PET STUDIES OF METABOLISM AND HEMODYNAMICS IN STROKE

我们建议调查几个密切相关的研究问题 人类脑血管疾病，使用发射断层扫描策略和 短寿命放射性标记示踪物质(主要是(15)0-水， (15)O-氧和(11)C-一氧化碳)来表征局部代谢 和血流动力学。(1)无症状性颅外颈动脉 研究动脉病变以确定血流动力学障碍。 与分级狭窄相关。主要的假设是直径 75%以上的狭窄会导致局部血流动力学改变，包括 最初表现为局部血容量(LCBV)增加，血流量正常 (LCBF)，这与局部氧利用率下降(LCMR02)相关 有严重血管狭窄或闭塞。(2)近期患病的病人 对短暂性脑缺血发作进行研究，以确定发作的频率和 LCBF和lCMRO2的残余缺血后损伤程度。 采用标准化的感觉运动激活任务来确定 TIA后状态是否与血流动力学受损和 与年龄匹配的非短暂性脑缺血发作对照组相比，代谢激活。(3)我们 打算评估发射断层扫描在监测中的能力 通过研究急性给药治疗药物的反应性 近期完全性血栓栓塞性脑梗塞患者治疗前后对比分析 低分子右旋糖苷急性血液稀释。我们试图确定 这种治疗是否改善了局部血流和氧的提取 与缺血灶相邻。(4)序贯双示踪技术是 用于定量测定局部血脑屏障通透性 弥散限制放射性示踪剂(如~(11)C-安替比林)在肺癌患者中的应用 新近完成的血栓栓塞性半球卒中；屏障改变 与局部流动模式和计算机断层扫描相关联 大脑中心区和边缘区的脑梗塞和水肿表现 不同年龄的梗死灶。(5)同时，我们建议实施和 验证同时确定的一个数学策略 局部血流量与局部脑：脑分区系数。此外, 我们建议对现有的氧气提取数学模型进行改进 通过将模型重新表述为线性微分式来表示分数 可用动态逼近技术求解的方程， 并明确将放射性衰变纳入其中。

We propose to investigate several closely interrelated research issues in human cerebrovascular disease, using emission-tomographic strategies and short-lived radiolabeled tracer substances (chiefly (15)0-water, (15)O-oxygen, and (11)C-carbon monoxide) to characterize local metabolism and hemodynamics. (1) Patients with asymptomatic extracranial carotid artery lesions are studied to determine the hemodynamic impediment associated with graded stenosis. The chief hypothesis is that diameter stenoses above 75% induce local hemodynamic alterations, consisting initially of increased local blood volume (lCBV) with normal blood flow (lCBF), and that decreased local oxygen utilization (lCMR02) correlates with severe vascular stenosis or occlusion. (2) Patients with recent transient cerebral ischemic attacks are studied to define the frequency and extent of residual postischemic impairments of lCBF and lCMRO2. Standardized sensorimotor activation tasks are employed to determine whether the post-TIA state is associated with impaired hemodynamic and metabolic activation as compared to age-matched non-TIA controls. (3) We intend to assess the capability of emission tomography in monitoring responsiveness to acutely administered therapeutic agents by studying patients with recent completed thromboembolic infarction before and after acute hemodilution with low molecular weight dextran. We seek to determine whether this treatment improves local flow and oxygen extraction in and adjacent to the ischemic focus. (4) A sequential dual-tracer technique is used to quantitate local blood-brain barrier permeability to diffusion-limited radiotracers (such as (11)C-antipyrine) in patients with recent completed thromboembolic hemispheric strokes; barrier alterations are correlated with local flow patterns and with computed-tomographic appearances of infarct and adema in central and marginal zones of cerebral infarcts of different ages. (5) Concurrently, we propose to implement and validate a mathematical strategy for the simultaneous determination of local blood flow and local brain:brain partition coefficient. In addition, we propose to improve the existing mathematical model of oxygen extraction fraction by reformulating the model in terms of linear differential equations amenable to solution by the technique of dynamic approximation, and by explicitly incorporating radioactive decay.