OPTICAL MICROANGIOGRAHY OF CEREBROVASCULAR PERFUSION

描述(申请人提供)：用于量化血流量、血管重塑和血氧饱和度(SaO2)的非侵入性技术，精确到毛细血管水平的分辨率，对于改善对中风等神经血管和神经代谢疾病的理解、诊断和治疗至关重要。目前还没有一种成像技术可以无创地同时测量这些参数，而不需要在体内微循环中使用外源性造影剂。我们开创了一种非侵入性3D光学成像技术--光学微血管成像(OMAG)，以应对这一挑战。在母项目R01中，我们成功地展示了OMAG以毛细血管水平分辨率生成组织结构和血流的实时3D图像，成像深度可达2 mm，无需外源性造影剂(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，成功地从光学散射的巨大噪声背景中提取血流信号，这是几乎所有高分辨率光学成像技术的障碍。作为我们研究的直接结果，现在在临床前(小动物模型)和临床环境(人类视网膜)中成像功能3D微血管网络是可行的。自从我们第一次报道OMAG以来，这一领域呈指数级增长，有几家公司计划销售OMAG产品。既然我们已经成功地开发了用于成像功能微循环的OMAG，我们将把我们的研究努力转向开发下一代OMAG成像模式。这项下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，我们将首先开发一种多功能OMAG(MfOMAG)系统，该系统能够测量脑血流和氧合的快速和长期反应。然后，我们将把这个系统与一种新的光谱激光散斑成像结合起来，我们将使用它作为指南，立即磨练到损伤区域，以便用mfOMAG进行彻底的评估。最后，我们将确定mfOMAG在连续监测实验性中风后小鼠脑血流变化和血管重塑方面的应用。

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.