In vivo imaging of central nervous system fluid spaces using synchrotron radiation-based micro computed tomography

TL;DR

This paper introduces a novel in vivo imaging technique using synchrotron radiation-based micro CT to visualize mouse CNS fluid spaces at micrometer resolution across the whole brain, enabling dynamic studies of CSF distribution and movement.

Contribution

The study presents a new in vivo imaging method that combines high resolution and whole-brain coverage, filling a gap between existing microscopy and MRI techniques.

Findings

Achieved 6.3 μm resolution whole-brain imaging in mice.

Observed CSF contrast agent distribution over time.

Quantified choroid plexus movement.

Abstract

Current approaches to in vivo imaging of the mouse central nervous system (CNS) do not offer a combination of micrometer resolution and a whole-brain field of view. To address this limitation, we introduce an approach based on synchrotron radiation-based hard X-ray micro computed tomography (SR$\mu$CT). We performed intravital SR$\mu$CT acquisitions of mouse CNS fluid spaces at three synchrotron radiation facilities. Imaging was conducted on both anesthetized free-breathing and ventilated animals, with and without retrospective cardiac gating. We achieved whole-brain imaging at 6.3 $\mu$m uniform voxel size, observed the distribution of cerebrospinal fluid (CSF) contrast agent over time and quantified choroid plexus movement. SR$\mu$CT bridges the gap between multiphoton microscopy and magnetic resonance imaging, offering dynamic imaging with micrometer-scale resolution and whole-organ field of view. Intravital SR$\mu$CT will play a crucial role in validating and integrating hypotheses on CSF dynamics and solute transport by providing unique data that cannot be acquired otherwise.