Dynamic fluctuations in brain iron content during migraine attacks: insights from relaxometry and diffusion tensor imaging

Background: There is evidence that iron metabolism may play a role in the underlying pathophysiological mechanism of migraine. Studies using $R_2^{\ast }$ (=1/ $T_2^{\ast }$ ) relaxometry, a common MRI-based iron mapping technique, have reported increased $R_2^{\ast }$ values in various brain structures of migraineurs, indicating iron accumulation compared to healthy controls.

Purpose: To investigate whether there are short-term changes in $R_2^{\ast }$ during a migraine attack.

Population: 26-year-old male patient diagnosed with episodic migraine with aura according to ICHD-3 criteria.

Sequence: 3 T, 64-channel head coil, for quantification of $R_2^{\ast }$ relaxation a multi-echo gradient echo (GRE) sequence with TE = 4.92, 9.84, 14.7, 19.6, 24.6 and 29.51 ms, TR = 35 ms, flip angle = 15°, and 0.9 × 0.9 × 0.9 mm³ isotropic resolution was used.

Assessment: Quantitative MRI, including $R_2^{\ast }$ relaxometry and diffusion tensor imaging (DTI), was acquired from a migraine patient on 21 consecutive days, including migraine-free days and days with a migraine attack.

Statistical test: Statistical analysis was performed using R, the Shapiro-Wilk test, the t-test and Mann Whitney U test, analysis of variance (ANOVA) or Kruskal-Wallis test, depending on the distribution of the data. p-value <0.05 was considered significant.

Results: Significant difference in $R_2^{\ast }$ was found between the left and right hemispheres during a migraine attack. An increase in $R_2^{\ast }$ was observed in the left hemisphere, whereas in the right hemisphere $R_2^{\ast }$ was found to decrease. In the left cerebral white matter, $R_2^{\ast }$ increased by 1.8% (p = 0.021), in the right cerebral white matter, $R_2^{\ast }$ anisotropy decreased by 17% (p = 0.011) during a migraine attack.

Data conclusion: Our study showed a decrease and increase in iron content during the migraine cycle. Furthermore, during a migraine attack, white matter iron content increased, accompanied by a decrease in anisotropic tissue components, suggesting additional changes in vascular components.