Age-related alterations in axonal microstructure in the corpus callosum measured by high-gradient diffusion MRI
Age-related alterations in axonal microstructure in the corpus callosum measured by high-gradient diffusion MRI
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DOI：
10.1016/j.neuroimage.2019.02.036
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发表时间：
2019-05-01
期刊：
影响因子：
5.7
通讯作者：
Huang, Susie Y.
中科院分区：
文献类型：
--
作者：
Fan, Qiuyun;Tian, Qiyuan;Huang, Susie Y.
大脑白质在正常衰老过程中表现出与年龄相关的退行性变化，包括轴突密度的降低和轴突结构的改变。在整个生命周期中测量这些微观结构变化的非侵入性方法对于了解与年龄相关的白质变性的基质和区域变异性是非常有价值的。扩散磁共振成像 (MRI) 的最新进展利用高梯度强度来提高对活人大脑中轴突尺寸和密度的敏感性。在这里，我们使用高梯度强度扩散 MRI 检查了 36 名健康成年人（22-72 岁）大脑中轮廓明确的中央白质束中年龄与轴突直径和堆积密度指数之间的关系。最近经过验证的方法，通过以 300 mT/m 最大梯度强度获得的扩散 MRI 测量来推断有效轴突室尺寸和堆积密度，该方法应用于体内人脑，以获得胼胝体、其子区域以及小镊子和大镊子中相邻前部和后部纤维的轴突直径和密度指数。还探讨了轴突指标、胼胝体面积和区域灰质体积之间的关系。结果显示，整个胼胝体的轴突直径指数随着年龄的增长而显着增加。对胼胝体亚区域的类似分析表明，轴突直径指数和轴突密度的年龄相关变化在胼胝体膝部最为明显，而在胼胝体压部相对不存在，这与之前的组织学研究结果一致。这些相关性的显着性反映在小镊子和大镊子中，这与之前报道的小镊子的 FA 随年龄增长而减少的情况一致，但大镊子的 FA 却没有减少。随着年龄的增长，轴突成像指标的变化与胼胝体面积和区域灰质体积的减少平行。在老年人中，认知测试的结果表明，胼胝体（尤其是胼胝体膝部）的有效隔室尺寸较大，与蒙特利尔认知评估得分较低之间存在关联，这主要是由于短期记忆缺陷所致。目前的研究表明，高梯度扩散 MRI 可能对传统 DTI 指标中反映的与年龄相关的白质变性的轴突基质敏感，并为白质微结构随年龄增长而发生的区域选择性改变提供了进一步的证据。
Cerebral white matter exhibits age-related degenerative changes during the course of normal aging, including decreases in axon density and alterations in axonal structure. Noninvasive approaches to measure these microstructural alterations throughout the lifespan would be invaluable for understanding the substrate and regional variability of age-related white matter degeneration. Recent advances in diffusion magnetic resonance imaging (MRI) have leveraged high gradient strengths to increase sensitivity toward axonal size and density in the living human brain. Here, we examined the relationship between age and indices of axon diameter and packing density using high-gradient strength diffusion MRI in 36 healthy adults (aged 22-72) in well-defined central white matter tracts in the brain. A recently validated method for inferring the effective axonal compartment size and packing density from diffusion MRI measurements acquired with 300 mT/m maximum gradient strength was applied to the in vivo human brain to obtain indices of axon diameter and density in the corpus callosum, its sub-regions, and adjacent anterior and posterior fibers in the forceps minor and forceps major. The relationships between the axonal metrics, corpus callosum area and regional gray matter volume were also explored. Results revealed a significant increase in axon diameter index with advancing age in the whole corpus callosum. Similar analyses in sub-regions of the corpus callosum showed that age-related alterations in axon diameter index and axon density were most pronounced in the genu of the corpus callosum and relatively absent in the splenium, in keeping with findings from previous histological studies. The significance of these correlations was mirrored in the forceps minor and forceps major, consistent with previously reported decreases in FA in the forceps minor but not in the forceps major with age. Alterations in the axonal imaging metrics paralleled decreases in corpus callosum area and regional gray matter volume with age. Among older adults, results from cognitive testing suggested an association between larger effective compartment size in the corpus callosum, particularly within the genu of the corpus callosum, and lower scores on the Montreal Cognitive Assessment, largely driven by deficits in short-term memory. The current study suggests that high-gradient diffusion MRI may be sensitive to the axonal substrate of age-related white matter degeneration reflected in traditional DTI metrics and provides further evidence for regionally selective alterations in white matter microstructure with advancing age.