Fast multiparametric MR imaging as early biomarkers of Alzheimer's Disease

摘要 如果不能治愈或预防，阿尔茨海默病(AD)将迅速成为一种压倒性的经济和 社会负担。随着旨在减少β-淀粉样蛋白(Aβ)负担的多项临床试验的失败，以及在 一般认为AD的发展停滞不前，有效的治疗AD社会认为潜在的 阿尔茨海默病的病因必须在认知表型出现之前进行分析。在这一背景下，发展 预测生物标记物和模型对于识别快速进展的高风险患者至关重要 AD的连续体，即从正常认知到轻度认知障碍(MCI)和从MCI到 痴呆症。以前的AD研究主要是利用磁共振成像(MRI)来评估 形态变化。我们的初步结果和其他研究表明，定量磁共振参数 如T1、T2，磁化率值对正常时效过程和AD很敏感。然而，他们的 由于扫描时间的限制，AD研究协议的广泛传播受到了限制。的首要目标是 建议建立一种快速磁共振技术，该技术不会增加常规磁共振的总扫描时间 协议；除了提供常规协议提供的所有信息外，它还将提供 专门针对AD诊断和预后需求的多个定量参数测量。 我们将1)开发一种快速和运动不敏感的磁共振技术(M3FAST-ECHO)，它可以产生多个 10分钟内的定量参数；2)验证体积测量和微出血 M3FAST-ECHO合成3DT1加权和磁化率加权成像的评价 30例轻度认知障碍患者和30例认知匹配的老年患者的ADNI对照研究 3)比较30例MCI患者的定量T1、T2*值和定量敏感值 30名年龄匹配的认知正常受试者，并将这些指标与神经心理学相关 在参与者中进行测量。成功完成目标将产生一种快速磁共振技术， 在不增加总体扫描时间的情况下提供多个参数mr图，并为 建立定量MR参数图值作为AD的敏感生物标志物。这将大大增强 我们评估和筛选阿尔茨海默病早期预测生物标志物的能力。跨学科 埃默里AD研究的团队和基础设施将确保研究和传播的成功实施 向整个AD研究社区介绍开发的技术。

Abstract Without a cure or prevention, Alzheimer's Disease (AD) rapidly will become an overwhelming economic and social burden. With the failure of multiple clinical trials targeting reduction of beta-amyloid (Aβ) burden and in general the stagnation of the development of effective treatment for AD, AD community believes that underlying causes of AD must be attacked before emergence of the cognitive phenotype. In this context, the development of predictive biomarkers and models is critical for identifying patients with high risk of rapid progression along the AD continuum, i.e. transitioning from normal cognition to mild cognitive impairment (MCI) and from MCI to dementia. Previous AD research has primarily been utilizing magnetic resonance imaging (MRI) for assessing morphological changes. Our preliminary results and other studies have shown that quantitative MR parameters such T1, T2, the magnetic susceptibility values are sensitive to normal ageing process and AD. However, their wide spread in AD research protocols has been limited due to scan time constraints. The overarching goal of the proposal is to establish a fast MR technique that does not increase overall scan time of a conventional MR protocol; and in addition to providing all the information the conventional protocol provides, it will also provide multiple quantitative parametric measurements specifically targeted to the needs of AD diagnosis and prognosis. We will 1) develop a fast and motion-insensitive MR technique (M3FAST-ECHO) that can generate multiple quantitative parameters within 10 minutes; 2) validate the volumetric measurement and microhemorrhage assessment from the synthetic 3D T1-weighted and the susceptibility weighted imaging from M3FAST-ECHO against standard ADNI protocol in 30 patients with mild cognitive impairment and 30 aged matched cognitively normal subjects; 3) compare quantitative T1, T2* and quantitative susceptibility values in 30 MCI patients and 30 aged matched cognitively normal subjects, and to correlate these metrics with neuropsychological measurements in the participants. The successful completion of the aims will result in a fast MR technique that provides multiple parametric MR maps without increasing overall scan time, and provide preliminary results for establishing values of quantitative MR parametric maps as sensitive biomarkers of AD. This will greatly enhance our ability to evaluate and screen for early predictive biomarkers of Alzheimer's Disease. The inter-disciplinary team and infrastructure for AD research at Emory will ensure successful execution of the study and dissemination of the developed techniques to the entire AD research community.