What Does FEXI Measure?

TL;DR

FEXI, a technique used in biomedical imaging to assess membrane permeability, is influenced not only by membrane exchange but also significantly by the geometry of tissue compartments, complicating its interpretation.

Contribution

This study reveals that FEXI's sensitivity extends beyond membrane exchange to include compartment geometry effects, challenging previous assumptions.

Findings

FEXI is affected by tissue geometry, not just membrane permeability.

Complex geometries can mimic exchange signals in FEXI measurements.

Interpretation of FEXI in brain tissue requires considering geometric effects.

Abstract

Filter-exchange imaging (FEXI) has already been utilized in several biomedical studies for evaluating the permeability of cell membranes. The method relies on suppressing the extracellular signal using strong diffusion weighting (the mobility filter causing a reduction in the overall diffusivity) and monitoring the subsequent diffusivity recovery. Using Monte Carlo (MC) simulations, we demonstrate that FEXI is not uniquely sensitive to the transcytolemmal exchange but also to the geometry of involved compartments: Complicated geometry offers locations where spins remain unaffected by the mobility filter; moving to other locations afterward, such spins contribute to the diffusivity recovery without actually permeating any membrane. This exchange mechanism challenges the interpretation of FEXI in complex media such as brain gray matter and opens large room for investigation towards crystallizing the genuine membrane permeation and characterizing the compartment geometry.