X-Ray Phase Contrast Tomography Reveals Early Vascular Alterations and Neuronal Loss in a Multiple Sclerosis Model

Abstract

The degenerative effects of multiple sclerosis at the level of the vascular and neuronal networks in the central nervous system are currently the object of intensive investigation. Preclinical studies have demonstrated the efficacy of mesenchymal stem cell (MSC) therapy in experimental autoimmune encephalomyelitis (EAE), the animal model for multiple sclerosis, but the neuropathology of specific lesions in EAE and the effects of MSC treatment are under debate. Because conventional imaging techniques entail protocols that alter the tissues, limiting the reliability of the results, we have used non-invasive X-ray phase-contrast tomography to obtain an unprecedented direct 3D characterization of EAE lesions at micro-to-nano scales, with simultaneous imaging of the vascular and neuronal networks. We reveal EAE-mediated alterations down to the capillary network. Our findings shed light on how the disease and MSC treatment affect the tissues, and promote X-ray phase-contrast tomography as a powerful tool for studying neurovascular diseases and monitoring advanced therapies.

X-ray phase contrast tomography for the investigation of amyotrophic lateral sclerosis

“…In contrast, recent works demonstrated that X-ray phasecontrast tomography (XPCT) enables the visualization of the 3D distribution of neuronal and vascular network of the whole spinal cord (Fratini et al, 2015;Cedola et al, 2017), with a micrometric to sub-micrometric spatial resolution with a simple and rapid sample preparation. In conventional radiography, the collected transmitted intensity is formed by the interaction of the incident X-ray beam with absorbing structures inside the sample.…”

Laboratory-based x-ray phase contrast CT technology for clinical intra-operative specimen imaging

“…Applications of X-ray Phase Contrast imaging (XPCi) are rapidly expanding, thanks to its ability to visualize and quantify features invisible to conventional X-ray imaging techniques on scales spanning from tens of microns to nanometers. [1][2][3][4][5] While for a long period this technique was limited to synchrotron radiation facilities, the development of new phase detection methodologies now enables XPCi with laboratory-based sources. [6][7][8][9][10] Despite XPCi not yet being available in hospitals, the improved visualization capabilities demonstrated so far suggest that healthcare would strongly benefit from a widespread application of XPCi.…”

Fractal Dimension Analysis of High-Resolution X-Ray Phase Contrast Micro-Tomography Images at Different Threshold Levels in a Mouse Spinal Cord

“…We have recently demonstrated that X-ray phase contrast micro-tomography (XrPCµT) enables the study of the vascular and neuronal networks simultaneously without sample sectioning [25]. In particular, XrPCµT imaging is a multiscale (spanning from mm to <µm) 3D imaging technique that can be used to evaluate morphological alterations in central nervous system (CNS) tissue [26]. However, XrPCµT images are characterized by small intensity variations which make the segmentation process challenging.…”