Abstract

A crucial issue in the development of therapies to treat pathologies of the central nervous system is represented by the availability of non-invasive methods to study the three-dimensional morphology of spinal cord, with a resolution able to characterize its complex vascular and neuronal organization. X-ray phase contrast micro-tomography enables a high-quality, 3D visualization of both the vascular and neuronal network simultaneously without the need of contrast agents, destructive sample preparations or sectioning. Until now, high resolution investigations of the post-mortem spinal cord in murine models have mostly been performed in spinal cords removed from the spinal canal. We present here post-mortem phase contrast micro-tomography images reconstructed using advanced computational tools to obtain high-resolution and high-contrast 3D images of the fixed spinal cord without removing the bones and preserving the richness of micro-details available when measuring exposed spinal cords. We believe that it represents a significant step toward the in-vivo application.

Highlights

  • The spinal cord (SC) is exposed to a wide variety of diseases

  • We analysed three different types of specimens: samples A were prepared without contrast agent, while sample B and sample C were injected with Iodixanol and Microfil NW-130 contrast agents, respectively

  • The micro-XPCT in propagation-based imaging (PBI) geometry has enabled us to obtain detailed high spatial resolution 3D images of intact fixed post-mortem healthy murine spinal cord surrounded by vertebrae

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Summary

Introduction

The spinal cord (SC) is exposed to a wide variety of diseases. In particular, the incidence of spinal cord injuries in the world is about 40-80 new cases per year per million inhabitants [1], corresponding to 250,000-500,000 new cases per year of people suffering from traumatic and non-traumatic spinal cord injuries. The non-traumatic injuries are due to neuroinflammation and neurodegeneration of the spinal cord In this context, it emerges the need of identifying and introducing non-invasive methods, with the ability to investigate the spinal cord anatomical conditions at a spatial resolution allowing the evaluation and the optimization of pharmacological or rehabilitation treatments. A variety of imaging techniques such as magnetic resonance imaging (MRI), ultrasound, positron emission tomography (PET) and X-ray computed tomography (CT) are in daily use for the investigation of the spinal cord. Magnetic resonance imaging at a microscopic level (micro-MRI) non-invasively penetrates the bones and yields reasonably well-resolved 3D images of the spinal cord inside the spinal canal [5]. Combined with angiography contrast agents, micro-CT has been widely used in the investigation of vascularization and angiogenesis in different organs, including the brain and the spinal cord [16,17]. The main drawback of micro-CT is the poor contrast resolution of soft tissues when applied without invasive contrast agents [10]

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