AUTHOR=Mahroo Amnah , Buck Mareike Alicja , Huber Jörn , Breutigam Nora-Josefin , Mutsaerts Henk J. M. M. , Craig Martin , Chappell Michael , Günther Matthias 

TITLE=Robust Multi-TE ASL-Based Blood–Brain Barrier Integrity Measurements

JOURNAL=Frontiers in Neuroscience

VOLUME=Volume 15 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2021.719676

DOI=10.3389/fnins.2021.719676

ISSN=1662-453X

ABSTRACT=Multiple echo-time arterial spin labeling (multi-TE ASL) offers estimation of blood-tissue exchange dynamics (Texch) by probing the T2 relaxation of the labelled spins. In this study, we provide a recipe for robust assessment of Texch as a proxy measure of blood brain barrier (BBB) integrity based on a test-retest analysis. This includes a novel scan protocol and an extension of the two-compartment model with ‘intra-voxel transit time’ (ITT) to address tissue transit effects. With the extended model, we intend to separate the underlying two distinct mechanisms of tissue transit and exchange time. The performance of the extended model in comparison with the two-compartment model was evaluated in simulations. Multi-TE ASL sequence with two different bolus durations was used to acquire in-vivo data (n=10). Cerebral blood flow (CBF), arterial transit time (ATT), and exchange time (Texch) were fitted with the two models and mean gray matter values were compared. Additionally, the extended model also extracted ITT parameter. Test-retest reliability of Texch was assessed for intra-session, inter-session and inter-visit pairs of measurements. Intra-class correlation (ICC) and within-subject Coefficient of Variance (CoV) for gray matter were computed to assess the precision of the method. Mean gray matter Texch and ITT values were found to be 227.9 ± 37.9 ms and 310.3 ± 52.9 ms, respectively. Texch estimated by the extended model was 32.6 ± 5.9 % lower than the two-compartment model. A significant ICC was observed for all three measures of Texch reliability (P<0.05). Texch intra-session CoV, inter-session CoV and inter-visit CoV were found to be 6.6%, 7.9%, and 8.4%, respectively. With the described improvements addressing intra-voxel transit effects, multi-TE ASL shows good reproducibility as a non-invasive measure of BBB permeability. These findings offer an encouraging step forward to apply this potential BBB permeability biomarker in clinical research.