NON-INVASIVE REAL-TIME LABEL-FREE 3D IMAGING OF RETINAL MICROCIRCULATION

视网膜微循环非侵入式实时无标记 3D 成像

• 批准号: 8639862
• 负责人: Ruikang Wang
• 金额: $ 46.58万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-02-01 至 2018-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8639862
• 关键词: Age related macular degeneration; Algorithms; Anaphylaxis; Angiography; Animal Model; Animals; Anterior; Architecture; Autopsy; Blood Vessels; Blood capillaries; Blood flow; Characteristics; Choroid; Choroid Diseases; Clinical; Comparative Study; Contrast Media; Coupled; Data; Development; Diabetic Retinopathy; Diagnosis; Dimensions; Disease Management; Doppler Ultrasound; Dyes; Eye; Face; Fluorescein Angiography; Foundations; Fundus; Future; Glaucoma; Goals; Histopathology; Human; Human Pathology; Image; Imagery; Imaging Device; Imaging Techniques; Injection of therapeutic agent; Investigation; Knowledge; Label; Laser-Doppler Velocimetry; Light; Maps; Measures; Microcirculation; Monitor; Morphologic artifacts; Morphology; Motion; Mus; Open-Angle Glaucoma; Ophthalmology; Optic Nerve; Optical Coherence Tomography; Optics; Outcomes Research; Pathogenesis; Pathology; Patients; Penetration; Perfusion; Physiology; Preventive; Process; Research; Resolution; Retina; Retinal; Retinal Diseases; Rheology; Risk; Scanning; Source; Speed; Structure; Supervision; System; Techniques; Technology; Testing; Therapeutic; Therapeutic Intervention; Thick; Three-Dimensional Image; Three-Dimensional Imaging; Time; Tissues; Translating; Trees; Vascular Diseases; base; blood perfusion; capillary; cyanine; design; design and construction; experience; imaging modality; improved; in vivo; in vivo imaging; medical schools; microangiography; novel; optical imaging; public health relevance; tool; two-dimensional; volunteer

DESCRIPTION (provided by applicant): Non-invasive Real-time Label-free 3D Imaging of Retinal Microcirculations PROJECT SUMMARY Non-invasive and label-free imaging techniques for assessing retinal blood perfusion in humans - down to capillary-level resolution, are of paramount importance for improved understanding, diagnosis, treatment and management of diseases that have a vascular component in their pathogenesis, e.g., age related macular degeneration (AMD), diabetic retinopathy (DR), and open angle glaucoma (OAG). Invasive imaging techniques, e.g., fluorescein angiography (FA) and indo-cyanine green angiography (ICGA), are currently used to visualize ocular perfusion and detect abnormal vessels. Both techniques have traditionally been utilized to make diagnoses and treatment decisions, but they can only provide two-dimensional (2D) images and require intravascular injections that risk complications, including anaphylaxis. No clinical imaging techniques currently exist that can offer detailed visualization and quantification of retinal microcirculation at capillary level resolution and at defined tissue depths. It would be highly advantageous to be capable of three-dimensional (3D) visualization of vascular perfusion with capillary-level resolution, both to revea the detailed functional architecture of the perfused microvascular network and to permit quantification of the perfusion status of the retina through volumetric rheology. This information would be fundamental to better understanding of vascular retinal and choroidal diseases, resulting in more informed and targeted treatment decisions. In this project, we propose to develop a clinically applicable 3D functional retinal optical microangiography (rOMAG) system. We envision that this novel, non-invasive, and label-free optical imaging method will quantify the morphology of blood vessels and permit assessment of their spatial relations in three dimensions. Concurrently, total retinal blood flow (RBF) and vascular volumes of the retina and choroid can be quantitatively assessed. To achieve this goal, we will first design and construct a novel, ultrafast rOMAG system based on spectral domain optical coherence tomography. The focus will be on solving challenges associated with creating a retinal imaging system that is capable of, simultaneously: 1) having increased light penetration into the choroid, 2) providing an imaging range of >6mm with acceptable system sensitivity roll-off characteristics so that it is able to image the whole posterior segment from anterior retina to posterior choroid in one scan, and 3) achieving an unprecedented imaging speed of 300kHz to enable acquiring 3D images within an acceptable time frame (~1 sec), an important requirement for patient examination comfort and minimization of motion artifact. We will then utilize a bench top setup to validate rOMAG's accuracy for visualizing the retinal and choroidal microvasculature, using an animal model and traditional histopathology approaches. After the technology has been tested and validated in animals, we will perform in vivo rOMAG pilot imaging studies in 140 subjects to demonstrate clinical feasibility and usefulness of this new non-invasive label-free 3D microangiography of vascular structure and function. This study will serve as the foundation for interpretation of rOMAG data in future.

描述（由申请人提供）：视网膜微循环的非侵入性实时无标记 3D 成像 项目摘要 用于评估人类视网膜血液灌注的无创和无标记成像技术（低至毛细血管水平分辨率）对于改善对发病机制中具有血管成分的疾病（例如年龄相关性黄斑变性）的理解、诊断、治疗和管理至关重要 （AMD）、糖尿病性视网膜病变（DR）和开角型青光眼（OAG）。侵入性成像技术，例如荧光素血管造影（FA）和吲哚绿血管造影（ICGA），目前用于可视化眼部灌注并检测异常血管。传统上，这两种技术都被用来做出诊断和治疗决策，但它们只能提供二维 (2D) 图像，并且需要血管内注射，从而存在并发症（包括过敏反应）的风险。目前还没有临床成像技术可以在毛细血管水平分辨率和定义的组织深度提供视网膜微循环的详细可视化和量化。能够以毛细血管水平分辨率对血管灌注进行三维（3D）可视化将是非常有利的，既可以揭示灌注微血管网络的详细功能结构，又可以通过体积流变学量化视网膜的灌注状态。这些信息对于更好地了解血管性视网膜和脉络膜疾病至关重要，从而做出更明智、更有针对性的治疗决策。 在这个项目中，我们建议开发一种临床适用的3D功能性视网膜光学微血管造影（rOMAG）系统。我们设想这种新颖的、非侵入性的、无标记的光学成像方法将量化血管的形态，并允许评估它们在三个维度上的空间关系。同时，可以定量评估视网膜总血流量（RBF）以及视网膜和脉络膜的血管体积。为了实现这一目标，我们将首先设计并构建一种基于谱域光学相干断层扫描的新型超快 rOMAG 系统。重点将是解决与创建视网膜成像系统相关的挑战，该系统能够同时：1）增加对脉络膜的光穿透，2）提供> 6毫米的成像范围和可接受的系统灵敏度滚降特性，以便能够在一次扫描中对从前视网膜到后脉络膜的整个后段进行成像，以及3）实现前所未有的300kHz成像速度 能够在可接受的时间范围（约 1 秒）内采集 3D 图像，这是患者检查舒适度和运动伪影最小化的重要要求。然后，我们将使用动物模型和传统的组织病理学方法，利用台式装置来验证 rOMAG 在可视化视网膜和脉络膜微血管系统方面的准确性。该技术在动物身上进行测试和验证后，我们将对 140 名受试者进行体内 rOMAG 试点成像研究，以证明这种新型非侵入性无标记血管结构和功能 3D 微血管造影的临床可行性和实用性。这项研究将为将来解释 rOMAG 数据奠定基础。