Altered brain tissue composition and microstructure during migraine attacks

Abstract Detailed pathophysiological mechanisms causing migraine are still elusive, however, there is evidence that iron metabolization might play a role. Studies using R2 (=1/T2) or R2* (=1/T2*) relaxometry, a common magnetic resonance imaging (MRI) based iron mapping technique, reported increased R2 and R2* values in various brain structures of patients with migraine, indicating an iron accumulation compared to healthy controls. The aim of this first-of-its-kind study was to investigate if there are alterations in R2* in the brain caused by the migraine cycle. Therefore, quantitative MRI, including R2* relaxometry and diffusion tensor imaging (DTI) of a patient with migraine was acquired on 21 consecutive days, comprising headache free days and days with a migraine attack. Combining R2* with DTI, allowed to separate isotropic and anisotropic R2* contributions in white matter. A significant difference in R2* between left and right hemisphere was found in the nucleus accumbens (p = 0.02), the amygdala (p < 0.001) and the pallidum (p < 0.001). During a migraine attack, R2* decreased in the amygdala of the left hemisphere by 13.9% (p = 0.01) and in the nucleus accumbens of the right hemisphere by 7.8% (p = 0.01). In contrast, R2* increased in the caudate of the left hemisphere by 5.3% (p = 0.01). In white matter, isotropic R2* increased by approximately 1.9% (p = 0.04) and anisotropic R2* decreased by approximately 30% (p = 0.02) during a migraine attack. Our study revealed a decrease and increase in iron content in various brain regions during the migraine cycle. Furthermore, white mater iron content increased accompanied by a decrease in anisotropic tissue components during a migraine attack. The observed alterations in R2* indicate that the iron content fluctuates over time depending on the migraine phase. However, the altered iron content reaches normal levels after the migraine attack resolved.