Glymphatic imaging using MRI

Taoka, Toshiaki; Naganawa, Shinji

doi:10.1002/jmri.26892

Cited by 127 publications

(166 citation statements)

References 65 publications

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“…The GBCA leaks from the impaired portion of the BBB, the peripheral part of the cranial nerves, choroid plexus, circumventricular organs, and subarachnoid vessels. [2][3][4][5]14,20,25,27 It has been reported that the CSF signal intensity in the lateral ventricles and the prepontine cistern was decreased at 24 h compared to 3 h post-administration of GBCA. 1 Decreased enhancement in the CSF at 24 h is consistent with the results of the present study.…”

Section: Csf Enhancementmentioning

confidence: 99%

“…2,3,21,22 The glymphatic system is the waste clearance system of the brain and has attracted much attention from a wide range of investigators. [23][24][25] Establishment of a method for the evaluation of the glymphatic system is a hot research topic in the neuroscience field. 26 Currently, the distribution patterns of intravenously administered GBCA in various fluid spaces of humans are under intense investigation as the first step of the glymphatic system and as a measure of BBB integrity.…”

Section: Introductionmentioning

confidence: 99%

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Intracranial Distribution of Intravenously Administered Gadolinium-based Contrast Agent over a Period of 24 Hours: Evaluation with 3D-real IR Imaging and MR Fingerprinting

et al. 2021

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Purpose: To evaluate the feasibility for the detection of slight contrast effects after intravenous administration of single dose gadolinium-based contrast agent (IV-SD-GBCA), the time course of the GBCA distribution up to 24 h was examined in various fluid spaces and brain parenchyma using 3D-real IR imaging and MR fingerprinting (MRF). Methods:Twenty-four patients with a suspicion of endolymphatic hydrops were scanned at pre-administration and at 10 min, 4 and 24 h post-IV-SD-GBCA. 3D-real IR images and MRF at the level of the internal auditory canal were obtained. The signal intensity on the 3D-real IR image of the cerebrospinal fluid (CSF) in the cerebellopontine angle cistern (CPA), Sylvian fissure (Syl), lateral ventricle (LV), and cochlear perilymph (CPL) was measured. The T 1 and T 2 values of cerebellar gray (GM) and white matter (WM) were measured using MRF. Each averaged value at the various time points was compared using an analysis of variance.

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Section: Csf Enhancementmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Intracranial Distribution of Intravenously Administered Gadolinium-based Contrast Agent over a Period of 24 Hours: Evaluation with 3D-real IR Imaging and MR Fingerprinting

et al. 2021

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“…Several studies have underlined the potential of Diffusion MRI to investigate the glymphatic system [7,22–24] and the ADC has been proposed as a biomarker of AQP gene expression, as earlier studies have demonstrated that the ADC obtained with high b values was correlated with the amount of increasing expression of AQP1 in glioblastoma cell lines [37]. In this study, we have investigated whether two diffusion MRI markers, Sindex and sADC, could detect changes in astrocyte activity induced by a pharmacological challenge.…”

Section: Discussionmentioning

confidence: 99%

“…This clearance system has been evidenced initially using fluorescent tracers and 2-photon microscopy in rodents [1], however MRI offers a more versatile approach. MRI studies have relied on the intrathecal or intravenous injections of gadolinium-based contrast agents (GBCAs) as tracers [7,17].…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, alternative methods are needed to investigate the glymphatic system non-invasively, especially in the human brain. Fluid-dynamics driven and BOLD fast MRI have the potential to evaluate CSF pulsations in the ventricles and hemodynamics [11,20,21], while IVIM and diffusion MRI have been shown as promising methods for the evaluation of the ISF [7,22–24].…”

Section: Introductionmentioning

confidence: 99%

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Diffusion MRI reveals in vivo and non-invasively changes in astrocyte function induced by an aquaporin-4 inhibitor

Debacker¹,

Djemaï²,

Tsurugizawa³

et al. 2020

Preprint

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21The Glymphatic System (GS) has been proposed as a mechanism to clear brain tissue from waste. Its 22 dysfunction might lead to several brain pathologies, including the Alzheimer's disease. A key 23 component of the GS and brain tissue water circulation is the astrocyte which is regulated by 24 acquaporin4 (AQP4), a membrane-bound water channel on the astrocytic end-feet. Here we 25 investigated the potential of diffusion MRI to monitor astrocyte activity in a mouse brain model 26 through the inhibition of AQP4 channels with TGN-020. Upon TGN-020 injection, we observed a 27 significant decrease in the Sindex, a diffusion marker of tissue microstructure, and a significant increase 28 of the water diffusion coefficient (sADC) in cerebral cortex and hippocampus compared to saline 29 injection. These results indicate the suitability of diffusion MRI to monitor astrocytic activity in vivo 30 and non-invasively. 31

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Noninvasive Characterization of Human Glymphatics and Meningeal Lymphatics in an in vivo Model of Blood–Brain Barrier Leakage

Lirng

Ling

et al. 2020

Annals of Neurology

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Objective To evaluate human glymphatics and meningeal lymphatics noninvasively. Methods This prospective study implemented 3‐dimensional (3D) isotropic contrast‐enhanced T2 fluid‐attenuated inversion recovery (CE‐T2‐FLAIR) imaging with a 3T magnetic resonance machine to study cerebral glymphatics and meningeal lymphatics in patients with reversible cerebral vasoconstriction syndrome (RCVS) with (n = 92) or without (n = 90) blood–brain barrier (BBB) disruption and a diseased control group with cluster headache (n = 35). The contrast agent gadobutrol (0.2mmol/kg [0.2ml/kg]) was administered intravenously in all study subjects. Results In total, 217 patients (182 RCVS, 35 cluster headache) were analyzed and separated into 2 groups based on the presence or absence of visible gadolinium (Gd) leakage. Para‐arterial tracer enrichment was clearly depicted in those with overt BBB disruption, while paravenous and parasinus meningeal contrast enrichment was evident in both groups. Paravenous and parasinus contrast enrichment remained in RCVS patients in the remission stage and in cluster headache patients, suggesting that these meningeal lymphatic channels were universal anatomical structures rather than being phase‐ or condition‐specific. Additionally, we demonstrated nodular leptomeningeal enhancement in 32.3% of participants, which might represent potential lymphatic reservoirs. Four selected RCVS patients who received consecutive contrasted 3D isotropic FLAIR imaging after gadobutrol administration showed that the Gd persisted for at least 54 minutes and was completely cleared within 18 hours. Interpretation This large‐scale in vivo study successfully demonstrated the putative human para‐arterial glymphatic transports and meningeal lymphatics by clear depiction of para‐arterial, parasinus, and paravenous meningeal contrast enrichment using high‐resolution 3D isotropic CE‐T2‐FLAIR imaging noninvasively; this technique may serve as a basis for further studies to delineate clinical relevance of glymphatic clearance. ANN NEUROL 2021;89:111–124

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Glymphatic imaging using MRI

Cited by 127 publications

References 65 publications

Intracranial Distribution of Intravenously Administered Gadolinium-based Contrast Agent over a Period of 24 Hours: Evaluation with 3D-real IR Imaging and MR Fingerprinting

Intracranial Distribution of Intravenously Administered Gadolinium-based Contrast Agent over a Period of 24 Hours: Evaluation with 3D-real IR Imaging and MR Fingerprinting

Diffusion MRI reveals in vivo and non-invasively changes in astrocyte function induced by an aquaporin-4 inhibitor

Noninvasive Characterization of Human Glymphatics and Meningeal Lymphatics in an in vivo Model of Blood–Brain Barrier Leakage

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