Feasibility and Potential of Quantitative Susceptibility Mapping in Neurodegeneration with Brain Iron Accumulation (NBIA) at Clinical Magnetic Field
European Society for Magnetic Resonance in Medicine and Biology, 41st annual scientific meeting; MR to the limits and beyond, Oct 2025, Marseille, France.
Poster presentation
Stéphane Roche (1) , Samira Mchinda (1) , Anis Benyahia (1) , Ludovic De Rochefort (1) , Cyril Goizet (2, 3) , Patricia Fergelot Maurin (2, 3) , Thomas Tourdias (4) , Chloé Angelini (2, 3)
Introduction: Neurodegeneration with brain iron accumulation (NBIA) is a group of extremely rare diseases characterized by intracerebral iron accumulation and progressive neurodegeneration. To date, 11 genes have been implicated in NBIA 1. The pathophysiology of NBIA is partially understood, although several pathways have already been identified, including mitochondrial homeostasis, lipid peroxidation, autophagy and iron metabolism. Although some imaging patterns suggest a specific NBIA subtype, there is no correlation between evolution of iron accumulation, stage of the disease and specific NBIA subtype. A quantitative measure of the iron load could then be used as a biomarker of the disease and for evaluating the pathology severity. Quantitative Susceptibility Mapping (QSM) provides an iron-load quantitative metric2,3, with promising investigations in NBIA at ultra-high magnetic field4,5. Here we show feasibility in a clinical context at 3T.
Materials and methods: MRI data were acquired at Bordeaux Hospital (France) on a General Electric 3 Tesla scanner with 48Rx head coil. A 3D gradient echo multi-echo sequence (SWAN) was applied following the consensus guidelines6 (TA=4.8 min, FoV=224x224x176 mm, voxel size=1 mm isotropic, TR=34.7 ms, TE1=4.34 ms, ∆TE=5 ms, number of echoes=6, flip angle=16°, bandwidth=280 Hz/px, with compress-sensing) after a quality-control analysis on phantom and on a volunteer, the protocol was applied to NBIA patients. QSM reconstructions were performed in a secured-cloud European-based infrastructure7. A pipeline was implemented in Python, to compute R2* and QSM maps using MEDI3,8, and extract values for several regions of interest (ROIs). Basal ganglia ROIs were segmented manually for each subject. Mean and standard deviations were computed in each ROI.
Results: We successfully implemented and validated an acquisition protocol for QSM in accordance with the QSM consensus guidelines, including the ability to use the compressed sensing option to reduce acquisition time without affecting phase for QSM on a clinical 3T system. Based on our quality-control procedures, with the applied protocol, we obtained on phantom a signal-to-noise ratio close to 225 with 1 mm isotropic acquisition providing QSM without significant bias (less than 1 ppb) and a standard deviation below 1 ppb. On the volunteer, average signal-to-noise ratio on the brain was larger than 100, indicating a field-mapping precision better than 1 ppb. Patients analysed are three women, respectively affected by BPAN (linked to a mutation in the WDR45 gene), PKAN (PANK2), and MPAN (C19orf12). Increased iron accumulation in the basal ganglia was observed in NBIA, with a ~5-fold increase in pallidum on average, with values reaching up to more than 1000 ppb (Fig. 1), and a ~2-fold increase in caudate, putamen and substantia nigra on average over each ROIs. Interestingly, our results suggest a specific iron distribution profile in basal ganglia for each patient (Fig. 2), mainly in subtantia nigra and in pallidum.
Conclusion: QSM give access to brain iron accumulation in NBIA patients on a clinical 3T system with clear individual iron accumulation profiles. These preliminary results indicate that QSM could be a useful biomarker to better understand the links between subtypes, affected regions, disease progression and iron accumulation. In the care pathway, it could be used for diagnosis and follow-up in rare diseases involving brain iron accumulation. QSM may provide a useful biomarker to evaluate efficiency and safety in the context of new therapy development.
