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

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 ( $$ ) explicitly representing intra- and extravascular signal components, and (iii) a two-compartment model additionally accounting for finite compartmental $$ 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.