CEREBRAL BLOOD FLOW PATTERNS IN ALZHEIMER'S DISEASE

我们建议研究局部脑血流(RCBF)成像 会在大脑中产生和以前一样的异常模式 经FDG正电子发射断层扫描(PET)证实 对阿尔茨海默型痴呆(ATD)患者的研究。宠物研究将 使用Donner 280晶体断层扫描仪和新的Donner 600晶体(2.5-4 mm 分辨率)用15O-H2O进行断层扫描测量rCBF，15O2测量氧气 利用18F-FDG测定代谢。单光子发射 计算机断层扫描(SPECT)研究也将使用 哈佛多探测器系统的改装和 ~(123)I-N-异丙基-对碘苯丙胺(IMP)研究rCBF。主题将是 根据严谨的医学和神经心理学研究选定 标准，将包括家族性和散发性ATD。因为有很多人 受试者将成为正在进行的需求研究的一部分，使用PET进行研究 大脑新陈代谢，预计会有较高的随访率和较低的自然损耗， 而且很可能有很高的尸检相关性。 数据将通过比较以下各项的相对水平进行定量分析 每个患者不同脑区的活动，并通过计算 RCBF率、局部脑葡萄糖代谢率(RCMRglu)和 脑局部O2代谢率(RCMRO2)。据推测， RCBF的异常模式将有助于痴呆组的区分。 此外，我们将分析数据以检查rCBF之间的相关性 和神经心理异常，并评价SPECT-IMP方法 与正电子发射计算机断层扫描研究相比。 主要的假设是，在许多情况下， 对ATD患者大脑代谢的研究将显示类似的结果 RCBF异常。SPECT研究将验证IMP作为一种 病理组织中的血流示踪剂，并评估这一能力的降低 用于区分痴呆类型的成本成像方法。基础医学 科学提案包括研究流动-新陈代谢脱钩 在早期阿尔茨海默氏病中，特别是在颞叶皮质。而当 我们相信，流动-代谢耦合将被证明是完好无损的。 在这种疾病中，我们假设流动代谢的焦点区域 使用高分辨率的Donner 600可以实现解耦 水晶断层摄影术。这一发现将对我们的 了解阿尔茨海默病的发病机制，以及 规划治疗策略。

We propose to study whether regional cerebral blood flow (rCBF) imaging will give the same pattern of abnormalities in the brain as has been demonstrated by fluorodeoxyglucose (FDG) positron emission tomography (PET) studies in patients with Alzheimer-type dementia (ATD). PET studies will use the Donner 280 crystal tomograph and a new Donner 600 crystal (2.5-4mm resolution) tomograph with 15O-H2O to measure rCBF, 15O2 for oxygen utilization and 18F-FDG to measure metabolism. Single photon emission computed tomography (SPECT) studies will also be performed using a modification of the Harvard multidetector system and 123I-N-isopropyl-p-iodoamphetamine (IMP) to study rCBF. Subjects will be selected according to rigorous medical and neuropsychological research criteria and will include both familial and sporadic ATD. Since many subjects will be part of ongoing demential research using PET to study brain metabolism, a high rate of follow-up with low attrition is predicted, and a high rate of autopsy correlation is likely. Data will be analyzed quantitatively by comparing relative levels of activity in different brain regions for each patient and by calculation of rates of rCBF, regional cerebral metabolic rates of gluocse (rCMRglu), and regional cerebral metabolic rates of O2 (rCMRO2). It is hypothesized that patterns of abnormal rCBF will allow differentiation of dementia groups. In addition, we will analyze the data to examine correlations between rCBF and neuropsychological abnormalities, and to evaluate the SPECT-IMP method in comparison to PET studies. The major hypothesis is that the abnormalities seen in numerous investigations of cerebral metabolism in ATD will show similar abnormalities in rCBF. The SPECT studies will validate the use of IMP as a flow tracer in pathological tissue, and evaluate the ability of this lower cost imaging modality to differentiate dementia types. A basic medical science proposal includes the investigation of a flow-metabolism decoupling in early Alzheimer's disease, particularly in the temporal cortex. While we believe that flow-metabolism coupling will be shown to be grossly intact in the disease, we hypothesize that focal regions of flow-metabolism uncoupling will be demonstrable using the high resolution Donner 600 crystal tomograph. This finding will be of great importance for our understanding of the pathogenesis of Alzheimer's disease, as well as for planning therapeutic strategies.