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Selective nigrosome vulnerability in Parkinson's disease revealed by histology-anchored ultra-high-field quantitative MRI

Created on 01 Oct 2026

Authors

Li, R., Kirilina, E., Bazin, P.-L., Stige, K. E., Unsgard, R., Brammerloh, M., Gylterud Kvalsgard, I., Kristoffersen, A. L., Berntsen, E. M., Goa, P. E., Damier, P., Tzoulis, C., Doan, T. P.

Abstract

Selective vulnerability is a hallmark of Parkinson's disease (PD): post-mortem, dopamine-containing cell loss in the substantia nigra first and most severely affects calbindin-poor compartments termed nigrosomes. Testing this in vivo has been limited by circularity, as MRI studies have delineated nigrosomes from the same disease-related contrast they then measure. Here, we warp histology-derived, calbindin-validated probabilistic masks of nigrosomes 1-5 into a cohort-specific multimodal 7 Tesla quantitative MRI template, providing a degeneration-independent anatomical scaffold, in 28 patients with PD and 28 age- and sex-matched controls. In controls, nigrosomes differ from the surrounding nigral matrix in magnetic susceptibility and R1. PD shifts nigrosomal values upward relative to the matrix in susceptibility, R2*, and R1, concentrated in nigrosomes 1, 2, and 4, whereas whole-nigra analysis shows no group difference. Within the matrix, disease effects are largest caudally and emerge dorsally from the ventral tier, and susceptibility alterations in nigrosomes 1 and 4 track contralateral motor symptoms asymmetry. The multimodal pattern suggests that the detectable signal reflects predominantly secondary, iron-associated glial processes rather than neuronal loss itself. These findings recover the post-mortem spatial pattern of nigral vulnerability in vivo and establish a degeneration-independent framework for subregional nigral imaging in PD.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 01 Oct 2026.

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