Parasagittal Dural Space and Cerebrospinal Fluid (CSF) Changes Across the Lifespan in Healthy Adults: Implications for Glymphatic Flow

Background: Recent studies have suggested the importance of a glymphatic clearance pathway for brain parenchymal metabolic waste products. One fundamental but relatively under-explored component of this pathway is the anatomic region surrounding the superior sagittal sinus, which has been hypothesized to encompass lymphatic vessels. This so-called parasagittal dural (PSD) space likely plays a physiologically significant role at the distal intracranial component of the human glymphatic circuit, yet owing to the relative novelty of this discovery, fundamental gaps persist in our knowledge of how this space changes with normal aging and intracranial bulk fluid transport. Methods: We tested the hypotheses that volumetric magnetic resonance imaging (MRI) measures of the PSD space (i) are directly related to cerebrospinal fluid (CSF) flow at the cerebral aqueduct, and (ii) increase with age. Healthy participants (n=62; age range = 20-83 years) provided informed, written consent and multi-modal 3 Tesla MRI was performed including phase contrast assessment of the CSF flow through the aqueduct of Sylvius, T1-weighted and T2-weighted MRI for tissue volume and PSD assessment. Standard anatomical and cognitive testing were applied to confirm inclusion criteria. 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 flux (significance criteria: two-sided p<0.05). Results: A significant enlargement of PSD volume in relation to normal aging (p<0.001, Spearman’s- =0.6), CSF volume (p<0.001, Spearman’s- =0.6) and bulk CSF flux through the aqueduct of Sylvius (anterograde and retrograde, p<0.001) were observed. The elevation in PSD volume was not significantly related to changes in tissue volume (p=0.11 and p=0.24 for gray and white matter, respectively). Findings are consistent with PSD volume increasing with age and bulk CSF flux.Conclusions: The findings of this study are two folds, first they highlight the feasibility of quantifying PSD volume non-invasively in vivo in humans using machine learning and non-contrast MRI. Second, that PSD volume increases with age, and relates to bulk CSF volume and flux. 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.

Measuring Aqueduct of Sylvius Cerebrospinal Fluid Flow in Multiple Sclerosis Using Different Software

Aqueduct of Sylvius (AoS) cerebrospinal fluid flow can be quantified using phase-contrast (PC) Magnetic Resonance Imaging. The software used for AoS segmentation might affect the PC-derived measures. We analyzed AoS PC data of 30 people with multiple sclerosis and 19 normal controls using three software packages, and estimated cross-sectional area (CSA), average and highest AoS velocity (Vmean and Vmax), flow rate and volume. Our aims were to assess the repeatability and reproducibility of each PC-derived measure obtained with the various software packages, including in terms of group differentiation. All the variables had good repeatability, except the average Vmean, flow rate and volume obtained with one software package. Substantial to perfect agreement was seen when evaluating the overlap between the AoS segmentations obtained with different software packages. No variable was significantly different between software packages, with the exception of Vmean diastolic peak and CSA. Vmax diastolic peak differentiated groups, regardless of the software package. In conclusion, a clinical study should preliminarily evaluate the repeatability in order to interpret its findings. Vmax seemed to be a repeatable and reproducible measure, since the pixel with its value is usually located in the center of the AoS, and is thus unlikely be affected by ROI size.