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

描述（由申请人提供）：用于评估人类视网膜血流灌注的无创和无标签成像技术-低至毛细血管水平分辨率，对于提高对具有血管成分发病的疾病的理解，诊断，治疗和管理至关重要，例如年龄相关性黄斑变性（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（FA）和印度花青绿血管造影（ICGA），目前用于可视化眼部灌注和检测异常血管。传统上，这两种技术都被用于诊断和治疗决策，但它们只能提供二维（2D）图像，并且需要血管内注射，这可能导致并发症，包括过敏反应。目前还没有临床成像技术可以在毛细血管水平分辨率和确定的组织深度上提供视网膜微循环的详细可视化和量化。具有毛细血管水平分辨率的血管灌注三维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对视网膜的灌注状态进行量化。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，从而产生更明智和有针对性的治疗决策。在本项目中，我们建议开发一种临床应用的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、无创的、无标签的光学成像方法将量化血管的形态，并允许在三维空间中评估它们的空间关系。同时，可以定量评估视网膜总血流量（RBF）和视网膜和脉络膜的血管体积。为了实现这一目标，我们将首先设计和构建一个基于谱域光学相干层析成像的新型超快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)增加了进入脉络膜的光线穿透，2)提供了bbbb6mm的成像范围，具有可接受的系统灵敏度滚转特性，使其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，3)实现了前所未有的300kHz成像速度，以便在可接受的时间框架（~1秒）内获得3D图像，这是患者检查舒适度和最小化运动伪影的重要要求。然后，我们将利用工作台设置来验证rOMAG可视化视网膜和脉络膜微血管的准确性，使用动物模型和传统的组织病理学方法。在该技术在动物身上进行测试和验证后，我们将在140名受试者中进行体内rOMAG试点成像研究，以证明这种新的无创无标签3D微血管成像血管结构和功能的临床可行性和实用性。本研究将为今后对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.