Blood-brain barrier water exchange measurements using FEXI: Impact of modeling paradigm and relaxation timeeffects.

Abstract

To evaluate potential modeling paradigms and the impact of relaxation time effects on human blood-brain barrier (BBB) water exchange measurements using FEXI (BBB-FEXI), and to quantify the accuracy, precision, and repeatability of BBB-FEXI exchange rate estimates at 3 . Three modeling paradigms were evaluated: (i) the apparent exchange rate (AXR) model; (ii) a two-compartment model ( ) explicitly representing intra- and extravascular signal components, and (iii) a two-compartmentmodeladditionally accounting for finite compartmental and relaxation times ( ). Each model had three free parameters. Simulations quantified biases introduced by the assumption of infinite relaxation times in the AXR and models, as well as the accuracy and precision of all three models. The scan-rescan repeatability of all paradigms was quantified for the first time in vivo in 10 healthy volunteers (age range 23-52 years; five female). The assumption of infinite relaxation times yielded exchange rate errors in simulations up to 42%/14% in the AXR/ models, respectively. Accuracy was highest in the compartmental models; precision was best in the AXR model. Scan-rescan repeatability in vivo was good for all models, with negligible bias and repeatability coefficients in grey matter of , , and . Compartmental modelling of BBB-FEXI signals can provide accurate and repeatable measurements of BBB water exchange; however, relaxation time and partial volume effects may cause model-dependent biases.