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Brain-wide glymphatic enhancement and clearance in humans assessed with MRI
Ringstad G, Valnes LM, Dale AM, Pripp AH, Vatnehol SS, Emblem KE, Mardal KA, Eide PK.. JCI insight, 2018-07-12
Topic: Brain proteins, microglia and lab models
Plain-language summary
To what extent does the subarachnoid cerebrospinal fluid (CSF) compartment communicate directly with the extravascular compartment of human brain tissue? Interconnection between the subarachnoid CSF compartment and brain perivascular spaces is reported in some animal studies, but with controversy, and in vivo CSF tracer studies in humans are lacking. In the present work, we examined the distribution of a CSF tracer in the human brain by MRI over a prolonged time span. For this, we included a reference cohort, representing close to healthy individuals, and a cohort of patients with dementia and anticipated compromise of CSF circulation (idiopathic normal pressure hydrocephalus). The MRI contrast agent gadobutrol, which is confined to the extravascular brain compartment by the intact blood-brain barrier, was used as a CSF tracer. Standardized T1-weighted MRI scans were performed before and after intrathecal gadobutrol at defined time points, including at 24 hours, 48 hours, and 4 weeks. All MRI scans were aligned and brain regions were segmented using FreeSurfer, and changes in normalized T1 signals over time were quantified as percentage change from baseline. The study provides in vivo evidence of access to all human brain subregions of a substance administered intrathecally. Clearance of the tracer substance was delayed in the dementia cohort. These observations translate previous findings in animal studies into humans and open new prospects concerning intrathecal treatment regimens, extravascular contrast-enhanced MRI, and assessment of brain clearance function.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Ringstad, G., Valnes, L. M., Dale, A. M., Pripp, A. H., Vatnehol, S. S., Emblem, K. E., et al. (2018). Brain-wide glymphatic enhancement and clearance in humans assessed with MRI. JCI insight. https://doi.org/10.1172/jci.insight.121537
Vancouver
Ringstad G, Valnes LM, Dale AM, Pripp AH, Vatnehol SS, Emblem KE, et al. Brain-wide glymphatic enhancement and clearance in humans assessed with MRI. JCI insight. 2018. doi:10.1172/jci.insight.121537. PMID: 29997300.
BibTeX
@article{ringstad2018-29997300,
author = {Ringstad, G. and Valnes, L. M. and Dale, A. M. and Pripp, A. H. and Vatnehol, S. S. and Emblem, K. E. and Mardal, K. A. and Eide, P. K.},
title = {{Brain-wide glymphatic enhancement and clearance in humans assessed with MRI}},
journal = {JCI insight},
year = {2018},
doi = {10.1172/jci.insight.121537},
pmid = {29997300},
url = {https://doi.org/10.1172/jci.insight.121537}
}
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record names 8 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
Key findings
- Standardized T1-weighted MRI scans were performed before and after intrathecal gadobutrol at defined time points, including at 24 hours, 48 hours, and 4 weeks.
- All MRI scans were aligned and brain regions were segmented using FreeSurfer, and changes in normalized T1 signals over time were quantified as percentage change from baseline.
- The study provides in vivo evidence of access to all human brain subregions of a substance administered intrathecally.
- Clearance of the tracer substance was delayed in the dementia cohort.
- These observations translate previous findings in animal studies into humans and open new prospects concerning intrathecal treatment regimens, extravascular contrast-enhanced MRI, and assessment of brain clearance function.
Why it matters
Using an injected tracer and MRI, this study showed that a substance given into the spinal fluid reached all regions of the human brain, and that its clearance was delayed in a group of patients with dementia. It is an early look at how fluid moves through the brain and does not test any treatment, cure or prevention.
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Study details
- Evidence strengthModerate
How this study scored 54/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomized / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (JCI insight) |
| Journal's citation record | 2 / 4 | JCI Insight: journal h-index 173 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 2 / 5 | 2018 — within 10 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 531 times (OpenAlex, 2026-10-10) |
| Citations per year | 5 / 5 | 53.1 citations a year over 10 year(s) since 2018 |
| Impact for its field and year | 4 / 6 | Cited 15.1× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 7 other studies in this library |
| Still being cited | 4 / 4 | Cited 248 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Per Kristian Eide: h-index 62 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of California San Diego: institution h-index 1,852 (OpenAlex) |
| Multicenter collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 29997300) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 54 / 100 | — |
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