Functional Optical Coherence Tomography for Imaging of Cortical Hemodynamics

描述（由申请人提供）：光学相干断层扫描（OCT）是一种光学成像模式，可以原位和真实的实时对生物组织中的微结构进行微米级断层扫描横截面成像。由于高轴向分辨率，OCT非常适合对具有层状结构的组织（例如视网膜）进行成像。在过去5年中，OCT技术的最新进展使得OCT成像速度和灵敏度有了显著提高。重要的是，高速OCT能够实现快速容积成像，并促进新的对比度来源，如多普勒和光谱OCT。该提案的一个中心目标是，OCT技术的进步将使深度分辨，定量血流动力学和代谢测量功能激活过程中的大脑具有高时空分辨率。该提案将开发新的技术和方法，以增强OCT定量测量血流量、血容量、血细胞比容、氧饱和度和毛细血管扩张的能力。这些技术和方法将被应用于研究躯体感觉激活过程中的神经血管耦合和氧消耗。该计划的具体目标是：1。开发用于脑成像的高速OCT显微镜平台。将开发两个光谱/傅立叶域OCT显微镜平台，一个在近红外波长下工作，另一个在可见光波长下工作。2.开发并验证OCT测量血流量、血容量、红细胞压积、血氧饱和度和毛细血管扩张的方法。将开发定量测量皮质血流动力学的方法。这些方法将在循环全血样本中进行体外验证，并通过与双光子显微镜和光学固有信号成像（OISI）进行比较进行体内验证。该目标将表征OCT相对于用于测量皮质血流动力学的其他成像技术的性能。3.表征层流响应并量化功能激活期间的耗氧量。目标2中开发的方法将用于根据血管隔室和皮质层表征皮质血流动力学反应，并定量测量体感激活期间的耗氧量。该计划的结果将回答有关微观水平上的血流动力学和代谢反应的基本问题，这将有助于解释宏观测量，如BOLD fMRI，并提高对脑血管生理学和病理学的理解。 公共卫生相关性：项目叙述本提案的假设是，光学相干断层扫描（OCT）能够对血流、血容量、血细胞比容、氧饱和度和毛细血管扩张进行深度分辨的定量测量，可用于研究神经血管耦合。该计划将开发用于深度分辨体内脑成像的高速OCT显微镜技术，并开发和验证使用这些技术测量皮质血流动力学的方法。这些技术和方法将被应用于表征层血流动力学反应和氧代谢在体感激活。

DESCRIPTION (provided by applicant): Optical coherence tomography (OCT) is an optical imaging modality that can perform micron scale, tomographic cross-sectional imaging of microstructure in biological tissues in situ and in real time. Due to the high axial resolution, OCT is ideally suited for imaging tissues with a laminar structure, such as the retina. Recent advances in OCT technology over the past 5 years have enabled dramatic advances in OCT imaging speed and sensitivity. Importantly, high-speed OCT enables rapid volumetric imaging, and facilitates new sources of contrast such as Doppler and spectroscopic OCT. A central goal of this proposal is that the advances in OCT technology will enable depth-resolved, quantitative hemodynamic and metabolic measurements during functional activation in the brain with high spatiotemporal resolution. This proposal will develop novel technologies and methods to enhance the capability of OCT to quantitatively measure blood flow, blood volume, hematocrit, oxygen saturation, and capillary dilation. These technologies and methods will be applied to study neurovascular coupling and oxygen consumption during somatosensory activation. The specific aims of this program are: 1. Develop high-speed OCT microscope platforms for brain imaging. Two spectral / Fourier domain OCT microscope platforms, one operating at near-infrared wavelengths and the other operating at visible wavelengths, will be developed. 2. Develop and validate methods of measuring of blood flow, blood volume, hematocrit, oxygen saturation and capillary dilation with OCT. Methods of quantitatively measuring cortical hemodynamics will be developed. These methods will be validated in vitro in circulating whole blood samples, and in vivo by comparison with two photon microscopy and optical intrinsic signal imaging (OISI). This aim will characterize the performance of OCT relative to other imaging technologies used for measuring cortical hemodynamics. 3. Characterize the laminar response and quantify oxygen consumption during functional activation. The methods developed in Aim 2 will be used to characterize the cortical hemodynamic response according to vascular compartment and cortical layer, and to quantitatively measure oxygen consumption during somatosensory activation. The results of this program will answer fundamental questions about the hemodynamic and metabolic responses at the microscopic level, which will aid interpretation of macroscopic measurements such as BOLD fMRI and improve understanding of cerebrovascular physiology and pathology. PUBLIC HEALTH RELEVANCE: PROJECT NARRATIVE The hypothesis of this proposal is that optical coherence tomography (OCT) enables depth-resolved, quantitative measurements of blood flow, blood volume, hematocrit, oxygen saturation, and capillary dilation which can be used to study neurovascular coupling. This program will develop high-speed OCT microscopy technologies for depth-resolved in vivo brain imaging and develop and validate methods of measuring cortical hemodynamic using these technologies. These technologies and methods will be applied to characterize the laminar hemodynamic response and oxygen metabolism during somatosensory activation.