In radiology textbooks, perivascular spaces (PVS) are described as non-enhancing structures after intravenous administration of gadolinium based contrast agent (IV-Gd). PVS can exist throughout the brain, but are most frequently seen in the inferior third of the basal ganglia near the anterior commissure (AC). We routinely perform MR imaging for the assessment of endolymphatic hydrops 4 hours after single dose IV-Gd. ^{1, 2} We occasionally noticed that the PVS would show high signals on heavily T2-weighted 3D-FLAIR (hT2-FL) images obtained 4 hours after single dose IV-Gd. Slight enhancement of CSF on hT2-FL acquired 4 hours after IV-Gd had been reported in healthy subjects with normal renal function;³ however, enhancement of PVS in healthy subjects had not been reported. Enhancement of PVS, though, had been reported in a patient with renal insufficiency.⁴ The PVS represent an entrance point to the glymphatic system, a recently discovered macroscopic waste clearance system of the brain.⁵

The purpose of this study was to retrospectively evaluate the contrast enhancement of PVS both prior to and 4 hours after IV-Gd in subjects that underwent MRI.

In 8 healthy men (ages: 29-53) and 14 patients with suspected endolymphatic hydrops (7 men, 7 women; ages: 27-78), MR cisternography (MRC) and hT2-FL had been obtained at 3T prior to and 4 hours after single dose IV-Gd. No subjects had renal insufficiency. Slice thickness, field of view, matrix size and slice position were identical in both MRC and hT2-FL. Voxel size was 0.5 x 0.5 x 1.0 mm³. On the axial MRC parallel to the AC-PC line, 1 cm circular regions of interest (ROI) were drawn on the MRC image centered on the PVS bilaterally in both the basal ganglia and center of thalamus for signal reference. The 3 mm diameter ROIs were set within the bilateral CSF spaces of the ambient cistern. The ROIs were copied onto the hT2-FL. Signal intensity of the ROI was measured on the hT2-FL.

The signal intensity ratio (SIR) was defined as: SIR (PVS) = signal intensity (SI) of PVS / SI of thalamus, SIR (CSF) = SI of CSF/ SI of thalamus. The average of the bilateral values was used for evaluation.

The signal enhancement ratio (SER) of the PVS was given as SER= SIR of post/ SIR of pre. SIR (CSF), SIR (PVS) and SI of the thalamus were compared prior to and 4 hours post IV-Gd using the student’s t-test. The SER of volunteers and patients were compared using Mann-Whitney’s test.

The SIR (CSF) increased significantly from 1.14+/-0.38 to 3.00+/-1.15 after IV-Gd administration (p<0.01) and SIR (PVS) increased significantly from 1.28+/-0.34 to 2.68+/-1.54 after IV-Gd (p<0.01). No significant difference was found between the SI of the thalamus prior to or 4 hours after IV-Gd. SER of the PVS showed no significant difference between volunteers and patients.Visually, some PVS signals are higher than that of the CSF (Fig). Simple penetration of CSF into the interstitial fluid of the PVS cannot explain this increased PVS signal. This suggests the absorption of water in the PVS or secretion of gadolinium into the PVS. Thus, the active function of the PVS could be investigated using MR imaging in the future. The findings of the present study suggest that the blood-CSF barrier and CSF-Interstitial fluid (IF) barrier might be more leaky than the blood-brain barrier. Deposition of gadolinium in brain parenchyma such as in the dentate nucleus and globus pallidus is a recent hot topic in the field of MRI.⁶ Gadolinium might penetrate into brain parenchyma through the CSF and PVS (i.e. the glymphatic system). In recent studies, the glymphatic system has been suggested to play an important role in the accumulation of beta amyloid in the brain.⁵ The results of the present study might open the door to examination of the glymphatic system in humans using MRI.Enhancement of PVS 4 hours after IV-Gd was confirmed in human subjects without renal insufficiency. This might represent the first steps using MR imaging to evaluate the glymphatic system in humans.