Using Manganese‐Enhanced <scp>DCE</scp> ‐ <scp>MRI</scp> to Assess Blood‐Cerebrospinal Fluid Barrier Transport

ABSTRACT Purpose We developed a dynamic, heavily T2‐weighted (hT2w) FLAIR protocol to resolve acute Mn 2+ transport kinetics, as a proxy for Ca 2+ , across the choroid plexus (ChP)—cerebrospinal fluid (CSF) interface, in vivo. By quantifying intercompartmental Mn 2+ dynamics, and comparing these with Gd‐DOTA, we sought to characterize blood‐CSF‐barrier (BCSFB)‐mediated tracer transport, combining high in‐plane resolution and 4‐min temporal sampling. Methods hT2w‐FLAIR DCE MRI was conducted in anesthetized C57BL/6 mice, receiving intravenous Mn 2+ or Gd‐DOTA. Semi‐quantitative tracer kinetic modeling permitted regional and inter‐tracer comparisons. Results Mn 2+ rapidly crossed from the vasculature into the CSF, across the ChP, with similar arrival times and time‐to‐peak across compartments. Mn 2+ delivery into the ChP exhibited a 5.7‐fold steeper uptake rate ( p = 0.031) and a 5.6‐fold higher peak signal amplitude ( p = 0.0028) than in the LV‐CSF. In contrast, Gd‐DOTA exhibited a 2.2‐fold shorter ChP plateau duration ( p = 0.034) and 2.2‐fold faster ChP clearance rate ( p = 0.0047), compared to Mn 2+ . Within the CSF, there were significant temporal delays with Gd‐DOTA relative to Mn 2+ : a lengthened arrival (eight‐fold, p = 0.045) and time‐to‐peak (six‐fold, p = 0.024). Conclusion Our hT2w‐FLAIR DCE‐MRI approach captured the early BCSFB transport window for Mn 2+ , providing distinct ChP and LV‐CSF kinetics at a higher temporal resolution and with reduced CSF signal contamination compared to prior approaches. These findings highlight that MRI tracer choice strongly shapes measured BCSFB kinetics, and supports the use of Mn 2+ as a tool for probing compartment‐specific ChP transport.

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Publication Details

Journal
Magnetic Resonance in Medicine
Published
2026-07-26
DOI
https://doi.org/10.1002/mrm.70531
Primary Topic
Cerebrospinal fluid and hydrocephalus
Type
article
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article

Using Manganese‐Enhanced DCE ‐ MRI to Assess Blood‐Cerebrospinal Fluid Barrier Transport

Phillip Muza, Daniel J. Stuckey, Mark F. Lythgoe, Ian F. Harrison et al.
Magnetic Resonance in Medicine
Cerebrospinal fluid and hydrocephalus
article

Using Manganese‐Enhanced DCE ‐ MRI to Assess Blood‐Cerebrospinal Fluid Barrier Transport

Phillip Muza, Daniel J. Stuckey, Mark F. Lythgoe, Ian F. Harrison, Christina Katsiva, Jack A. Wells, Tammy L. Kalber, Shereen Nizari, Zhiping Feng, Charith Perera
article en

Abstract

ABSTRACT Purpose We developed a dynamic, heavily T2‐weighted (hT2w) FLAIR protocol to resolve acute Mn 2+ transport kinetics, as a proxy for Ca 2+ , across the choroid plexus (ChP)—cerebrospinal fluid (CSF) interface, in vivo. By quantifying intercompartmental Mn 2+ dynamics, and comparing these with Gd‐DOTA, we sought to characterize blood‐CSF‐barrier (BCSFB)‐mediated tracer transport, combining high in‐plane resolution and 4‐min temporal sampling. Methods hT2w‐FLAIR DCE MRI was conducted in anesthetized C57BL/6 mice, receiving intravenous Mn 2+ or Gd‐DOTA. Semi‐quantitative tracer kinetic modeling permitted regional and inter‐tracer comparisons. Results Mn 2+ rapidly crossed from the vasculature into the CSF, across the ChP, with similar arrival times and time‐to‐peak across compartments. Mn 2+ delivery into the ChP exhibited a 5.7‐fold steeper uptake rate ( p = 0.031) and a 5.6‐fold higher peak signal amplitude ( p = 0.0028) than in the LV‐CSF. In contrast, Gd‐DOTA exhibited a 2.2‐fold shorter ChP plateau duration ( p = 0.034) and 2.2‐fold faster ChP clearance rate ( p = 0.0047), compared to Mn 2+ . Within the CSF, there were significant temporal delays with Gd‐DOTA relative to Mn 2+ : a lengthened arrival (eight‐fold, p = 0.045) and time‐to‐peak (six‐fold, p = 0.024). Conclusion Our hT2w‐FLAIR DCE‐MRI approach captured the early BCSFB transport window for Mn 2+ , providing distinct ChP and LV‐CSF kinetics at a higher temporal resolution and with reduced CSF signal contamination compared to prior approaches. These findings highlight that MRI tracer choice strongly shapes measured BCSFB kinetics, and supports the use of Mn 2+ as a tool for probing compartment‐specific ChP transport.

Magnetic Resonance in Medicine
UCL Biomedical Research Centre (GB), University College London (GB)
Openalex Percentile: Top 13%
Cerebrospinal fluid and hydrocephalus
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