Susceptibility Magnetic Resonance Imaging Correlates with Glial Density and Tau in the Substantia Nigra Pars Compacta

• Published in: Movement disorders 2023-03, Vol.38 (3), p.464-473
• Main Authors: Wang, Ernest W., Brown, Gregory L., Lewis, Mechelle M., Jellen, Leslie C., Pu, Cunfeng, Johnson, Melinda L., Chen, Hairong, Kong, Lan, Du, Guangwei, Huang, Xuemei
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; Atrophy; Autopsy; Basal ganglia; Brain diseases; Brain mapping; Central nervous system diseases; Dopamine receptors; glia; Gliosis; Humans; Iron; Lewy bodies; Magnetic resonance imaging; Magnetic Resonance Imaging - methods; Mesencephalon; Movement disorders; Neurodegeneration; Neurodegenerative diseases; Neuronal-glial interactions; Neuropathology; Paralysis; Parkinson Disease - diagnostic imaging; Parkinson Disease - pathology; Parkinsonian Disorders - pathology; parkinsonism; Pars Compacta; Progressive supranuclear palsy; Retrospective Studies; Substantia nigra; Substantia Nigra - diagnostic imaging; Substantia Nigra - pathology; substantia nigra pars compacta; Susceptibility; susceptibility MRI; Synuclein; tau; Tau protein
• ISSN: 0885-3185; 1531-8257
• DOI: 10.1002/mds.29311

ABSTRACT Background Susceptibility magnetic resonance imaging (MRI) is sensitive to iron‐related changes in the substantia nigra pars compacta (SNc), the key pathologic locus of parkinsonisms. It is unclear, however, if iron deposition in the SNc is associated with its neurodegeneration. Objective The objective of this study was to test whether susceptibility MRI metrics in parkinsonisms are associated with SNc neuropathologic features of dopaminergic neuron loss, gliosis, and α‐synuclein and tau burden. Methods This retrospective study included 27 subjects with both in vivo MRI and postmortem data. Multigradient echo imaging was used to derive the apparent transverse relaxation rate (R2*) and quantitative susceptibility mapping (QSM) in the SNc. Archived midbrain slides that were stained with hematoxylin and eosin, anti‐α‐synuclein, and anti‐tau were digitized to quantify neuromelanin‐positive neuron density, glial density, and the percentages of area occupied by positive α‐synuclein and tau staining. MRI‐histology associations were examined using Pearson correlations and regression. Results Twenty‐four subjects had postmortem parkinsonism diagnoses (Lewy body disorder, progressive supranuclear palsy, multiple system atrophy, and corticobasal degeneration), two had only Alzheimer's neuropathology, and one exhibited only mild atrophy. Among all subjects, both R2* and QSM were associated with glial density (r ≥ 0.67; P