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

摘要 阿尔茨海默病(AD)的AT(N)框架为AD的研究提供了系统的指导 β-淀粉样蛋白(A-β)斑块(A)、神经原纤维Tau缠结(T)和 神经变性(N)。现有的AT(N)成像标记通常被定义为皮质的平均测量 先验确定的区域，不足以描述异质性病理和萎缩 AD的模式。为了让个别受试者的AT(N)身份得到更个人化的描述，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的异质性可能源于 消息来源。首先是经常存在非典型的AD病理和脑萎缩模式，这些模式偏离了 典型的布拉克阶段。第二个是皮质解剖学的高度可变性以及由此产生的巨大差异。 在所谓的“相应”位置的皮质厚度，即使是健康的大脑也是如此。第三个是目前缺乏 对AT(N)成像标记物在描述不同疾病轨迹中的作用的理解 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 在脑形态分析方面，我们将开发工具来量化皮质tau和Aβ病理的地形图， 为早期发现局限性脑萎缩构建个性化分析框架，并应用这些工具 从健康与老龄化大脑研究-健康差异(HABS-HD)(n=3000)到多种族队列 研究AT(N)影像标记在不同人群中的异质性。有三个具体目标 在我们的项目中：1.在tau和淀粉样蛋白PET成像中开发基于表面的地形模式建模 用于AD病理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解决萎缩。3.描述……的影响 个体化影像标记物在疾病分期和亚型上的健康差异。总而言之，我们的主要 目标是创建新的计算工具来创建个性化的AT(N)成像标记并应用 他们试图在健康差距的背景下描述AD病理的异质性。所有工具和映像 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 在不同人群中提高AT(N)病理亚型和分期的最新水平。

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.