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

描述(申请人提供)：视网膜微循环的非侵入性实时无标记3D成像项目概述用于评估人类视网膜血流灌注的非侵入性和无标记成像技术--低至毛细血管水平的分辨率，对于改善对疾病的理解、诊断、治疗和管理至关重要，这些疾病在其发病机制中包含血管成分，例如老年性黄斑变性(AMD)、糖尿病视网膜病变(DR)和开角型青光眼(OAG)。侵入性成像技术，如荧光素血管造影术(FA)和吲哚青绿血管造影术(ICGA)，目前被用于显示眼血流灌注和检测异常血管。这两种技术传统上都被用来进行诊断和治疗决策，但它们只能提供二维(2D)图像，需要血管内注射，有可能出现包括过敏反应在内的并发症。目前还没有临床成像技术可以提供毛细血管水平分辨率和特定组织深度的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进行血管灌注的三维(3D)可视化将是非常有利的，既可以揭示灌流的微血管网络的详细功能结构，又可以通过体积流变学来量化视网膜的灌流状态。这些信息将是更好地了解血管视网膜和脉络膜疾病的基础，从而产生更知情和更有针对性的治疗决定。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成像(ROMAG)系统。我们设想，这种新的、非侵入性的、无标记的光学成像方法将量化血管的形态，并允许在三维上评估它们的空间关系。同时，可以定量评估视网膜和脉络膜的总视网膜血流量(RBF)和血管容量。为了实现这一目标，我们将首先设计和构建一种基于光谱域光学相干层析成像的新型超快ROMAG系统。重点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)增加光对脉络膜的穿透率，2)提供&gt；6 mm的成像范围，具有可接受的系统灵敏度滚动特性，以便它能够在一次扫描中对从视网膜前到后脉络膜的整个后段进行成像，以及3)实现前所未有的300 kHz成像速度，以便能够在可接受的时间框架(~1秒)内获取3D图像，这是患者检查舒适度和最大限度减少运动伪影的重要要求。然后，我们将使用动物模型和传统的组织病理学方法，利用工作台设置来验证Romag在可视化视网膜和脉络膜微血管方面的准确性。在动物身上测试和验证了这项技术之后，我们将在140名受试者中进行ROMAG体内先导成像研究，以证明这种新的无创、无标签的血管结构和功能3D微血管成像的临床可行性和有效性。这项研究将为今后ROMAG数据的解释奠定基础。

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.