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 (τ ), and water exchange rate (k ) were quantified, and permeability surface area product (PS ), total extraction fraction (E ), and capillary volume (V ) were derived simultaneously by a three-compartment single-pass approximation (SPA) model on group-averaged data. With information (i.e., V and τ ) obtained from three-compartment SPA modeling, a simplified linear regression of logarithm (LRL) approach was proposed for individual k quantification, and E and PS 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 k 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, k  = 126.3/106.7 min , PS  = 151.6/93.8 ml/100 g/min, E  = 94.7/92.2%, τ  = 1409.2/1431.8 ms, and V  = 1.2/0.9 ml/100 g in gray/white matter, respectively. Temporal SNR of MCDW-pCASL perfusion signals increased 3-fold, and individual k maps calculated by the LRL method achieved higher spatial resolution (3.5 mm isotropic) as compared with DP pCASL (3.5 × 3.5 × 8 mm ).

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 k quantification.