Arterial Spin Labeling (ASL) is a method for non-contrast-enhanced perfusion imaging mainly used in the brain and offers the possibility to obtain reliable information about underlying pathologies that influence perfusion [1]. One pathology that influences cerebral blood flow (CBF) are carotid artery stenoses that cause reduced blood flow in the affected hemisphere [2]. It has been shown multiple times that perfusion imaging can easily detect such an abnormality as these methods acquire the reduced signal in the affected hemisphere [3,4]. ASL is performed by magnetically labeling inflowing blood by inversion of the blood spins and then waiting until the blood has arrived in the brain tissue which is commonly denoted as the Post-Labeling Delay (PLD). Additionally, a second image without inversion is acquired and subsequently subtracted to remove the signal of static brain tissue, resulting in a perfusion weighted image [1]. As the affected hemisphere in the case of unilateral arterial stenosis receives less blood compared to the contralateral side at the same time, a signal difference thus corresponds to reduced blood flow caused by the stenosis. ASL can be performed using a single PLD as just described, but also using multiple PLDs to track the blood signal over time and create arrival time maps and catch the signal variations over time as it is commonly performed in contrast-agent enhanced perfusion imaging such as dynamic susceptibility contrast (DSC) imaging [5,6]. However, acquiring multiple PLDs is time-consuming and the risk of movement between the individual scans is high which influences the accuracy of the acquired images and makes the clinical use on a daily basis unattractive. As these issues make time-resolved acquisitions less attractive for clinical routine use despite being commonly denoted as providing a higher accuracy in diagnostic performance in multiple diseases, there is an underutilization of ASL in clinical routine [[7], [8], [9], [10]]. Finally, a different approach that can be used are two PLDs that can be used to gather information about the changes at two time-points while keeping the time penalty at a minimum [11]. Therefore, when comparing the benefits and drawbacks between single-, two- and multi-PLD ASL, the question remains which approach should be used in a clinical routine setting. Previous work already investigated both symptomatic and asymptomatic carotid artery stenosis by assessing collateral flow or calculating the spatial coefficient of variation using multi-PLD ASL or using the arterial transit artifact (i.e., remaining label in the major arteries) in single-PLD ASL as surrogate marker for the detection and evaluation of carotid artery stenosis [[12], [13], [14]]. A direct comparison whether multi-PLD or single/two-PLD is the method of choice when it comes to a clinical setting however remains unanswered. As most clinically used scanners only have single-PLD available rather than a time-efficient multi-PLD solution, the aim of this study therefore is to directly compare the single-PLD, two-PLD and multi-PLD approach as tools for both the initial diagnosis of unilateral asymptomatic carotid artery stenosis, and also for follow-up evaluation.
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