Multimodal dopaminergic and free-water imaging in Parkinson's disease

Jing Yang¹, Derek B Archer², Roxana G Burciu³, Martijn L T M Müller⁴, Arnab Roy⁵, Edward Ofori⁶, Nicolaas I Bohnen⁷, Roger L Albin⁸, David E Vaillancourt⁹

Affiliations

¹ Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL,USA; Department of Neurology, West China Hospital of Sichuan University, Chengdu, China. Electronic address: jingyang_cc@163.com.
² Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL,USA. Electronic address: archerdb@ad.ufl.edu.
³ Department of Kinesiology and Applied Physiology, University of Delaware, Newark, DE, USA. Electronic address: roxana.g.burciu@ufl.edu.
⁴ Department of Radiology, University of Michigan, Ann Arbor, MI, USA; University of Michigan, Morris K Udall Center of Excellence for Parkinson's Disease Research, Ann Arbor, MI, USA. Electronic address: mtmuller@umich.edu.
⁵ Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL,USA. Electronic address: aroy1@ufl.edu.
⁶ College of Health Solutions, Arizona State University, Phoenix, AZ, USA. Electronic address: eofori@hhp.ufl.edu.
⁷ Department of Radiology, University of Michigan, Ann Arbor, MI, USA; University of Michigan, Morris K Udall Center of Excellence for Parkinson's Disease Research, Ann Arbor, MI, USA; Department of Neurology, University of Michigan, Ann Arbor, MI, USA; Neurology Service and GRECC, VAAAHS, Ann Arbor, MI, USA. Electronic address: nbohnen@umich.edu.
⁸ University of Michigan, Morris K Udall Center of Excellence for Parkinson's Disease Research, Ann Arbor, MI, USA; Department of Neurology, University of Michigan, Ann Arbor, MI, USA; Neurology Service and GRECC, VAAAHS, Ann Arbor, MI, USA. Electronic address: ralbin@med.umich.edu.
⁹ Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL,USA; Department of Neurology, University of Florida, Gainesville, FL,USA; Department of Biomedical Engineering, University of Florida, Gainesville, FL, USA. Electronic address: vcourt@ufl.edu.

PMID: 30639168
PMCID: PMC6589363
DOI: 10.1016/j.parkreldis.2019.01.007

Multimodal dopaminergic and free-water imaging in Parkinson's disease

Jing Yang et al. Parkinsonism Relat Disord. 2019 May.

. 2019 May:62:10-15.

doi: 10.1016/j.parkreldis.2019.01.007. Epub 2019 Jan 6.

Authors

Jing Yang¹, Derek B Archer², Roxana G Burciu³, Martijn L T M Müller⁴, Arnab Roy⁵, Edward Ofori⁶, Nicolaas I Bohnen⁷, Roger L Albin⁸, David E Vaillancourt⁹

Affiliations

¹ Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL,USA; Department of Neurology, West China Hospital of Sichuan University, Chengdu, China. Electronic address: jingyang_cc@163.com.
² Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL,USA. Electronic address: archerdb@ad.ufl.edu.
³ Department of Kinesiology and Applied Physiology, University of Delaware, Newark, DE, USA. Electronic address: roxana.g.burciu@ufl.edu.
⁴ Department of Radiology, University of Michigan, Ann Arbor, MI, USA; University of Michigan, Morris K Udall Center of Excellence for Parkinson's Disease Research, Ann Arbor, MI, USA. Electronic address: mtmuller@umich.edu.
⁵ Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL,USA. Electronic address: aroy1@ufl.edu.
⁶ College of Health Solutions, Arizona State University, Phoenix, AZ, USA. Electronic address: eofori@hhp.ufl.edu.
⁷ Department of Radiology, University of Michigan, Ann Arbor, MI, USA; University of Michigan, Morris K Udall Center of Excellence for Parkinson's Disease Research, Ann Arbor, MI, USA; Department of Neurology, University of Michigan, Ann Arbor, MI, USA; Neurology Service and GRECC, VAAAHS, Ann Arbor, MI, USA. Electronic address: nbohnen@umich.edu.
⁸ University of Michigan, Morris K Udall Center of Excellence for Parkinson's Disease Research, Ann Arbor, MI, USA; Department of Neurology, University of Michigan, Ann Arbor, MI, USA; Neurology Service and GRECC, VAAAHS, Ann Arbor, MI, USA. Electronic address: ralbin@med.umich.edu.
⁹ Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL,USA; Department of Neurology, University of Florida, Gainesville, FL,USA; Department of Biomedical Engineering, University of Florida, Gainesville, FL, USA. Electronic address: vcourt@ufl.edu.

PMID: 30639168
PMCID: PMC6589363
DOI: 10.1016/j.parkreldis.2019.01.007

Abstract

Introduction: When using free-water diffusion imaging or positron emission tomography (PET), it is established that substania nigra microstructure and presynaptic dopamine activity are impaired in early PD. It is not well understood if these two forms of degeneration are redundant, or if they each provide a unique contribution to the clinical motor and cognitive symptoms.

Methods: A total of 129 PD and 75 control individuals underwent motor and cognitive evaluations, and in vivo [11C]dihydrotetrabenazine (DTBZ) monoaminergic brain PET imaging and diffusion imaging. Correlations between free-water in the substantia nigra and striatal PET measures were analyzed. Unbiased multiple regression using a backward elimination method was performed between clinical severity and all imaging measures.

Results: Inverse correlations were found between free-water in posterior substantia nigra and DTBZ binding in putamen and caudate. Multiple regression revealed that increased free-water in the posterior substantia nigra, decreased DTBZ binding in putamen, and age were predictors of higher Hoehn and Yahr stage, MDS-UPDRS III scores, and posture and gait sub-scores. Increased posterior substantia nigra free-water alone was associated tremor scores. Free-water in caudate and putamen did not predict measures of motor performance. Decreased DTBZ binding in caudate, increased free-water in caudate and posterior substantia nigra were associated with higher dementia ratings.

Conclusions: These findings suggest that free-water in the posterior substantia nigra and presynaptic dopamine imaging in striatum are uniquely associated with the clinical symptoms of PD, indicating that each imaging modality may be measuring a unique mechanism relevant to nigrostriatal degeneration.

Keywords: Basal ganglia; Diffusion magnetic resonance imaging; Multimodal imaging; PET; Parkinson's disease; Substantia nigra.

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Figures

**Figure 1**
A. Regions of interest for Diffusion MRI. The regions used in this study for diffusion MRI are shown for caudate, putamen, globus pallidus (GP), anterior substantia nigra (aSN), and posterior substantia nigra (pSN). Each region is shown in MNI space on a B0 image. B. Group comparison of imaging measures between Parkinson’s disease group and controls. Mean values for DTBZ DVR in putamen, DTBZ DVR in caudate, free-water in pSN, free-water in aSN, free-water in putamen, and free-water in caudate were shown for controls and PD patients. Each bar represented the group mean and errors bars represented ± standard error of the mean. *Statistically significant between-group differences. C. Multiple regression to associate imaging measures with clinical features in patients with Parkinson’s disease. The predicted versus actual plots for MDS-UPDRS III score is shown. The significant predictors for MDS-UPDRS III score in the regression model were listed on the right. DTBZ DVR = [¹¹C]dihydrotetrabenazine distribution volume ratio; MDS-UPDRS III = the motor section of the Movement Disorder Society Unified Parkinson’s Disease Rating Scale; DTBZ DVR = [¹¹C]dihydrotetrabenazine distribution volume ratio.

See this image and copyright information in PMC

References

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Multimodal dopaminergic and free-water imaging in Parkinson's disease

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Multimodal dopaminergic and free-water imaging in Parkinson's disease

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