OPTICAL MICROANGIOGRAHY OF CEREBROVASCULAR PERFUSION

描述（由申请人提供）：用于量化血流、血管重塑和血氧饱和度（SaO2）直至毛细血管水平分辨率的无创技术对于改善神经血管和神经代谢疾病（如卒中）的理解、诊断和治疗至关重要。目前还没有成像技术，可以非侵入性地同时测量这些参数，而不使用外源性造影剂在体内微循环。我们开创了一种非侵入性3D光学成像技术，光学微血管造影术（OMAG），以满足这一挑战。在母项目R01中，我们成功证明了OMAG可以在毛细血管水平分辨率下生成组织结构和血流的实时3D图像，成像深度高达2 mm，无需外源性造影剂（参见进度报告中的出版物列表）。此外，我们还展示了一些新的方法，成功地从巨大的“噪声”背景下的光学散射，几乎所有的高分辨率光学成像技术结婚的障碍提取血流信号。作为我们研究的直接结果，现在可以在临床前（小动物模型）和临床环境（人类视网膜）中对功能性3D微血管网络进行成像。自从我们第一次出版报道OMAG以来，该领域已经呈指数级增长，并且有几家公司计划销售OMAG产品。现在，我们已经成功地开发了OMAG成像功能性微循环，我们将把我们的研究工作对下一代OMAG成像方式的发展。这种新一代技术将允许在扫描的组织体积内同时监测毛细血管水平的深度分辨脑血流量（CBF）、微血管形态和SaO2。为了实现这一目标，我们将首先开发一个多功能OMAG（mfOMAG）系统，能够测量脑血流和氧合的快速和长期反应。然后，我们将联合收割机这个系统与一种新的光谱激光散斑成像，我们将使用它作为指导，立即磨练到受伤的地区进行彻底的评估与mfOMAG。最后，我们将确定连续监测小鼠实验性中风后脑血流变化和血管重塑的mfOMAG的效用。

DESCRIPTION (provided by applicant): Non-invasive techniques for quantifying blood flow, vascular remodeling and blood oxygen saturation (SaO2) down to capillary-level resolution are of paramount importance for the improved understanding, diagnosis and treatment of neurovascular and neurometabolic disorders such as stroke. Currently there are no imaging techniques that can non-invasively and simultaneously measure these parameters without the use of exogenous contrast agents in the microcirculation in vivo. We have pioneered a non-invasive 3D optical imaging technology, optical microangiography (OMAG), that meets this challenge. In the parent R01 project, we have successfully demonstrated that OMAG generates real-time 3D images of both tissue structure and blood flow at capillary level resolution with an imaging depth up to 2 mm without the need for exogenous contrast agents (see publication list in the progress report). In addition, we also demonstrated a number of novel methods to successfully extract the blood flow signals from huge 'noise' background of optical scattering, an obstacle married with almost all high-resolution optical imaging techniques. As a direct result of our research, it is now practical to image functional 3D microvascular networks in pre-clinical (small animal models) and clinical settings (human retina). Since our first publication that reported OMAG, the field has grown exponentially, and there are several companies planning to market the OMAG product. Now that we have successfully developed OMAG for imaging functional microcirculations, we will direct our research efforts towards the development of the next generation OMAG imaging modality. This next generation technology will allow depth-resolved cerebral blood flow (CBF), microvascular morphology and SaO2 at the capillary level to be simultaneously monitored within a scanned tissue volume. To achieve this goal, we will first develop a multifunctional OMAG (mfOMAG) system capable of measuring rapid and long term responses of cerebral blood flow and oxygenation. We will then combine this system with a novel spectral laser-speckle imaging which we will use as a guide to immediately hone into injured regions for a thorough evaluation with mfOMAG. Finally, we will determine the utility of mfOMAG for serial monitoring of cerebral blood flow changes and vascular remodeling following experimental stroke in mice.