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

Abstract

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 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. Results: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 mm 3 isotropic) as compared with DP pCASL (3.5 × 3.5 × 8 mm 3 ). 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 w quantification. K E Y W O R D S blood-brain barrier (BBB), diffusion-weighted arterial spin labeling (DW-ASL), water exchange rate (k w ), water permeability (PS w )This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Quantification of T1 and T2 of subarachnoid CSF: Implications for water exchange between CSF and brain tissues

“…Based on our T 1 data, the brain-CSF exchange rate, k, is approximately 0.94 min −1 . This rate is much slower than the water exchange rate across the blood-brain barrier (over 100 min −1 in human adults [27][28][29][30][31] ) but is consistent with the findings by Petitclerc et al, who reported that the water exchange time from the brain tissue (or blood) to the CSF was 60s in the SAS. 17 Our simulation results also demonstrated the effect of tissue T 1 on the SAS CSF T 1 value.…”

Regional differences in the link between water exchange rate across the blood–brain barrier and cognitive performance in normal aging

“…The use of a relatively low-resolution DP-ASL sequence limits our ability to investigate potential lateralization effects in the relationship between k w and cognition, particularly affecting voxel clusters near the midline. Future research using higher-resolution DP-ASL sequences [ 109 ] will be better positioned to investigate potential lateralization effects.…”

Developing blood-brain barrier arterial spin labelling as a non-invasive early biomarker of Alzheimer’s disease (DEBBIE-AD): a prospective observational multicohort study protocol

“… 17 We will extend this number to provide a more robust estimation of reproducibility by including 50 healthy controls for test–retest analysis. Additionally, the Dementia Prevention Research Clinic (DPRC) cohort aims to compare DW-ASL 18 with ME-ASL measurements in 40 healthy controls to investigate if the two ASL techniques used to measure BBB water permeability provide similar information.…”

“…RQ1A will investigate the reproducibility of BBB-ASL in a larger cohort of healthy volunteers (n=50). Additionally, we aim to compare the two most-used BBB-ASL acquisition techniques: multi-echo (ME) and diffusion-weighted (DW) ASL 17 18…”