Most magnetic resonance imaging (MRI) studies investigating the relationship between regional brain myelination or axonal density and aging have relied upon nonspecific methods to probe myelin and axonal content, including diffusion tensor imaging and relaxation time mapping. While these studies have provided pivotal insights into changes in cerebral architecture with aging and pathology, details of the underlying microstructural alterations have not been fully elucidated. In the current study, we used the BMC-mcDESPOT analysis, a direct and specific multicomponent relaxometry method for imaging of myelin water fraction (MWF), a marker of myelin content, and NODDI, an emerging multicomponent diffusion technique, for neurite density index (NDI) imaging, a proxy of axonal density. We investigated age-related differences in MWF and NDI in several white matter brain regions in a cohort of cognitively unimpaired participants over a wide age range. Our results indicate a quadratic, inverted U-shape, relationship between MWF and age in all brain regions investigated, suggesting that myelination continues until middle age followed by a decrease at older ages, in agreement with previous work. We found a similarly complex regional association between NDI and age, with several cerebral structures also exhibiting a quadratic, inverted U-shape, relationship. This novel observation suggests an increase in axonal density until the fourth decade of age followed by a rapid loss at older ages. We also observed that these age-related differences in MWF and NDI vary across different brain regions, as expected. Finally, our study indicates no significant association between MWF and NDI in most cerebral structures investigated, although this association approached significance in a limited number of brain regions, indicating the complementary nature of their information and encouraging further investigation. Overall, we find evidence of nonlinear associations between age and myelin or axonal density in a sample of well-characterized adults, using direct myelin and axonal content imaging methods.

中文翻译：

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使用多分量扩散和弛豫磁共振成像揭示神经突密度和髓鞘含量与年龄的非线性关联

大多数调查区域脑髓鞘形成或轴突密度与衰老之间关系的磁共振成像 (MRI) 研究依赖于非特异性方法来探测髓鞘和轴突含量，包括扩散张量成像和弛豫时间映射。虽然这些研究为大脑结构随衰老和病理变化的变化提供了关键见解，但潜在的微观结构改变的细节尚未完全阐明。在当前的研究中，我们使用了 BMC-mcDESPOT 分析，一种直接和特定的多组分弛豫方法，用于对髓鞘水分数 (MWF)（髓鞘含量的标志物）和 NODDI（一种新兴的多组分扩散技术，用于神经突密度指数）进行成像。 NDI）成像，轴突密度的代表。我们调查了一个年龄范围广泛的认知未受损参与者队列中几个白质大脑区域的 MWF 和 NDI 与年龄相关的差异。我们的结果表明 MWF 与所研究的所有大脑区域的年龄之间存在二次倒 U 形关系，这表明髓鞘形成一直持续到中年，然后在老年时减少，这与之前的工作一致。我们发现 NDI 和年龄之间存在类似的复杂区域关联，几个大脑结构也表现出二次、倒 U 形关系。这一新颖的观察表明轴突密度增加，直到 40 岁，然后在年龄较大时迅速丧失。正如预期的那样，我们还观察到 MWF​​ 和 NDI 的这些与年龄相关的差异在不同的大脑区域中有所不同。最后，我们的研究表明，在大多数被调查的大脑结构中，MWF 和 NDI 之间没有显着关联，尽管这种关联在有限数量的大脑区域中具有显着性，表明它们信息的互补性并鼓励进一步研究。总体而言，我们使用直接髓鞘和轴突内容成像方法在一个特征明确的成人样本中发现了年龄与髓鞘或轴突密度之间非线性关联的证据。