Quantification of magnetic susceptibility to assess intracerebral iron levels: towards a biomarker for monitoring the progression of intracerebral iron accumulation in NBIA?
Chloé Angelini (1, 2) , Cyril Goizet (3, 2) , Patricia Fergelot (1, 2) , Ludovic de Rochefort (4) , Samira Mchinda (4) , Anis Benyahia (4) , Thomas Tourdias (5, 6) , Stephane Roche (4)
13e assises de génétique humaine et médicale, Jan 2026, Cannes, France
- U1211 INSERM/MRGM – Laboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux)
- INCIA – Institut de Neurosciences cognitives et intégratives d’Aquitaine
- Service de génétique médicale
- Ventio
- U1215 Inserm – UB – Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale
- Neuroimagerie Diagnostique et Thérapeutique, CHU de Bordeaux
Introduction: Neurodegenerative disorders with intracerebral iron accumulation (NBIA) are a group of ultra-rare diseases characterised by iron accumulation visible on brain MRI and progressive neurodegeneration. To date, 11 genes have been identified. The pathophysiology of these diseases involves, in particular, mitochondrial homeostasis, lipid peroxidation, autophagy and iron metabolism, but remains only partially understood. Radiologically, certain imaging patterns are suggestive of specific subtypes, but there is no clear correlation between iron accumulation and the stage of the disease. Current assessment of iron on brain MRI is qualitative, and a quantitative measurement could serve as a useful biomarker for monitoring disease progression. Quantitative Susceptibility Mapping (QSM) enables such quantification. We present here a feasibility study conducted in three female patients with NBIA.
Materials and methods: MRI scans were performed at Bordeaux University Hospital (CER-BDX 2025-224) using a General Electric 3 Tesla MRI system with a 48-channel coil. A 3D gradient-echo sequence (SWAN) was added to the conventional sequences. Following quality control on a phantom, data were collected from three female patients and a matched healthy volunteer. QSM reconstructions were performed using a Python pipeline, based on the MEDI algorithm, to generate R2* and QSM maps and to extract values from the basal ganglia, which had been manually segmented.
Results: The three patients were adult females, carrying BPAN (WDR45 gene), PKAN (PANK2) and MPAN (C19orf12) respectively. Analysis of their MRI scans revealed a significant increase in iron load, particularly in the pallidum (five times that of the control group) as well as in the caudate nucleus, putamen and substantia nigra (twice that of the control group). Each patient exhibited a distinct iron distribution profile, particularly in the pallidum and substantia nigra.
Conclusion: QSM enables accurate quantification of cerebral iron accumulation in NBIA patients using 3T MRI, and reveals distinct profiles across the NBIA subtypes assessed. These preliminary results suggest that QSM could become a relevant biomarker for accurately assessing intracerebral iron load and disease progression over time. It could therefore be incorporated into clinical monitoring and used to evaluate the efficacy of new therapeutic approaches, as an objective and quantitative endpoint.