Confirmation of Age-dependence in the Leakage of Contrast Medium around the Cortical Veins into Cerebrospinal Fluid after Intravenous Administration of Gadolinium-based Contrast Agent

Abstract

It has been reported previously that intravenously administered gadolinium-based contrast agent (GBCA) leaks into the subarachnoid space around the cortical veins at 4 h after injection in all old people over 37 years, but not in younger people up to 37 years of age in 3D-real IR images. The purpose of this study was to investigate whether there was a strict threshold of 37 years of age for the leakage of the GBCA into the subarachnoid space. Methods: The subjects included 190 patients, that were scanned for 3D-real IR images at 4 hours after intravenous injection of GBCA as a diagnostic test for endolymphatic hydrops. The patient's age ranged from 14 to 81 years. Two experienced neuroradiologists evaluated the images to determine whether the GBCA leakage around the cortical veins was positive or negative. Any discrepancies between the two observers were discussed and a consensus was obtained. A Mann-Whitney U test and receiver operating characteristic (ROC) curve analysis were used to compare the positive and the negative group and to set the age cutoff value for the prediction of GBCA leakage. Results: The GBCA leakage around the cortical veins was negative in 35 patients and positive in 155 patients. The average age was 33 ± 11 years in the negative group, and 55 ± 12 years in the positive group (P < 0.01). In the ROC analysis for the age and leakage of the GBCA, an area under the curve was 0.905 and the cutoff age was 37.317 years (sensitivity of 0.942 and specificity of 0.771). Conclusion: Intravenously administered GBCA leaks into the subarachnoid space around the cortical veins in most patients over 37 years of age. However, it should be noted that it can be found occasionally in patients under 37 years of age.

The Glymphatic System: A Review of the Challenges in Visualizing its Structure and Function with MR Imaging

“…Taken together the recent findings in MR imaging, studies regarding the parasagittal dura, either by intrathecal or intravenous administration of GBCA, 86,88,90,100 indicate that the parasagittal dura might serve a filtering function for ISF at the outlet of the glymphatic system in the CNS to systemic venous circulation and the lymphatic system. Aging and deterioration of this filtering function might be key to reveal the mystery of neurodegenerative diseases.…”

“…85 The longitudinal assessment of 3D-real IR images after the intravenous administration of GBCA can help analyze the morphological microstructure of the downstream region and understand the relationship with glymphatic system function. Furthermore, the degree of leakage of GBCA from the subpial space around the cortical veins to the surrounding subarachnoid space observed after intravenous administration of GBCA was shown to be significantly accelerated by aging 86,87 (Fig. 2).…”

“…Meanwhile, it is important in the study of the glymphatic system to elucidate the detailed anatomy of the connections from the perivenous space around the veins in the brain, to the subpial space around the cortical veins, and finally, to meningeal lymphatic vessels. [84][85][86][87] Also, it is crucial to reveal the relationship between cyst formation in the vicinity of these connections and the stagnation of ISF flow. 90 These studies will help us to understand the glymphatic system and the kinetics of drugs in the CNS.…”

Imaging for central nervous system (CNS) interstitial fluidopathy: disorders with impaired interstitial fluid dynamics

“…At approximately 4 h after intravenous injection of GBCA, transport of GBCA into the perivascular space at the base of the brain can be observed on heavily T2-weighted fluid-attenuated inversion recovery images [ 18 – 24 ]. On delayed imaging after injection, intravenously administered GBCAs demonstrate leakage from the cortical veins, which increase with age [ 25 , 26 ]. Additionally, the space between the pial sheath surrounding the cortical veins and venous wall was shown as enhanced, which appears as connected to the meningeal lymphatics that run along the superior sagittal sinus [ 27 ].…”

Evaluating the Effect of Arterial Pulsation on Cerebrospinal Fluid Motion in the Sylvian Fissure of Patients with Middle Cerebral Artery Occlusion Using Low b-value Diffusion-weighted Imaging

“…Since the introduction of the Glymphatic system by Iliff et al, 1 several studies have been published on the dynamics between cerebrospinal fluid (CSF) and interstitial fluid (ISF). [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] However, there are several unsolved questions about the dynamics between CSF and ISF; one of them is the mechanism behind the pulsatile motion of CSF. Multiple studies have been published on the CSF dynamics within the brain parenchyma.…”