Quantification of blood–brain barrier water exchange and permeability with multidelay diffusion‐weighted pseudo‐continuous arterial spin labeling

Purpose To present a pulse sequence and mathematical models for quantification of blood–brain barrier water exchange and permeability. Methods Motion‐compensated diffusion‐weighted (MCDW) gradient‐and‐spin echo (GRASE) pseudo‐continuous arterial spin labeling (pCASL) sequence was proposed to acquire intravascular/extravascular perfusion signals from five postlabeling delays (PLDs, 1590–2790 ms). Experiments were performed on 11 healthy subjects at 3 T. A comprehensive set of perfusion and permeability parameters including cerebral blood flow (CBF), capillary transit time (τc), and water exchange rate (kw) were quantified, and permeability surface area product (PSw), total extraction fraction (Ew), and capillary volume (Vc) were derived simultaneously by a three‐compartment single‐pass approximation (SPA) model on group‐averaged data. With information (i.e., Vc and τc) obtained from three‐compartment SPA modeling, a simplified linear regression of logarithm (LRL) approach was proposed for individual kw quantification, and Ew and PSw can be estimated from long PLD (2490/2790 ms) signals. MCDW‐pCASL was compared with a previously developed diffusion‐prepared (DP) pCASL sequence, which calculates kw by a two‐compartment SPA model from PLD = 1800 ms signals, to evaluate the improvements. Results Using three‐compartment SPA modeling, group‐averaged CBF = 51.5/36.8 ml/100 g/min, kw = 126.3/106.7 min−1, PSw = 151.6/93.8 ml/100 g/min, Ew = 94.7/92.2%, τc = 1409.2/1431.8 ms, and Vc = 1.2/0.9 ml/100 g in gray/white matter, respectively. Temporal SNR of MCDW‐pCASL perfusion signals increased 3‐fold, and individual kw maps calculated by the LRL method achieved higher spatial resolution (3.5 mm3 isotropic) as compared with DP pCASL (3.5 × 3.5 × 8 mm3). Conclusion MCDW‐pCASL allows visualization of intravascular/extravascular ASL signals across multiple PLDs. The three‐compartment SPA model provides a comprehensive measurement of blood–brain barrier water dynamics from group‐averaged data, and a simplified LRL method was proposed for individual kw quantification.