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Optimized Arterial Spin Labeling MRI in Mild Cognitive Impairment

优化动脉旋转标记 MRI 在轻度认知障碍中的应用

基本信息

批准号：
9069708
负责人：
DAVID A WOLK
金额：
$ 32.67万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-08-01 至 2018-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9069708
关键词：
Address Alzheimer&apos s Disease Apolipoprotein E Atrophic Biological Markers Biological Neural Networks Brain Cerebrovascular Circulation Clinical Clinical Trials Coupled Data Data Analyses Data Set Discrimination Disease Disease Progression Etiology Future Genes Goals Hippocampus (Brain)Image Impaired cognition Individual Inflammation Injury Intervention Lead Length Magnetic Resonance Imaging Maps Measures Medial Metabolic Modality Molecular Monitor Nerve Degeneration Parietal Participant Pathology Patients Play Population Positron-Emission Tomography Predictive Value Prevalence Psychometrics Public Health Radiation Research Rest Role Sample Size Sampling Site Spin Labels Staging Stress Tests Structure Symptoms Techniques Temporal Lobe Testing Therapeutic Variant Work aging population base biomarker development clinical practice cohort data acquisition disorder control fluorodeoxyglucose positron emission tomography follow-up glucose metabolism imaging biomarker interest mRNA Differential Displays mild cognitive impairment molecular marker neuroimaging outcome forecast research clinical testing screening success synaptic function tau Proteins

项目摘要

DESCRIPTION (provided by applicant): A major goal in Alzheimer's disease (AD) research is to develop biomarkers that are sensitive to early disease, predict decline in those with mild symptoms (e.g. Mild Cognitive Impairment, or MCI), and reflect disease progression. Over the last two decades, a number of candidate neuroimaging, molecular,and psychometric measures have demonstrated variable success in accomplishing these goals. While significant advances have been made with molecular markers (e.g. CSF A�1-42) that are sensitive to specific pathology, these techniques appear relatively insensitive to clinical status or disease progression. On both empirical and theoretical grounds, brain measures that reflect synaptic function are thought to be the most sensitive to the consequences of early AD pathology and predictive of future decline. Fluorodeoyglucose (FDG) PET, a measure of glucose metabolism (CMRGlu), has demonstrated considerable promise in this regard. Arterial spin labeling (ASL) MRI, which is sensitive to cerebral blood flow (CBF) reflective of metabolic activity, may provide overlapping information with FDG-PET, but has several potential advantages: 1) ASL can be acquired in several minutes during routine MR imaging that most patients will obtain as part of their clinical evaluation, and, thus, is less expensive and burdensome~ 2) ASL does not require IV contrast or radiation exposure~ 3) ASL is potentially more accessible than PET~ 4) Short activation or task-related sequences can more easily be implemented with potential for increased sensitivity to early functional change. Further, since ASL is acquired along with other MRI sequences, one can potentially take advantage of orthogonal measures of brain structure and function, the combination of which may offer the fullest characterization of disease state. The central goal of this proposal is to demonstrate that 'state-of-the art' ASL-MRI produces largely equivalent information to FDG-PET in a cohort of amnestic MCI patients. In particular, we will determine the relative capacity of these modalities to determine clinical status [MCI vs healthy control (HC)], disease state (presence/absence of AD CSF profile), and predict future progression. 'Optimized' ASL sequences, leveraging numerous advancements in data acquisition and analysis, will also be compared to a commercially available ASL measure being implemented in the Alzheimer's disease Neuroimaging Initiative renewal (ADNI 2), to determine the relative value of these ASL variants. Additionally, task-related ASL will be explored for its potential to further enhance the predictive value of rest ASL alone. To achieve these aims, MCI patients and HC will undergo a baseline ASL-MRI and FDG-PET scan~ we will also obtain CSF molecular markers (tau/A�). Longitudinal clinical follow-up and a 1-year repeat MRI will allow for assessment of disease progression and determination of the relative predictive value of these imaging biomarkers. Finally, we will utilize the analytic pipeline developed in this project o analyze ASL data from ADNI 2, which will potentially enhance power to address some of the above questions and serve as a replication dataset.

描述（由申请人提供）：阿尔茨海默病（AD）研究的一个主要目标是开发对早期疾病敏感的生物标志物，预测轻度症状（例如轻度认知障碍，或 MCI）患者的病情衰退，并反映疾病进展。在过去的二十年中，许多候选神经影像学、分子和心理测量方法在实现这些目标方面取得了不同程度的成功。虽然对特定病理敏感的分子标记（例如 CSF A�1-42）取得了重大进展，但这些技术似乎对临床状态或疾病进展相对不敏感。从经验和理论的角度来看，反映突触功能的大脑测量被认为对早期 AD 病理学的后果最敏感，并可预测未来的衰退。氟脱氧葡萄糖 (FDG) PET 是葡萄糖代谢 (CMRGlu) 的一种测量方法，在这方面已显示出巨大的前景。动脉自旋标记 (ASL) MRI 对反映代谢活动的脑血流 (CBF) 敏感，可以提供与 FDG-PET 重叠信息，但具有几个潜在优势： 1) ASL 可以在常规 MR 成像过程中在几分钟内获得，大多数患者将作为临床评估的一部分获得该成像，因此成本较低且负担较重 ~ 2) ASL 不需要 IV 造影剂或辐射暴露 ~ 3) ASL 可能比 PET 更容易获得 ~ 4) 可以更容易地实施短激活或任务相关序列，并有可能提高灵敏度到早期的功能改变。此外，由于 ASL 是与其他 MRI 序列一起获取的，因此人们可以潜在地利用大脑结构和功能的正交测量，它们的组合可以提供疾病状态的最全面的表征。该提案的中心目标是证明“最先进的”ASL-MRI 在一组遗忘性 MCI 患者中产生的信息与 FDG-PET 基本相同。特别是，我们将确定这些方式的相对能力，以确定临床状态 [MCI 与健康对照 (HC)]、疾病状态（AD CSF 谱的存在/不存在）并预测未来的进展。利用数据采集和分析方面的众多进步的“优化”ASL 序列还将与阿尔茨海默病神经影像计划更新 (ADNI 2) 中实施的市售 ASL 测量进行比较，以确定这些 ASL 变体的相对价值。此外，还将探索与任务相关的 ASL 的潜力，以进一步提高单独休息 ASL 的预测价值。为了实现这些目标，MCI患者和HC将接受基线ASL-MRI和FDG-PET扫描〜我们还将获得CSF分子标志物（tau/A�）。纵向临床随访和 1 年重复 MRI 将允许评估疾病进展并确定这些成像生物标志物的相对预测价值。最后，我们将利用本项目中开发的分析管道来分析来自 ADNI 2 的 ASL 数据，这将有可能增强解决上述一些问题的能力并用作复制数据集。