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Arterial Spin Labeling (ASL) is a non-invasive, non-contrast, perfusion imaging technique which is inherently SNR limited. It is, therefore, important to carefully design scan protocols to ensure accurate measurements. Many pseudo-continuous ASL (PCASL) protocol designs have been proposed for measuring cerebral blood flow (CBF), but it has not yet been demonstrated which design offers the most accurate and repeatable CBF measurements. In this study, a wide range of literature PCASL protocols were first optimized for CBF accuracy and then compared using Monte Carlo simulations and in vivo experiments. The protocols included single-delay, sequential and time-encoded multi-timepoint protocols, and several novel protocol designs, which are hybrids of time-encoded and sequential multi-timepoint protocols. It was found that several multi-timepoint protocols produced more confident, accurate, and repeatable CBF estimates than the single-delay protocol, while also generating maps of arterial transit time. Of the literature protocols, the time-encoded protocol with T1-adjusted label durations gave the most confident and accurate CBF estimates in vivo (16% and 40% better than single-delay), while the sequential multi-timepoint protocol was the most repeatable (20% more repeatable than single-delay). One of the novel hybrid protocols, HybridT1-adj, was found to produce the most confident, accurate and repeatable CBF estimates out of all the protocols tested in both simulations and in vivo (24%, 47%, and 28% more confident, accurate, and repeatable than single-delay in vivo). The HybridT1-adj protocol makes use of the best aspects of both time-encoded and sequential multi-timepoint protocols and should be a useful tool for accurately and efficiently measuring CBF.

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ASL, Accuracy, Arterial spin labeling, CBF, Cerebral blood flow, Perfusion, Protocol optimization, Repeatability, Adult, Brain, Cerebrovascular Circulation, Female, Humans, Magnetic Resonance Imaging, Male, Monte Carlo Method, Perfusion Imaging, Reproducibility of Results, Spin Labels, Young Adult