Non‐Contrast Assessment of Blood–Brain Barrier Permeability to Water: Improved Signal Modeling and Data Acquisition

ABSTRACT Purpose Water‐extraction‐with‐phase‐contrast‐arterial‐spin‐tagging (WEPCAST) MRI is a non‐contrast method to estimate the blood–brain barrier (BBB) permeability to water. Similar to other arterial‐spin‐labeling (ASL) based techniques, signal‐to‐noise ratio is a limitation. This study aims to enhance its reliability via theoretical and experimental improvements. Methods We propose a generalized‐venous‐signal (GVS) model to describe the signal evolution of WEPCAST MRI, with which the control and labeled signals can be utilized to simultaneously estimate the water extraction fraction ( E ) and venous transit time (VTT). We conducted studies to test its feasibility and inter‐visit reproducibility. We further made an experimental improvement by adding a 1‐min blood T 1 scan and investigating its benefit in reducing inter‐subject variations. Results When applying the GVS model‐based method at different locations along the superior sagittal sinus (SSS), VTT increased from anterior to posterior segments while E remained constant, consistent with known physiology. BBB permeability‐surface‐area‐product (PS) revealed a significantly lower CoV of 5.0% ± 4.1% when using the GVS method, in comparison with 8.9% ± 6.5% using the peak‐detection method ( p = 0.002). Blood T 1 was found to be 1725.7 ± 37.2 ms in males and 1799.2 ± 122.4 ms in females. After including subject‐specific blood T 1 in the parametric estimation, inter‐subject CoV in PS was found to be 6.8%, compared with a CoV of 14.2% when using an assumed blood T 1 ( p = 0.004). VTT estimated from WEPCAST was consistent with that measured with a dedicated sequence ( R = 0.757, p = 0.011). Conclusion The reliability of WEPCAST MRI for the measurement of BBB permeability can be improved by incorporating GVS model and individual blood T 1 .