Abstract

A deeper knowledge of the architecture of the peripheral nerve with three-dimensional (3D) imaging of the nerve tissue at the sub-cellular scale may contribute to unravel the pathophysiology of neuropathy. Here we demonstrate the feasibility of X-ray phase contrast holographic nanotomography to enable 3D imaging of nerves at high resolution, while covering a relatively large tissue volume. We show various subcomponents of human peripheral nerves in biopsies from patients with type 1 and 2 diabetes and in a healthy subject. Together with well-organized, parallel myelinated nerve fibres we show regenerative clusters with twisted nerve fibres, a sprouted axon from a node of Ranvier and other specific details. A novel 3D construction (with movie created) of a node of Ranvier with end segment of a degenerated axon and sprout of a regenerated one is captured. Many of these architectural elements are not described in the literature. Thus, X-ray phase contrast holographic nanotomography enables identifying specific morphological structures in 3D in peripheral nerve biopsies from a healthy subject and from patients with type 1 and 2 diabetes.

Highlights

  • A deeper knowledge of the architecture of the peripheral nerve with three-dimensional (3D) imaging of the nerve tissue at the sub-cellular scale may contribute to unravel the pathophysiology of neuropathy

  • Histological technique with light and electron microscopy is the standard imaging technique for neuropathology, where thin sections are cut from the sample or teased nerve fibres are harvested for evaluation in a microscope[28]

  • We evaluated the feasibility of using X-ray phase contrast holographic nanotomography to investigate the 3D micro-morphology of a human peripheral nerve from single patients with type 1 and type 2 diabetes as well as from a healthy subject

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Summary

Introduction

A deeper knowledge of the architecture of the peripheral nerve with three-dimensional (3D) imaging of the nerve tissue at the sub-cellular scale may contribute to unravel the pathophysiology of neuropathy. X-ray phase contrast holographic nanotomography enables identifying specific morphological structures in 3D in peripheral nerve biopsies from a healthy subject and from patients with type 1 and 2 diabetes. X-ray phase contrast holographic nanotomography, with a resolution in-between that of light and electron microscope, has recently been used to visualize myelinated nerve fibres and various subcomponents in sciatic nerves of healthy mice[17] with isotropic voxel sizes below 100 nm. Our aim was to evaluate the feasibility of using X-ray phase contrast holographic nanotomography to make a detailed map of the myelinated nerve fibres, including the nodes of Ranvier, and the intricate three-dimensional (3D) anatomical structures in human nerve biopsies from the upper extremity in a healthy subject and from two patients with type 1 and 2 diabetes

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