Parasagittal dural space and cerebrospinal fluid (CSF) flow across the lifespan in healthy adults

Abstract

Background Recent studies have suggested alternative cerebrospinal fluid (CSF) clearance pathways for brain parenchymal metabolic waste products. One fundamental but relatively under-explored component of these pathways is the anatomic region surrounding the superior sagittal sinus, which has been shown to have relevance to trans-arachnoid molecular passage. This so-called parasagittal dural (PSD) space may play a physiologically significant role as a distal intracranial component of the human glymphatic circuit, yet fundamental gaps persist in our knowledge of how this space changes with normal aging and intracranial bulk fluid transport. Methods We re-parameterized MRI methods to assess CSF circulation in humans using high resolution imaging of the PSD space and phase contrast measures of flow through the cerebral aqueduct to test the hypotheses that volumetric measures of PSD space (1) are directly related to CSF flow (mL/s) through the cerebral aqueduct, and (2) increase with age. Multi-modal 3-Tesla MRI was applied in healthy participants (n = 62; age range = 20–83 years) across the adult lifespan whereby phase contrast assessments of CSF flow through the aqueduct were paired with non-contrasted T1-weighted and T2-weighted MRI for PSD volumetry. PSD volume was extracted using a recently validated neural networks algorithm. Non-parametric regression models were applied to evaluate how PSD volume related to tissue volume and age cross-sectionally, and separately how PSD volume related to CSF flow (significance criteria: two-sided p < 0.05). Results A significant PSD volume enlargement in relation to normal aging (p < 0.001, Spearman’s-$$\rho$$ ρ = 0.6), CSF volume (p < 0.001, Spearman’s-$$\rho$$ ρ = 0.6) and maximum CSF flow through the aqueduct of Sylvius (anterograde and retrograde, p < 0.001) were observed. The elevation in PSD volume was not significantly related to gray or white matter tissue volumes. Findings are consistent with PSD volume increasing with age and bulk CSF flow. Conclusions Findings highlight the feasibility of quantifying PSD volume non-invasively in vivo in humans using machine learning and non-contrast MRI. Additionally, findings demonstrate that PSD volume increases with age and relates to CSF volume and bi-directional flow. Values reported should provide useful normative ranges for how PSD volume adjusts with age, which will serve as a necessary pre-requisite for comparisons to persons with neurodegenerative disorders.

Human parasagittal dura is a potential neuroimmune interface

“…Both increasing age and male sex correlated positively with PSD volume, consistent with earlier findings 25,26 . Patients with AD had less visible intradural channels compared to younger non-AD individuals in a limited post-mortem study 21 .…”

“…The method to segment PSD is not a standardised procedure. Two previous studies 25,26 used different protocols to examine and segment PSD and the resulting volumes are not comparable. However, we used the same scanner, coil, protocol, and segmentation method to achieve comparable results within this study, even if the volumes per se are not directly comparable with other studies.…”

Age-related Decline of Intrinsic Cerebrospinal Fluid Outflow in Healthy Humans Detected with Non-contrast Spin-labeling MR Imaging

“…Two studies have previously identified agerelated increases in the volume of the PSD. 40,41 As such, one hypothesis for our finding is that overall flow metrics are decreased due to increasing volume of the CSF and ISF space, leading to increased stagnation and reduced relative waste clearance. In an another work, Taoka et al demonstrated age-dependent intrinsic decreased diffusivity of the perivascular and perivenous space using diffusion weighted image analysis along the perivascular space (DWI-ALPS), 42 with further studies also demonstrating decreased diffusivity in the setting of mild cognitive impairment and Alzheimer's disease.…”

Choroid plexus perfusion and bulk cerebrospinal fluid flow across the adult lifespan

“…Work from Hett et al focused on quantifying more distal components of the brain's waste clearance system in the parasagittal dural space (PSD), finding that PSD volume increased with age and maximum bidirectional CSF flow through the aqueduct. 41 It is important to note the opposite CSF flow sign convention used between Hett and colleagues and this study. Future work should focus on developing noninvasive methods and post-processing techniques to accurately visualize and quantify remaining components of the brain's waste clearance system.…”