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, density), 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, and used a scanning electron microscope to image the entirety of 24 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 which, producing 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 remarkable right-left symmetry. Results confirm the modality-based organization of the dorsal column in the human, as 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.

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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, density), 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, and used a scanning electron microscope to image the entirety of 24 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 which, producing 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 remarkable right-left symmetry. Results confirm the modality-based organization of the dorsal column in the human, as 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.

The white matter is organized into “tracts” or “bundles,” which connect different parts of the central nervous system. Knowing where these tracts are located in each individual is important for understanding the cause of potential sensorial, motor or cognitive deficits and for developing appropriate treatments. Traditionally, tracts are found using tracer injection, which is a difficult, slow and poorly scalable technique. However, axon populations from a given tract exhibit specific characteristics in terms of morphometrics and myelination. Hence, the delineation of tracts could, in principle, be done based on their morphometry. The objective of this study was to generate automatic parcellation of the rat spinal white matter tracts using the manifold information from scanning electron microscopy images of the entire spinal cord. The axon morphometrics (axon density, axon diameter, myelin thickness and g-ratio) were computed pixelwise following automatic axon segmentation using AxonSeg. The parcellation was based on an agglomerative clustering algorithm to group the tracts. Results show that axon morphometrics provide sufficient information to automatically identify some white matter tracts in the spinal cord, however, not all tracts were correctly identified. Future developments of microstructure quantitative MRI even bring hope for a personalized clustering of white matter tracts in each individual patient. The generated atlas and the associated code can be found at https://github.com/neuropoly/tract-clustering.

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