NeuroPoly Lab, Institute of Biomedical Engineering, Polytechnique Montreal, Montreal, QC, Canada.
Laboratory for the Study of Calcified Tissues and Biomaterials, Faculty of Dental Medicine, University of Montreal, Montreal, QC, Canada.
Neuroimage. 2019 Jan 15;185:119-128. doi: 10.1016/j.neuroimage.2018.10.033. Epub 2018 Oct 13.
Due to the technical challenges of large-scale microscopy and analysis, to date only limited knowledge has been made available about axon morphometry (diameter, shape, myelin thickness, volume fraction), thereby limiting our understanding of neuronal microstructure and slowing down research on neurodegenerative pathologies. This study addresses this knowledge gap by establishing a state-of-the-art acquisition and analysis framework for mapping axon morphometry, and providing the first comprehensive mapping of axon morphometry in the human spinal cord. We dissected, fixed and stained a human spinal cord with osmium tetroxide, and used a scanning electron microscope to image the entirety of 23 axial slices, covering C1 to L5 spinal levels. An automatic method based on deep learning was then used to segment each axon and myelin sheath to produce maps of axon morphometry. These maps were then registered to a standard spinal cord magnetic resonance imaging (MRI) template. Between 500,000 (lumbar) and 1 million (cervical) myelinated axons were segmented at each level of this human spinal cord. Morphometric features show a large disparity between tracts, but high right-left symmetry. Our results suggest a modality-based organization of the dorsal column in the human, as it has been observed in the rat. The generated axon morphometry template is publicly available at https://osf.io/8k7jr/ and could be used as a reference for quantitative MRI studies. The proposed framework for axon morphometry mapping could be extended to other parts of the central or peripheral nervous system that exhibit coherently-oriented axons.
由于大规模显微镜和分析技术的挑战，迄今为止，我们对轴突形态计量学（直径、形状、髓鞘厚度、体积分数）的了解非常有限，这限制了我们对神经元微观结构的理解，并减缓了神经退行性病理研究的进展。本研究通过建立一个用于映射轴突形态计量学的最先进的采集和分析框架，解决了这一知识空白，并首次全面绘制了人类脊髓中的轴突形态计量学图谱。我们对人类脊髓进行解剖、固定和锇四氧化染色，然后使用扫描电子显微镜对 23 个轴向切片的全部进行成像，涵盖 C1 至 L5 脊髓水平。然后，使用基于深度学习的自动方法对每个轴突和髓鞘进行分割，生成轴突形态计量学图谱。这些图谱随后被注册到标准的脊髓磁共振成像（MRI）模板上。在这个人类脊髓的每个水平上，我们分别分割了 50 万（腰椎）和 100 万（颈椎）个有髓轴突。形态计量学特征显示在束之间存在很大差异，但左右高度对称。我们的结果表明，人类背柱存在基于模态的组织，就像在大鼠中观察到的那样。生成的轴突形态计量学模板可在 https://osf.io/8k7jr/ 上公开获取，并可作为定量 MRI 研究的参考。提出的轴突形态计量学映射框架可以扩展到具有一致取向轴突的中枢或周围神经系统的其他部分。
