Optimal sequences and sequence parameters for GBCA-enhanced MRI of the glymphatic system: a systematic literature review

Liesje S.P. Mijnders*, Feline W.R. Steup, Mette Lindhout, Paul A.van der Kleij, Wyger M. Brink, Aart J.van der Molen

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review


Background: The glymphatic system (GS) is a recently discovered waste clearance system in the brain. Purpose: To evaluate the most promising magnetic resonance imaging (MRI) sequence(s) and the most optimal sequence parameters for glymphatic MRI (gMRI) 4–24 h after administration of gadolinium-based contrast agent (GBCA). Material and Methods: Multiple literature databases were systematically searched for articles regarding gMRI or MRI of the perilymph in the inner ear until 11 May 2020. All relevant MRI sequence parameters were tabulated for qualitative analysis. Their potential was assessed based on detection of low dose GBCA, primarily measured as signal intensity (SI) ratio. Results: Thirty articles were included in the analysis. Three-dimensional fluid attenuated inversion recovery (3D-FLAIR), 3D Real Inversion Recovery (3D-Real IR), and multiple 3D T1-weighted gradient echo sequences were used. In perilymph, 3D-FLAIR with a TE of at least 400 ms yielded the highest SIRs. In the qualitative analysis of inner ear studies using 3D-FLAIR, TR was in the range of 4400–10,000 ms, TI 1500–2600 ms, refocusing flip angle (rFA) (range 120°–180°), and echo train length (ETL) 23–173. In the gMRI studies, quantitative analysis was not possible. In the qualitative analysis, 3D-FLAIR was used in the majority (8/12) of the studies, usually with TR 4800–9000 ms, TI 1650–2500 ms, TE 311–561 ms, rFA 90°–120°, and ETL 167–278. Conclusion: Long TE 3D-FLAIR is the most promising sequence for detection of low-dose GBCA in the GS. Clinical and/or phantom studies on other MRI parameters are needed for further optimization of gMRI.

Original languageEnglish
Pages (from-to)1324-1332
Number of pages9
JournalActa Radiologica
Issue number10
Publication statusAccepted/In press - 2020
Externally publishedYes


  • cerebrospinal fluid
  • gadolinium
  • Glymphatic system
  • magnetic resonance imaging
  • systematic review


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