Perfusion imaging by arterial spin labeling in migraine: A literature review

Abstract

Arterial spin labeling (ASL) is a non-invasive magnetic resonance imaging (MRI) method for the assessment of cerebral blood flow (CBF). This review summarizes recent ASL-based investigations in adult and pediatric patients with migraine with aura, migraine without aura, and chronic migraine. A systematic search according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted within PubMed and reference sections of articles identified from April 2014 to November 2022. Out of 236 initial articles, 20 remained after filtering, encompassing data from 1155 subjects in total. Cross-sectional studies in adults showed inconsistent results, while longitudinal studies demonstrated that cerebral perfusion changes over the migraine cycle can be tracked using ASL. The most consistent findings were observed in ictal states among pediatric migraine patients, where studies showed hypoperfusion matching aura symptoms during early imaging followed by hyperperfusion. Overall, ASL is a useful but currently underutilized modality for evaluating cerebral perfusion in patients with migraine. The generalizability of results is currently limited by heterogeneities regarding study design and documentation of clinical variables (e.g., relation of attacks to scanning timepoint, migraine subtypes). Future MRI studies should consider augmenting imaging protocols with ASL to further elucidate perfusion dynamics in migraine.

Keywords: Arterial spin labeling; cerebral blood flow; headache; magnetic resonance imaging; perfusion.

Figure 1.

Concept of pseudo-continuous arterial spin labeling (pCASL). (a) Inflowing blood is magnetically labeled (indicated by the yellow section of the internal carotid artery [ICA]) when passing the labeling plane (light yellow) using a train of short radiofrequency pulses. The cerebral volume of interest (green box) is imaged, and the tissue signal is not influenced by any labeled blood (blue overlay). (b) As the now labeled blood continues to travel towards the brain to perfuse the tissue, the tissue magnetization is altered (blue/yellow overlay). The transit time is considered by introducing a post-label delay (PLD) prior to imaging. By subtracting from the prior image with no effective labeling (a), perfusion can by quantified in terms of cerebral blood flow (CBF). Figure created with BioRender.com.

Figure 2.

Literature selection. This figure shows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow chart for our literature search and demonstrates the number of studies excluded at different stages of the literature search procedure. Examples for exclusion reasons: article types outside the inclusion criteria (e.g., literature reviews, case reports); false topic, referring to articles not dealing with ASL investigations of migraine; too few participants. Literature search was conducted according to a previously registered protocol (International Prospective Register of Systematic Reviews [PROSPERO] database, CRD42021238822, Supplementary Material 1), with the following adaptions after the initial search: extension of surveyed timeframe from January 2021 to November 2022; inclusion of studies in pediatric cohorts; longitudinal studies with a threshold of a minimum of 10 instead of 15 investigated participants.

Figure 3.

Migraine pain matrix and cross-sectional perfusion changes in migraine patients compared to healthy controls (HC). This figure depicts areas involved in the perception of migraine pain as reported by Ashina (a, green), vice versa the perfusion changes of migraine patients compared to HC are shown as reported in the reviewed literature (b, red & blue). Red markers indicate hyperperfusion, and blue markers indicate hypoperfusion in patients compared to HC. Data visualized in b is taken from the cross-sectional studies reviewed across all subtypes of migraine. Notably, while some overlap appears to exist (thalamus [Th], superior temporal gyrus [STG], insula [Ins], visual cortex [VisC], precentral gyrus [PrCG], and postcentral gyrus [PoCG]), the observed perfusion changes were mostly identified in different studies with no replication between different publications. AuC: auditory cortex; CrbVerm: cerebellar vermis; ECT: ectorhinal cortex; MFG: middle frontal gyrus; NucA: nucleus accumbens; OFC: orbitofrontal cortex; RspC: retrosplenial cortex; r: right; SpV: spinal trigeminal nucleus; SPL: superior parietal lobule; SSN: superior salivatory nucleus; SMA: supplementary motor area; vl: ventrolateral; V5: visual motion area. Areas within the left hemisphere are labeled with initial letter “l”, areas within the right hemisphere are labeled with initial letter “r”. Figure created with BioRender.com.

Figure 4.

Cortical spreading depolarization (CSD) and perfusion. This figure depicts a schematic representation of the presumed connection between CSD and perfusion. (a) CSD (right hemisphere, green) begins in occipital areas and spreads in rostral direction. (b) Following initial depolarization, hyperpolarization (yellow) sets in, accompanied by initial hypoperfusion (left hemisphere, blue). (c) Following initial hypoperfusion, a relative hyperperfusion analogous to postischemic luxury perfusion sets in (left hemisphere, gradient red). (d) In the subacute phase, hyperperfusion has supplanted the initial hypoperfusion (left hemisphere, red). Figure created with BioRender.com.