7T multimodal MRI reveals structural-functional-quantitative susceptibility mapping abnormalities of new daily persistent headache

New daily persistent headache (NDPH) is a rare, refractory primary headache with an unclear pathophysiological mechanism. Previous neuroimaging studies on NDPH have been largely limited to 3T MRI, which fails to thoroughly reveal microstructural changes, particularly subregional abnormalities and iron metabolism alterations. Based on this, the present study employs 7T multimodal imaging techniques to investigate structural, functional, and iron metabolism abnormalities in the whole brain and, in particular, the changes in subregions of the limbic system. A total of 23 individuals with NDPH and 23 healthy controls (HCs) underwent 7T MRI, including T1-weighted three-dimensional magnetization-prepared 2 rapid acquisition gradient echo (3D-T1WI-MP2RAGE) and resting-state fMRI (rs-fMRI); among these patients, 19 also underwent quantitative susceptibility mapping (QSM). Structural volumes, functional metrics (fractional amplitude of low-frequency fluctuations [fALFF], regional homogeneity [ReHo]), and iron deposition (assessed via QSM) were analyzed, and their correlations with clinical parameters (e.g., headache history, anxiety/depression scores) were examined. Compared to HCs, individuals with NDPH exhibited significantly less volume in the right accumbens area and left caudal anterior cingulate cortex after false discovery rate (FDR) correction. Widespread changed fALFF and ReHo values were observed, with correlations to clinical features. QSM values were decreased in right paracentral, right cuneus and left precentral with increasing in left rostral middle frontal. 7T multimodal MRI identifies widespread structural, functional, and iron metabolism abnormalities in NDPH, particularly in limbic subregions, highlighting a “pain-emotion” interaction mechanism. These findings provide preliminary insights into NDPH pathogenesis.