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, kb, 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 T1 values. Here, a gadolinium-based contrast agent is used to increase this T1 difference and enable the signal components to be disentangled. The optimal post-contrast blood T1 [Formula] 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 [Formula] at 3T as 0.8 s. Simulations showed kb could be estimated in individual cortical regions with a relative error{epsilon} < 1% and coefficient of variation CoV = 30 %; however, a high dependence on blood T1 was also observed. In volunteer data, mean parameter values in grey matter were: arterial transit time tA = 1.15{+/-}0.49 s, cerebral blood flow f = 58.0{+/-}14.3 ml blood / min / 100 ml tissue, water exchange rate kb = 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 T1 values.