Examination of optimized protocols for pCASL: Sensitivity to macrovascular contamination, flow dispersion, and prolonged arterial transit time

Purpose: Previously, multi-post-labeling delays (PLD) pseudo-continuous arterial spin labeling (pCASL) protocols have been optimized for the estimation accuracy of the cerebral blood flow (CBF) with/without the arterial transit time (ATT) under a standard kinetic model and a normal ATT range. This study aims to examine the estimation errors of these protocols under the effects of macrovascular contamination, flow dispersion, and prolonged arrival times, all of which might differ substantially in elderly or pathological groups. Methods: Simulated data for four protocols with varying degrees of arterial blood volume (aBV), flow dispersion, and ATTs were fitted with different kinetic models, both with and without explicit correction for macrovascular signal contamination (MVC), to obtain CBF and ATT estimates. Sensitivity to MVC was defined and calculated when aBV > 0.5%. A previously acquired dataset was retrospectively analyzed to compare with simulation. Results: All protocols showed underestimation of CBF and ATT in the prolonged ATT range. With MVC, the protocol optimized for CBF only (CBFopt) had the lowest sensitivity value to MVC, 33.47% and 60.21% error per 1% aBV in simulation and in vivo, respectively, among multi-PLD protocols. All multi-PLD protocols showed a significant decrease in estimation error when an extended kinetic model was used. Increasing flow dispersion at short ATTs caused increasing CBF and ATT overestimation in all protocols. Conclusion: CBFopt was the least sensitive protocol to prolonged ATT and MVC for CBF estimation while maintaining reasonably good performance in estimating ATT. Explicitly including a macrovascular component in the kinetic model was shown to be a feasible approach in controlling for MVC.