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Advances in the clinical application of MRI in the glymphatic system of the brain
SHEN Wenzhuo  LI Yonggang 

Cite this article as: SHEN W Z, LI Y G. Advances in the clinical application of MRI in the glymphatic system of the brain[J]. Chin J Magn Reson Imaging, 2024, 15(3): 212-217. DOI:10.12015/issn.1674-8034.2024.03.035.


[Abstract] The glymphatic system (GS) is a recently discovered mechanism of brain waste elimination, and its disruption is strongly associated to a variety of neurological diseases. The GS has been widely studied using MRI because of its advantages of high soft tissue resolution and multimodal imaging. Providing a substantial basis for the research of the kinetics and structure of the GS and related diseases, MRI contributes as the principal imaging technique. The author will present an overview of the GS and highlight recent advances in MRI of the GS and their application in the investigation of neurological diseases, aiming to stress the importance of glymphatic dysfunction in neuroimaging investigations and provide help for the diagnosis, treatment and prognosis of neurological diseases related to the GS.
[Keywords] glymphatic system；magnetic resonance imaging；diffusion tensor imaging；nervous system disease

SHEN Wenzhuo1   LI Yonggang2*  

1 College of Basic Medical Science, China Three Gorges University, Yichang 443002, China

2 Department of Radiology, the First Affiliated Hospital of Soochow University, Suzhou 215006, China

Corresponding author: LI Y G, E-mail: liyonggang224@163.com

Conflicts of interest   None.

Received  2023-07-03
Accepted  2024-02-23
DOI: 10.12015/issn.1674-8034.2024.03.035
Cite this article as: SHEN W Z, LI Y G. Advances in the clinical application of MRI in the glymphatic system of the brain[J]. Chin J Magn Reson Imaging, 2024, 15(3): 212-217. DOI:10.12015/issn.1674-8034.2024.03.035.

[1]
ILIFF J J, WANG M, LIAO Y, et al. A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid β[J/OL]. Sci Transl Med, 2012, 4(147): 147ra111 [2023-09-24]. https://pubmed.ncbi.nlm.nih.gov/22896675/. DOI: 10.1126/scitranslmed.3003748.
[2]
LI G, CAO Y, TANG X, et al. The meningeal lymphatic vessels and the glymphatic system: Potential therapeutic targets in neurological disorders[J]. J Cereb Blood Flow Metab, 2022, 42(8): 1364-1382. DOI: 10.1177/0271678x221098145.
[3]
GOUVEIA-FREITAS K, BASTOS-LEITE A J. Perivascular spaces and brain waste clearance systems: Relevance for neurodegenerative and cerebrovascular pathology[J]. Neuroradiology, 2021, 63(10): 1581-1597. DOI: 10.1007/s00234-021-02718-7.
[4]
MATHIISEN T M, LEHRE K P, DANBOLT N C, et al. The perivascular astroglial sheath provides a complete covering of the brain microvessels: An electron microscopic 3D reconstruction[J]. Glia, 2010, 58(9): 1094-1103. DOI: 10.1002/glia.20990.
[5]
ISHIDA K, YAMADA K, NISHIYAMA R, et al. Glymphatic system clears extracellular tau and protects from tau aggregation and neurodegeneration[J/OL]. J Exp Med, 2022, 219(3): e20211275 [2023-09-24]. https://pubmed.ncbi.nlm.nih.gov/35212707/. DOI: 10.1084/jem.20211275.
[6]
LOUVEAU A, SMIRNOV I, KEYES T J, et al. Structural and functional features of central nervous system lymphatic vessels[J]. Nature, 2015, 523(7560): 337-341. DOI: 10.1038/nature14432.
[7]
ABSINTA M, HA S K, NAIR G, et al. Human and nonhuman primate meninges harbor lymphatic vessels that can be visualized noninvasively by MRI[J/OL]. eLife, 2017, 6: e29738 [2023-09-24]. https://pubmed.ncbi.nlm.nih.gov/28971799/. DOI: 10.7554/eLife.29738.
[8]
NAGANAWA S, ITO R, TAOKA T, et al. The space between the pial sheath and the cortical venous wall may connect to the meningeal lymphatics[J]. Magn Reson Med Sci, 2020, 19(1): 1-4. DOI: 10.2463/mrms.bc.2019-0099.
[9]
KLOSTRANEC J M, VUCEVIC D, BHATIA K D, et al. Current concepts in intracranial interstitial fluid transport and the glymphatic system: Part Ⅱ-imaging techniques and clinical applications[J]. Radiology, 2021, 301(3): 516-532. DOI: 10.1148/radiol.2021204088.
[10]
ILIFF J J, LEE H, YU M, et al. Brain-wide pathway for waste clearance captured by contrast-enhanced MRI[J]. J Clin Invest, 2013, 123(3): 1299-1309. DOI: 10.1172/jci67677.
[11]
LIN L, HAO X, LI C, et al. Impaired glymphatic system in secondary degeneration areas after ischemic stroke in rats[J/OL]. J Stroke Cerebrovasc Dis, 2020, 29(7): 104828 [2023-09-24]. https://pubmed.ncbi.nlm.nih.gov/32404284/. DOI: 10.1016/j.jstrokecerebrovasdis.2020.104828.
[12]
XUE Y, LIU X, KOUNDAL S, et al. In vivo T1 mapping for quantifying glymphatic system transport and cervical lymph node drainage[J/OL]. Sci Rep, 2020, 10(1): 14592 [2023-09-24]. https://pubmed.ncbi.nlm.nih.gov/32884041/. DOI: 10.1038/s41598-020-71582-x.
[13]
RINGSTAD G, VALNES L M, DALE A M, et al. Brain-wide glymphatic enhancement and clearance in humans assessed with MRI[J/OL]. JCI Insight, 2018, 3(13): e121537 [2023-09-24]. https://pubmed.ncbi.nlm.nih.gov/29997300/. DOI: 10.1172/jci.insight.121537.
[14]
DYKE J P, XU H S, VERMA A, et al. Mri characterization of early cns transport kinetics post intrathecal gadolinium injection: Trends of subarachnoid and parenchymal distribution in healthy volunteers[J]. Clin Imaging, 2020, 68: 1-6. DOI: 10.1016/j.clinimag.2020.04.043.
[15]
NAGANAWA S, NAKANE T, KAWAI H, et al. Gd-based contrast enhancement of the perivascular spaces in the basal ganglia[J]. Magn Reson Med Sci, 2017, 16(1): 61-65. DOI: 10.2463/mrms.mp.2016-0039.
[16]
TAOKA T, JOST G, FRENZEL T, et al. Impact of the glymphatic system on the kinetic and distribution of gadodiamide in the rat brain: Observations by dynamic mri and effect of circadian rhythm on tissue gadolinium concentrations[J]. Invest Radiol, 2018, 53(9): 529-534. DOI: 10.1097/rli.0000000000000473.
[17]
LEE S, YOO R E, CHOI S H, et al. Contrast-enhanced MRI T1 mapping for quantitative evaluation of putative dynamic glymphatic activity in the human brain in sleep-wake states[J]. Radiology, 2021, 300(3): 661-668. DOI: 10.1148/radiol.2021203784.
[18]
BERGER F, KUBIK-HUCH R A, NIEMANN T, et al. Gadolinium distribution in cerebrospinal fluid after administration of a gadolinium-based mr contrast agent in humans[J]. Radiology, 2018, 288(3): 703-709. DOI: 10.1148/radiol.2018171829.
[19]
MIJNDERS L S, STEUP F W, LINDHOUT M, et al. Optimal sequences and sequence parameters for gbca-enhanced MRI of the glymphatic system: A systematic literature review[J]. Acta Radiol, 2021, 62(10): 1324-1332. DOI: 10.1177/0284185120969950.
[20]
KUDO K, HARADA T, KAMEDA H, et al. Indirect proton mr imaging and kinetic analysis of (17)o-labeled water tracer in the brain[J]. Magn Reson Med Sci, 2018, 17(3): 223-230. DOI: 10.2463/mrms.mp.2017-0094.
[21]
DEBACKER C, DJEMAI B, CIOBANU L, et al. Diffusion MRI reveals in vivo and non-invasively changes in astrocyte function induced by an aquaporin-4 inhibitor[J/OL]. PLoS One, 2020, 15(5): e0229702 [2023-09-24]. https://pubmed.ncbi.nlm.nih.gov/32413082/. DOI: 10.1371/journal.pone.0229702.
[22]
TAOKA T, MASUTANI Y, KAWAI H, et al. Evaluation of glymphatic system activity with the diffusion MR technique: Diffusion tensor image analysis along the perivascular space (DTI-ALPS) in Alzheimer's disease cases[J]. Jpn J Radiol, 2017, 35(4): 172-178. DOI: 10.1007/s11604-017-0617-z.
[23]
CHEN M, CHEN C, SHEN Z, et al. Extracellular ph is a biomarker enabling detection of breast cancer and liver cancer using cest MRI[J]. Oncotarget, 2017, 8(28): 45759-45767. DOI: 10.18632/oncotarget.17404.
[24]
JABEHDAR MARALANI P, CHAN R W, LAM W W, et al. Chemical exchange saturation transfer MRI: What neuro-oncology clinicians need to know[J/OL]. Technol Cancer Res Treat, 2023, 22: 15330338231208613 [2023-09-24]. https://pubmed.ncbi.nlm.nih.gov/37872686/. DOI: 10.1177/15330338231208613.
[25]
CHEN Y, DAI Z, FAN R, et al. Glymphatic system visualized by chemical-exchange-saturation-transfer magnetic resonance imaging[J]. ACS Chem Neurosci, 2020, 11(13): 1978-1984. DOI: 10.1021/acschemneuro.0c00222.
[26]
XU L, LAI L, WEN Y, et al. Angiopep-2, an MRI biomarker, dynamically monitors amyloid deposition in early alzheimer's disease[J]. ACS Chem Neurosci, 2023, 14(2): 226-234. DOI: 10.1021/acschemneuro.2c00513.
[27]
WANG Z, SONG Z, ZHOU C, et al. Reduced coupling of global brain function and cerebrospinal fluid dynamics in parkinson's disease[J]. J Cereb Blood Flow Metab, 2023, 43(8): 1328-1339. DOI: 10.1177/0271678x231164337.
[28]
HAN F, CHEN J, BELKIN-ROSEN A, et al. Reduced coupling between cerebrospinal fluid flow and global brain activity is linked to Alzheimer disease-related pathology[J/OL]. PLoS Biol, 2021, 19(6): e3001233 [2023-09-24]. https://pubmed.ncbi.nlm.nih.gov/34061820/. DOI: 10.1371/journal.pbio.3001233.
[29]
YAO X Y, GAO M C, BAI S W, et al. Enlarged perivascular spaces, neuroinflammation and neurological dysfunction in nmosd patients[J/OL]. Front Immunol, 2022, 13: 966781 [2023-09-24]. https://pubmed.ncbi.nlm.nih.gov/36248814/. DOI: 10.3389/fimmu.2022.966781.
[30]
ZHANG H, WEI W, ZHAO M, et al. Interaction between Aβ and tau in the pathogenesis of alzheimer's disease[J]. Int J Biol Sci, 2021, 17(9): 2181-2192. DOI: 10.7150/ijbs.57078.
[31]
IGARASHI H, SUZUKI Y, KWEE I L, et al. Water influx into cerebrospinal fluid is significantly reduced in senile plaque bearing transgenic mice, supporting beta-amyloid clearance hypothesis of Alzheimer's disease[J]. Neurol Res, 2014, 36(12): 1094-1098. DOI: 10.1179/1743132814y.0000000434.
[32]
NEHRA G, BAUER B, HARTZ A M S. Blood-brain barrier leakage in alzheimer's disease: From discovery to clinical relevance[J/OL]. Pharmacol Ther, 2022, 234: 108119 [2023-09-24]. https://pubmed.ncbi.nlm.nih.gov/35108575/. DOI: 10.1016/j.pharmthera.2022.108119.
[33]
KAMAGATA K, ANDICA C, TAKABAYASHI K, et al. Association of mri indices of glymphatic system with amyloid deposition and cognition in mild cognitive impairment and Alzheimer disease[J/OL]. Neurology, 2022, 99(24): e2648-e2660 [2023-09-24]. https://pubmed.ncbi.nlm.nih.gov/36123122/. DOI: 10.1212/wnl.0000000000201300.
[34]
REEVES B C, KARIMY J K, KUNDISHORA A J, et al. Glymphatic system impairment in Alzheimer's disease and idiopathic normal pressure hydrocephalus[J]. Trends Mol Med, 2020, 26(3): 285-295. DOI: 10.1016/j.molmed.2019.11.008.
[35]
RINGSTAD G, VATNEHOL S A S, EIDE P K. Glymphatic MRI in idiopathic normal pressure hydrocephalus[J]. Brain, 2017, 140(10): 2691-2705. DOI: 10.1093/brain/awx191.
[36]
GEORGIOPOULOS C, TISELL A, HOLMGREN R T, et al. Noninvasive assessment of glymphatic dysfunction in idiopathic normal pressure hydrocephalus with diffusion tensor imaging[J]. J Neurosurg, 2023: 1-9. DOI: 10.3171/2023.6.Jns23260.
[37]
SI X, GUO T, WANG Z, et al. Neuroimaging evidence of glymphatic system dysfunction in possible rem sleep behavior disorder and parkinson's disease[J/OL]. NPJ Parkinsons Dis, 2022, 8(1): 54 [2023-09-24]. https://pubmed.ncbi.nlm.nih.gov/35487930/. DOI: 10.1038/s41531-022-00316-9.
[38]
SHEN T, YUE Y, BA F, et al. Diffusion along perivascular spaces as marker for impairment of glymphatic system in parkinson's disease[J/OL]. NPJ Parkinsons Dis, 2022, 8(1): 174 [2023-09-24]. https://pubmed.ncbi.nlm.nih.gov/36543809/. DOI: 10.1038/s41531-022-00437-1.
[39]
CAROTENUTO A, CACCIAGUERRA L, PAGANI E, et al. Glymphatic system impairment in multiple sclerosis: Relation with brain damage and disability[J]. Brain, 2022, 145(8): 2785-2795. DOI: 10.1093/brain/awab454.
[40]
GOULAY R, FLAMENT J, GAUBERTI M, et al. Subarachnoid hemorrhage severely impairs brain parenchymal cerebrospinal fluid circulation in nonhuman primate[J]. Stroke, 2017, 48(8): 2301-2305. DOI: 10.1161/strokeaha.117.017014.
[41]
TOH C H, SIOW T Y. Glymphatic dysfunction in patients with ischemic stroke[J/OL]. Front Aging Neurosci, 2021, 13: 756249 [2023-09-24]. https://pubmed.ncbi.nlm.nih.gov/34819849/. DOI: 10.3389/fnagi.2021.756249.
[42]
ZHANG W, ZHOU Y, WANG J, et al. Glymphatic clearance function in patients with cerebral small vessel disease[J/OL]. Neuroimage, 2021, 238: 118257 [2023-09-24]. https://pubmed.ncbi.nlm.nih.gov/34118396/. DOI: 10.1016/j.neuroimage.2021.118257.
[43]
XU D, ZHOU J, MEI H, et al. Impediment of cerebrospinal fluid drainage through glymphatic system in glioma[J/OL]. Front Oncol, 2021, 11: 790821 [2023-09-24]. https://pubmed.ncbi.nlm.nih.gov/35083148/. DOI: 10.3389/fonc.2021.790821.
[44]
KAUR J, DING G, ZHANG L, et al. Imaging glymphatic response to glioblastoma[J/OL]. Cancer Imaging, 2023, 23(1): 107 [2023-09-24]. https://pubmed.ncbi.nlm.nih.gov/37904254/. DOI: 10.1186/s40644-023-00628-w.
[45]
ZHAO P, LE Z, LIU L, et al. Therapeutic delivery to the brain via the lymphatic vasculature[J]. Nano Lett, 2020, 20(7): 5415-5420. DOI: 10.1021/acs.nanolett.0c01806.
[46]
KIM J, LEE D A, LEE H J, et al. Glymphatic system dysfunction in patients with cluster headache[J/OL]. Brain Behav, 2022, 12(6): e2631 [2023-09-24]. https://pubmed.ncbi.nlm.nih.gov/35582786/. DOI: 10.1002/brb3.2631.
[47]
LEE D A, LEE H J, PARK K M. Normal glymphatic system function in patients with migraine: A pilot study[J]. Headache, 2022, 62(6): 718-725. DOI: 10.1111/head.14320.

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