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Substantia Nigra Volume Dissociates Bradykinesia and Rigidity from Tremor in Parkinson’s Disease: A 7 Tesla Imaging Study

Poston, Kathleen L. and Ua Cruadhlaoich, Matthew A. I. and Santoso, Laura F. and Bernstein, Jeffrey D. and Liu, Tian and Wang, Yi and Rutt, Brian and Kerchner, Geoffrey A. and Zeineh, Michael M. (2020) Substantia Nigra Volume Dissociates Bradykinesia and Rigidity from Tremor in Parkinson’s Disease: A 7 Tesla Imaging Study. Journal of Parkinson's Disease, 10 (2). pp. 591-604. ISSN 1877-7171.

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Background: In postmortem analysis of late stage Parkinson’s disease (PD) neuronal loss in the substantial nigra (SN) correlates with the antemortem severity of bradykinesia and rigidity, but not tremor. Objective: To investigate the relationship between midbrain nuclei volume as an in vivo biomarker for surviving neurons in mild-to-moderate patients using 7.0 Tesla MRI. Methods: We performed ultra-high resolution quantitative susceptibility mapping (QSM) on the midbrain in 32 PD participants with less than 10 years duration and 8 healthy controls. Following blinded manual segmentation, the individual volumes of the SN, subthalamic nucleus, and red nucleus were measured. We then determined the associations between the midbrain nuclei and clinical metrics (age, disease duration, MDS-UPDRS motor score, and subscores for bradykinesia/rigidity, tremor, and postural instability/gait difficulty). Results: We found that smaller SN correlated with longer disease duration (r = –0.49, p = 0.004), more severe MDS-UPDRS motor score (r = –0.42, p = 0.016), and more severe bradykinesia-rigidity subscore (r = –0.47, p = 0.007), but not tremor or postural instability/gait difficulty subscores. In a hemi-body analysis, bradykinesia-rigidity severity only correlated with SN contralateral to the less-affected hemi-body, and not contralateral to the more-affected hemi-body, possibly reflecting the greatest change in dopamine neuron loss early in disease. Multivariate generalized estimating equation model confirmed that bradykinesia-rigidity severity, age, and disease duration, but not tremor severity, predicted SN volume.

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Additional Information:© 2020 IOS Press. This article is published online with Open Access and distributed under the terms of the Creative Commons Attribution Non-Commercial License (CC BY-NC 4.0). Accepted 19 February 2020; Published: 03 April 2020. We would like to acknowledge Dr. Jaimie Henderson for his assistance in our initial stages of developing 7T midbrain imaging protocols. We would like to thank Dr. Jong Yoon for his insightful discussions and David Everling for his assistance with the 7T scan acquisition. This research was supported by grants from the Seiger Family Foundation (KLP), the National Institutes of Health (NS075097-KLP; AG047366-KLP; P41EB015891-BR and MMZ; S10RR026351-BR and MMZ; NS072370, NS090464, NS095562-YW), the Michael J. Fox Foundation for Parkinson’s Research (KLP and GAK), the Center for Biomedical Imaging at Stanford (GAK), the Caltech Summer Undergraduate Research Fellowship program (LFS), and GE Healthcare (BR and MMZ). Conflicts of Interest: Dr. Poston has received consulting fees from Allergan and Curasen, and research grants from Sanofi. Dr. Wang has share ownership in Medimagemetric LLC to disclose. Dr. Rutt receives research funding from GE Healthcare. Dr. Kerchner is a full-time employee of F. Hoffman-La Roche, Ltd. Dr. Zeineh receives research funding from GE Healthcare. The other authors have nothing to disclose.
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Seiger Family FoundationUNSPECIFIED
Michael J. Fox FoundationUNSPECIFIED
Stanford UniversityUNSPECIFIED
Caltech Summer Undergraduate Research Fellowship (SURF)UNSPECIFIED
Subject Keywords:Parkinson’s disease, substantia nigra, ultra-high field MRI, quantitative susceptibility mapping
Issue or Number:2
Record Number:CaltechAUTHORS:20200413-105322056
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:102504
Deposited By: Tony Diaz
Deposited On:13 Apr 2020 18:36
Last Modified:11 Nov 2020 00:52

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