Investigating cerebrospinal fluid dynamics in neurological disease with positron emission tomography

There has been a lot of recent interest in the fluid systems of the brain and how they mediate the transport of waste and nutrients. The glymphatic system, originally named and described by Iliff and colleagues in 2012,1 has been suggested to play an important role in this area, although a lot about the system remains unknown. The general description of the glymphatic system involves cerebrospinal fluid entering the brain parenchyma via the spaces that surround penetrating arteries. Cerebrospinal fluid combines with interstitial fluid in the parenchyma where waste and other solutes are collected. The combination of cerebrospinal and interstitial fluid is then cleared via a number of clearance pathways.

Various neuroimaging techniques have been used to further describe the anatomy and behaviour of the glymphatic system, most of which utilize magnetic resonance imaging techniques. The KCL molecular imaging group has been working to validate a positron emission tomography (PET) technique to assess brain cerebrospinal fluid dynamics in health and neurological disease. The technique involves quantifying the PET signal in the lateral ventricles and comparing these values between patient and healthy control groups. Work has included applications in Alzheimer’s disease, multiple sclerosis, and traumatic brain injury. Initial results indicate that cerebrospinal fluid dynamics are altered in the diseased groups under investigation compared to controls, as indicated by reduced lateral ventricle signal in patient groups compared to controls.2 Future work aims to incorporate magnetic resonance imaging techniques, including exploring the relationship between structural changes in choroid plexus and parivascular spaces and the lateral ventricle PET signal. We are investigating use of a variety of PET tracers and comparing automated vs. manual segmentation techniques for the lateral ventricle and choroid plexus regions. We hope that this work will contribute to the overall understanding of disease development and progression, as well as with treatment planning as we learn more about how potential treatments may be transported to and circulated in the brain.

The Glymphatic system – Adapted from Schubert et al 2019

References

  1. Iliff, J. J. et al. A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid β. Sci. Transl. Med. 4, 147ra111 (2012).
  2. Schubert, J. J. et al. Dynamic 11 C-PiB PET shows cerebrospinal fluid flow alterations in Alzheimer’s disease and multiple sclerosis. J. Nucl. Med. 60, 1452–1460 (2019).