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

A 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, k b , but to estimate k b in practice it is necessary to separate the intra- and extravascular signals. This is challenging in standard ASL data owing to the small difference in T 1 values. Here, a gadolinium-based contrast agent is used to increase this T 1 difference and enable the signal components to be disentangled. The optimal post-contrast blood T 1 at 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 optimal at 3T as 0.8 s. Simulations showed k b could be estimated in individual cortical regions with a relative error ϵ < 1% and coefficient of variation CoV = 30 %; however, a high dependence on blood T 1 was also observed. In volunteer data, mean parameter values in grey matter were: arterial transit time t A = 1.15±0.49 s, cerebral blood flow f = 58.0±14.3 ml blood / min / 100 ml tissue, water exchange rate k b = 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 measured T 1 values.