Shape-based personalized AT(N) imaging markers of Alzheimer's disease

基于形状的个性化阿尔茨海默病 AT(N) 成像标记

• 批准号: 10667903
• 负责人: Yonggang Shi
• 金额: $ 217万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-01 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10667903
• 关键词: 3-Dimensional; Accounting; African American population; Algorithmic Analysis; Algorithms; Alzheimer' s Disease; Alzheimer' s disease pathology; Alzheimer' s disease risk; Amyloid; Amyloid beta-Protein; Anatomy; Area; Atrophic; Biological Markers; Brain; Brain imaging; Categories; Cognitive; Communities; Computing Methodologies; Data Set; Detection; Development; Disease; Early Diagnosis; Ethnic Population; Face; Geometry; Goals; Graph; Health; Heterogeneity; Image; Individual; Liquid substance; Location; Magnetic Resonance Imaging; Maps; Measures; Methods; Mexican Americans; Minority Groups; Modeling; Nerve Degeneration; Not Hispanic or Latino; Pathology; Pattern; Phenotype; Plasma; Population; Population Heterogeneity; Positron-Emission Tomography; Public Health; Research; Role; Senile Plaques; Shapes; Source; Staging; Surface; System; Techniques; Thick; Variant; Work; aging brain; amyloid pathology; beta amyloid pathology; brain shape; cerebral atrophy; cohort; computerized tools; disease disparity; disorder subtype; experience; health disparity; imaging biomarker; improved; in vivo; large scale data; multi-ethnic; novel; racial population; shape analysis; tau Proteins; tau aggregation; tool

Abstract The AT(N) framework of Alzheimer’s disease (AD) provides a systematic guidance to study AD based on quantitative measures of biological markers of β-amyloid (Aβ) plaques (A), neurofibrillary tau tangles (T), and neurodegeneration (N). Existing AT(N) imaging markers are typically defined as average measures of cortical regions determined a priori, which are insufficient to characterize the heterogeneous pathology and atrophy patterns of AD. To allow more personalized characterization of the AT(N) status of individual subjects, we will develop in this project novel imaging markers based on advanced shape analysis techniques. From the perspective of imaging marker development, challenges to study the heterogeneity of AD can arise from multiple sources. The first is the frequent existence of atypical AD pathology and brain atrophy patterns that deviate from canonical Braak stages. The second is the high variability of cortical anatomy and the resulting large variations of cortical thickness at so called “corresponding” locations of even healthy brains. The third is the current lack of understanding about the role of AT(N) imaging markers in characterizing the diverse disease trajectories in minority groups including African Americans and Mexican Americans. Building upon our extensive experience in brain shape analysis, we will develop tools to quantify the topographic pattern of cortical tau and Aβ pathology, build a personalized analysis framework for the early detection of localized brain atrophy, and apply these tools to the multi-ethnic cohort from the Health & Aging Brain Study – Health Disparities (HABS-HD) (n=3000) to characterize the heterogeneity of AT(N) imaging markers in diverse populations. There are three specific aims in our project: 1. To develop surface-based modeling of topographic patterns in tau and amyloid PET imaging for personalized subtyping and staging of AD pathology. 2. To develop personalized imaging measures of brain atrophy by resolving variability due to cortical folding and shape differences. 3. To characterize the impact of health disparity on disease staging and subtyping with personalized imaging markers. In summary, our main goal is to create novel computational tools for the creation of personalized AT(N) imaging markers and apply them to characterize the heterogeneity of AD pathology in the context of health disparity. All tools and imaging markers developed in this project will be distributed freely to research community, which we believe will greatly enhance the state-of-the-art in the subtyping and staging of AT(N) pathology in diverse populations.

摘要 阿尔茨海默病（AD）的AT（N）框架为基于以下方面的AD研究提供了系统的指导： β-淀粉样蛋白（A β）斑块（A）、神经元tau蛋白缠结（T）和 神经变性（N）。现有的AT（N）成像标记物通常被定义为皮质神经元的平均测量值。 先验确定的区域，不足以表征异质性病理和萎缩 AD的模式为了更个性化地表征个体受试者的AT（N）状态，我们将 在这个项目中开发基于先进形状分析技术的新型成像标记。从 从成像标记物发展的角度来看，研究AD异质性的挑战可能来自多种因素， 源第一个是经常存在非典型AD病理和脑萎缩模式， 典型Braak阶段。第二个是皮质解剖结构的高度变异性和由此产生的大的变化 在所谓的"相应"位置的皮质厚度甚至健康的大脑。三是当前缺乏 了解AT（N）成像标记物在表征不同疾病轨迹中的作用， 少数民族包括非洲裔美国人和墨西哥裔美国人。基于我们丰富的经验 在脑形状分析中，我们将开发工具来量化皮质tau和A β病理的地形图模式， 建立一个个性化的分析框架，用于早期发现局限性脑萎缩，并应用这些工具 健康与衰老大脑研究-健康差异（HABS-HD）的多种族队列（n = 3000）到 表征不同人群中AT（N）成像标记物的异质性。具体目标有三个 在我们的项目中：1.开发tau蛋白和淀粉样蛋白PET成像中地形图模式的基于表面的建模 用于AD病理学的个性化亚型和分期。2.开发个性化的脑成像测量方法 通过解决由于皮质折叠和形状差异引起的变异性来萎缩。3.为了描述 个性化影像学标记物对疾病分期和亚型的健康差异。总之，我们的主要 目标是创建用于创建个性化AT（N）成像标记物的新型计算工具，并应用于 他们的特点的异质性AD病理的背景下，健康的差距。所有工具和成像 在这个项目中开发的标记将免费分发给研究社区，我们相信这将大大 提高不同人群AT（N）病理学亚型和分期的最新水平。