Dentate nucleus iron deposition is a potential biomarker for tremor-dominant Parkinson’s disease

• Type of Material: Article
• Authors: Naying He, Emory University; Pei Huang, Shanghai Jiao Tong University School of Medicine; Huawei Ling, Shanghai Jiao Tong University School of Medicine; Jason Langley, Georgia Institute of Technology; Chunlei Liu, Duke University; Bei Ding, Shanghai Jiao Tong University School of Medicine; Juan Huang, Shanghai Jiao Tong University School of Medicine; Hongmin Xu, Shanghai Jiao Tong University School of Medicine; Yong Zhang, GE Healthcare; Zhongping Zhang, GE Healthcare; Xiaoping P Hu, Emory University; Shengdi Chen, Shanghai Jiao Tong University School of Medicine; Fuhua Yan, Shanghai Jiao Tong University School of Medicine
• Language: English
• Date: 2017-04-01
• Publisher: Wiley: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2016 John Wiley & Sons, Ltd.
• Final Published Version (URL): http://dx.doi.org/10.1002/nbm.3554
• Title of Journal or Parent Work: NMR in Biomedicine
• ISSN: 0952-3480
• Volume: 30
• Issue: 4
• Start Page: e3554
• End Page: e3554
• Grant/Funding Information: CL is supported in part by the National Institutes of Health through grants NIMH R01MH096979 and NINDS R01NS079653, and by the National Natural Science Foundation of China through grant 81428013.; The study was supported in part through State Key Clinical Department of Medical Imaging, National Natural Science Fund (81430022, 81371407), and SHSMU-ION Research Center for Brain Disorders.; XH and JL are supported in part by the Michael J. Fox Foundation (MJF 10854).
• Keywords: MULTIPLE-SCLEROSIS; Life Sciences & Biomedicine; akinetic rigidity-dominant phenotype; IN-VIVO; Radiology, Nuclear Medicine & Medical Imaging; STIMULATION; PROGRESSION; Science & Technology; DIAGNOSIS; Technology; SUBSTANTIA-NIGRA; Biophysics; NONMOTOR SYMPTOMS; tremor-dominant phenotype; SUBTYPES; iron deposition; Parkinson's disease; HUMAN BRAIN; Spectroscopy; quantitative susceptibility mapping; MRI
• Research Categories: Engineering, Biomedical; Health Sciences, Medicine and Surgery; Health Sciences, Radiology

Abstract

Parkinson's disease (PD) is a heterogeneous neurodegenerative disorder with variable clinicopathologic phenotypes and underlying neuropathologic mechanisms. Each clinical phenotype has a unique set of motor symptoms. Tremor is the most frequent initial motor symptom of PD and is the most difficult symptom to treat. The dentate nucleus (DN) is a deep iron-rich nucleus in the cerebellum and may be involved in PD tremor. In this study, we test the hypothesis that DN iron may be elevated in tremor-dominant PD patients using quantitative susceptibility mapping. Forty-three patients with PD [19 tremor dominant (TD)/24 akinetic rigidity (AR) dominant] and 48 healthy gender- and age-matched controls were recruited. Multi-echo gradient echo data were collected for each subject on a 3.0-T MR system. Inter-group susceptibility differences in the bilateral DN were investigated and correlations of clinical features with susceptibility were also examined. In contrast with the AR-dominant group, the TD group was found to have increased susceptibility in the bilateral DN when compared with healthy controls. In addition, susceptibility was positively correlated with tremor score in drug-naive PD patients. These findings indicate that iron load within the DN may make an important contribution to motor phenotypes in PD. Moreover, our results suggest that TD and AR-dominant phenotypes of PD can be differentiated on the basis of the susceptibility of the DN, at least at the group level.