Functional magnetic resonance imaging of regional impaired cerebrovascular reactivity for migraineurs in the interictal state

There is still an unmet need of mapping the potential impairment of cerebrovascular reactivity (CVR) in episodic migraineurs in the interictal state. We mapped CVR of 6 episodic migraineurs and 5 headache-free controls (HC) with blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) under carbon dioxide (CO2) challenge of 30-second epochs with an elevated end-tidal partial pressure of CO2 (PETCO2) by 4-8mmHg. Three migraineurs have migraine without aura (MOA) and the other three have migraine with aura (MA). We found that only MOA subjects showed a reduced or negative BOLD response to CO2 at the red nucleus. All 3 MOA subjects were characterized by bilateral posterior communicating artery hypoplasia (bPCAH) identified by MR angiography (MRA). MOA and HC subjects did not show any significant difference in BOLD responses to CO2 challenge in cortical and white matter while MA subjects showed poor positive association between BOLD responses and PETCO2 in large territories of the cortex and white matter tracts. The combined use of fMRI under CO2 challenge and MRA presented a unique approach to investigate the mechanisms of episodic migraine in the interictal state demonstrating for the first time negative CVR at the red nucleus of the midbrain in patients with MOA. CVR maps obtained from both the midbrain and cortical regions provided various signatures to explore the differences between migraineurs and HC and between MOA and MA.