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都是针对大脑微循环的。因此，在这些研究中，对血流和氧合等血液动力学参数的体内定量测量是至关重要的。尽管基于光学和磁共振的技术广泛应用于此类脑卒中实验研究，但现有技术存在明显的局限性。特别是，大多数技术仅限于测量单个动物在单个测量周期内单个血流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或氧合，或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，我们将推进两种光学成像技术，这两种技术在中风研究中显示出重大的前景。在Aim 1中，我们将推进用于脑血流成像的激光散斑对比成像，通过开发多曝光散斑成像来实现基线血流量水平的成像。我们最近的研究结果表明，多曝光散斑成像能够克服传统单曝光散斑成像的许多局限性。在目标2中，我们将开发一种仪器，通过将数字微镜装置与磷光猝灭测量相结合，用于高分辨率绘制绝对皮质氧合水平。该方法将与多曝光散斑成像相结合，同时成像绝对氧合和血流。然后，我们将在Aim 3中使用该仪器量化中风后的急性和慢性血流动力学改变。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卒中结果进行比较。

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.