MAGNETIC RESONSANCE ASSESSMENT OF TRANSIENT CEREBRAL ISCHEMIA

这个项目的长期目标是了解所涉及的过程 以及如何非侵入性地定量一些 通过磁共振成像（MRI）来观察这些过程，并使用MRI来 预测人类脑缺血的结果。 该信息可以 也指导中风患者的治疗，改善他们的神经系统 结果。 一种高度可重复的，容易可逆的单侧大鼠模型， 大脑中动脉（MCA）闭塞（0、40和120分钟， 永久性闭塞）。 要测量的五个MRI参数 是质子自旋密度（p）、自旋-晶格和自旋-自旋弛豫时间 (T1和T2），水的“表观”扩散系数 （ADCw）和脑血流量（MRI-CBF）。 对于特定目标1，大脑 血流量（CBF）将几乎同时在大鼠脑中测量 14 C-碘安替比林定量放射自显影（OAR-LCBF）和 闭塞MCA后不同时间的MRI-CBF。 这些数据将用于 为了验证流动在内部和周围不断变化的假设， 在闭塞和再灌注期间的缺血脑组织， MRI检测到的变化与 由QAR-LCBF确定的那些更可靠。 为特定 目的2a，组织学指标（神经元密度和活力以及 MRI测量脑组织含水量和MRI-CBF 将在永久性或永久性 或短暂性大脑中动脉闭塞 这些结果将用于测试 缺血脑中神经元改变和组织损伤假说 一次或多次将被MRI的一些组合准确地反映， 测量水和/或MRI-CBF的状态。 对于具体目标2b， 永久性或短暂性脑梗死后CBF和ADCw之间的时间关系 MCA闭塞将使用来自前述研究的一些数据进行研究。 实验 本分析将检验的假设是， 脑组织中的ADCw，在缺血发作后不久，与脑缺血相关。 CBF的变化，但在以后的时间变得相对独立的流量。 最后，对于特定目标3，脑梗死体积将为 从缺血后7天采集的一组组织切片测量 并用于识别一组MRI参数导出的梗塞估计， 预测组织学确定的梗死体积 这些 数据将用于检验假设，即 可以预测MCA闭塞后7天的组织学指示损伤 通过MRI参数和测量时间的某种组合。 的 这项研究的意义在于临床开发的潜力 相关的，非侵入性的方法来识别阶段，严重程度， 治疗和人类中风引起的脑损伤的神经学结果。

The long range goal of this project is to understand the processes involved in cerebral ischemia and stroke and how to non-invasively quantitate some of these processes by magnetic resonance imaging (MRI) and use MRI to predict the outcome of cerebral ischemia in humans. This information could also guide the treatment of stroke patients and improve their neurological outcome. A highly reproducible, readily reversible rat model of unilateral middle cerebral artery (MCA) occlusion (0, 40, and 120 minutes and permanent occlusion) will be used. The five MRI parameters to be measured are proton spin density (p), spin-lattice and spin-spin relaxation times (T1 and T2, respectively), the "apparent" diffusion coefficient of water (ADCw) and cerebral blood flow (MRI-CBF). For Specific Aim 1, cerebral blood flow (CBF) will be virtually simultaneously measured in rat brain with 14C-iodoantipyrine quantitative autoradiography (OAR-LCBF) and with MRI-CBF at various times after occluding the MCA. These data will be used to test the hypothesis that flow continually changes within and around ischemic brain tissue during the periods of occlusion and reperfusion and that the changes detected by MRI are parallel with but not identical to those determined by QAR-LCBF, which are the more reliable. For Specific Aim 2a, histological indices (neuronal density and viability and volume of damage) and MRI measures of the state of water in brain tissue and MRI-CBF will be concurrently quantitated at specific times after either permanent or transient MCA occlusion. These results will be used to test athe hypothesis that neuronal alterations and tissue damage in ischemic brain at one or more times will be accurately reflected by some combination of MRI measures of the state of water and/or MRI-CBF. For Specific Aim 2b, the temporal relationship between CBF and ADCw following permanent or transient MCA occlusion will be investigated with some of the data from the preceding experiments. The hypothesis that will be tested with this analysis is that ADCw in brain tissue, shortly after the onset of ischemia is coupled to the changes in CBF but at later times becomes relatively independent of flow. Finally, for Specific Aim 3, the volume of brain infarction will be measured from a set of histological sections taken at 7 days post-ischemia and used to identify a set of MRI parameter derived estimates of infarct volume that predict the histologically determined volume of infarct These data will be used to test the hypothesis that the severity of histologically indicated injury 7 days after MCA occlusion can be predicted by some combination of MRI parameters and time(s) of measurement. The significance of this research is the potential to develop clinically relevant, noninvasive methods for identifying the stage, severity, treatment, and neurologic outcome of stroke-induced brain injury in humans.