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Updated: Aug 5, 2026
Functional Neuroimaging Using Ultrasonic Blood-brain Barrier Disruption and Manganese-enhanced MRI
Published on: July 12, 2012
Using Manganese-Enhanced DCE-MRI to Assess Blood-Cerebrospinal Fluid Barrier Transport
Charith Perera1, Zhiping Feng1, Shereen Nizari1
1UCL Centre for Advanced Biomedical Imaging, Division of Medicine, University College London, London, UK.
Purpose:
We developed a dynamic, heavily T2-weighted (hT2w) FLAIR protocol to resolve acute Mn2+ transport kinetics, as a proxy for Ca2+, across the choroid plexus (ChP)-cerebrospinal fluid (CSF) interface, in vivo. By quantifying intercompartmental Mn2+ 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 Mn2+ or Gd-DOTA. Semi-quantitative tracer kinetic modeling permitted regional and inter-tracer comparisons.
Results:
Mn2+ rapidly crossed from the vasculature into the CSF, across the ChP, with similar arrival times and time-to-peak across compartments. Mn2+ 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 Mn2+. Within the CSF, there were significant temporal delays with Gd-DOTA relative to Mn2+: 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 Mn2+, 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 Mn2+ as a tool for probing compartment-specific ChP transport.
Insights
Manganese-2+ (Mn2+) dynamics across the blood-CSF-barrier were visualized using a novel MRI technique. This method offers better resolution for studying Mn2+ transport kinetics compared to Gadolinium-DOTA.
Area of Science:
- Neuroimaging
- Biophysics
Background:
- The blood-cerebrospinal fluid barrier (BCSFB) regulates transport into the central nervous system.
- Understanding BCSFB kinetics is crucial for diagnosing and treating neurological disorders.
Purpose of the Study:
- To develop and validate a dynamic, heavily T2-weighted (hT2w) FLAIR MRI protocol for assessing manganese (Mn2+) transport kinetics across the choroid plexus (ChP)-cerebrospinal fluid (CSF) interface in vivo.
- To compare Mn2+ transport dynamics with Gd-DOTA to characterize BCSFB-mediated tracer transport.
Main Methods:
- Anesthetized C57BL/6 mice underwent hT2w-FLAIR dynamic contrast-enhanced (DCE) MRI.
- Intravenous administration of Mn2+ or Gd-DOTA was performed.
- Semi-quantitative tracer kinetic modeling was used for analysis.
Main Results:
- Mn2+ rapidly crossed the ChP into the CSF with similar arrival and peak times.
- Mn2+ showed a significantly steeper uptake rate and higher peak signal in the ChP compared to the lateral ventricle CSF.
- Gd-DOTA exhibited faster ChP plateau clearance and significant temporal delays in CSF arrival and peak time compared to Mn2+.
Conclusions:
- The hT2w-FLAIR DCE-MRI approach effectively captured the early BCSFB transport window for Mn2+.
- This method provides distinct ChP and LV-CSF kinetics with high temporal resolution and reduced CSF signal contamination.
- MRI tracer choice significantly influences measured BCSFB kinetics, supporting Mn2+ for probing ChP transport.
