X-ray Phase Contrast Tomography Serves Preclinical Investigation of Neurodegenerative Diseases.

Francesca Palermo,Ginevra Begani Provinciali,Lorenzo Massimi,Antonio Uccelli,Margie P Olbinado,Nicole Kerlero De Rosbo,Inna Bukreeva,Michela Fratini,Claudia Balducci,Laura Maugeri,Maura Catalano,Nicola Pieroni,Alessia Sanna,Alessia Cedola,Giuseppe Gigli

doi:10.3389/fnins.2020.584161

Abstract

We report a qualitative study on central nervous system (CNS) damage that demonstrates the ability of X-ray phase contrast tomography (XPCT) to confirm data obtained with standard 2D methodology and permits the description of additional features that are not detected with 2D or other 3D techniques. In contrast to magnetic resonance or computed tomography, XPCT makes possible the high-resolution 3D imaging of soft tissues classically considered “invisible” to X-rays without the use of additional contrast agents, or without the need for intense processing of the tissue required by 2D techniques. Most importantly for studies of CNS diseases, XPCT enables a concomitant multi-scale 3D biomedical imaging of neuronal and vascular networks ranging from cells through to the CNS as a whole. In the last years, we have used XPCT to investigate neurodegenerative diseases, such as Alzheimer’s disease (AD) and multiple sclerosis (MS), to shed light on brain damage and extend the observations obtained with standard techniques. Here, we show the cutting-edge ability of XPCT to highlight in 3D, concomitantly, vascular occlusions and damages, close associations between plaques and damaged vessels, as well as dramatic changes induced at neuropathological level by treatment in AD mice. We corroborate data on the well-known blood-brain barrier dysfunction in the animal model of MS, experimental autoimmune encephalomyelitis, and further show its extent throughout the CNS axis and at the level of the single vessel/capillary.

Highlights

Neurodegeneration is a process by which a progressive loss of neuronal structure and function occurs in many central nervous system (CNS) pathologies; it is generally associated with neuroinflammation
Jumping from 2D to 3D represented an outstanding breakthrough in the general quality of imaging and information obtained, magnetic resonance imaging (MRI), positron emission tomography (PET), and X-ray-computed tomography fail to provide a satisfactory answer to the unmet medico-imaging needs for these diseases
Since in the biomedical samples the refraction effect can be 1000 times higher with respect to the absorption effect, X-ray phase contrast tomography (XPCT) is a unique technique of tomography to image low-absorbing tissues

Summary

Introduction

Neurodegeneration is a process by which a progressive loss of neuronal structure and function occurs in many central nervous system (CNS) pathologies; it is generally associated with neuroinflammation. The research in human neurological diseases has greatly benefited from pre-clinical research in experimental in vitro and in vivo models. In this context, for example, several of the therapeutic approaches that have led in the past 30 years to an increasing number of drugs for multiple sclerosis (MS), such as glatiramer acetate (Ben-Nun et al, 1996) and natalizumab (Yednock et al, 1992) in particular, have been developed in its murine model, experimental autoimmune encephalomyelitis (EAE) (Constantinescu et al, 2011). MRI and PET are limited in terms of spatial resolution, and X-ray computed tomography, whilst providing 3D visualization of X-ray-absorbing tissues, fails in the analysis of soft tissues, such as the CNS

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