Relaxation-exchange magnetic resonance imaging (REXI): a non-invasive imaging method for evaluating trans-barrier water exchange in the choroid plexus

Abstract

Background: The choroid plexus (CP) plays a crucial role in cerebrospinal fluid (CSF) production and brain homeostasis. However, non-invasive imaging techniques to assess its function remain limited. This study was conducted to develop a novel, contrast-agent-free MRI technique, termed relaxation-exchange magnetic resonance imaging (REXI), for evaluating CP-CSF water transport, a potential biomarker of CP function.

Methods: REXI utilizes the inherent and large difference in magnetic resonance transverse relaxation times (T₂s) between CP tissue (e.g., blood vessels and epithelial cells) and CSF. It uses a filter block to remove most CP tissue magnetization (shorter T₂), a mixing block for CP-CSF water exchange with mixing time t_m, and a detection block with multi-echo acquisition to determine the CP/CSF component fraction after exchange. The REXI pulse sequence was implemented on a 9.4 T preclinical MRI scanner. For validation of REXI's ability to measure exchange, we conducted preliminary tests on urea-water proton-exchange phantoms with various pH levels. We measured the steady-state water efflux rate from CP to CSF in rats and tested the sensitivity of REXI in detecting CP dysfunction induced by the carbonic anhydrase inhibitor acetazolamide.

Results: REXI pulse sequence successfully captured changes in the proton exchange rate (from short-T₂ component to long-T₂ component [i.e., k_sl]) of urea-water phantoms at varying pH, demonstrating its sensitivity to exchange processes. In rat CP, REXI significantly suppressed the CP tissue signal, reducing the short-T₂ fraction (f_short) from 0.44 to 0.23 (p < 0.0001), with significant recovery to 0.28 after a mixing time of 400 ms (p = 0.014). The changes in f_short at various mixing times can be accurately described by a two-site exchange model, yielding a steady-state water efflux rate from CP to CSF (i.e., k_bc) of 0.49 s^-1. A scan-rescan experiment demonstrated that REXI had excellent reproducibility in measuring k_bc (intraclass correlation coefficient = 0.90). Notably, acetazolamide-induced CSF reduction resulted in a 66% decrease in k_bc within rat CP.

Conclusions: This proof-of-concept study demonstrates the feasibility of REXI for measuring trans-barrier water exchange in the CP, offering a promising biomarker for future assessments of CP function.

Keywords: Blood cerebrospinal fluid barrier; Choroid plexus; Contrast-agent-free; Magnetic resonance imaging; Relaxation exchange.