Optical Imaging of Baseline Blood Flow and Oxygenation During Stroke

描述(由申请人提供)：目前在动物模型中开发的许多中风疗法针对的是大脑微循环。因此，对血流和氧合等血流动力学参数进行体内定量测量是这些研究的关键。虽然几种基于光学和MR的技术被广泛应用于这种实验性卒中研究，但现有的技术受到显著的限制。特别是，大多数技术仅限于在单个测量周期内测量单个动物内单个血流动力学参数的相对变化。因此，这些方法不能用来确定绝对血流量或氧合，也不能用来评估慢性血流动力学变化，这可能会阻碍评估中风疗法的努力，这些疗法试图通过刺激血管生成或增强一氧化氮合成来逐渐恢复缺血组织的血流和氧气供应。因此，这项提议的总体目标是开发一种能够成像基线脑血流动力学(血流和氧合)的光学仪器，并使用该仪器来量化缺血后发生的急性和慢性血流动力学变化。为了实现这一目标，我们将推进两项光学成像技术，这两项技术已在中风研究中显示出重大前景。在目标1中，我们将改进用于脑血流成像的激光散斑对比成像，通过发展多曝光散斑成像来实现对基线血流水平的成像。我们最近的结果表明，多曝光散斑成像能够克服传统的单曝光散斑成像的许多局限性。在目标2中，我们将开发一种将数字微镜设备与磷光猝灭测量相结合的高分辨率绘制绝对皮质氧合水平的仪器。这种方法将与多次曝光散斑成像相结合，用于同时进行绝对氧合和血流成像。然后，我们将在目标3中使用该仪器来量化中风后的急性和慢性血流动力学变化。特别是，我们将绘制整个缺血区的绝对血流量和氧合水平，并将慢性血流动力学与行为和解剖中风的结果进行比较。 公共卫生相关性：该项目的目标是开发新的成像技术，旨在进一步了解急性和慢性中风期间发生的生理变化。预计这一结果将促进目前对中风生理学的理解，从而更好地治疗中风患者。

DESCRIPTION (provided by applicant): Many stroke therapies currently under development in animal models target the cerebral microcirculation. As a result, quantitative in vivo measurement of hemodynamic parameters such as blood flow and oxygenation are critical needs in these studies. Although several optical and MR based techniques are widely used in such experimental stroke studies, the existing techniques suffer from significant limitations. In particular, most techniques are limited to measurement of the relative change of a single hemodynamic parameter within a single animal during a single measurement period. As a result these methods cannot be used to determine absolute blood flow or oxygenation, or to assess chronic hemodynamic changes, which can hinder efforts to evaluate stroke therapies that attempt to gradually restore blood flow and oxygen delivery to ischemic tissue by stimulating angiogenesis or by enhancing nitric oxide synthesis. Therefore, the overall goal of this proposal is to develop an optical instrument capable of imaging baseline cerebral hemodynamics (blood flow and oxygenation) and to use this instrument to quantify the acute and chronic hemodynamic changes that occur following ischemia. To accomplish this goal we will advance two optical imaging techniques that have shown significant promise in stroke studies. In Aim 1 we will advance laser speckle contrast imaging for imaging cerebral blood flow to enable imaging of baseline blood flow levels by developing multi-exposure speckle imaging. Our recent results have demonstrated that multi-exposure speckle imaging is capable of overcoming many of the limitations of traditional single exposure speckle imaging. In Aim 2 we will develop an instrument for high resolution mapping of absolute cortical oxygenation levels by combining a digital micromirror device with phosphorescence quenching measurements. This approach will be combined with the multi-exposure speckle imaging for simultaneous imaging of absolute oxygenation and blood flow. We will then use this instrument to quantify the acute and chronic hemodynamic alterations following stroke in Aim 3. In particular we will map the absolute blood flow and oxygenation levels throughout the ischemic territory and compare the chronic hemodynamics with behavioral and anatomical stroke outcomes. PUBLIC HEALTH RELEVANCE: The goal of this project is to develop new imaging technology designed to further the knowledge of the physiologic changes that occur during acute and chronic stroke. It is expected the results will advance current understanding of stroke physiology, resulting in better treatment of stroke patients.