Diagnostics to look beyond the normal appearing brain tissue (NABT)? A neuroimaging study of patients with primary headache and NABT using magnetization transfer imaging and diffusion magnetic resonance.

OBJECTIVE: Novel diagnostics can allow us to "look beyond" normal-appearing brain tissue (NABT) to unravel subtle alterations pertinent to the pathophysiology of primary headache, one of the most common complaints of patients who present to their physician across the medical specialties. Using both magnetization transfer imaging (MTI) and diffusion weighted imaging (DWI), we assessed the putative microstructural changes in patients with primary headache who display the NABT on conventional magnetic resonance imaging (conventional MRI). METHODS: Subjects were 53 consecutive patients with primary headache disorders (40 = migraine with aura; 9 = tension headache; 4 = cluster headache) and 20 sex- and age-matched healthy volunteers. All subjects underwent evaluation with MRI, MTI, and DWI in order to measure the magnetization transfer ratio (MTR) and the apparent diffusion coefficient (ADC), respectively, in eight and six different regions of interest (ROIs). RESULTS: Compared to healthy controls, we found a significant 4.3 % increase in the average ADC value of the occipital white matter in the full sample of patients (p = 0.035) and in patients with migraine (p = 0.046). MTR values did not differ significantly in ROIs between patients and healthy controls (p > 0.05). CONCLUSIONS: The present study lends evidence, for the first time to the best of our knowledge, for a statistically significant microstructural change in the occipital lobes, as measured by ADC, in patients with primary headache who exhibit a NABT on MRI. Importantly, future longitudinal mechanistic clinical studies of primary headache (e.g., vis-à-vis neuroimaging biomarkers) would be well served by characterizing, via DWI, occipital white matter microstructural changes to decipher their broader biological significance.