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 阿尔茨海默病 (AD) 的 AT(N) 框架为研究 AD 提供了系统指导 β-淀粉样蛋白 (Aβ) 斑块 (A)、神经原纤维 tau 缠结 (T) 和神经原纤维 tau 缠结的生物标记物的定量测量 神经变性（N）。现有的 AT(N) 成像标记通常定义为皮质的平均测量值 先验确定的区域不足以表征异质病理和萎缩 AD 的模式。为了对个体受试者的 AT(N) 状态进行更个性化的描述，我们将 在该项目中开发基于先进形状分析技术的新型成像标记。从 从成像标记物开发的角度来看，研究 AD 异质性的挑战可能来自多种因素 来源。首先是非典型 AD 病理学和脑萎缩模式的频繁存在，偏离了 典型的布拉克阶段。第二个是皮质解剖结构的高度可变性以及由此产生的巨大变化 即使是健康大脑的所谓“相应”位置的皮质厚度。三是目前缺乏 了解 AT(N) 成像标记物在表征不同疾病轨迹方面的作用 少数群体包括非裔美国人和墨西哥裔美国人。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 病理学的拓扑模式， 建立用于早期检测局部脑萎缩的个性化分析框架，并应用这些工具 健康与老龄化大脑研究 – 健康差异 (HABS-HD) (n=3000) 的多种族队列 表征不同人群中 AT(N) 成像标记的异质性。具体目标有3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而引起的变异性萎缩。 3. 描述影响 使用个性化成像标记物对疾病分期和亚型进行健康差异。综上所述，我们的主要 目标是创建新颖的计算工具来创建个性化 AT(N) 成像标记并应用 它们可以描述健康差异背景下 AD 病理学的异质性。所有工具和成像 该项目中开发的标记将免费分发给研究界，我们相信这将极大地促进 提高不同人群中 AT(N) 病理学亚型和分期的最新水平。