Publication date: Jul 04, 2025

Dorsal nigral hyperintensity (DNH) abnormality associated with excessive iron deposition in the substantia nigra, is recognized as an imaging characteristic of Parkinson’s disease (PD) and can be effectively visualized using 7T MRI. This study was aimed to develop and validate the optimal DNH assessment method as a biomarker for PD, idiopathic rapid eye movement sleep behavior disorder (iRBD), and Parkinson-plus syndromes, and to explore the nigral iron deposition patterns in these diseases. Three-dimensional gradient-echo T2*-weighted images were acquired by 7T MRI from a total of 402 patients and 100 healthy controls (HCs) in two independent cohorts (development and validation cohorts). Seven methods, including four dichotomous methods and three DNH rating scales, were used to assess DNH and evaluate their diagnostic performance. R2* mapping and principal component analysis were performed to assess nigral iron deposition patterns. Bilateral DNH detection rates in the development cohort were 22. 6% for early-stage PD, 3. 7% for advanced PD, 93. 5% for iRBD, 5. 7% for MSA-parkinsonian type, 78. 8% for MSA-cerebellar type, 11. 8% for progressive supranuclear palsy (PSP), and 100% for HC, with similar rates in the validation cohort. A cut-off of 6 on the 6-point visibility scale demonstrated a 100% accuracy for diagnosing early-stage PD in both the development and the validation cohorts. This scale exhibited moderate differential diagnostic performance between early-stage PD and iRBD (area under the curve [AUC] = 0. 940) or MSA-C (AUC = 0. 892). Iron deposition was predominantly in the dorsal and posterior substantia nigra of PD and PSP, the intermediate and posterior substantia nigra of MSA-P, and the ventral substantia nigra of MSA-C. DNH may be preserved in approximately one-quarter of early-stage PD and most MSA-C cases. The 6-point visibility scale on 7T effectively distinguished PD from HC, iRBD, and MSA-C. The nigral iron deposition pattern in PD may help distinguish PD from MSA-P and MSA-C, although it overlaps with that of PSP.

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