Do enlarged white matter perivascular spaces reflect brain clearance dysfunction? Insights from intrathecal
Vanja Cengija1, Per Kristian Eide2,3, Geir Ringstad4,5
1Oslo University Hospital, Oslo, Norway. vancen@ous-hf.no.
Purpose:
Visible perivascular spaces of cerebral white matter at magnetic resonance imaging (MRI) were in several studies proposed to be an integral part of brain-wide perivascular clearance pathways, and their enlargement could therefore serve as markers of perivascular clearance dysfunction. We studied whether MRI-visible perivascular spaces in subcortical white matter communicate with subarachnoid cerebrospinal fluid (CSF).
Methods:
MRI-visible perivascular spaces of the basal ganglia served as controls. Intrathecal 0.5 mmol gadobutrol was utilized as CSF tracer, and T1-weighted MRI was performed before, and at multiple time points after (3, 6, 24 and 48 h) injection. Perivascular spaces with diameter ≥ 2 mm were included in the analysis, and a circular region of interest was placed manually within one perivascular space and in adjacent brain parenchyma of each region.
Results:
The study included 27 symptomatic individuals undergoing clinical work-up of various CSF circulation disorders, but in whom no treatable condition was found. Perivascular spaces of both white matter and basal ganglia enhanced with intrathecal gadobutrol, confirming CSF exchange with perivascular spaces. While perivascular spaces of basal ganglia enhanced most with peak at 6 h (233.2% [34.9 to 431.5%]) (p < 0.01), coinciding with peak enhancement in subarachnoid CSF, perivascular spaces of white matter enhanced less and more slowly with peak at 48 h (159.1% [37.9 to 280.3%]) (p < 0.01).
Conclusions:
The various degrees of CSF exchange with MRI-visible subcortical perivascular spaces suggest these may be dilated for different reasons, therefore questioning their validity as markers of perivascular clearance function.
Insights
Enlarged perivascular spaces in white matter show cerebrospinal fluid (CSF) exchange, but at a slower rate than basal ganglia spaces. This suggests varying dilation reasons, questioning their use as markers for perivascular clearance dysfunction.
Area of Science:
- Neuroimaging
- Cerebrospinal Fluid Dynamics
- White Matter Hyperintensities
Background:
- Visible perivascular spaces (PVS) on MRI are linked to brain clearance pathways.
- Enlarged PVS may indicate impaired perivascular clearance.
- The communication of white matter PVS with the subarachnoid space is not fully understood.
Purpose of the Study:
- To investigate the communication between MRI-visible PVS in subcortical white matter and the subarachnoid cerebrospinal fluid (CSF).
- To evaluate the potential of enlarged PVS as markers of perivascular clearance dysfunction.
Main Methods:
- Utilized intrathecal gadobutrol as a CSF tracer in 27 individuals.
- Performed T1-weighted MRI at multiple time points post-injection (3, 6, 24, 48 hours).
- Analyzed PVS (diameter ≥ 2 mm) in white matter and basal ganglia (control).
Main Results:
- Both white matter and basal ganglia PVS showed enhancement with intrathecal gadobutrol, confirming CSF exchange.
- Basal ganglia PVS exhibited peak enhancement at 6 hours, coinciding with subarachnoid CSF.
- White matter PVS showed less and slower enhancement, peaking at 48 hours.
Conclusions:
- The differential rates of CSF exchange in PVS suggest varying causes for their dilation.
- The validity of MRI-visible subcortical PVS as universal markers for perivascular clearance dysfunction is questioned.
- Further research is needed to understand the specific mechanisms behind PVS enlargement.
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