Using multi-modal MRI techniques to measure glymphatic function in-vivo

Background: The brain lacks conventional lymphatic vessels, however it has its own macroscopic waste clearance system, which is called the glymphatic system. It utilizes perivascular tunnels surrounded by astroglia cells and promote cerebrospinal-interstitial fluid exchange. Rodent studies have suggested that glymphatic system is active during sleep. Imaging the glymphatic system without a contrast agent is a challenging task. Aims: I propose that glymphatic system related changes can be detected with non-invasive MRI techniques sensitive to fluid motion (diffusion weighted MRI) and changes in intra-, extracellular volume fraction (sodium MRI) by comparing acquisitions obtained during wake and sleep. Methods: 21 healthy young participants (6 females, 22.3 ± 3.2 years) were scanned in two separate sessions, after a night of normal sleep and after a full night of sleep deprivation. In the sleep deprivation session participants also received 10mg of Zolpidem to increase the chance of falling asleep in the scanner. Multiple MRI modalities were acquired: sodium, high resolution anatomical, diffusion weighted and arterial spin labelling (ASL) images. Results and discussion: Physiological recordings and questionnaires indicated that participants were able to achieve sleep in the scanner. ASL indicated reduced cerebral blood flow (CBF) during sleep session, which was in line published literature. Sodium MRI indicated increased sodium signal during sleep, which might be due to glymphatic system related expansion in extracellular space. Although, sodium data is likely to be compromised by technical issues. Significant changes in diffusion were observed during sleep (decrease in diffusion kurtosis), which was in line with the hypothesized increase glymphatic function during sleep. Conclusion: My study highlighted the issues with acquiring and quantifying sodium MRI data during sleep. In future studies one should acquire higher order diffusion weighted data and measure diffusion kurtosis as it shows better sensitivity to glymphatic system related changes than classical diffusion measures.