Direction and magnitude of cerebrospinal fluid flow vary substantially across central nervous system diseases

Abstract

Background Several central nervous system diseases are associated with disturbed cerebrospinal fluid (CSF) flow patterns and have typically been characterized in vivo by phase-contrast magnetic resonance imaging (MRI). This technique is, however, limited by its applicability in space and time. Phase-contrast MRI has yet to be compared directly with CSF tracer enhanced imaging, which can be considered gold standard for assessing long-term CSF flow dynamics within the intracranial compartment. Methods Here, we studied patients with various CSF disorders and compared MRI biomarkers of CSF space anatomy and phase-contrast MRI at level of the aqueduct and cranio-cervical junction with dynamic intrathecal contrast-enhanced MRI using the contrast agent gadobutrol as CSF tracer. Tracer enrichment of cerebral ventricles was graded 0–4 by visual assessment. An intracranial pressure (ICP) score was used as surrogate marker of intracranial compliance. Results The study included 94 patients and disclosed marked variation of CSF flow measures across disease categories. The grade of supra-aqueductal reflux of tracer varied, with strong reflux (grades 3–4) in half of patients. Ventricular tracer reflux correlated with stroke volume and aqueductal CSF pressure gradient. CSF flow in the cerebral aqueduct was retrograde (from 4th to 3rd ventricle) in one third of patients, with estimated CSF net flow volume about 1.0 L/24 h. In the cranio-cervical junction, net flow was cranially directed in 78% patients, with estimated CSF net flow volume about 4.7 L/24 h. Conclusions The present observations provide in vivo quantitative evidence for substantial variation in direction and magnitude of CSF flow, with re-direction of aqueductal flow in communicating hydrocephalus, and significant extra-cranial CSF production. The grading of ventricular reflux of tracer shows promise as a clinical useful method to assess CSF flow pattern disturbances in patients. Graphic abstract

Intrathecal Contrast-Enhanced Magnetic Resonance Imaging of Cerebrospinal Fluid Dynamics and Glymphatic Enhancement in Idiopathic Normal Pressure Hydrocephalus

“…Estimation of tracer enrichment within ventricles using FreeSurfer software showed that tracer enrichment closely follows the categorical grading of reflux. Phase-contrast MRI supports the net retrograde aqueductal flow of CSF in iNPH ( 17 , 50 , 51 ). Others also reported net retrograde CSF flow within the cerebral aqueduct in patients with communicating hydrocephalus ( 50 , 52 – 56 ).…”

“…Others also reported net retrograde CSF flow within the cerebral aqueduct in patients with communicating hydrocephalus ( 50 , 52 – 56 ). On the contrary, other disease categories of CSF disturbance, e.g., idiopathic intracranial hypertension and spontaneous intracranial hypotension or brain cysts, demonstrated no ventricular reflux of tracer ( 17 ). Likewise, individuals without CSF disturbance showed no ventricular tracer reflux ( 17 ), or net retrograde aqueductal flow ( 51 ).…”

“…(b) We have previously introduced a grading of ventricular reflux of CSF tracer as a marker of pathological CSF redistribution ( 17 , 18 ). From T1 weighted images, ventricular reflux was graded at 24 h after intrathecal MRI contrast agent administration as follows: Grade 0: No supra-aqueductal reflux.…”

“…Adding to the established imaging biomarkers, we recently proposed functional imaging biomarkers for iNPH disease, based on imaging of CSF redistribution (degree of ventricular reflux), and imaging of CSF and glymphatic enhancement ( 17 , 18 ). The association between neurodegeneration and impaired clearance of toxic metabolic by-products from CSF and the brain has recently emerged as a possible crucial mechanism behind iNPH disease ( 18 ).…”

Immediate Impact of Yogic Breathing on Pulsatile Cerebrospinal Fluid Dynamics

“…Recent studies have implicated 1) forced inspiration in humans 12 , 2) cardiac pulsation with some contribution from respiration in humans 37 , and 3) cardiac pulsation in rodents 7 , as major drivers of CSF flow. Recent work by extension has also examined the magnitude, direction, and sensitivity of CSF movement to respiratory performances and locations [14][15][16]45,46 , and more recently, low-frequency oscillations (e.g., vasomotion; ~ <0.1 Hz) 9,47,48 including during sleep 9 . For instance, in a recent study conducted while subjects sleeping in an MRI scanner, Fultz and colleagues 9 demonstrated that CSF flow oscillations during non-rapid eye movement (NREM) sleep were (5.52 dB) larger and slower (0.05 Hz vasomotion) compared to wakefulness (0.25 Hz respiratory), and suggested that increased pulsatile CSF dynamics during sleep may alter the brain's waste clearance due to increased mixing and diffusion 2,49 .…”