What does FEXI measure?

Abstract

Summary 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 simulations, we demonstrate that FEXI is sensitive not uniquely to the transcytolemmal exchange but also to the geometry of involved compartments: complex geometry offers locations where spins remain unaffected by the mobility filter; moving to other locations afterwards, such spins contribute to the diffusivity recovery without actually permeating any membrane. This exchange mechanism is a warning for those who aim to use FEXI in complex media such as brain gray matter and opens wide scope for investigation towards crystallizing the genuine membrane permeation and characterizing the compartment geometry.

Measuring water exchange on a preclinical MRI system using filter exchange and diffusion time dependent kurtosis imaging

“…For FEXI, this is reflected in a simple exponential functional form of Eq. (1) that neglects any power-law tails of the signal's cumulants in each compartment due to the incomplete coarse-graining over the compartments' microstructure (the breakdown of this assumption was recently discussed in 36 ); for DKI(t), Eqs. ( 2)-( 3) similarly neglect such effects, specifically assuming that all the t-dependence of kurtosis stems from the exchange.…”

Compartmental anisotropy of filtered exchange imaging (FEXI) in human white matter: What is happening in FEXI?

“…Thus, in WM, there is a need for a different, more inclusive explanation of FEXI signal changes, in line with previous studies based on NMR experiments 47 and numerical simulations. 26,27 This need is also supported by the different AXR values estimated from the same filtering direction but different detection directions (Figure 4).…”

“…3), and a negative value would indicate that the slow diffusion component is filtered out more strongly than the fast component, in line with an ADC ′ increased by diffusion filtering reported in a recent simulation study. 27 This apparently contradictory result is direct experimental evidence that, at least for FEXI in the WM, the description needs to be adjusted to account for the signal loss due to selective filtering of diffusion components from at least two restricted compartments. This interpretation is also supported by smaller σ values compared to those from FEXI conv when using trace-weighted detection following anisotropic diffusion filters (FEXI X|Tr , FEXI Y|Tr , FEXI Z|Tr ) or FEXI Tr|Tr .…”

“…Recent studies have reported anisotropic behavior of AXR in WM of the brain, both post‐mortem 25 and in vivo 26 . Computer simulations also have suggested other potential sources of anisotropic exchange, such as the involvement of additional water compartments 26 and the geometry of the microstructure 27 . However, these previous studies have yielded inconsistent results on the anisotropy and reached different conclusions, leaving the understanding of the anisotropic behavior of AXR in the WM incomplete.…”

Editor's Choice: What does filter exchange imaging measure?

“…Although it has been clear already from its invention that the exchange it measures need not involve transcytolemmal exchange, FEXI is often interpreted as reporting on the intra‐/extracellular exchange rate. Now, Khateri et al provide several clear demonstrations of the shortcomings of such a simplistic view 1 . Using numerical simulations in systems of varying complexity, they show how FEXI applied in single compartment systems with no cross‐membrane exchange can feign the behavior of transcytolemmal exchange.…”