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, (Figure presented.), but to estimate (Figure presented.) 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 (Figure presented.) values. Here, a gadolinium-based contrast agent is used to increase this (Figure presented.) difference and enable the signal components to be disentangled. The optimal post-contrast blood (Figure presented.) ((Figure presented.)) 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 (Figure presented.) at 3 T as 0.8 s. Simulations showed that (Figure presented.) could be estimated in individual cortical regions with a relative error (Figure presented.) % and coefficient of variation (Figure presented.) %; however, a high dependence on blood (Figure presented.) was also observed. In volunteer data, mean parameter values in grey matter were: arterial transit time (Figure presented.) s, cerebral blood flow (Figure presented.) mL blood/min/100 mL tissue and water exchange rate (Figure presented.) 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 (Figure presented.) values.