The Regulation of Cerebral Spinal Fluid Flow and Its Relevance to the Glymphatic System

Abstract

Purpose of review: The glymphatic system is a relatively new concept that has been associated with regulation of cerebrospinal fluid (CSF), as well as brain waste clearance. Novel techniques to study glymphatic dysfunction have in turn prompted a reassessment of brain physiology and underlying elements of neurological disease. This review incorporates a contemporary imaging perspective focused on understanding the regulation of CSF flow, thus expanding the putative clinical relevance of this system and the relationships between CSF flow and glymphatic function.

Recent findings: MR imaging studies, especially those that employ intrathecal gadolinium contrast, have identified potentially new pathways regulating CSF production, absorption, and clearance. These studies, when viewed in the context of more historical anatomic descriptors of CSF production and absorption, provide a more robust description of CSF physiology and waste clearance. CSF production and resorption are under-investigated and could be related to various pathophysiologic processes in neurodegeneration. Anatomically based clinical exemplars of CSF clearance are discussed. Future studies should focus on linking glymphatic functionality with neurological disease.

Keywords: Arachnoid granulations; Glymphatic; Neurodegeneration; Neuroimaging; Perivascular space.

Fig. 1. Anatomical Points of Interest in CSF Circulation and Glymphatic Flow.

Important points of interest labeled: a) Cross section of the superior sagittal sinus region, showing the superior sagittal sinus, parasagittal dural space (PDS), and arachnoid granulations b) Anatomy of an arachnoid granulation, where subarachnoid flow of CSF reabsorbs into dural venous sinuses c) Cranial nerves, showing location of CSF flow around cranial nerves (i.e. cribiform plate, CNI) d) Cerebral aqueduct and 4^th ventricle, detailing the path of CSF flow from the third ventricle to the central canal and subarachnoid space e) Axial cross-sectional anatomy of the spinal canal with the relationship of the lymphatic vessels to the thecal sac, epidural space and spinal nerve roots. f) Cervical lymphatic flow, detailing the lymph vessels and nodes. g) Choroid Plexus, predominantly located in the lateral ventricles, where CSF is produced and secreted in the ventricular system.

Fig. 2. MRI Imaging of the Choroid Plexus.

A) T1, B) FLAIR and C) Arterial Spin Labeled MR images at the level of the atria of the lateral ventricles in a 23-year-old female. Blood flow within the choroid plexus (arrows) can be reliably measured using the arterial spin labeling technique.