Purpose Arterial spin labeling (ASL) MRI is a non‐invasive perfusion imaging technique that is inherently SNR limited, so scan protocols ideally need to be rigorously optimized to provide the most accurate measurements. A general framework is presented for optimizing ASL experiments to achieve optimal accuracy for perfusion estimates and, if required, other hemodynamic parameters, within a fixed scan time. The effectiveness of this framework is then demonstrated by optimizing the post‐labeling delays (PLDs) of a multi‐PLD pseudo‐continuous ASL experiment and validating the improvement using simulations and in vivo data. Theory and Methods A simple framework is proposed based on the use of the Cramér‐Rao lower bound to find the protocol design which minimizes the predicted parameter estimation errors. Protocols were optimized for cerebral blood flow (CBF) accuracy or both CBF and arterial transit time (ATT) accuracy and compared to a conventional multi‐PLD protocol, with evenly spaced PLDs, and a single‐PLD protocol, using simulations and in vivo experiments in healthy volunteers. Results Simulations and in vivo data agreed extremely well with the predicted performance of all protocols. For the in vivo experiments, optimizing for just CBF resulted in a 48% and 15% decrease in CBF errors, relative to the reference multi‐PLD and single‐PLD protocols, respectively. Optimizing for both CBF and ATT reduced CBF errors by 37%, without a reduction in ATT accuracy, relative to the reference multi‐PLD protocol. Conclusion The presented framework can effectively design ASL experiments to minimize measurement errors based on the requirements of the scan.

This review article provides an overview of the current status of velocity-selective arterial spin labeling (VSASL) perfusion MRI and is part of a wider effort arising from the International Society for Magnetic Resonance in Medicine (ISMRM) Perfusion Study Group. Since publication of the 2015 consensus paper on arterial spin labeling (ASL) for cerebral perfusion imaging, important advancements have been made in the field. The ASL community has, therefore, decided to provide an extended perspective on various aspects of technical development and application. Because VSASL has the potential to become a principal ASL method because of its unique advantages over traditional approaches, an in-depth discussion was warranted. VSASL labels blood based on its velocity and creates a magnetic bolus immediately proximal to the microvasculature within the imaging volume. VSASL is, therefore, insensitive to transit delay effects, in contrast to spatially selective pulsed and (pseudo-) continuous ASL approaches. Recent technical developments have improved the robustness and the labeling efficiency of VSASL, making it a potentially moreThis is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

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 T 1 -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, Hybrid T1 -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 Hybrid T1 -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.