CHOLINERGIC AND COGNITIVE FUNCTION USING PHARMACOLOGIC ASL-PERFUSION MRI

使用药理学 ASL 灌注 MRI 观察胆碱能和认知功能

• 批准号: 7718942
• 负责人: TAMARA G FONG
• 金额: $ 0.1万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7718942
• 关键词: Affect; Aging; Anatomy; Anti-Cholinergics; Blood; Blood flow; Brain; Cerebrovascular Circulation; Cholinergic Agents; Cognition; Cognitive; Computer Retrieval of Information on Scientific Projects Database; Condition; Contrast Media; Crossover Design; Data; Delirium; Dementia; Disease; Double-Blind Method; Electromagnetics; Functional disorder; Funding; Grant; Institution; Invasive; Label; MRI Scans; Magnetic Resonance Imaging; Measurement; Measures; Mecamylamine; Methods; Neurons; Neurotransmitters; Performance; Perfusion; Pharmaceutical Preparations; Pilot Projects; Placebo Control; Placebos; Play; Radioactivity; Research; Research Personnel; Resolution; Resources; Role; Scopolamine; Source; Spin Labels; Study Subject; System; Techniques; Testing; Tracer; United States National Institutes of Health; Water; cholinergic; cognitive function; in vivo; normal aging; response

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This pilot project will explore the utility of combined pharmacologic manipulation and arterial spin-labeled perfusion MRI (ASL-pMRI) as an in vivo probe of cholinergic function. There is ample data that the cholinergic system plays a key role in cognition, and that cholinergic dysfunction occurs under a variety of conditions, including normal aging, dementia, and delirium. Methods to investigate cholinergic function in vivo are needed to better understand how the cholinergic system is affected in aging and in disease states. Pharmacologic MRI, by measuring the effects of drug challenges on neuronal activity, can provide an indirect measurement of neurotransmitter function with high anatomic resolution. ASL-pMRI is a technique that uses electromagnetic labeling of water in arterial blood as a diffusible tracer, rather than exogenous contrast agents or radioactivity, to generate highly accurate, non-invasive quantitative measurements of cerebral blood flow, and for these reason is ideally suited for pharmacologic MRI. We propose to use ASL-pMRI to more fully characterize the normal cerebral blood flow response to cholinergic modulation, and to correlate these changes in blood flow with cognitive performance. In this study subjects will be tested under 4 different treatment conditions using anticholinergic drugs: 1) scopolamine; 2) mecamylamine; 3) combined scopolamine and mecamylamine; and 4) placebo, in a double blind, placebo-controlled, crossover design. Under each treatment condition subjects will undergo ASL-pMRI scans and detailed cognitive testing. Comparison of global and regional brain perfusion will be made both within- and across-subjects, and correlated with performance on cognitive testing.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 该试点项目将探索联合药物操作和动脉自旋标记灌注MRI（ASL-pMRI）作为胆碱能功能的体内探针的实用性。 有大量的数据表明，胆碱能系统在认知中起着关键作用，并且胆碱能功能障碍发生在各种条件下，包括正常衰老、痴呆和谵妄。 需要研究体内胆碱能功能的方法，以更好地了解胆碱能系统在衰老和疾病状态下如何受到影响。 药理学MRI通过测量药物激发对神经元活性的影响，可以提供具有高解剖分辨率的神经递质功能的间接测量。ASL-pMRI是一种使用动脉血中水的电磁标记作为可扩散示踪剂而不是外源性造影剂或放射性的技术，以产生脑血流的高度准确的非侵入性定量测量，并且由于这些原因，非常适合于药理学MRI。我们建议使用ASL-pMRI来更全面地表征正常脑血流对胆碱能调节的反应，并将这些血流变化与认知表现相关联。 在本研究中，受试者将在4种不同的治疗条件下使用抗胆碱能药物进行测试：1）东莨菪碱; 2）美卡拉明; 3）东莨菪碱和美卡拉明联合治疗;以及4）安慰剂，采用双盲、安慰剂对照、交叉设计。 在每种治疗条件下，受试者将接受ASL-pMRI扫描和详细的认知测试。 将在受试者内和受试者间比较整体和局部脑灌注，并将其与认知测试的表现相关联。