduction; Speed; Supervision; Time; Tissues; Training; Translating; Vascular System; Visible Radiation; adaptive optics; algorithm training; base; choroidal circulation; clinical application; clinical translation; deep learning; design; hemodynamics; human imaging; imaging modality; improved; in vivo; learning network; learning strategy; lens; machine learning framework; multidisciplinary; novel; novel imaging technique; optical imaging; phosphorescence; porphyrin a; programs; quantitative imaging; response; retina circulation; retinal imaging; sensor; success; tool; two photon microscopy; two-photon

PROJECT SUMMARY It is widely accepted that oxygen deficiency is a culprit and a marker of several major retinal diseases, including diabetic retinopathy, age-related macular degeneration, glaucoma etc. However, it remains to be extremely challenging to measure oxygen in vivo in the eye, and no tools currently exist that can provide 3D oxygen distributions in the retina with high spatial resolution at appropriate imaging speeds. The goal of this project is to overcome these limitations and develop a new optical imaging technique for volumetric oxygen mapping in retina. Our approach will leverage the recently developed potent oxygen probes (such as Oxyphor 2P), whose phosphorescence decay times serve as quantitative markers of local oxygen partial pressures (pO2) in living tissues. To enable volumetric imaging with high throughput, we propose to develop a novel imaging instrument, termed oblique scanning laser ophthalmoscope (oSLO). oSLO is based on the concept of single lens scanned light sheet microscopy and enables volumetric phosphorescence lifetime imaging without time- consuming plane-by-plane pixel-wise sectioning. Our new method should be able to achieve 10 kilohertz voxel rate that is three orders of magnitude higher than the current state-of-the-art two-photon phosphorescence lifetime microscopy (2PLM). In this project we will: (Aim 1) develop a phosphorescence lifetime-based oSLO for volumetric pO2 mapping in living retina in mouse. The new design will allow parallel detection of signals at depth from each scanned location, so that the need in conventional depth sectioning is eliminated and imaging throughput is greatly increased. We will (Aim 2) dynamically image responses of retina and choroid to systemic hypoxia challenge using Oxyphor 2P. We will (Aim 3) then bridge oSLO measurements and label-free applications by multimodal imaging with visible light optical coherence tomography (vis-OCT). Using vascular pO2 as the ground-truth, we will develop a deep spectral training (DSL) algorithm to supervise the inverse calculation of vis-OCT for robust and reliable label-free retinal oximetry. This study will enable the first direct quantitative imaging of interactions between the two circulatory systems in retina (i.e. retinal and choroidal circulation), providing unprecedented information about retinal oxygen supply. IMPACT ON PUBLIC HEALTH: Successful completion of this program will deliver a new ground-breaking methodology for mapping oxygen in the retina that will greatly improve our understanding of retinal diseases.

项目摘要 人们普遍认为，缺氧是罪魁祸首，也是几种主要视网膜疾病的标志， 包括糖尿病性视网膜病，与年龄相关的黄斑变性，青光眼等 在眼睛中测量体内的氧气极具挑战性，目前没有任何工具可以提供3D 在适当的成像速度下具有高空间分辨率的视网膜中的氧分布。目标的目标 项目是要克服这些局限性，并开发一种用于体积氧的新光学成像技术 在视网膜中映射。我们的方法将利用最近开发的有效氧探针（例如氧 2p），其磷光衰减时间是局部氧部分压力的定量标记（PO2） 在活组织中。为了启用具有高吞吐量的体积成像，我们建议开发一种新型成像 仪器称为斜扫描激光眼镜镜（OSLO）。奥斯陆基于单一的概念 镜头扫描光片显微镜，并实现无时间的磷光寿命成像 逐个平面像素分段消耗平面平面。我们的新方法应该能够达到10千霍兹素体素 速率比当前的最新两光子磷光高三个数量级 终生显微镜（2PLM）。在这个项目中，我们将：（目标1）开发基于磷光寿命的奥斯陆 用于在鼠标中活着的视网膜中的体积PO2映射。新设计将允许在 每个扫描位置的深度，因此消除了常规深度切片的需求并成像 吞吐量大大增加。我们将（AIM 2）动态图像视网膜和脉络膜对全身的反应 使用氧气2p的缺氧挑战。我们将（AIM 3）然后桥接奥斯陆测量和无标签 通过可见光光学相干断层扫描（VIS-OCT）进行多模式成像的应用。使用血管 PO2作为基础真相，我们将开发深度频谱培训（DSL）算法来监督逆向 计算可靠且可靠的无标签视网膜血氧仪的Vis-OCT。这项研究将使第一个直接 视网膜中两个循环系统之间相互作用的定量成像（即视网膜和脉络膜 循环），提供有关视网膜氧气供应的前所未有的信息。对公共卫生的影响： 该计划的成功完成将提供一种新的开创性方法，用于映射氧气 将大大提高我们对视网膜疾病的理解的视网膜。