Share：
Share this content in WeChat
X
[Chinese][PDF]931
• Review •
Current status and challenges of MRI technology in the study of the glymphatic system in the human brain
DU Xiaolan  DUAN Xirui  LI Guochen  TAN Na  ZHOU Xinyan  LIAO Chengde 

Cite this article as: DU X L, DUAN X R, LI G C, et al. Current status and challenges of MRI technology in the study of the glymphatic system in the human brain[J]. Chin J Magn Reson Imaging, 2024, 15(11): 180-184. DOI:10.12015/issn.1674-8034.2024.11.028.


[Abstract] The glymphatic system is a crucial system within the central nervous system responsible for clearing metabolic waste and maintaining fluid homeostasis, and it has recently become a hot topic in neuroscience research. Non-invasive MRI is a commonly used technique to assess the structure and function of the glymphatic system in the human brain. Specific MRI techniques include gadolinium-enhanced dynamic imaging, diffusion tensor imaging analysis, perivascular space imaging, choroid plexus volume analysis, arterial spin labeling, and blood oxygen level-dependent imaging. This article reviews the application and advancements of non-invasive MRI techniques in the study of the glymphatic system in the human brain, detailing their advantages and limitations to provide a reference for further clinical research.
[Keywords] glial lymphatic system；central nervous system；cerebrospinal fluid；magnetic resonance imaging；diffusion tensor imaging analysis along the perivascular space；perivascular space

DU Xiaolan   DUAN Xirui   LI Guochen   TAN Na   ZHOU Xinyan   LIAO Chengde*  

Department of Radiology, Yan'an Hospital of Kunming City, Kunming650051, China

Corresponding author: LIAO C D, E-mail: chengdeliao@qq.com

Conflicts of interest   None.

Received  2024-08-01
Accepted  2024-11-08
DOI: 10.12015/issn.1674-8034.2024.11.028
Cite this article as: DU X L, DUAN X R, LI G C, et al. Current status and challenges of MRI technology in the study of the glymphatic system in the human brain[J]. Chin J Magn Reson Imaging, 2024, 15(11): 180-184. DOI:10.12015/issn.1674-8034.2024.11.028.

[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 [2024-08-01]. https://www.science.org/doi/10.1126/scitranslmed.3003748. DOI: 10.1126/scitranslmed.3003748.
[2]
EIDE P K, RINGSTAD G. MRI with intrathecal MRI gadolinium contrast medium administration: a possible method to assess glymphatic function in human brain[J/OL]. Acta Radiol Open, 2015, 4(11): 205846011560963 [2024-08-01]. https://pmc.ncbi.nlm.nih.gov/articles/PMC4652208. DOI: 10.1177/2058460115609635.
[3]
REHMAN M U, SEHAR N, RASOOL I, et al. Glymphatic pathway: An emerging perspective in the pathophysiology of neurodegenerative diseases[J/OL]. Int J Geriatr Psychiatry, 2024, 39(6): e6104 [2024-08-01]. DOI: 10.1002/gps.6104.
[4]
RASMUSSEN M K, MESTRE H, NEDERGAARD M. Fluid transport in the brain[J]. Physiol Rev, 2022, 102(2): 1025-1151. DOI: 10.1152/physrev.00031.2020.
[5]
GAN Y, THOMAS J H, KELLEY D H. Gaps in the wall of a perivascular space act as valves to produce a directed flow of cerebrospinal fluid: a hoop-stress model[J/OL]. J R Soc Interface, 2024, 21(213): 20230659 [2024-08-01]. https://pubmed.ncbi.nlm.nih.gov/38565158/. DOI: 10.1098/rsif.2023.0659.
[6]
BRAUN M, SEVAO M, KEIL S A, et al. Macroscopic changes in aquaporin-4 underlie blast traumatic brain injury-related impairment in glymphatic function[J]. Brain, 2024, 147(6): 2214-2229. DOI: 10.1093/brain/awae065.
[7]
DING Z, FAN X, ZHANG Y, et al. The glymphatic system: a new perspective on brain diseases[J/OL]. Front Aging Neurosci, 2023, 15: 1179988 [2024-08-01]. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/37396658/. DOI: 10.3389/fnagi.2023.1179988.
[8]
JACOBSEN H H, SANDELL T, JØRSTAD Ø K, et al. In vivo evidence for impaired glymphatic function in the visual pathway of patients with normal pressure hydrocephalus[J/OL]. Invest Ophthalmol Vis Sci, 2020, 61(13): 24 [2024-08-01]. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/33201186/. DOI: 10.1167/iovs.61.13.24.
[9]
MUCCIO M, CHU D, MINKOFF L, et al. Upright versus supine MRI: effects of body position on craniocervical CSF flow[J/OL]. Fluids Barriers CNS, 2021, 18(1): 61 [2024-08-01]. https://pmc.ncbi.nlm.nih.gov/articles/PMC8710028/. DOI: 10.1186/s12987-021-00296-7.
[10]
ZHU Y, WANG G, KOLLURU C, et al. Transport pathways and kinetics of cerebrospinal fluid tracers in mouse brain observed by dynamic contrast-enhanced MRI[J/OL]. Sci Rep, 2023, 13(1): 13882 [2024-08-01]. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/37620371/. DOI: 10.1038/s41598-023-40896-x.
[11]
SPERRE A, KARSRUD I, RODUM A H S, et al. Prospective safety study of intrathecal gadobutrol in different doses[J]. AJNR Am J Neuroradiol, 2023, 44(5): 511-516. DOI: 10.3174/ajnr.A7841.
[12]
ROVIRA À, QUATTROCCHI C C. Safe and optimized use of gadolinium-based contrast agents in neuroimaging[J]. Eur Radiol, 2023, 34(7): 4567-4569. DOI: 10.1007/s00330-023-10456-y.
[13]
DEIKE-HOFMANN K, REUTER J, HAASE R, et al. Glymphatic pathway of gadolinium-based contrast agents through the brain: Overlooked and misinterpreted[J]. Invest Radiol, 2019, 54(4): 229-237. DOI: 10.1097/RLI.0000000000000533.
[14]
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.
[15]
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.
[16]
ZHANG W, ZHOU Y, WANG J, et al. Glymphatic clearance function in patients with cerebral small vessel disease[J/OL]. NeuroImage, 2021, 238: 118257 [2024-08-01]. https://linkinghub.elsevier.com/retrieve/pii/S1053-8119(21)00534-6. DOI: 10.1016/j.neuroimage.2021.118257.
[17]
MENG J C, SHEN M Q, LU Y L, et al. Correlation of glymphatic system abnormalities with Parkinson's disease progression: a clinical study based on non-invasive fMRI[J/OL]. J Neurol, 2023 [2024-08-01]. https://link.springer.com/10.1007/s00415-023-12004-6. DOI: 10.1007/s00415-023-12004-6.
[18]
PARK J H, BAE Y J, KIM J S, et al. Glymphatic system evaluation using diffusion tensor imaging in patients with traumatic brain injury[J]. Neuroradiology, 2023, 65(3): 551-557. DOI: 10.1007/s00234-022-03073-x.
[19]
TOH C H, SIOW T Y. Glymphatic Dysfunction in patients with ischemic stroke[J/OL]. Front Aging Neurosci, 2021, 13: 756249 [2024-08-01]. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/34819849/. DOI: 10.3389/fnagi.2021.756249.
[20]
SIOW T Y, TOH C H, HSU J L, et al. Association of sleep, neuropsychological performance, and gray matter volume with glymphatic function in community-dwelling older adults[J/OL]. Neurology, 2022, 98(8): e829-e838 [2024-08-01]. https://www.neurology.org/doi/10.1212/WNL.0000000000013215. DOI: 10.1212/WNL.0000000000013215.
[21]
RINGSTAD G. Glymphatic imaging: a critical look at the DTI-ALPS index[J]. Neuroradiology, 2024, 66(2): 157-160. DOI: 10.1007/s00234-023-03270-2.
[22]
KOUNDAL S, ELKIN R, NADEEM S, et al. Optimal mass transport with lagrangian workflow reveals advective and diffusion driven solute transport in the glymphatic system[J/OL]. Sci Rep, 2020, 10(1): 1990 [2024-08-01]. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/32029859/. DOI: 10.1038/s41598-020-59045-9.
[23]
TAOKA T, ITO R, NAKAMICHI R, et al. Reproducibility of diffusion tensor image analysis along the perivascular space (DTI-ALPS) for evaluating interstitial fluid diffusivity and glymphatic function: CHanges in Alps index on Multiple conditiON acquIsition eXperiment (CHAMONIX) study[J]. Jpn J Radiol, 2022, 40(2): 147-158. DOI: 10.1007/s11604-021-01187-5.
[24]
HARRISON I F, SIOW B, AKILO A B, et al. Non-invasive imaging of CSF-mediated brain clearance pathways via assessment of perivascular fluid movement with diffusion tensor MRI[J/OL]. Elife, 2018, 7: e34028 [2024-08-01]. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/30063207/. DOI: 10.7554/eLife.34028.
[25]
PETITCLERC L, HIRSCHLER L, WELLS J A, et al. Ultra-long-TE arterial spin labeling reveals rapid and brain-wide blood-to-CSF water transport in humans[J/OL]. NeuroImage, 2021, 245: 118755 [2024-08-01]. https://linkinghub.elsevier.com/retrieve/pii/S1053-8119(21)01027-2. DOI: 10.1016/j.neuroimage.2021.118755.
[26]
HAN G, ZHOU Y, ZHANG K, et al. Age- and time-of-day dependence of glymphatic function in the human brain measured via two diffusion MRI methods[J/OL]. Front Aging Neurosci, 2023, 15: 1173221 [2024-08-01]. https://doi.org/10.3389/fnagi.2023.1173221. DOI: 10.3389/fnagi.2023.1173221.
[27]
LIN S, LIN X, CHEN S, et al. Association of MRI indexes of the perivascular space network and cognitive impairment in patients with obstructive sleep apnea[J/OL]. Radiology, 2024, 311(3): e232274 [2024-08-01]. https://pubmed.ncbi.nlm.nih.gov/38888481/. DOI: 10.1148/radiol.232274.
[28]
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 [2024-05-16]. https://www.neurology.org/doi/10.1212/WNL.0000000000201300. DOI: 10.1212/WNL.0000000000201300.
[29]
DUERING M, BIESSELS G J, BRODTMANN A, et al. Neuroimaging standards for research into small vessel disease—advances since 2013[J]. Lancet Neurol, 2023, 22(7): 602-618. DOI: 10.1016/S1474-4422(23)00131-X.
[30]
SACCHI L, ARCARO M, CARANDINI T, et al. Association between enlarged perivascular spaces and cerebrospinal fluid aquaporin-4 and tau levels: report from a memory clinic[J/OL]. Front Aging Neurosci, 2023, 15: 1191714 [2024-08-01]. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/37547746/. DOI: 10.3389/fnagi.2023.1191714.
[31]
YUAN Z, LI W, TANG H, et al. Enlarged perivascular spaces in patients with migraine: a case–control study based on 3T MRI[J]. Ann Clin Transl Neurol, 2023, 10(7): 1160-1169. DOI: 10.1002/acn3.51798.
[32]
BEST J G, AMBLER G, WILSON D, et al. Clinical associations and prognostic value of MRI-visible perivascular spaces in patients with ischemic stroke or TIA: A pooled analysis[J/OL]. Neurology, 2024, 102(1): e207795 [2024-08-01]. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/38165371/. DOI: 10.1212/WNL.0000000000207795.
[33]
MOSES J, SINCLAIR B, LAW M, et al. Automated methods for detecting and quantitation of enlarged perivascular spaces on MRI[J]. J Magn Reson Imaging, 2023, 57(1): 11-24. DOI: 10.1002/jmri.28369.
[34]
HONG H, TOZER D J, MARKUS H S. Relationship of perivascular space markers with incident dementia in cerebral small vessel disease[J]. Stroke, 2024, 55(4): 1032-1040. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/38465597/. DOI: 10.1161/STROKEAHA.123.045857.
[35]
WAYMONT J M J, VALDÉS HERNÁNDEZ M del C, BERNAL J, et al. Systematic review and meta-analysis of automated methods for quantifying enlarged perivascular spaces in the brain[J/OL]. NeuroImage, 2024, 297: 120685 [2024-08-01]. https://linkinghub.elsevier.com/retrieve/pii/S1053-8119(24)00180-0. DOI: 10.1016/j.neuroimage.2024.120685.
[36]
SATO Y, NAKAJIMA S, SHIRAGA N, et al. Three-dimensional multi-scale line filter for segmentation and visualization of curvilinear structures in medical images[J]. Med Image Anal, 1998, 2(2): 143-168. DOI: 10.1016/S1361-8415(98)80009-1.
[37]
BALLERINI L, LOVREGLIO R, VALDÉS HERNÁNDEZ M del C, et al. Perivascular spaces segmentation in brain MRI using optimal 3D filtering[J/OL]. Sci Rep, 2018, 8(1): 2132 [2024-08-01]. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/29391404/. DOI: 10.1038/s41598-018-19781-5.
[38]
VALDÉS HERNÁNDEZ M del C, DUARTE COELLO R, XU W, et al. Influence of threshold selection and image sequence in in-vivo segmentation of enlarged perivascular spaces[J/OL]. J Neurosci Methods, 2024, 403: 110037 [2024-08-01]. https://linkinghub.elsevier.com/retrieve/pii/S0165-0270(23)00256-X. DOI: 10.1016/j.jneumeth.2023.110037.
[39]
LAN H, LYNCH K M, CUSTER R, et al. Weakly supervised perivascular spaces segmentation with salient guidance of Frangi filter[J]. Magn Reson Med, 2023, 89(6): 2419-2431. DOI: 10.1002/mrm.29593.
[40]
CHAE S, YANG E, MOON W J, et al. Deep cascade of convolutional neural networks for quantification of enlarged perivascular spaces in the basal ganglia in magnetic resonance imaging[J/OL]. Diagnostics, 2024, 14(14): 1504 [2024-08-01]. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/39061641/. DOI: 10.3390/diagnostics14141504.
[41]
WILLIAMSON B J, KHANDWALA V, WANG D, et al. Automated grading of enlarged perivascular spaces in clinical imaging data of an acute stroke cohort using an interpretable, 3D deep learning framework[J/OL]. Sci Rep, 2022, 12(1): 788 [2024-08-01]. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/35039524/. DOI: 10.1038/s41598-021-04287-4.
[42]
GUEYE M, PREZIOSA P, RAMIREZ G A, et al. Choroid plexus and perivascular space enlargement in neuropsychiatric systemic lupus erythematosus[J]. Mol Psychiatry, 2024, 29(2): 359-368. DOI: 10.1038/s41380-023-02332-4.
[43]
JEONG S H, PARK C J, CHA J, et al. Choroid plexus volume, amyloid burden, and cognition in the Alzheimer's disease continuum[J/OL]. Aging Dis, 2024 [2024-08-01]. https://www.aginganddisease.org/EN/10.14336/AD.2024.0118. DOI: 10.14336/AD.2024.0118.
[44]
EISMA J J, MCKNIGHT C D, HETT K, et al. Deep learning segmentation of the choroid plexus from structural magnetic resonance imaging (MRI): validation and normative ranges across the adult lifespan[J/OL]. Fluids Barriers CNS, 2024, 21(1): 21 [2024-08-01]. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/38424598/. DOI: 10.1186/s12987-024-00525-9.
[45]
JOSEPH C R, LIM J K, GROHOL B N, et al. Identifying delay in glymphatic clearance of labeled protons post-acute head trauma utilizing 3D ASL MRI (arterial spin labeling): a pilot study[J/OL]. Sci Rep, 2024, 14(1): 6188 [2024-08-01]. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/38485759/. DOI: 10.1038/s41598-024-56236-6.
[46]
JOSEPH C R, KREILACH A, REYNA V A, et al. Utilizing reduced labeled proton clearance to identify preclinical Alzheimer disease with 3D ASL MRI[J]. Case Rep Neurol, 2023, 15(1): 177-186. DOI: 10.1159/000530980.
[47]
RAITAMAA L, KAUTTO J, TUUNANEN J, et al. Association of body-mass index with physiological brain pulsations across adulthood -a fast fMRI study[J]. Int J Obes, 2024, 48(7): 1011-1018. DOI: 10.1038/s41366-024-01515-5.
[48]
WILLIAMS S D, SETZER B, FULTZ N E, et al. Neural activity induced by sensory stimulation can drive large-scale cerebrospinal fluid flow during wakefulness in humans[J/OL]. PLoS Biol, 2023, 21(3): e3002035 [2024-08-01]. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/36996009/. DOI: 10.1371/journal.pbio.3002035.
[49]
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.
[50]
LIU X. Decoupling between brain activity and cerebrospinal fluid movement in neurological disorders[J/OL]. J Magn Reson Imaging, 2023: jmri.29148 [2024-08-01]. https://doi.org/10.1002/jmri.29148. DOI: 10.1002/jmri.29148.
[51]
ALSHUHRI M S, GALLAGHER L, WORK L M, et al. Direct imaging of glymphatic transport using H217O MRI[J/OL]. JCI Insight, 2021, 6(10): e141159 [2024-08-01]. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/33857020/. DOI: 10.1172/jci.insight.141159.
[52]
HE Y, GUAN J, LAI L, et al. Imaging of brain clearance pathways via MRI assessment of the glymphatic system[J]. Aging, 2023, 15(24): 14945-14956. DOI: 10.18632/aging.205322.

PREV Progress of functional magnetic resonance imaging technology in explaining the mechanism of acupuncture acupuncture treatment of ischemic stroke
NEXT Advances in structural and functional imaging in asymptomatic carotid artery stenosis
  


LINK


Tel & Fax: +8610-67113815    E-mail: editor@cjmri.cn