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 kb 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 ( T-1,b(post)) at 3 T 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 T-1,b(post) at 3 T as 0.8 s. Simulations showed that k(b) could be estimated in individual cortical regions with a relative error & varepsilon; < 1% and coefficient of variation CoV = 3 %; 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 and 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.