Along-axon diameter variation and axonal orientation dispersion revealed with 3D electron microscopy: implications for quantifying brain white matter microstructure with histology and diffusion MRI
Along-axon diameter variation and axonal orientation dispersion revealed with 3D electron microscopy: implications for quantifying brain white matter microstructure with histology and diffusion MRI
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DOI：
10.1007/s00429-019-01844-6
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发表时间：
2019-05-01
影响因子：
3.1
通讯作者：
Fieremans, Els
中科院分区：
文献类型：
--
作者：
Lee, Hong-Hsi;Yaros, Katarina;Fieremans, Els
弥散MRI信号的组织微观结构建模是一个活跃的研究领域，致力于弥合宏观MRI分辨率和细胞水平组织结构之间的差距。这种神经元组织的建模依赖于一些关于轴突纤维束微观结构特征的假设，例如轴突形状（例如，完美的圆柱体）和纤维方向弥散。然而，这些假设尚未得到足够高分辨率的三维组织学的验证。在这里，我们重建了小鼠脑胼胝体的顺序扫描电镜图像，并引入了一种基于随机漫步器（RaW）的算法来快速分割单个轴突内空间和髓鞘。通过传统的基于机器学习的雕刻的基于人类注释的分割证实，我们的半自动算法是可靠的，并且更节省时间。基于分割，我们计算了尺寸相关参数（内轴突直径、分布、沿轴突变化和髓鞘g比）和方向相关参数（纤维方向分布及其旋转不变量、色散角）的mri相关估计。报告的弥散角与先前的二维组织学研究和弥散MRI测量一致，而报告的直径超过了其他小鼠脑研究。此外，我们计算了这些量在实际弥散MRI实验中如何作为弥散时间的函数演变，从而提供了微观结构的粗粒度窗口，并表明取向相关指标在临床和临床前弥散时间范围内的弥散时间依赖性可以忽略不计。然而，mri测量的内轴突直径，以最宽的截面为主，由于轴突直径的粗粒化变化，随着扩散时间的推移，有效地减少了17%。此外，我们的三维测量显示，沿轴突的直径有显著的变化。因此，从MRI中估计的纤维取向弥散应该是相对稳定的，而表观内轴突直径对实验设置很敏感，不能用完美的圆柱形轴突来建模。
Tissue microstructure modeling of diffusion MRI signal is an active research area striving to bridge the gap between macroscopic MRI resolution and cellular-level tissue architecture. Such modeling in neuronal tissue relies on a number of assumptions about the microstructural features of axonal fiber bundles, such as the axonal shape (e.g., perfect cylinders) and the fiber orientation dispersion. However, these assumptions have not yet been validated by sufficiently high-resolution 3-dimensional histology. Here, we reconstructed sequential scanning electron microscopy images in mouse brain corpus callosum, and introduced a random-walker (RaW)-based algorithm to rapidly segment individual intra-axonal spaces and myelin sheaths of myelinated axons. Confirmed by a segmentation based on human annotations initiated with conventional machine-learning-based carving, our semi-automatic algorithm is reliable and less time-consuming. Based on the segmentation, we calculated MRI-relevant estimates of size-related parameters (inner axonal diameter, itsdistribution, along-axon variation, and myelin g-ratio), and orientation-related parameters (fiber orientation distribution and its rotational invariants; dispersion angle). The reported dispersion angle is consistent with previous 2-dimensional histology studies and diffusion MRI measurements, while the reported diameter exceeds those in other mouse brain studies. Furthermore, we calculated how these quantities would evolve in actual diffusion MRI experiments as a function of diffusion time, thereby providing a coarse-graining window on the microstructure, and showed that the orientation-related metrics have negligible diffusion time-dependence over clinical and pre-clinical diffusion time ranges. However, the MRI-measured inner axonal diameters, dominated by the widest cross sections, effectively decrease with diffusion time by 17% due to the coarse-graining over axonal caliber variations. Furthermore, our 3d measurement showed that there is significant variation of the diameter along the axon. Hence, fiber orientation dispersion estimated from MRI should be relatively stable, while the apparent inner axonal diameters are sensitive to experimental settings, and cannot be modeled by perfectly cylindrical axons.