Optical Imaging of Baseline Blood Flow and Oxygenation During Stroke

描述（由申请人提供）：目前正在动物模型中开发的许多中风疗法针对脑微循环。 因此，在这些研究中，血液动力学参数（如血流和氧合）的定量体内测量是至关重要的。 尽管在这种实验性中风研究中广泛使用了几种基于光学和MR的技术，但是现有技术受到显著的限制。 特别地，大多数技术限于在单个测量时段期间测量单个动物内的单个血液动力学参数的相对变化。 因此，这些方法不能用于确定绝对血流量或氧合，或评估慢性血液动力学变化，这可能会阻碍评估中风治疗的努力，这些中风治疗试图通过刺激血管生成或通过增强一氧化氮合成来逐渐恢复缺血组织的血流量和氧输送。 因此，本提案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，我们将提出两个光学成像技术，已显示出显着的承诺，在中风的研究。 在目标1中，我们将推进用于成像脑血流的激光散斑对比度成像，以通过开发多次曝光散斑成像来实现基线血流水平的成像。 我们最近的研究结果表明，多曝光散斑成像是能够克服许多传统的单曝光散斑成像的局限性。 在目标2中，我们将开发一种仪器，通过结合数字荧光装置和磷光猝灭测量，来高分辨率地绘制绝对皮层氧合水平。 该方法将与多次曝光散斑成像相结合，用于绝对氧合和血流的同时成像。 然后，我们将使用该仪器来量化目标3中卒中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域的绝对血流和氧合水平，并将慢性血流动力学与行为和解剖学卒中结局进行比较。 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卒中期间发生的生理变化。 预计这些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.