Arterial spin labeling MRI applied to migraine: current insights and future perspectives

Abstract

Introduction: Advanced neuroimaging techniques have extensively contributed to elucidate the complex mechanisms underpinning the pathophysiology of migraine, a neurovascular disorder characterized by episodes of headache associated with a constellation of non-pain symptoms. The present manuscript, summarizing the most recent progresses of the arterial spin labelling (ASL) MRI techniques and the most significant findings from ASL studies conducted in migraine, is aimed to clarify how ASL investigations are contributing to the evolving insight on migraine pathophysiology and their putative role in migraine clinical setting. ASL techniques, allowing to quantitatively demonstrate changes in cerebral blood flow (CBF) both during the attacks and in the course of interictal period, could represent the melting point between advanced neuroimaging investigations, conducted with pure scientific purposes, and conventional neuroimaging approaches, employed in the diagnostic decision-making processes.

Main body: Converging ASL evidences have demonstrated that abnormal CBF, exceeding the boundaries of a single vascular territory, with biphasic trend dominated by an initial hypoperfusion (during the aura phenomenon but also in the first part of the headache phase) followed by hyperperfusion, characterizes migraine with aura attack and can represent a valuable clinical tool in the differential diagnosis from acute ischemic strokes and epileptic seizures. Studies conducted during migraine without aura attacks are converging to highlight the involvement of dorsolateral pons and hypothalamus in migraine pathophysiology, albeit not able to disentangle their role as "migraine generators" from mere attack epiphenomenon. Furthermore, ASL findings tend to support the presence of perfusion abnormalities in brain regions known to be involved in aura ignition and propagation as well as in areas involved in multisensory processing, in both patients with migraine with aura and migraine without aura.

Conclusion: Although ASL studies have dramatically clarified quality and timing of perfusion abnormalities during migraine with aura attacks, the same cannot be said for perfusion changes during migraine attacks without aura and interictal periods. Future studies with more rigorous methodological approaches in terms of study protocol, ASL technique and sample selection and size are mandatory to exploit the possibility of better understanding migraine pathophysiology and identifying neuroimaging biomarkers of each migraine phase in different migraine phenotypes.

Keywords: Arterial spin labelling; Cerebral blood flow; MRI; Migraine with aura; Migraine without aura.

Fig. 1

ASL perfusion changes for each phase of migraine cycle. A and B CBF maps showing an early left hemisphere hypoperfusion followed by hyperperfusion in areas congruous with aura symptoms (exceeding the boundaries of single vascular territories) (modified from Boulouis et al., 2016 [18]). C Reduced regional CBF in lateral hypothalamus and visual cortex during the preictal phase of migraine attack (modified from Meylakh et al., 2020 [38]). D Increased regional CBF in limbic circuit during the headache phase of migraine (migraine without aura attack) (modified from Stankewitz et al., 2021 [43]). E Increased regional CBF in extrastriate cortex and superior temporal gyrus during the interictal period (migraine with aura) (modified from Michels et al., 2019 [28])