Arterial Spin Labeling (ASL) is a non-invasive MRI technique to measure cerebral blood flow (CBF) and other perfusion related parameters such as arterial transit time (ATT). At present, main areas of interest clinically are cerebrovascular disease, dementia and neuro-oncology.
Arterial Spin Labeling (ASL) is a non-invasive MRI technique to measure cerebral blood flow (CBF) and other perfusion related parameters such as arterial transit time (ATT). At present, main areas of interest clinically are cerebrovascular disease, dementia and neuro-oncology [1].
Cerebrovascular disease
In cerebrovascular disease, ASL is of particular interest owing to its quantitative nature and its capability to determine cerebral arterial territories. In acute stroke, the source of the collateral blood supply in the penumbra may be visualised. In chronic cerebrovascular disease, the extent and severity of compromised cerebral perfusion can be visualised, which may be used to guide therapeutic or preventative intervention. ASL has potential for the detection and follow-up of arteriovenous malformations. While ASL in the context of (sub)acute ischaemia has probably only limited value, its role in assessing risks and consequences of chronic cerebrovascular disease is supported by the published literature. In particular, ASL can be used to assess the cerebrovascular reserve and the hypoperfusion syndrome. The cerebrovascular reserve capacity (CRC) describes to what extent cerebral perfusion is able to increase in the context of vasodilatatory challenges. While at present the CRC is not taken into account to set the indication for carotid artery surgery, recent studies indicate that the risk of cerebral infarction in patients with carotid artery stenosis is considerably higher with reduced CRC [2]. ASL is well suited to assess the CRC because measurements can be repeated, are non-invasive and are quantitative. Exogenous contrast-enhanced techniques, as well as being invasive, suffer from circulating contrast medium for several days, precluding repeated measurements within this time frame.
Dementia
In the work-up of dementia patients, ASL is proposed as a diagnostic alternative to PET. It can easily be added to the routinely performed structural MRI examination. In patients with established Alzheimer’s disease and frontotemporal dementia, hypoperfusion patterns are seen that are similar to hypometabolism patterns seen with PET. CBF measurements derived from ASL correlate with gold standard H2[15O]-PET [3,4]. Diagnosis and evaluation of neurodegenerative disease is a rapidly expanding application of ASL, particularly with recent growth in biomarker exploration for Alzheimer’s disease (AD) and dementia. Not only does the quantification of perfusion offer a role in monitoring disease progression, which is potentially useful for clinical trials of new therapies, it may also be able to provide helpful diagnostic information if characteristic perfusion patterns can be established. Changes in brain metabolism and perfusion often precede observable structural changes such as atrophy in neurodegenerative diseases. This is most commonly assessed with fluor-deoxyglucose (FDG)-PET, which is not always cost-effective [5] and has limited availability, in contrast to ASL, which can be added to the routine structural MRI examination at low incremental cost and only 5 minutes of additional scan time.
Neuro-oncology
Studies on ASL in brain tumour imaging indicate a high correlation between areas of increased CBF as measured with ASL and increased cerebral blood volume as measured with dynamic susceptibility contrast enhanced perfusion imaging. Major advantages of ASL for brain tumour imaging are the fact that CBF measurements are not influenced by breakdown of the blood brain barrier, as well as its quantitative nature, facilitating multicentre and longitudinal studies. While it may not be appropriate to compare perfusion values determined with different techniques, multiple studies seem to indicate that DSC and ASL findings correlate well. Although DSC perfusion is more widely used to evaluate brain tumours, Lehmann et al. [6] found that pCASL detected gliomas, metastases, and meningiomas on a 3T scanner as accurately as DSC, and Järnum et al. [7] reported a similar correlation for a variety of tumour classifications. More recently, Hirai et al. [8] found that ASL measurements nearly matched DSC quantifications of regional CBF in gliomas, and van Westen et al. [9] reported ASL and DSC blood volume correlation for various intracranial tumours. Perfusion in high-grade tumours can be measured with ASL before and after treatment to assess response and progression. This is useful in the context of anti-angiogenic treatment: in a case report of a patient treated for recurrent glioblastoma, ASL illustrated tumour progression before conventional MRI did [10]. ASL was furthermore reported to be more effective than DSC at distinguishing radiotherapy-induced necrosis from high-grade glioma recurrence (sensitivity >90%) [11].
Is the clinic ready for ASL?
Despite all available evidence that ASL performs as well, if not better than contrast-enhanced perfusion imaging, routine clinical use of ASL is still limited to few centres. Why is this? There are a number of potential factors, such as the low SNR compared to other imaging modalities. ASL techniques can be complicated and have traditionally not been widely compatible with commercial scanners. The utility and benefits of ASL are often eclipsed by the greater prevalence of modalities such as DSC-MRI; some clinicians may not request ASL as they are not accustomed to non-invasive CBF quantification [12]. In addition to a lack of awareness of the potential clinical utility of ASL, several other issues can be identified that seem to impede widespread clinical use. These include difficulties with image post-processing, a wide variety of available acquisition techniques and parameters, and a lack of guidelines for interpretation [13]. Communication may resolve some of these issues. The establishment of the ASL-network has been a joint effort to rectify the ASL information gap by providing a centralised communication platform [14]. The white paper on the clinical implementation of ASL [15] aimed to reduce the confusion that comes with the many different implementations and provides clear guidelines for sequence implementation.
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