Optical Imaging of Baseline Blood Flow and Oxygenation During Stroke

 描述(申请人提供)：脑血流的定量成像在临床前卒中研究中是必不可少的，用于监测潜在治疗的疗效和 了解血管重组在功能恢复中的作用。同样，在人类的神经血管手术中，血流的实时成像是至关重要的，因为术中需要可视化血管通畅和组织灌流。激光散斑对比成像因其提供实时图像的仪器非常简单，且不需要外源性造影剂而得到了广泛的应用。然而，激光散斑成像仅限于成像一个受试者内的相对血流变化，而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)的斑点成像扩展，可以对中风后许多周的小鼠脑血流进行慢性成像。然而，尽管取得了这一进展，但由于缺乏对测量信号的物理来源的理解，跨对象比较仍然具有挑战性。我们知道，散斑图像代表了对潜在微血管血流的空间综合测量，但这种综合的确切性质是复杂的，人们对此知之甚少。MESI的精确校准需要了解每个检测到的光子与组织中每个运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，这种详细程度不能通过实验来确定。在这个项目中，我们将把一套新的显微镜工具与物理上真实的计算模型结合起来，这些新工具将使我们能够以前所未有的细节建立这种关系，并校准MESI以进行皮质中的绝对血流成像。为此，我们将创建一台单独的显微镜，使用多光子荧光显微镜获取MESI表面图像以及血管结构的三维图像，并使用光学相干断层扫描技术测量皮质每一血管段的血流。这些三维结构和血流信息将被用作MESI计算模型的输入，该模型将使我们能够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在小鼠中建立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构的能力。最后， 我们将把MESI成像应用到临床环境中，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.