In Vivo Molecular Imaging of Neuroinflammation in Patients with Migraine

Abstract

While the neural correlates of migraine have been widely studied, it remains unclear whether glial cells contribute to neuroinflammation in migraine. One marker of glial activation is the presence of elevated levels of 18 kDa translocator protein (TSPO), and earlier studies have shown that individuals suffering from migraine with aura (MWA) exhibit increased brain TSPO PET signal in a widespread set of regions, compared to healthy controls (Albrecht et al., Neurology 2019, Hadjikhani et al., 2020). The purpose of the present study was to apply [11C]PBR28 PET neuroimaging to extend our initial observations from patients suffering from MWA to include patients with migraine without aura. A total of 24 migraine patients and 17 healthy controls were scanned in a Siemens 3T with PET insert and injected with [11C]PBR28 radioactive tracer. For all subjects, 30-minute static SUV images were acquired ∼60-90 minutes after injection of the tracer. SUV maps were registered to MNI space and smoothed with an 8mm Gaussian filter. SUV ratio (SUVR) images were obtained via intensity-normalization using the cerebellum as pseudo-reference region (showing no statistical difference between the two groups; p>0.5). A non-parametric voxel-wise analysis of the whole brain was performed to evaluate the presence of group differences in the [11C]PBR28 signal. Results show that [11C]PBR28 elevations were observed in the thalamus, insula, hippocampus, pallidum, putamen, SCC and frontal orbital cortex. These cortical and subcortical regions uptake increases were similar to those observed in our previous study in patients with MWA. This work provides in vivo evidence that migraine, with or without aura, may be accompanied by neuroinflammation in humans, paving the way to therapeutic strategies targeting glial activation. Grant support from Boosting mind-body mechanisms and outcomes for chronic pain P01 AT009965-01.