Abstract
OBJECTIVE: Neurodegeneration with brain iron accumulation (NBIA) comprises rare genetic disorders characterized by predominantly extrapyramidal symptoms and iron deposition in the basal ganglia. Conventional magnetic resonance imaging (MRI) detects qualitative changes but cannot accurately quantify iron accumulation. Quantitative susceptibility mapping (QSM) allows precise in vivo quantification of iron, providing insight into the pathophysiology of the disease. METHODS: We studied 27 genetically confirmed NBIA patients and 11 age-matched healthy controls using susceptibility-weighted imaging (SWI) on a 3 Tesla MRI scanner. Basal ganglia regions of interest (ROIs) were manually delineated and QSM values were extracted. RESULTS: Sixteen NBIA patients and 11 controls were analyzed. QSM showed significantly higher iron in the globus pallidus (GP) (p = 0.008), with PKAN patients showing a 2.5-fold increase in GP iron (p = 0.001). MPAN patients showed 2.5 times higher iron in both GP and substantia nigra (SN). A GP iron level > 0.1133 ppm increased the likelihood of PKAN 18-fold. Atypical PKAN cases had 2.5 times higher SN iron levels compared to classic cases. INTERPRETATION: QSM is a sensitive and noninvasive tool for detecting and quantifying iron accumulation in NBIA. The GP consistently showed the highest susceptibility values across subtypes, emphasizing its significant role in disease pathology. Distinct patterns of iron deposition in different NBIA subtypes may reflect subtype-specific mechanisms with diagnostic and therapeutic relevance. Age-related susceptibility changes were found to be significant, reinforcing the need to account for age when interpreting QSM data. More importantly, QSM may serve as a candidate biomarker for longitudinal disease monitoring in future clinical trials targeting disease-modifying therapies in NBIA.