Inherited leukodystrophies (LD) are rare genetic white matter disorders. Identifying quantitative imaging biomarkers could significantly assist in diagnosis and therapeutic monitoring. While white matter degeneration is the hallmark of LD, the involvement of deep gray matter (DGM) nuclei remains underexplored. Recently developed techniques, like DECOMPOSE-QSM, help separate iron and myelin in the brain, potentially offering insights into DGM pathological alterations in LD.

This preliminary study examined DGM nuclei in LD patients to analyze myelination and iron deposition patterns. Five patients (aged 23-30) with different genetic mutations and nine healthy controls (aged 30-40) were studied via MRI, including multi-echo GRE, T2-weighted FLAIR, and T1-weighted MPRAGE sequences. From GRE phase data, susceptibility maps were computed via iLSQR and paramagnetic and diamagnetic susceptibility components (PCS and DCS) were estimated using DECOMPOSE-QSM. Regions of interest (ROIs) in DGM structures like the caudate nucleus and putamen were analyzed for age-corrected susceptibility differences.

Results showed increased susceptibility in globus pallidus and putamen in LD patients and higher PCS not only in these ROIs but also in substantia nigra, potentially indicating higher PCS sensitivity to iron overload than QSM. We found lower absolute DCS in globus pallidus, putamen, and dentate nucleus, suggesting a reduction of myelination. The t-score analysis of individual subjects revealed distinct patterns of alterations, which may be specific to each genetic mutation.

This study highlights the significance of iron and myelin changes in DGM structures in LD. Mapping these alterations could provide valuable biomarkers for diagnosing and tracking disease progression in LD patients.

Acknowledgement

This study was partially supported by the Italian Ministry of Health under the grant “RC 2024” to IRCCS Fondazione Stella Maris and the grant FIABA PNRR-MR1-2022-12375648 funded by the European Union – Next Generation EU – NRRP M6C2 – Investment 2.1 Enhancement and strengthening of biomedical research in the NHS.