Disentangling normal aging from Alzheimer's disease in structural magnetic resonance images
Disentangling normal aging from Alzheimer's disease in structural magnetic resonance images
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DOI：
10.1016/j.neurobiolaging.2014.07.046
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发表时间：
2015-01-01
影响因子：
4.2
通讯作者：
Ayache, Nicholas
中科院分区：
文献类型：
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作者：
Lorenzi, Marco;Pennec, Xavier;Ayache, Nicholas
在受阿尔茨海默病（AD）影响的患者的脑中观察到的形态学是不同生物学过程的组合，例如正常衰老和AD特有的病理性物质损失。区分这些生物学因素的能力对于可靠地评估病理性AD相关结构变化至关重要，特别是在疾病的最早期、前驱期和临床前阶段。在这里，我们提出了一种基于非线性图像配准的方法来估计和分析从观察到的大脑形态老化和病理的相对贡献。特别是，我们首先定义了一个纵向模型的大脑的正常老化过程，从序列T1加权磁共振成像扫描65名健康参与者。纵向模型，然后用作参考的横截面分析。给定一个新的大脑图像，我们然后估计其相对于衰老模型的解剖年龄;这被定义为相对于基线健康人群平均年龄的形态年龄变化。最后，我们将特定的形态过程定义为去除估计的正常老化过程后观察到的解剖结构的剩余部分。来自105名健康受试者、110名轻度认知障碍（MCI）受试者、86名MCI转化为AD的受试者和134名AD患者的实验结果提供了对AD时间跨度内观察到的解剖学变化的新描述：正常衰老、正常衰老风险、转化为MCI和AD的最新阶段。更先进的AD阶段与大脑中的形态年龄变化增加和强烈的疾病特异性形态变化，主要影响脑室，颞极，内嗅皮层，和大脑皮层。我们的模型表明，AD的特点是局部疾病特异性大脑变化以及加速的全球衰老过程。因此，这种方法可能代表一种更精确的工具，以确定疾病修饰药物临床试验中的潜在临床结果。(C)2015 Elsevier Inc. All rights reserved.
The morphology observed in the brains of patients affected by Alzheimer's disease (AD) is a combination of different biological processes, such as normal aging and the pathological matter loss specific to AD. The ability to differentiate between these biological factors is fundamental to reliably evaluate pathological AD-related structural changes, especially in the earliest phase of the disease, at prodromal and preclinical stages. Here we propose a method based on non-linear image registration to estimate and analyze from observed brain morphologies the relative contributions from aging and pathology. In particular, we first define a longitudinal model of the brain's normal aging process from serial T1-weight magnetic resonance imaging scans of 65 healthy participants. The longitudinal model is then used as a reference for the cross-sectional analysis. Given a new brain image, we then estimate its anatomical age relative to the aging model; this is defined as a morphological age shift with respect to the average age of the healthy population at baseline. Finally, we define the specific morphological process as the remainder of the observed anatomy after the removal of the estimated normal aging process. Experimental results from 105 healthy participants, 110 subjects with mild cognitive impairment (MCI), 86 with MCI converted to AD, and 134 AD patients provide a novel description of the anatomical changes observed across the AD time span: normal aging, normal aging at risk, conversion to MCI, and the latest stages of AD. More advanced AD stages are associated with an increased morphological age shift in the brain and with strong disease-specific morphological changes affecting mainly ventricles, temporal poles, the entorhinal cortex, and hippocampi. Our model shows that AD is characterized by localized disease-specific brain changes as well as by an accelerated global aging process. This method may thus represent a more precise instrument to identify potential clinical outcomes in clinical trials for disease modifying drugs. (C) 2015 Elsevier Inc. All rights reserved.