MRI coupled with clinically-applicable iron oxide nanoparticles reveals choroid plexus involvement in a murine model of neuroinflammation

Violaine Hubert,Fabien Chauveau,Elodie Ong,Emmanuelle Canet-Soulas,Marlène Wiart,Camille Amaz,Chloé Dumot

doi:10.1038/s41598-019-46566-1

Abstract

Choroid plexus (ChPs) are involved in the early inflammatory response that occurs in many brain disorders. However, the activation of immune cells within the ChPs in response to neuroinflammation is still largely unexplored in-vivo. There is therefore a crucial need for developing imaging tool that would allow the non-invasive monitoring of ChP involvement in these diseases. Magnetic resonance imaging (MRI) coupled with superparamagnetic particles of iron oxide (SPIO) is a minimally invasive technique allowing to track phagocytic cells in inflammatory diseases. Our aim was to investigate the potential of ultrasmall SPIO (USPIO)-enhanced MRI to monitor ChP involvement in-vivo in a mouse model of neuroinflammation obtained by intraperitoneal administration of lipopolysaccharide. Using high resolution MRI, we identified marked USPIO-related signal drops in the ChPs of animals with neuroinflammation compared to controls. We confirmed these results quantitatively using a 4-points grading system. Ex-vivo analysis confirmed USPIO accumulation within the ChP stroma and their uptake by immune cells. We validated the translational potential of our approach using the clinically-applicable USPIO Ferumoxytol. MR imaging of USPIO accumulation within the ChPs may serve as an imaging biomarker to study ChP involvement in neuroinflammatory disorders that could be applied in a straightforward way in clinical practice.

Highlights

Neuroinflammation is known to be a common factor of many central nervous system (CNS) pathologies, often associated with worsened outcome
Using in-vivo Magnetic resonance imaging (MRI), we identified extensive ultrasmall superparamagnetic particles of iron oxides (SPIOs) (USPIO)-related signal drops in the choroid plexus (ChPs) of animals with neuroinflammation compared to controls
These results suggest that minimally invasive MR imaging of USPIOs accumulation within the ChPs may serve as an imaging biomarker of ChPs involvement in presence of neuroinflammation

Summary

Introduction

Neuroinflammation is known to be a common factor of many central nervous system (CNS) pathologies, often associated with worsened outcome. Millward and coll[14,15], have shown that this technique allowed to monitor the early involvement of ChPs in a mouse model of multiple sclerosis (experimental auto-immune encephalomyelitis or EAE) These results were obtained using very small SPIOs (VSOP, hydrodynamic diameter range: 6–9 nm) that are similar in terms of physicochemical properties to VSOP C18414. Ferumoxytol-enhanced MRI has been shown to allow the imaging of immune cells trafficking across brain parenchyma in rodent models of multiple sclerosis[19] and cerebral tumors[20]. These works did not examine ChPs involvement. To demonstrate the translational potential of our approach, we replicated the experiments using Ferumoxytol (hydrodynamic diameter range: 17–31 nm)

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