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 在脑缺血和卒中中如何无创地定量一些 对这些过程进行磁共振成像(MRI)，并使用MRI来 预测人类脑缺血的结果。这些信息可能 也指导中风患者的治疗，改善他们的神经功能 结果。一种重复性好、可逆性强的单侧大鼠模型 大脑中动脉(MCA)闭塞(0、40和120分钟和 永久遮挡)将被使用。需要测量的五个磁共振参数 质子自旋密度(P)、自旋-晶格和自旋-自旋弛豫时间 (分别为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)将在大鼠脑内几乎同时测量 ~(14)C-安替比林定量放射自显影(OAR-LCBF)和~(14)C-安替比林定量放射自显影 阻断大脑中动脉后不同时间行MRI-CBF检查。将使用这些数据 要检验流量在内部和周围不断变化的假设 脑缺血再灌注期和再灌注期的脑缺血组织 核磁共振检测到的变化与之平行但不完全相同 由QAR-LCBF确定的指标更可靠。对于特定的 目标2a，组织学指标(神经元密度、存活率和体积 损伤)和脑组织水状态的MRI测量及MRI-CBF 将在特定时间同时定量，在永久 或一过性大脑中动脉闭塞。这些结果将被用来测试AAT 脑缺血区神经元改变和组织损伤假说 一个或多个时间将被MRI的某些组合准确反映 水和/或磁共振脑血流状态的测量。对于特定的目标2b， 永久性和暂时性CBF与ADCw的时间关系 将使用前面的一些数据来调查大脑中动脉闭塞 实验。这一分析将检验的假设是 脑组织中的ADCw，在缺血发作后不久与 CBF的变化，但在以后的时间变得相对独立于血流。 最后，对于特定目标3，脑梗塞体积将为 从缺血后7天的一组组织切片测量 并用于识别一组由MRI参数得出的梗死区估计 预测组织学确定的脑梗塞体积的体积 数据将被用来检验以下假设： 大脑中动脉闭塞后7天的组织学损伤是可以预测的 通过结合一些磁共振参数和时间(S)进行测量。这个 这项研究的意义在于具有临床发展的潜力。 相关的、非侵入性的方法来识别分期、严重程度、 中风引起的人类脑损伤的治疗和神经学结果。

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.