Quantitative evaluation of brain iron accumulation in different stages of Parkinson's disease.
Hoehn and Yahr scale
Parkinson's disease
iron
magnetic resonance imaging
quantitative susceptibility mapping
Journal
Journal of neuroimaging : official journal of the American Society of Neuroimaging
ISSN: 1552-6569
Titre abrégé: J Neuroimaging
Pays: United States
ID NLM: 9102705
Informations de publication
Date de publication:
03 2022
03 2022
Historique:
revised:
23
11
2021
received:
26
10
2021
accepted:
23
11
2021
pubmed:
15
12
2021
medline:
22
3
2022
entrez:
14
12
2021
Statut:
ppublish
Résumé
Excessive brain iron deposition is involved in Parkinson's disease (PD) pathogenesis. However, the correlation of iron accumulation in various brain nuclei is not well-established in different stages of the disease. This cross-sectional study aims to evaluate quantitative susceptibility mapping (QSM) as an imaging technique to measure brain iron accumulation in PD patients in different stages compared to healthy controls. Ninety-six PD patients grouped by their Hoehn and Yahr (H&Y) stages and 31 healthy controls were included in this analysis. The magnetic susceptibility values of the substantia nigra (SN), red nucleus (RN), caudate, putamen, and globus pallidus were obtained and compared. Iron level was increased in the SN of PD patients in all stages versus controls (p < .001), with no significant difference within stages. Iron in the RN was significantly increased in stage II versus controls (p = .013) and combined stages III and IV versus controls (p < .001). The iron levels in caudate, putamen, and globus pallidus were not different between any groups. Our data suggest iron accumulation occurs early in the disease course and only in the SN and RN of these patients. This is a large cross-sectional study of brain iron deposition in PD patients according to H&Y staging. Prospective studies are warranted to further validate QSM as a method to follow brain iron, which could serve as a disease biomarker and a therapeutic target.
Sections du résumé
BACKGROUND AND PURPOSE
Excessive brain iron deposition is involved in Parkinson's disease (PD) pathogenesis. However, the correlation of iron accumulation in various brain nuclei is not well-established in different stages of the disease. This cross-sectional study aims to evaluate quantitative susceptibility mapping (QSM) as an imaging technique to measure brain iron accumulation in PD patients in different stages compared to healthy controls.
METHODS
Ninety-six PD patients grouped by their Hoehn and Yahr (H&Y) stages and 31 healthy controls were included in this analysis. The magnetic susceptibility values of the substantia nigra (SN), red nucleus (RN), caudate, putamen, and globus pallidus were obtained and compared.
RESULTS
Iron level was increased in the SN of PD patients in all stages versus controls (p < .001), with no significant difference within stages. Iron in the RN was significantly increased in stage II versus controls (p = .013) and combined stages III and IV versus controls (p < .001). The iron levels in caudate, putamen, and globus pallidus were not different between any groups.
CONCLUSIONS
Our data suggest iron accumulation occurs early in the disease course and only in the SN and RN of these patients. This is a large cross-sectional study of brain iron deposition in PD patients according to H&Y staging. Prospective studies are warranted to further validate QSM as a method to follow brain iron, which could serve as a disease biomarker and a therapeutic target.
Substances chimiques
Iron
E1UOL152H7
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
363-371Subventions
Organisme : NINDS NIH HHS
ID : R01 NS095562
Pays : United States
Informations de copyright
© 2021 American Society of Neuroimaging.
Références
Fearnley JM, Lees AJ. Ageing and Parkinson's disease: substantia nigra regional selectivity. Brain 1991;114:2283-301.
Damier P, Hirsch EC, Agid Y, et al. The substantia nigra of the human brain. II. Patterns of loss of dopamine-containing neurons in Parkinson's disease. Brain 1999;122:1437-48.
Ke Y, Qian ZM. Iron misregulation in the brain: a primary cause of neurodegenerative disorders. Lancet Neurol. 2003;2:246-53.
Ward RJ, Zucca FA, Duyn JH, et al. The role of iron in brain ageing and neurodegenerative disorders. Lancet Neurol. 2014;13:1045-60.
Oakley AE, Collingwood JF, Dobson J, et al. Individual dopaminergic neurons show raised iron levels in Parkinson disease. Neurology 2007;68:1820-5.
Jiang H, Wang J, Rogers J, et al. Brain iron metabolism dysfunction in Parkinson's disease. Mol Neurobiol. 2017;54:3078-101.
Wang JY, Zhuang QQ, Zhu LB, et al. Meta-analysis of brain iron levels of Parkinson's disease patients determined by postmortem and MRI measurements. Sci Rep. 2016;6:36669.
Belaidi AA, Bush AI. Iron neurochemistry in Alzheimer's disease and Parkinson's disease: targets for therapeutics. J Neurochem. 2016;139(Suppl 1):179-97.
Good PF, Olanow CW, Perl DP. Neuromelanin-containing neurons of the substantia nigra accumulate iron and aluminum in Parkinson's disease: a LAMMA study. Brain Res. 1992;593:343-6.
Sian-Hulsmann J, Mandel S, Youdim MB, et al. The relevance of iron in the pathogenesis of Parkinson's disease. J Neurochem. 2011;118:939-57.
Faucheux BA, Martin ME, Beaumont C, et al. Neuromelanin associated redox-active iron is increased in the substantia nigra of patients with Parkinson's disease. J Neurochem. 2003;86:1142-8.
Dexter DT, Wells FR, Lees AJ, et al. Increased nigral iron content and alterations in other metal ions occurring in brain in Parkinson's disease. J Neurochem. 1989;52:1830-6.
Gaasch JA, Lockman PR, Geldenhuys WJ, et al. Brain iron toxicity: differential responses of astrocytes, neurons, and endothelial cells. Neurochem Res. 2007;32:1196-208.
Kaur D, Yantiri F, Rajagopalan S, et al. Genetic or pharmacological iron chelation prevents MPTP-induced neurotoxicity in vivo: a novel therapy for Parkinson's disease. Neuron 2003;37:899-909.
Devos D, Moreau C, Devedjian JC, et al. Targeting chelatable iron as a therapeutic modality in Parkinson's disease. Antioxid Redox Signal 2014;21:195-210.
Lull ME, Block ML. Microglial activation and chronic neurodegeneration. Neurotherapeutics. 2010;7:354-65.
Zhang W, Yan ZF, Gao JH, et al. Role and mechanism of microglial activation in iron-induced selective and progressive dopaminergic neurodegeneration. Mol Neurobiol. 2014;49:1153-65.
Wallis LI, Paley MN, Graham JM, et al. MRI assessment of basal ganglia iron deposition in Parkinson's disease. J Magn Reson Imaging 2008;28:1061-7.
Yan F, He N, Lin H, et al. Iron deposition quantification: applications in the brain and liver. J Magn Reson Imaging 2018;48:301-17.
Tang MY, Chen TW, Zhang XM, et al. GRE T2 *-weighted MRI: principles and clinical applications. Biomed Res Int. 2014;2014:312142.
Wang Y, Liu T. Quantitative susceptibility mapping (QSM): decoding MRI data for a tissue magnetic biomarker. Magn Reson Med. 2015;73:82-101.
Braffman BH, Grossman RI, Goldberg HI, et al. MR imaging of Parkinson disease with spin-echo and gradient-echo sequences. AJR Am J Roentgenol. 1989;152:159-65.
Wang Y, Spincemaille P, Liu Z, et al. Clinical quantitative susceptibility mapping (QSM): biometal imaging and its emerging roles in patient care. J Magn Reson Imaging. 2017;46:951-71.
De Rochefort L, Liu T, Kressler B, et al. Quantitative susceptibility map reconstruction from MR phase data using Bayesian regularization: validation and application to brain imaging. Magn Reson Med. 2010;63:194-206.
Deh K, Nguyen TD, Eskreis-Winkler S, et al. Reproducibility of quantitative susceptibility mapping in the brain at two field strengths from two vendors. J Magn Reson Imaging. 2015;42:1592-600.
Deh K, Kawaji K, Bulk M, et al. Multicenter reproducibility of quantitative susceptibility mapping in a gadolinium phantom using MEDI+0 automatic zero referencing. Magn Reson Med. 2019;81:1229-36.
Persson N, Wu J, Zhang Q, et al. Age and sex related differences in subcortical brain iron concentrations among healthy adults. Neuroimage. 2015;122:385-98.
Zhang Y, Gauthier SA, Gupta A, et al. Longitudinal change in magnetic susceptibility of new enhanced multiple sclerosis (MS) lesions measured on serial quantitative susceptibility mapping (QSM). J Magn Reson Imaging 2016;44:426-32.
Deistung A, Schweser F, Reichenbach JR. Overview of quantitative susceptibility mapping. NMR Biomed. 2017;30. https://doi.org/10.1002/nbm.3569
Haacke EM, Liu S, Buch S, et al. Quantitative susceptibility mapping: current status and future directions. Magn Reson Imaging 2015;33:1-25.
Liu C, Li W, Tong KA, et al. Susceptibility-weighted imaging and quantitative susceptibility mapping in the brain. J Magn Reson Imaging 2015;42:23-41.
Eskreis-Winkler S, Zhang Y, Zhang J, et al. The clinical utility of QSM: disease diagnosis, medical management, and surgical planning. NMR Biomed. 2017;30. https://doi.org/10.1002/nbm.3668
Kirui DK, Khalidov I, Wang Y, et al. Targeted near-IR hybrid magnetic nanoparticles for in vivo cancer therapy and imaging. Nanomedicine 2013;9:702-11.
Stuber C, Pitt D, Wang Y. Iron in multiple sclerosis and its noninvasive imaging with quantitative susceptibility mapping. Int J Mol Sci. 2016;17:100.
Acosta-Cabronero J, Cardenas-Blanco A, Betts MJ, et al. The whole-brain pattern of magnetic susceptibility perturbations in Parkinson's disease. Brain 2017;140:118-31.
Barbosa JH, Santos AC, Tumas V, et al. Quantifying brain iron deposition in patients with Parkinson's disease using quantitative susceptibility mapping, R2 and R2*. Magn Reson Imaging 2015;33:559-65.
Du G, Liu T, Lewis MM, et al. Quantitative susceptibility mapping of the midbrain in Parkinson's disease. Mov Disord. 2016;31:317-24.
Ghassaban K, He N, Sethi SK, et al. Regional high iron in the substantia nigra differentiates Parkinson's disease patients from healthy controls. Front Aging Neurosci. 2019;11:106.
Cheng Q, Huang J, Liang J, et al. Evaluation of abnormal iron distribution in specific regions in the brains of patients with Parkinson's disease using quantitative susceptibility mapping and R2* mapping. Exp Ther Med. 2020;19:3778-86.
Langkammer C, Pirpamer L, Seiler S, et al. Quantitative susceptibility mapping in Parkinson's disease. PLoS One 2016;11:e0162460.
Chen Q, Chen Y, Zhang Y, et al. Iron deposition in Parkinson's disease by quantitative susceptibility mapping. BMC Neurosci. 2019;20:23.
Shahmaei V, Faeghi F, Mohammdbeigi A, et al. Evaluation of iron deposition in brain basal ganglia of patients with Parkinson's disease using quantitative susceptibility mapping. Eur J Radiol Open. 2019;6:169-74.
Thomas GEC, Leyland LA, Schrag AE, et al. Brain iron deposition is linked with cognitive severity in Parkinson's disease. J Neurol Neurosurg Psychiatry 2020;91:418-25.
He N, Ling H, Ding B, et al. Region-specific disturbed iron distribution in early idiopathic Parkinson's disease measured by quantitative susceptibility mapping. Hum Brain Mapp 2015;36:4407-20.
An H, Zeng X, Niu T, et al. Quantifying iron deposition within the substantia nigra of Parkinson's disease by quantitative susceptibility mapping. J Neurol Sci. 2018;386:46-52.
Guan X, Xuan M, Gu Q, et al. Regionally progressive accumulation of iron in Parkinson's disease as measured by quantitative susceptibility mapping. NMR Biomed. 2017;30. https://doi.org/10.1002/nbm.3489
Movement Disorder Society Task Force on Rating Scales for Parkinson's Disease. The Unified Parkinson's Disease Rating Scale (UPDRS): status and recommendations. Mov Disord. 2003;18:738-50.
Smith SM. Fast robust automated brain extraction. Hum Brain Mapp 2002;17:143-55.
Zhang Y, Brady M, Smith S. Segmentation of brain MR images through a hidden Markov random field model and the expectation-maximization algorithm. IEEE Trans Med Imaging 2001;20:45-57.
Smith SM, Jenkinson M, Woolrich MW, et al. Advances in functional and structural MR image analysis and implementation as FSL. Neuroimage 2004;23(Suppl 1):S208-19.
Jenkinson M, Smith S. A global optimisation method for robust affine registration of brain images. Med Image Anal 2001;5:143-56.
Zhou D, Cho J, Zhang J, et al. Susceptibility underestimation in a high-susceptibility phantom: dependence on imaging resolution, magnitude contrast, and other parameters. Magn Reson Med. 2017;78:1080-6.
Liu Z, Spincemaille P, Yao Y, et al. MEDI+0: morphology enabled dipole inversion with automatic uniform cerebrospinal fluid zero reference for quantitative susceptibility mapping. Magn Reson Med. 2018;79:2795-803.
Patenaude B, Smith SM, Kennedy DN, et al. A Bayesian model of shape and appearance for subcortical brain segmentation. Neuroimage 2011;56:907-22.
Yushkevich PA, Piven J, Hazlett HC, et al. User-guided 3D active contour segmentation of anatomical structures: significantly improved efficiency and reliability. Neuroimage 2006;31:1116-28.
Sun J, Lai Z, Ma J, et al. Quantitative evaluation of iron content in idiopathic rapid eye movement sleep behavior disorder. Mov Disord 2020;35:478-85.
Zucca FA, Segura-Aguilar J, Ferrari E, et al. Interactions of iron, dopamine and neuromelanin pathways in brain aging and Parkinson's disease. Prog Neurobiol. 2017;155:96-119.
Hoehn MM, Yahr MD. Parkinsonism: onset, progression and mortality. Neurology 1967;17:427-42.
Marek KL, Seibyl JP, Zoghbi SS, et al. [123I] beta-CIT/SPECT imaging demonstrates bilateral loss of dopamine transporters in hemi-Parkinson's disease. Neurology 1996;46:231-7.
Milardi D, Cacciola A, Cutroneo G, et al. Red nucleus connectivity as revealed by constrained spherical deconvolution tractography. Neurosci Lett. 2016;626:68-73.
Lewis MM, Du G, Kidacki M, et al. Higher iron in the red nucleus marks Parkinson's dyskinesia. Neurobiol Aging 2013;34:1497-503.
Habas C, Cabanis EA. Cortical projection to the human red nucleus: complementary results with probabilistic tractography at 3 T. Neuroradiology 2007;49:777-84.
Belhaj-Saif A, Cheney PD. Plasticity in the distribution of the red nucleus output to forearm muscles after unilateral lesions of the pyramidal tract. J Neurophysiol. 2000;83:3147-53.
Murakami Y, Kakeda S, Watanabe K, et al. Usefulness of quantitative susceptibility mapping for the diagnosis of Parkinson disease. AJNR Am J Neuroradiol. 2015;36:1102-08.
Hider RC, Roy S, Ma YM, et al. The potential application of iron chelators for the treatment of neurodegenerative diseases. Metallomics. 2011;3:239-49.
Abbruzzese G, Cossu G, Balocco M, et al. A pilot trial of deferiprone for neurodegeneration with brain iron accumulation. Haematologica. 2011;96:1708-11.
Boddaert N, Le Quan Sang KH, Rotig A, et al. Selective iron chelation in Friedreich ataxia: biologic and clinical implications. Blood 2007;110:401-8.
Olivieri S, Conti A, Iannaccone S, et al. Ceruloplasmin oxidation, a feature of Parkinson's disease CSF, inhibits ferroxidase activity and promotes cellular iron retention. J Neurosci. 2011;31:18568-77.
Grolez G, Moreau C, Sablonniere B, et al. Ceruloplasmin activity and iron chelation treatment of patients with Parkinson's disease. BMC Neurol. 2015;15:74.
Ulla M, Bonny JM, Ouchchane L, et al. Is R2* a new MRI biomarker for the progression of Parkinson's disease? A longitudinal follow-up. PLoS One 2013;8:e57904.