Multimodal Imaging of Substantia Nigra in Parkinson's Disease with Levodopa-Induced Dyskinesia

Dongning Su; Yawen Gan; Zhe Zhang; Yusha Cui; Zhijin Zhang; Zhu Liu; Zhan Wang; Junhong Zhou; Vesna Sossi; A Jon Stoessl; Tao Wu; Jing Jing; Tao Feng

doi:10.1002/mds.29320

Multimodal Imaging of Substantia Nigra in Parkinson's Disease with Levodopa-Induced Dyskinesia

Mov Disord. 2023 Apr;38(4):616-625. doi: 10.1002/mds.29320. Epub 2023 Feb 17.

Authors

Dongning Su^{1

2}, Yawen Gan^{1

2}, Zhe Zhang^{2

3}, Yusha Cui^{1

2}, Zhijin Zhang^{1

2}, Zhu Liu^{1

2}, Zhan Wang^{1

2}, Junhong Zhou^{4

5}, Vesna Sossi^{6

7}, A Jon Stoessl^{7

8}, Tao Wu^{1

2}, Jing Jing^{1

2

3}, Tao Feng^{1

2}

Affiliations

¹ Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
² China National Clinical Research Center for Neurological Diseases, Beijing, China.
³ Tiantan Neuroimaging Center of Excellence, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
⁴ Hinda and Arthur Marcus Institute for Aging Research, Hebrew SeniorLife, Roslindale, Boston, Massachusetts, USA.
⁵ Harvard Medical School, Boston, Massachusetts, USA.
⁶ Department of Physics and Astronomy, University of British Columbia, Vancouver, British Columbia, Canada.
⁷ Djavad Mowafaghian Centre for Brain Health, Pacific Parkinson's Research Centre, University of British Columbia & Vancouver Coastal Health, Vancouver, British Columbia, Canada.
⁸ Division of Neurology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.

PMID: 36799459
DOI: 10.1002/mds.29320

Abstract

Background: Degeneration of the substantia nigra (SN) may contribute to levodopa-induced dyskinesia (LID) in Parkinson's disease (PD), but the exact characteristics of SN in LID remain unclear.

Objective: To further understand the pathogenesis of patients with PD with LID (PD-LID), we explored the structural and functional characteristics of SN in PD-LID using multimodal magnetic resonance imaging (MRI).

Methods: Twenty-nine patients with PD-LID, 37 patients with PD without LID (PD-nLID), and 28 healthy control subjects underwent T1-weighted MRI, quantitative susceptibility mapping, neuromelanin-sensitive MRI, multishell diffusion MRI, and resting-state functional MRI. Different measures characterizing the SN were obtained using a region of interest-based approach.

Results: Compared with patients with PD-nLID and healthy control subjects, the quantitative susceptibility mapping values of SN pars compacta (SNpc) were significantly higher (P = 0.049 and P = 0.00002), and the neuromelanin contrast-to-noise ratio values in SNpc were significantly lower (P = 0.012 and P = 0.000002) in PD-LID. The intracellular volume fraction of the posterior SN in PD-LID was significantly higher compared with PD-nLID (P = 0.037). Resting-state fMRI indicated that PD-LID in the medication off state showed higher functional connectivity between the SNpc and putamen compared with PD-nLID (P = 0.031), and the functional connectivity changes in PD-LID were positively correlated with Unified Dyskinesia Rating Scale total scores (R = 0.427, P = 0.042).

Conclusions: Our multimodal imaging findings highlight greater neurodegeneration in SN and the altered nigrostriatal connectivity in PD-LID. These characteristics provide a new perspective into the role of SN in the pathophysiological mechanisms underlying PD-LID. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Keywords: MRI; Parkinson's disease; levodopa-induced dyskinesia; multimodal; substantia nigra.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Dyskinesias*
Humans
Levodopa / adverse effects
Magnetic Resonance Imaging / methods
Multimodal Imaging
Parkinson Disease* / diagnostic imaging
Parkinson Disease* / drug therapy
Parkinson Disease* / pathology
Substantia Nigra / diagnostic imaging
Substantia Nigra / pathology

Substances

Levodopa