Feasibility of relaxation-exchange magnetic resonance imaging (REXI) for measuring water exchange across the blood–CSF barrier in the human choroid plexus

The choroid plexus (CP) is important for cerebrospinal fluid (CSF) secretion and forms the blood-CSF barrier (BCSFB), which is essential for brain homeostasis. However, noninvasive methods for evaluating BCSFB function remain limited. Previously, we introduced a novel magnetic resonance imaging (MRI) technique, relaxation-exchange MRI (REXI), to quantify water exchange between CP and CSF in rats by leveraging the substantial difference in transverse relaxation times between CP tissue and CSF. Here, we adapted REXI to human applications by implementing segmented echo-planar imaging readout for enhanced acquisition speed, optimizing key parameters based on the Cramér-Rao lower bound, and refining the analysis methodology. We conducted simulations and phantom experiments for methodological validation. Subsequently, we performed a scan-rescan experiment in healthy volunteers (n = 6, mean-age ∼22 years), revealing relatively good repeatability in measurements of the apparent water exchange rate <i>k</i>_BCSFB (intraclass correlation coefficient = 0.84). REXI detected a 34% decrease in <i>k</i>_BCSFB among middle-aged healthy adults (n = 6, mean-age ∼55 years) compared with young healthy adults (n = 9, mean-age ∼23 years, <i>p = </i>0.0048). These results demonstrate the feasibility of REXI in quantifying water exchange in human CP in vivo, providing a promising tool for future investigations of BCSFB function.