Selective nigrosome vulnerability in Parkinson's disease revealed by histology-anchored ultra-high-field quantitative MRI
- 1Norwegian University of Science and Technology; University of Oslo; Ostfold Hospital Trust.
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.
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BibTeX
@misc{li2026selective,
title = {{Selective nigrosome vulnerability in Parkinson's disease revealed by histology-anchored ultra-high-field quantitative MRI}},
author = {R. Li and E. Kirilina and P.-L. Bazin and K. E. Stige and R. Unsgard and M. Brammerloh and I. Gylterud Kvalsgard and A. L. Kristoffersen and E. M. Berntsen and P. E. Goa and P. Damier and C. Tzoulis and T. P. Doan},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.24.754224},
url = {https://www.biorxiv.org/content/10.64898/2026.09.24.754224v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Selective nigrosome vulnerability in Parkinson's disease revealed by histology-anchored ultra-high-field quantitative MRI
AU - R. Li
AU - E. Kirilina
AU - P.-L. Bazin
AU - K. E. Stige
AU - R. Unsgard
AU - M. Brammerloh
AU - I. Gylterud Kvalsgard
AU - A. L. Kristoffersen
AU - E. M. Berntsen
AU - P. E. Goa
AU - P. Damier
AU - C. Tzoulis
AU - T. P. Doan
PY - 2026
DA - 2026/09/24
PB - bioRxiv
DO - 10.64898/2026.09.24.754224
UR - https://www.biorxiv.org/content/10.64898/2026.09.24.754224v1
AB - 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.
ER -