Blood-brain barrier water exchange measurements using contrast-enhanced ASL

Abstract

AbstractA technique for quantifying regional blood-brain barrier (BBB) water exchange rates using contrast-enhanced arterial spin labelling (CE-ASL) is presented and evaluated in simulations and in vivo. The two-compartment ASL model describes the water exchange rate from blood to tissue,kb, but to estimatekbin practice it is necessary to separate the intra- and extravascular signals. This is challenging in standard ASL data owing to the small difference inT1values. Here, a gadolinium-based contrast agent is used to increase thisT1difference and enable the signal components to be disentangled. The optimal post-contrast bloodT1at 3T was determined in a sensitivity analysis, and the accuracy and precision of the method quantified using Monte Carlo simulations. Proof-of-concept data were acquired in six healthy volunteers (five female, age range 24 – 46 years). The sensitivity analysis identified the optimalat 3T as 0.8 s. Simulations showedkbcould be estimated in individual cortical regions with a relative errorϵ< 1% and coefficient of variation CoV = 30 %; however, a high dependence on bloodT1was also observed. In volunteer data, mean parameter values in grey matter were: arterial transit timetA= 1.15±0.49 s, cerebral blood flowf= 58.0±14.3 ml blood / min / 100 ml tissue, water exchange ratekb= 2.32 ± 2.49 s−1. CE-ASL can provide regional BBB water exchange rate estimates; however, the clinical utility of the technique is dependent on the achievable accuracy of measuredT1values.