Background <p>The underlying pathogenesis of New daily persistent headache (NDPH) is currently unknown. Abnormal iron deposition in specific brain regions has been reported to be associated with the pathogenesis of migraine. This study aimed to investigate the role of iron metabolism disorders in the pathogenesis of NDPH using quantitative susceptibility mapping (QSM).</p> Methods <p>Twenty-five NDPH patients and 43 gender- and age-matched healthy controls (HCs) were recruited. 3D T1-weighted images (T1WI) and QSM sequences were performed at a 3.0 T MRI scanner. Voxel-based analysis was used to compare differences in iron content between NDPH and HC groups after QSM maps were normalized to the Montreal Neurological Institute space. The correlations between QSM values and clinical assessment scale scores were also assessed.</p> Results <p>There were significant differences in iron levels in the right cerebellar lobule VIII, right insula, and left gyrus rectus between the NDPH patients and the HC group. Compared to the HC group, patients with NDPH showed higher iron deposition in these three regions. There was no significant correlation between the QSM values and the scores of the clinical scales in these three regions.</p> Conclusions <p>Our findings indicated that the metabolic disorder of iron deposition in specific areas of the brain may be related to the underlying pathogenesis of patients with NDPH. These findings should be regarded as preliminary exploratory results, suggesting a possible involvement of iron metabolism in the mechanisms of NDPH, which requires further validation in subsequent studies.</p>