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 $$ {k}_{\mathrm{b}} $$ , but to estimate k b $$ {k}_{\mathrm{b}} $$ 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 $$ {T}_1 $$ values. Here, a gadolinium-based contrast agent is used to increase this T 1 $$ {T}_1 $$ difference and enable the signal components to be disentangled. The optimal post-contrast blood T 1 $$ {T}_1 $$ ( T 1 , b post $$ {T}_{1,\mathrm{b}}^{\mathrm{post}} $$ ) 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 $$ {T}_{1,\mathrm{b}}^{\mathrm{post}} $$ at 3 T as 0.8 s. Simulations showed that k b $$ {k}_{\mathrm{b}} $$ could be estimated in individual cortical regions with a relative error ϵ < 1 $$ \epsilon <1 $$ % and coefficient of variation CoV = 30 $$ \mathrm{CoV}=30 $$ %; however, a high dependence on blood T 1 $$ {T}_1 $$ was also observed. In volunteer data, mean parameter values in grey matter were: arterial transit time t A = 1 . 15 ± 0 . 49 $$ {t}_{\mathrm{A}}=1.15\pm 0.49 $$  s, cerebral blood flow f = 58 . 0 ± 14 . 3 $$ f=58.0\pm 14.3 $$  mL blood/min/100 mL tissue and water exchange rate k b = 2 . 32 ± 2 . 49 $$ {k}_{\mathrm{b}}=2.32\pm 2.49 $$ 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 $$ {T}_1 $$ values.