Microscale Oxygenation Mapping During Stroke

中风期间的微尺度氧合图

• 批准号: 8631856
• 负责人: Andrew K Dunn
• 金额: $ 38.89万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2018-05-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8631856
• 关键词: Acute; Address; Amplifiers; Blood - brain barrier anatomy; Blood Vessels; Blood capillaries; Brain; Brain Injuries; Cardiovascular Diseases; Cause of Death; Cell Death; Cerebral Ischemia; Chronic; Chronic Phase; Complex; Dendrites; Dendritic Spines; Development; Dimensions; Disease; Dyes; Electrodes; Electron Spin Resonance Spectroscopy; Event; Focused Ultrasound Therapy; Future; Goals; Hour; Image; Imagery; Impairment; Individual; Investigation; Ischemia; Ischemic Stroke; Knowledge; Lasers; Location; Maps; Measurement; Mediating; Methodology; Methods; Microbubbles; Microscopy; Morphology; Nature; Neurodegenerative Disorders; Neurons; Optics; Oxygen; Oxygen measurement, partial pressure, arterial; Pathology; Penetration; Physiology; Plasma; Play; Procedures; Rehabilitation therapy; Reporting; Resolution; Rodent; Rodent Model; Role; Signal Transduction; Source; Speed; Spottings; Stroke; Structure; Surface; System; Therapeutic; Time; Tissues; Training; Tumor Angiogenesis; Ultrasonography; Work; acute stroke; arteriole; brain tissue; capillary; chronic stroke; deprivation; disability; imaging modality; improved; in vivo; insight; instrument; interest; motor impairment; phosphorescence; public health relevance; regenerative; tool; two-photon; venule

PROJECT SUMMARY The extent of brain injury following ischemic stroke is a time and space dependent function of the degree of oxygen deprivation. Although oxygen thresholds for ischemic damage have been investigated for many years, the detailed relationship between local oxygen levels and alterations in neuronal structure and function has been extremely challenging to study in vivo. Dendritic spines are of particular interest since they likely play a key role in cortical plasticity following brain injury and are a potential target for rehabilitative training strategies. However, the role of oxygen levels at the level of single dendrites is poorly understood, in large part due to a lack of methods capable of quantifying oxygenation with micron scale resolution in three dimensions. Although oxygen sensitive electrodes enable precise oxygen measurement at a single location, their invasive nature precludes them from chronic studies and for mapping oxygen distributions. Recent advances in oxygen sensitive phosphorescent dyes have opened up new possibilities for noninvasive oxygen mapping in rodent models when combined with multiphoton excitation. Despite the potential for this approach to yield new insight into microvascular oxygenation, low signals levels limit the speed and penetration depth of the oxygenation measurements. Therefore, the goal of this project is to develop an improved imaging method for three-dimensional determination of intra- and extra-vascular oxygenation levels simultaneously with imaging of dendritic morphology and to use this system to quantify the relationship between local oxygen levels and dendritic remodeling following cerebral ischemia. The technological advances in oxygen mapping will involve two components. First, we will improve the phosphorescence signal levels of the oxygen sensitive probe by developing a spatially multiplexed regenerative amplifier excitation source that will produce several spatially offset excitation spots. The minimal tradeoff in spatial resolution will be offset by the considerable gain in temporal resolution and imaging depth. Second, we will refine a method to transiently disrupt the blood brain barrier using microbubble-assisted focused ultrasound, which will permit delivery of the dye to the extravascular space. Together these advances will enable chronic measurement of oxygen levels with micron scale resolution. We will then use these tools to quantify the longitudinal oxygen gradients from surface and penetrating arterioles through capillaries and draining venules under baseline conditions and after occlusion of a single arteriole. Finally, we will quantify the relationship between oxygen levels surrounding individual dendrites and morphological changes in these dendrites during both acute and chronic ischemia.

项目摘要 缺血性中风后脑损伤的程度是该度的时间和空间依赖性功能 缺氧。尽管已经研究了缺血性损伤的氧阈值 多年来，局部氧气水平与神经元结构的改变之间的详细关系 在体内研究的功能极具挑战性。树突状刺特别感兴趣 由于它们在脑损伤后可能在皮质可塑性中起关键作用，并且是潜在的目标 康复培训策略。但是，氧气水平在单一树突水平上的作用是 理解很少，在很大程度上是由于缺乏能够用微米量化氧合的方法 尺度分辨率在三个维度上。尽管氧气敏感电极可实现精确的氧气 在一个位置的测量，它们的侵入性性质使他们无法从慢性研究和 映射氧分布。氧敏感磷光染料的最新进展已经打开 与多光子结合使用时，增加啮齿动物模型中无创氧图的新可能性 励磁。尽管这种方法有可能产生有关微血管氧合的新见解，但低 信号水平限制了氧合测量的速度和穿透深度。因此， 该项目的目标是开发一种改进的成像方法，以三维确定 与树突形态的成像同时进行血管内和血管外充氧水平， 使用该系统来量化局部氧气水平与树突重塑之间的关系 脑缺血之后。氧映射的技术进步将涉及两个 成分。首先，我们将通过 开发一种空间多路复用的再生放大器激发源，该源将产生多个 空间抵消激发点。空间分辨率的最低权衡将被 时间分辨率和成像深度的可观增长。其次，我们将完善一种方法 使用微气泡辅助聚焦超声瞬时破坏血脑屏障，这将 允许将染料递送到血管外空间。这些进步将使慢性 用微米尺度分辨率测量氧气水平。然后，我们将使用这些工具来量化 纵向氧梯度从表面和穿透毛细管穿透动脉和排水 基线条件下的静脉和单个小动脉阻塞后。最后，我们将量化 各个树突周围的氧气水平与形态学变化之间的关系 急性缺血和慢性缺血期间的树突。