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The whole-brain pattern of magnetic susceptibility perturbations in Parkinson's disease

Acosta-Cabronero, J; Cardenas-Blanco, A; Betts, MJ; Butryn, M; Valdes-Herrera, JP; Galazky, I; Nestor, PJ; (2016) The whole-brain pattern of magnetic susceptibility perturbations in Parkinson's disease. Brain , 140 (1) pp. 118-131. 10.1093/brain/aww278. Green open access

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Abstract

Although iron-mediated oxidative stress has been proposed as a potential pathomechanism in Parkinson's disease, the global distribution of iron accumulation in Parkinson's disease has not yet been elucidated. This study used a new magnetic resonance imaging contrast, quantitative susceptibility mapping, and state-of-the-art methods to map for the first time the whole-brain landscape of magnetostatic alterations as a surrogate for iron level changes in n = 25 patients with idiopathic Parkinson's disease versus n = 50 matched controls. In addition to whole-brain analysis, a regional study including sub-segmentation of the substantia nigra into dorsal and ventral regions and qualitative assessment of susceptibility maps in single subjects were also performed. The most remarkable basal ganglia effect was an apparent magnetic susceptibility increase-consistent with iron deposition-in the dorsal substantia nigra, though an effect was also observed in ventral regions. Increased bulk susceptibility, additionally, was detected in rostral pontine areas and in a cortical pattern tightly concordant with known Parkinson's disease distributions of α-synuclein pathology. In contrast, the normally iron-rich cerebellar dentate nucleus returned a susceptibility reduction suggesting decreased iron content. These results are in agreement with previous post-mortem studies in which iron content was evaluated in specific regions of interest; however, extensive neocortical and cerebellar changes constitute a far more complex pattern of iron dysregulation than was anticipated. Such findings also stand in stark contrast to the lack of statistically significant group change using conventional magnetic resonance imaging methods namely voxel-based morphometry, cortical thickness analysis, subcortical volumetry and tract-based diffusion tensor analysis; confirming the potential of whole-brain quantitative susceptibility mapping as an in vivo biomarker in Parkinson's disease.

Type: Article
Title: The whole-brain pattern of magnetic susceptibility perturbations in Parkinson's disease
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1093/brain/aww278
Publisher version: http://doi.org/10.1093/brain/aww278
Language: English
Additional information: © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Parkinson’s disease, biomarkers, cellular mechanisms, movement disorders, oxidative stress, Aged, Cerebellar Nuclei, Female, Humans, Iron, Magnetic Resonance Imaging, Male, Middle Aged, Parkinson Disease, Substantia Nigra
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Imaging Neuroscience
URI: https://discovery.ucl.ac.uk/id/eprint/1531827
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