Optical Imaging of Baseline Blood Flow and Oxygenation During Stroke

 描述（由申请人提供）：脑血流定量成像在临床前卒中研究中至关重要，用于监测潜在治疗的疗效， 了解血管重组在功能恢复中的作用。类似地，血流的实时成像在人类神经血管手术期间是至关重要的，其中需要血管通畅性和组织灌注的术中可视化。激光散斑衬度成像已经变得广泛使用，因为它提供了实时图像与非常简单的仪器和不需要外源性造影剂。然而，激光散斑成像仅限于对一个受试者内的相对血流变化进行成像，并且无法比较受试者之间的血流一直是一个主要限制。我们最近引入了一种称为多次曝光散斑成像（MESI）的散斑成像扩展，该扩展允许在中风后数周内对小鼠的脑血流进行慢性成像。尽管取得了这一进展，但由于对测量信号的物理来源缺乏了解，受试者之间的比较仍然具有挑战性。我们知道散斑图像代表了潜在微血管灌注的空间积分测量，但这种积分的确切性质是复杂的，并且知之甚少。MESI的精确校准需要了解每个检测到的光子与组织中每个移动粒子的详细散射相互作用，以及每个相互作用如何对整体散斑信号做出贡献。显然，这种细节水平无法通过实验确定。在这个项目中，我们将结合联合收割机一套新的显微镜工具与物理上逼真的计算模型，这些新的工具将使我们能够建立这种关系，在前所未有的细节和校准MESI的绝对血流成像在皮层。为了做到这一点，我们将创建一个单一的显微镜采集MESI表面图像沿着与三维图像的血管结构，使用多光子荧光显微镜，和血流测量在每个血管段的皮质，使用光学相干断层扫描。该三维结构和血流信息可用作MESI计算模型的输入，这将允许我们确定每个血管段如何对测量的MESI信号做出贡献。我们将使用这些工具来建立小鼠MESI的绝对校准，并使用校准来量化MESI检测中风后皮质血管重塑的能力。最后， 我们将把MESI成像应用于临床，并在神经血管外科手术中进行MESI的初步研究。

 DESCRIPTION (provided by applicant): Quantitative imaging of cerebral blood flow is essential in preclinical stroke studies for monitoring the efficacy of potential treatments and for understanding the role of vascular reorganization in functional recovery. Similarly, real-time imaging of blood flow is crucial during neurovascular surgery in humans, where intraoperative visualization of vascular patency and tissue perfusion are needed. Laser speckle contrast imaging has become widely used because it provides real-time images with very simple instrumentation and requires no exogenous contrast agents. However, laser speckle imaging is limited to imaging of relative blood flow changes within one subject, and the inability to compare flow across subjects has been a major limitation. We recently introduced an extension to speckle imaging called multi-exposure speckle imaging (MESI), that allowed chronic imaging of cerebral blood flow in mice over many weeks post-stroke. Despite this advance however comparisons across subjects remains challenging due to a lack of understanding of the physical origins of the measured signals. We know that speckle images represent a spatially integrated measure of the underlying microvascular perfusion, but the exact nature of this integration is complex and poorly understood. Exact calibration of MESI requires knowledge of the detailed scattering interactions of every detected photon with every moving particle in the tissue, as well as how each interaction contributes to the overall speckle signal. Clearly this level of detail cannot be determined experimentally. In this project we will combine a set of novel microscopy tools with a physically realistic computational model and together these new tools will allow us to establish this relationship in unprecedented detail and calibrate MESI for absolute blood flow imaging in the cortex. To do this we will create a single microscope to acquire MESI surface images along with three dimensional images of vascular structure using multiphoton fluorescence microscopy, and blood flow measurements in every vessel segment of the cortex using optical coherence tomography. This three-dimensional structural and blood flow information with be used as inputs to a computational model of MESI that will allow us to determine how each vessel segment contributes to the measured MESI signal. We will use these tools to establish absolute calibrations for MESI in mice and use the calibrations to quantify the ability of MESI to detect vascular remodeling in the cortex following stroke. Finally, we will translate MESI imaging to the clinical setting and perform a pilot study of MESI during neurovascular surgical procedures.