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Cited by 8Cerebrospinal fluid and hydrocephalusAdvanced MRI Techniques and ApplicationsBarrier Structure and Function Studies

Perivascular network segmentations derived from high-field MRI and their implications for perivascular and parenchymal mass transport in the rat brain

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Rey, Julian A., Farid, Uzair M., Najjoum, Christopher M., Brown, Alec, Magdoom, Kulam Najmudeen, Mareci, Thomas H., Sarntinoranont, Malisa·2023·Scientific Reports
DOI 10.1038/s41598-023-34850-0PMC PMC10244386
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Abstract

A custom segmentation workflow was applied to ex vivo high-field MR images of rat brains acquired following in vivo intraventricular contrast agent infusion to generate maps of the perivascular spaces (PVS). The resulting perivascular network segmentations enabled analysis of perivascular connections to the ventricles, parenchymal solute clearance, and dispersive solute transport within PVS. Numerous perivascular connections between the brain surface and the ventricles suggest the ventricles integrate into a PVS-mediated clearance system and raise the possibility of cerebrospinal fluid (CSF) return from the subarachnoid space to the ventricles via PVS. Assuming rapid solute exchange between the PVS and CSF spaces primarily by advection, the extensive perivascular network decreased the mean clearance distance from parenchyma to the nearest CSF compartment resulting in an over 21-fold reduction in the estimated diffusive clearance time scale, irrespective of solute diffusivity. This corresponds to an estimated diffusive clearance time scale under 10 min for amyloid-beta which suggests that the widespread distribution of PVS may render diffusion an effective parenchymal clearance mechanism. Additional analysis of oscillatory solute dispersion within PVS indicates that advection rather than dispersion is likely the primary transport mechanism for dissolved compounds greater than 66 kDa in the long (> 2 mm) perivascular segments identified here, although dispersion may be significant for smaller compounds in shorter perivascular segments.

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  • Prior studies have shown that albumin-binding dyes have reduced clearance to the periphery after ICV infusion in mice and accumulate in perivascular compartments after ICV injection in rats.

    “because prior studies have shown that albumin-binding dyes have reduced clearance to the periphery after ICV infusion in mice [23] and accumulate in perivascular compartments after ICV injection in rats [24, 25].”

    From Elucidating brain transport pathways and cell type-dependent gene silencing of a durable lipid–siRNA conjugate administered into cerebrospinal fluid (2025) · cites this paper as [24]

    The Results report extensive perivascular uptake after intraventricular infusion in rats, supporting the rat portion of the cited claim. The Methods identify the tracer as gadolinium-labeled albumin (Gd-DTPA-albumin), not an albumin-binding dye. The mouse clearance claim is attached to a different citation [23] and is not assessed here. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Albumin-binding dyes have reduced clearance to the periphery after ICV infusion in mice and accumulate in perivascular compartments after ICV injection in rats.

    “Prior studies have shown that albumin-binding dyes have reduced clearance to the periphery after intracerebroventricular (ICV) infusion in mice28 and accumulate in perivascular compartments after ICV injection in rats.15,29”

    From Lipid-siRNA conjugate accesses a perivascular transport mechanism and achieves widespread and durable knockdown in the central nervous system (2024) · cites this paper as [15]

    The Results report extensive perivascular uptake after intraventricular infusion in rats, but the tracer was Gd-DTPA-albumin, not an albumin-binding dye (Methods, Magnetic resonance imaging experiments; page unavailable). The mouse-clearance clause is attached to a different citation and is not assessed here. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • The striatum receives the most perivascular CSF flow.

    “Intriguingly, multiple orthogonal studies suggest that the striatum receives the most perivascular CSF flow, highlighting the potential of this transport pathway for accessing deep brain structures.15,16”

    From Lipid-siRNA conjugate accesses a perivascular transport mechanism and achieves widespread and durable knockdown in the central nervous system (2024) · cites this paper as [15]

    The Results report that the striatum had the highest average percentage of segmented perivascular volume after contrast-agent infusion. That measures tracer uptake, not CSF flow; the authors also note that infusion into periventricular tissue in one rat likely increased the striatal measurement. The Discussion says their MRI data do not establish the direction of transport, so the paper does not show that the striatum receives the most perivascular CSF flow. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

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Cited by

Sorted by citations

Authors
Rey, J. A., Farid, U. M., Najjoum, C. M., Brown, A., Magdoom, K. N., Mareci, T. H., & Sarntinoranont, M.
Affiliations
University of Florida (US)
Corresponding author
Sarntinoranont, Malisa
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2023-06-06
Volume
13
Issue
1
Pages
9205-9205
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/s41598-023-34850-0
PMC
PMC10244386
OpenAlex
W4379598818
Cited by
8
References
6
Citations by year
2026: 3 · 2025: 2 · 2024: 3
FWCI
0.97
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Science Foundation (1157490)
  • U.S. Department of Energy (DMR-1157490)
  • McKnight Foundation
  • University of Florida
  • National High Magnetic Field Laboratory (DMR-1157490, 1157490)
  • University of California, San Francisco
  • Division of Materials Research (11‐57490, DMR 1157490)
  • High Magnetic Field Laboratory, Chinese Academy of Sciences
  • State of Florida
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Cerebrospinal fluid and hydrocephalus
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
Keywords
perivascular spaces, high-field MRI, rat brain, cerebrospinal fluid, subarachnoid space, amyloid-beta clearance, advection, solute dispersion, ex vivo brain imaging
MeSH terms
Animals, Brain, Contrast Media, Diffusion, Magnetic Resonance Imaging, Subarachnoid Space, Rats

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