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Rapid imaging of intravenous gadolinium-based contrast agent (GBCA) entering ventricular cerebrospinal fluid (CSF) through the choroid plexus in healthy human subjects

Sun, Yuanqi ; Cao, Di ; Pillai, Jay J ; Paez, Adrian ; Li, Yinghao ; Gu, Chunming ; Pogson, Jacob M ; Knutsson, Linda LU orcid ; Barker, Peter B and van Zijl, Peter C M , et al. (2024) In Fluids and Barriers of the CNS 21(1).
Abstract

BACKGROUND: Pathways for intravenously administered gadolinium-based-contrast-agents (GBCAs) entering cerebrospinal-fluid (CSF) circulation in the human brain are not well-understood. The blood-CSF-barrier (BCSFB) in choroid-plexus (CP) has long been hypothesized to be a main entry-point for intravenous-GBCAs into CSF. Most existing studies on this topic were performed in animals and human patients with various diseases. Results in healthy human subjects are limited. Besides, most studies were performed using MRI methods with limited temporal resolution and significant partial-volume effects from blood and CSF.

METHODS: This study employs the recently developed dynamic-susceptibility-contrast-in-the-CSF (cDSC) MRI approach to... (More)

BACKGROUND: Pathways for intravenously administered gadolinium-based-contrast-agents (GBCAs) entering cerebrospinal-fluid (CSF) circulation in the human brain are not well-understood. The blood-CSF-barrier (BCSFB) in choroid-plexus (CP) has long been hypothesized to be a main entry-point for intravenous-GBCAs into CSF. Most existing studies on this topic were performed in animals and human patients with various diseases. Results in healthy human subjects are limited. Besides, most studies were performed using MRI methods with limited temporal resolution and significant partial-volume effects from blood and CSF.

METHODS: This study employs the recently developed dynamic-susceptibility-contrast-in-the-CSF (cDSC) MRI approach to measure GBCA-distribution in the CSF immediately and 4 h after intravenous-GBCA administration in healthy subjects. With a temporal resolution of 10 s, cDSC MRI can track GBCA-induced CSF signal changes during the bolus phase, which has not been investigated previously. It employs a long echo-time (TE = 1347 ms) to suppress tissue and blood signals so that pure CSF signal is detected with minimal partial-volume effects. GBCA concentration in the CSF can be estimated from cDSC MRI. In this study, cDSC and FLAIR MRI were performed immediately and 4 h after intravenous GBCA administration in 25 healthy volunteers (age 48.9 ± 19.5 years; 14 females). Paired t-tests were used to compare pre-GBCA and post-GBCA signal changes, and their correlations with age were evaluated using Pearson-correlation-coefficients.

RESULTS: At ~ 20 s post-GBCA, GBCA-induced cDSC signal changes were detected in the CSF around CP (ΔS/S = - 2.40 ± 0.30%; P < .001) but not in the rest of lateral ventricle (LV). At 4 h, significant GBCA-induced cDSC signal changes were observed in the entire LV (ΔS/S = - 7.58 ± 3.90%; P = .002). FLAIR MRI showed a similar trend. GBCA-induced CSF signal changes did not correlate with age.

CONCLUSIONS: These results provided direct imaging evidence that GBCAs can pass the BCSFB in the CP and enter ventricular CSF immediately after intravenous administration in healthy human brains. Besides, our results in healthy subjects established a basis for clinical studies in brain diseases exploiting GBCA-enhanced MRI to detect BCSFB dysfunction.

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publishing date
type
Contribution to journal
publication status
published
subject
keywords
Humans, Contrast Media/administration & dosage, Choroid Plexus/diagnostic imaging, Magnetic Resonance Imaging/methods, Male, Adult, Female, Gadolinium/administration & dosage, Middle Aged, Healthy Volunteers, Young Adult, Administration, Intravenous
in
Fluids and Barriers of the CNS
volume
21
issue
1
article number
72
publisher
BioMed Central (BMC)
external identifiers
  • pmid:39285434
  • scopus:85204298120
ISSN
2045-8118
DOI
10.1186/s12987-024-00571-3
language
English
LU publication?
no
additional info
© 2024. The Author(s).
id
a90017f5-f478-48fd-8c97-1047cd95c907
date added to LUP
2024-09-18 10:35:15
date last changed
2025-07-08 15:26:16
@article{a90017f5-f478-48fd-8c97-1047cd95c907,
  abstract     = {{<p>BACKGROUND: Pathways for intravenously administered gadolinium-based-contrast-agents (GBCAs) entering cerebrospinal-fluid (CSF) circulation in the human brain are not well-understood. The blood-CSF-barrier (BCSFB) in choroid-plexus (CP) has long been hypothesized to be a main entry-point for intravenous-GBCAs into CSF. Most existing studies on this topic were performed in animals and human patients with various diseases. Results in healthy human subjects are limited. Besides, most studies were performed using MRI methods with limited temporal resolution and significant partial-volume effects from blood and CSF.</p><p>METHODS: This study employs the recently developed dynamic-susceptibility-contrast-in-the-CSF (cDSC) MRI approach to measure GBCA-distribution in the CSF immediately and 4 h after intravenous-GBCA administration in healthy subjects. With a temporal resolution of 10 s, cDSC MRI can track GBCA-induced CSF signal changes during the bolus phase, which has not been investigated previously. It employs a long echo-time (TE = 1347 ms) to suppress tissue and blood signals so that pure CSF signal is detected with minimal partial-volume effects. GBCA concentration in the CSF can be estimated from cDSC MRI. In this study, cDSC and FLAIR MRI were performed immediately and 4 h after intravenous GBCA administration in 25 healthy volunteers (age 48.9 ± 19.5 years; 14 females). Paired t-tests were used to compare pre-GBCA and post-GBCA signal changes, and their correlations with age were evaluated using Pearson-correlation-coefficients.</p><p>RESULTS: At ~ 20 s post-GBCA, GBCA-induced cDSC signal changes were detected in the CSF around CP (ΔS/S = - 2.40 ± 0.30%; P &lt; .001) but not in the rest of lateral ventricle (LV). At 4 h, significant GBCA-induced cDSC signal changes were observed in the entire LV (ΔS/S = - 7.58 ± 3.90%; P = .002). FLAIR MRI showed a similar trend. GBCA-induced CSF signal changes did not correlate with age.</p><p>CONCLUSIONS: These results provided direct imaging evidence that GBCAs can pass the BCSFB in the CP and enter ventricular CSF immediately after intravenous administration in healthy human brains. Besides, our results in healthy subjects established a basis for clinical studies in brain diseases exploiting GBCA-enhanced MRI to detect BCSFB dysfunction.</p>}},
  author       = {{Sun, Yuanqi and Cao, Di and Pillai, Jay J and Paez, Adrian and Li, Yinghao and Gu, Chunming and Pogson, Jacob M and Knutsson, Linda and Barker, Peter B and van Zijl, Peter C M and Bakker, Arnold and Ward, Bryan K and Hua, Jun}},
  issn         = {{2045-8118}},
  keywords     = {{Humans; Contrast Media/administration & dosage; Choroid Plexus/diagnostic imaging; Magnetic Resonance Imaging/methods; Male; Adult; Female; Gadolinium/administration & dosage; Middle Aged; Healthy Volunteers; Young Adult; Administration, Intravenous}},
  language     = {{eng}},
  month        = {{09}},
  number       = {{1}},
  publisher    = {{BioMed Central (BMC)}},
  series       = {{Fluids and Barriers of the CNS}},
  title        = {{Rapid imaging of intravenous gadolinium-based contrast agent (GBCA) entering ventricular cerebrospinal fluid (CSF) through the choroid plexus in healthy human subjects}},
  url          = {{http://dx.doi.org/10.1186/s12987-024-00571-3}},
  doi          = {{10.1186/s12987-024-00571-3}},
  volume       = {{21}},
  year         = {{2024}},
}