MULTI-MODAL BRAIN IMAGING IN AGING AND DEMENTIA

衰老和痴呆症的多模态脑成像

• 批准号: 6949820
• 负责人: SUSAN Y BOOKHEIMER
• 金额: $ 13.99万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6949820
• 关键词: Alzheimer' s disease; aging; apolipoprotein E; bioimaging /biomedical imaging; brain disorder diagnosis; brain imaging /visualization /scanning; brain mapping; cognition disorders; dementia; diagnosis design /evaluation; early diagnosis; genetic polymorphism; genetic susceptibility; hippocampus; human subject; longitudinal human study; magnetic resonance imaging; mathematical model; model design /development; molecular probes; neural degeneration; neuropathology; pathologic process; patient oriented research; radiodiagnosis; small molecule

The goal of this Project is to develop and implement novel, high resolution structural and functional MRI, to identify the earliest apparent brain changes in subjects at risk for developing AD. Specifically, we will examine young and older control subjects with and without the APOE-4 allele, and patients with MCI and mild AD, in a cross-sectional comparison of age-related changes in the brain, and in a 2-year longitudinal follow-up, using MRI acquisition and analysis tools recently developed in our laboratory. We will focus on changes in the structure and function in the hippocampus, where ample evidence indicates the pathological process leading to AD arises. Our aims cover 3 general goals: 1) to identify subtle changes in brain structure, particularly in entorhinal cortex and in anterior hippocampus, in at-risk and cognitively declining subjects 2) to identify abnormalities in functional activity in individual sub-regions of the nippocampal complex using different memory paradigms, and 3) to develop integrative models for determining the relationship between these functional and structural MRI markers and PET markers of amyloid burden (based on [18F]DDNP) and nippocampal 5HT1A receptor activity (based on [18F]MPPF PET). For structural MRI, we will acquire small voxel T1 weighted volumetric scans, on which we will conduct voxel-based parametric maps of longitudinal change in grey matter distribution, as well as grey-matter segmented region of interest analysis to be shared with the other projects. Additionally, we will collect very high in-plane resolution images of the hippocampus (.3 mm) to serve as a basis for studies of 1) gray matter thickness in entorhinal cortex, individual CA fields, subiculum and parahippocampal gyrus; 2) sulcal variability maps, measuring small displacements in sulci secondary to subtle tissue loss; and 3) unfolded "flat maps" of the hippocampus to discriminate among subregions, in combination with 4) high resolution BOLD FMRI of the hippocampus during episodic encoding, retrieval, and novelty encoding paradigms. We will integrate these structural and functional imaging measures of regional nippocampal integrity with [18F]DDNP and [18F]MPPF maps to determine how amyloid burden relates to hippocampal morphometry and function, and how this relationship changes dynamically in genetically at-risk individuals. These studies will enable us to develop highly sensitive predictive formulas for identifying those most likely to show decline, and will help us to understand the pathophysiology of AD as it relates to neural loss and amyloidopathy.

该项目的目的是开发和实施新颖，高分辨率的结构和功能性MRI，以确定最早的大脑变化受到开发AD风险的受试者。具体而言，我们将在我们实验室中最近开发的MRI习得和分析工具中，在与年龄相关的大脑变化以及2年的纵向随访中，在与年龄相关的大脑变化以及在2年的纵向随访中进行了横截面比较，我们将检查有或没有APOE-4等位基因的年轻和旧对照受试者以及MCI和轻度AD的患者。我们将重点关注海马中的结构和功能的变化，其中充分的证据表明导致AD的病理过程。我们的目标涵盖了3个一般目标：1）确定大脑结构的细微变化， particularly in entorhinal cortex and in anterior hippocampus, in at-risk and cognitively declining subjects 2) to identify abnormalities in functional activity in individual sub-regions of the nippocampal complex using different memory paradigms, and 3) to develop integrative models for determining the relationship between these functional and structural MRI markers and PET markers of amyloid burden (based on [18F]DDNP) and胎儿5HT1A受体活性（基于[18F] MPPF PET）。对于结构性MRI，我们将获得小型体素T1加权体积扫描，我们将在其上进行基于Voxel的纵向参数图 灰质分布的变化以及与其他项目共享的灰色 - 可能分段的感兴趣分析区域。此外，我们将收集海马（.3 mm）的非常高的平面分辨率图像，以作为研究1）灰质厚度的基础，该灰质厚度，单个CA领域，ca田，亚ca和parahampocampal gyrus; 2）沟的可变性图，测量继发于微妙组织损失的硫的小位移； 3）在偶发编码，检索和新颖的编码范式的新颖性期间，海马的展开了海马的“扁平图”，以区分子区域之间的区分。我们将整合这些结构和功能成像措施 具有[18F] DDNP和[18F] MPPF地图的区域诊断完整性，以确定淀粉样蛋白负担与海马形态和功能的关系，以及这种关系如何在遗传风险的个体中动态变化。这些研究将使我们能够开发高度敏感的预测公式，以识别最有可能显示下降的人，并将帮助我们了解与神经损失和淀粉样病有关的AD的病理生理学。