NeuralCipher Research overview
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BackgroundThe pathophysiology of Huntington's disease (HD) remains obscure. Magnetic resonance imaging (MRI) can reveal in vivo molecular changes related to disease pathology.ObjectivesTo investigate catecholaminergic neuronal integrity and subcortical brain iron accumulation in HD employing neuromelanin-sensitive MRI, and quantitative susceptibility mapping (QSM-MRI).MethodsTwenty-five HD gene expansion carriers (HDGECs; 11 premanifest, mean predicted phenoconversion time 21.25 ± 8.28 years) and 25 healthy controls (HC) underwent clinical investigation, measurement of plasma neurofilament light chain (NfL) levels, neuromelanin-sensitive, and QSM-MRI on a 3 T scanner. For neuromelanin analysis, the substantia nigra (SN) and locus coeruleus (LC) areas and contrast-to-noise ratio (CNR) were computed. Regions of interest from the MuSus100 atlas were segmented for QSM-MRI analysis, and susceptibility values extracted using the whole brain mask as reference.ResultsManifest HDGECs showed, on neuromelanin-sensitive MRI analysis, reduced LC and SN areas, and LC CNR compared with HC (P ConclusionsOur findings confirm widespread iron subcortical accumulation in HD, reveal significant noradrenergic neuronal loss, and describe dopaminergic alteration which may reflect ongoing pathology along the nigrostriatal pathway. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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