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

Abstract

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 $T_1$ ( $T_{1,b}^{\text{post}}$ ) 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 $T_{1,b}^{\text{post}}$ at 3 T as 0.8 s. Simulations showed that $k_b$ could be estimated in individual cortical regions with a relative error $ϵ<1$ % and coefficient of variation $\text{CoV}=30$ %; however, a high dependence on blood $T_1$ was also observed. In volunteer data, mean parameter values in grey matter were: arterial transit time $t_A=1.15\pm 0.49$ s, cerebral blood flow $f=58.0\pm 14.3$ mL blood/min/100 mL tissue and water exchange rate $k_b=2.32\pm 2.49$ 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.

Keywords: arterial spin labelling; blood-brain barrier; gadolinium-based contrast agent; permeability; water exchange.