https://doi.org/10.1073/pnas.2407246121
Abstract
The glymphatic pathway was defined in rodents as a network of perivascular spaces (PVSs) that facilitates organized distribution of cerebrospinal fluid (CSF) into the brain parenchyma. To date, perivascular CSF and cerebral interstitial fluid exchange has not been shown in humans. Using intrathecal gadolinium contrast-enhanced MRI, we show that contrast-enhanced CSF moves through the PVS into the parenchyma, supporting the existence of a glymphatic pathway in humans.
The glymphatic pathway was described as a network of perivascular spaces (PVS) that facilitates the organized movement of cerebrospinal fluid (CSF) between the subarachnoid space and brain parenchyma (1). CSF mixes with interstitial fluid, promoting clearance of soluble by-products from the central nervous system. This is suspected to be impaired in sleep dysfunction, traumatic brain injury, and Alzheimer’s disease (2). Pioneering glymphatic studies in rodents showed CSF tracer flow through the subarachnoid space and into brain parenchyma along periarterial spaces (1, 3). Human intrathecal contrast-enhanced MRI similarly demonstrated parenchymal contrast enhancement in a centripetal pattern from the subarachnoid space, providing early evidence for human glymphatic function (4, 5). The PVS is postulated to be involved in this process (4, 6), yet perivascular CSF tracer transport has not been observed in humans. This is a proof-of-principle study demonstrating that intrathecal gadolinium-based contrast agents allow visualization of perivascular glymphatic flow in humans.
Results
Five neurosurgical patients (3 males) underwent transnasal transsphenoidal approach (n = 4) or frontotemporal craniotomy (n = 1; 8 centimeter craniotomy) for tumor resection, aged 29 to 65 y. Each subject required CSF diversion (range: 1.5 to 5.5 d). Subjects received intrathecal gadolinium-based contrast and underwent two delayed contrast-enhanced MRIs. No further CSF diversion occurred. There were no adverse effects. Contrast was best visualized on the T2/FLAIR sequence and observed at the first MRI scan in all 5 subjects. Contrast transport was variable between subjects.
In four subjects, MRIs were obtained at 24 h (timepoint 1, range: 21.8 to 24.8 h) and 48 h (timepoint 2, range: 43.6 to 48.8 h) after contrast. At 24 h, contrast circulated in the basal cisterns, posterior fossa, and superiorly toward the convexities, but had not reached the vertex. At 48 h, contrast reached the vertex in two subjects and diffused out of the subarachnoid space with traces in the cerebellar folia in the other two subjects. Additionally, one subject had MRIs at 12 and 24 h, revealing contrast in the posterior fossa, frontal, and ventral temporal subarachnoid spaces and along the posterior cerebral artery at 12 h, persisting at a lower intensity at 24 h.
MRI-visible PVS (MV-PVS) are characteristically hypointense on T1 and T2/FLAIR and hyperintense on T2 images (Fig. 1 A–F). Postcontrast, both hyperintense and hypointense MV-PVSs were observed in the white matter/centrum semiovale on T2/FLAIR (Fig. 1 C and G). Some T2/FLAIR hyperintense MV-PVSs were hypointense on T1, whereas others were isointense or not visible on T1. MV-PVSs hypointense on both T1 and T2/FLAIR appeared in regions without contrast in the overlying subarachnoid space, evidenced by CSF signal suppression on T2/FLAIR. At timepoint 2, some MV-PVS decreased in intensity, while others increased (Fig. 1 D and H). New enhancement of initially nonenhancing MV-PVSs was also observed at timepoint 2 (Fig. 1 D and H). MV-PVS signal intensity was negatively correlated with the distance between each MV-PVS and the contrast-containing subarachnoid space (Spearman’s rho = −0.54, P < 0.001; Fig. 2 A and B).
No comments:
Post a Comment
Note: Only a member of this blog may post a comment.