Quantification of blood-brain barrier water exchange and permeability with multidelay diffusion-weighted...

To present a pulse sequence and mathematical models for quantification of blood-brain barrier water exchange and permeability.

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_c ), and water exchange rate (k_w ) were quantified, and permeability surface area product (PS_w ), total extraction fraction (E_w ), and capillary volume (V_c ) were derived simultaneously by a three-compartment single-pass approximation (SPA) model on group-averaged data. With information (i.e., V_c and τ_c ) obtained from three-compartment SPA modeling, a simplified linear regression of logarithm (LRL) approach was proposed for individual k_w quantification, and E_w and PS_w 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_w by a two-compartment SPA model from PLD = 1800 ms signals, to evaluate the improvements.

Using three-compartment SPA modeling, group-averaged CBF = 51.5/36.8 ml/100 g/min, k_w  = 126.3/106.7 min^-1 , PS_w  = 151.6/93.8 ml/100 g/min, E_w  = 94.7/92.2%, τ_c  = 1409.2/1431.8 ms, and V_c  = 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_w 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 ).

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_w quantification.