Target audience

- Scientists studying brain clearance and neurodegeneration
- Clinicians with interests in neurodegeneration and neuroimaging

Objectives

- Learn key techniques for imaging fluid flow in the human brain
- Identify mechanisms governing brain clearance

Syllabus

Toxic waste products such as beta-amyloid must be removed from the brain via its waste clearance systems to maintain healthy function. This educational lecture will focus on the following key topics in emerging imaging techniques for assessing glymphatic function, and its potential relevance to neurodegeneration.
We first focus on MR techniques for imaging macroscopic CSF flow through the ventricles, aqueduct, and other large regions. Macroscopic CSF flow can be visualized via phase contrast imaging, which enables quantitative readouts, or fast fMRI, which enables simultaneous blood oxygenation level dependent measures. These imaging techniques have shown that CSF flow dynamics are pulsatile and coupled to blood flow. In addition, CSF flow dynamics increase dramatically during low arousal states such as sleep, consistent with rodent studies showing higher clearance rates during sleep.
At a microscopic scale, clearance relies on fluid flow through perivascular spaces. The anatomy of perivascular spaces can be visualized in clinical T1 or T2 MRI scans. Ultra-high field imaging can detect smaller perivascular spaces. Perivascular space size and number increases in aging, and is linked to multiple neurodegenerative disorders including Alzheimer’s disease, cerebral amyloid angiopathy, and Parkinson’s disease.
In addition to measuring fluid flow, waste clearance can be imaged directly using intrathecal contrast agents, followed by MR imaging to track tracer progress throughout the brain. Rodent studies first developed this method to spatially map clearance throughout the brain. Recent human studies have implemented this approach and have demonstrated that clearance decreases with age and increases in sleep. Translation to clinical populations is an area of ongoing investigation.
This lecture will address each of these topics with a particular focus on recent developments in MR imaging techniques, and recent findings in patient populations when available. It will additionally discuss the mechanisms driving brain clearance and open questions on their consequences for brain function, and their disruption in neurodegeneration.

Conclusion

Emerging MR techniques enable noninvasive or minimally invasive imaging of glymphatic function at multiple spatial scales. These methods have identified signatures of disrupted clearance in aging and in neurodegeneration, and point to vascular integrity and healthy sleep as key modulating factors. Ongoing research aims to understand the underlying mechanisms and continue to translate these imaging techniques to clinical applications.

Acknowledgements

No acknowledgement found.

References

No reference found.