Abstract

Current theories suggest that waste solutes are cleared from the brain via cerebrospinal fluid (CSF) flow, driven by pressure pulsations of possibly both cardiac and respiratory origin. In this study, we explored the importance of respiratory versus cardiac pressure gradients for CSF flow within one of the main conduits of the brain, the cerebral aqueduct. We obtained overnight intracranial pressure measurements from two different locations in 10 idiopathic normal pressure hydrocephalus (iNPH) patients. The resulting pressure gradients were analyzed with respect to cardiac and respiratory frequencies and amplitudes (182,000 cardiac and 48,000 respiratory cycles). Pressure gradients were used to compute CSF flow in simplified and patient-specific models of the aqueduct. The average ratio between cardiac over respiratory flow volume was 0.21 ± 0.09, even though the corresponding ratio between the pressure gradient amplitudes was 2.85 ± 1.06. The cardiac cycle was 0.25 ± 0.04 times the length of the respiratory cycle, allowing the respiratory pressure gradient to build considerable momentum despite its small magnitude. No significant differences in pressure gradient pulsations were found in the sleeping versus awake state. Pressure gradients underlying CSF flow in the cerebral aqueduct are dominated by cardiac pulsations, but induce CSF flow volumes dominated by respiration.

Highlights

  • The interplay between intracranial pressure (ICP) and cerebrospinal fluid (CSF) flow plays an important role in e.g. cerebral homeostasis[1], neurological conditions such as idiopathic normal pressure hydrocephalus[2], and cerebral metabolic waste clearance[3]

  • There is evidence that net CSF flow in the cerebral aqueduct is confounded by the respiratory cycle[15,19], questioning the validity of net CSF flow measured with cardiac gated PC-MRI

  • A total of 502 accepted 6-minute windows, consisting of approximately 182,000 cardiac cycles and 48,000 respiratory cycles were retrieved from the patients

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Summary

Introduction

The interplay between intracranial pressure (ICP) and cerebrospinal fluid (CSF) flow plays an important role in e.g. cerebral homeostasis[1], neurological conditions such as idiopathic normal pressure hydrocephalus (iNPH)[2], and cerebral metabolic waste clearance[3]. There is evidence that net CSF flow in the cerebral aqueduct is confounded by the respiratory cycle[15,19], questioning the validity of net CSF flow measured with cardiac gated PC-MRI. It is well-established that the dominating component of the ICP is the pressure pulsation of the cardiac cycle while the respiratory pulsation is considerably smaller[20]. The classical view of the third circulation as well as recent findings of net CSF flow within the cerebral aqueduct[14] suggest the existence of a static transmantle pressure gradient in addition to a pulsatile component. Stenosed aqueducts may have pressure drops that are orders of magnitude higher[28]

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