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

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.