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.

抽象的 阿尔茨海默氏病（AD）的AT（N）框架提供了基于研究AD的系统指导 β-淀粉样蛋白（Aβ）斑块（A），神经原纤维tau Tangles（T）和 神经变性（N）。现有在（n）成像标记通常定义为皮质的平均测量值 区域确定了先验的区域，不足以表征异质性病理和萎缩 广告的模式。为了允许对单个受试者的AT（N）状态的更多个性化表征，我们将 在这个项目中开发基于先进形状分析技术的新颖成像标记。来自 成像标志物发展的观点，研究AD的异质性的挑战可能来自多个 来源。首先是经常存在的非典型AD病理学和脑萎缩模式，它们偏离 规范的Braak阶段。第二个是皮质解剖学的高变异性和产生的大变化 即使是健康大脑的所谓“相应”位置的皮质厚度。第三是目前缺乏 了解AT（N）成像标记在表征潜水员疾病轨迹中的作用 包括非裔美国人和墨西哥裔美国人在内的少数群体。以我们丰富的经验为基础 在大脑形状分析中，我们将开发工具来量化皮质tau和Aβ病理的地形模式， 建立一个个性化的分析框架，以早日检测局部脑萎缩，并应用这些工具 从健康与衰老的大脑研究 - 健康差异（HABS-HD）（n = 3000）到多民族队列 表征了潜水员种群中AT（N）成像标记的异质性。有三个特定目标 在我们的项目中：1。开发tau和淀粉样蛋白宠物成像中地形图案的基于表面的建模 用于广告病理的个性化亚型和分期。 2。开发大脑的个性化成像测量 通过解决皮质折叠和形状差异引起的可变性来萎缩。 3。表征 疾病分期的健康差异和通过个性化成像标记的亚型。总而言之，我们的主要 目标是创建新颖的计算工具，以创建（n）成像标记的个性化并应用 他们在健康差异的背景下表征了AD病理的异质性。所有工具和成像 该项目中开发的标记将自由分发给研究社区，我们认为这将极大 在潜水员种群中（N）病理学的亚型和分期增强最新的分期。