Cerebral Blood Flow trajectory in the Alzheimer's Disease continuum

摘要： 阿尔茨海默病(AD)是一种以进行性痴呆为特征的神经退行性疾病 在65岁或以上的美国人中，几乎有10%。这种疾病的病理基础被认为是 涉及大脑淀粉样蛋白沉积，可通过脑脊液采样或PET扫描检测到。然而， AD进展率是高度可变的，仅淀粉样蛋白阳性就说明了AD进展率的适度增加 终生罹患阿尔茨海默病的风险脑血流量(CBF)是衡量脑血管完整性的指标， 也与局部大脑新陈代谢密切相关，从而为功能性 神经退行性变。先兆和完全性临床恶化对应的局部脑血流量减少 发展为阿尔茨海默病的研究以前曾在横断面研究中报道过。然而，它的轨迹从认知上来说 疾病阶段的正常状态及其与淀粉样蛋白沉积的相互作用不完全 明白了。动脉自旋标记(ASL)灌注MRI提供经济有效的无创定量 脑血流量，可在常规MRI设置下测量，但信噪比低，需要使用 先进的信号处理技术来评估生理变化。在这项提案中，我们将 利用阿尔茨海默病患者的数据描述AD患者局部脑血流的纵向变化 神经成像主动性(ADNI)和评估局部脑血流作为早期AD的预测价值 生物标志物。我们的重点将是确定显示出最早和最一致的变化的大脑区域 阿尔茨海默病患者的脑血流量。该项目将涉及开发定制的图像处理流水线进行处理 ADNI第三和第四阶段(ADNI2和ADNI3)的ASL MRI数据，其中将包括数据清理 以及开发自动化的数据质量评估指标。已使用多个ASL获取ADNI3数据 不同扫描平台的采集方法，并对其影响进行系统的研究 生成的CBF地图。此外，数据将在不同的ASL采集方法和扫描中同质化 促进跨扫描平台联合分析数据的平台。最后，我们还将对地区进行比较 CBF和区域结构容量测定，以检验它们提供互补信息的假设 疾病的状态和进展，以及评估他们的综合能力。

Summary: Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive dementia and affecting almost 10 percent of Americans of 65 years or older. The pathological basis of the disease is believed to involve deposition of cerebral amyloid, which can be detected with CSF sampling or PET scanning. However AD progression rates are highly variable and amyloid positivity alone accounts for a moderate increase to the risk of developing AD in the lifetime. Cerebral blood flow (CBF) is a measure of cerebrovascular integrity and is also tightly coupled to regional cerebral metabolism, thus providing a biomarker for functional neurodegeneration. Reductions in regional CBF corresponding to clinical deterioration in prodromal and fully developed AD have previously been reported in cross-sectional studies. However its trajectory from cognitively normal condition to the diseased stage and also its interaction with amyloid deposition is incompletely understood. Arterial Spin Labeled (ASL) perfusion MRI provides cost-effective non-invasive quantification of CBF and can be measured in routine MRI settings, but suffers from low signal to noise ratio necessitating use of advanced signal processing technique to assess physiological changes. In this proposal, we will characterize longitudinal changes in regional CBF in AD patients using data obtained from Alzheimer's disease neuroimaging initiative (ADNI) and assess the predictive value of regional CBF as an early stage AD biomarker. Our focus will be to identify the brain regions showing the earliest and most consistent changes in CBF in AD subjects. The project will involve developing customized image processing pipeline for processing ASL MRI data from the third and fourth stages of ADNI (ADNI2 and ADNI3), which will include data cleaning and developing automated data quality evaluation metric. ADNI3 data has been acquired using multiple ASL acquisition methods in different scanning platforms, and we will perform a systematic study of its effect on resulting CBF maps. Further, data will be homogenized across different ASL acquisition methods and scanning platforms to facilitate joint analysis of data across scanning platforms. Finally, we will also compare regional CBF and regional structural volumetry to test the hypothesis that they provide complementary information for disease status and progression as well as to assess their combined ability towards the same.