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1. Introduction
Alzheimer’s disease (AD) is a devastating neurodegenerative disorder with an important socioeconomic impact [1]. Mild cognitive impairment (MCI) is considered the prodromal phase of AD, and it is characterized by early cognitive symptoms not severe enough to meet the criteria for dementia [2]. With the prospect of disease-modifying therapies, it is desirable to detect signs of neurodegeneration at an earlier stage of the disease, before neuronal cell destruction is detectable at structural MR imaging as atrophy. Changes in regional brain function may be more dynamic and provide even greater sensitivity to early disease, disease progression, or responses to therapy than changes in regional gray matter volume depicted by structural MRI [3, 4].
Arterial spin labeling- (ASL-) based MRI methods have been applied for detecting regional cerebral blood flow (CBF) perfusion changes in patients with AD or MCI [5–16]. Since the inception of this technique more than 20 years ago [17], the quality of ASL-derived perfusion maps has reached a level that makes the method useful for many clinical and research applications. Important advantages of this technique are its noninvasiveness (since magnetically labeled protons in blood are used as a tracer) and short acquisition time at high magnetic field strengths (3.0 T) [18]. ASL has been validated extensively against other methods that use exogenous contrast agents, such as Positron Emission Tomography (PET) [19], and ASL implementation are now commercially available on all major MRI platforms, with demonstrated reproducibility in multicenter studies [20, 21]. The ability to quickly and noninvasively obtain CBF maps should greatly enhance the understanding of the hemodynamic mechanisms related to neurodegeneration [17, 22]. Since MRI scanners are more widely available than PET scanners (and also less expensive), ASL might become an alternative for FDG-PET [23, 24], allowing a higher throughput of patients. However, an important drawback for the implementation of ASL in clinical settings has been the lack of standardized protocols. Recently, international guidelines [25] and consensual initiatives have been developed to account for this issue.
Nevertheless, the results obtained from ASL studies in AD and MCI are still controversial....