scholarly journals Reliability of Dopamine Transporter PET Measurements with [18F]FE-PE2I in patients with Parkinson's Disease

2020 ◽  
Author(s):  
Vera S. Kerstens ◽  
Patrik Fazio ◽  
Mathias Sundgren ◽  
Granville J. Matheson ◽  
Erika Franzén ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Dopamine Transporter ◽  
Radioligand Binding ◽  
Binding Potential ◽  
Measurement Variability ◽  
Power Calculations ◽  
Affected Side ◽  
Progression Marker

Abstract Background. Reliable quantification of dopamine transporter (DAT), a biomarker for Parkinson’s disease (PD), is essential for diagnostic purposes as well as for evaluation of potential disease-modifying treatment. Due to degeneration of dopaminergic neurons and thus lower expected radioligand binding to DAT, higher measurement variability in PD patients might be expected than earlier reproducibility results in healthy controls. Therefore, we aimed to examine the test-retest properties of [18F]FE-PE2I-PET in PD patients. Methods. Nine patients with PD (Hoehn & Yahr stage < 3) were included (men/women: 6/3; mean age 65.2±6.8y). Each patient underwent two [18F]FE-PE2I-PET measurements within 7–28 days. The outcome measure was non-displaceable binding potential generated using wavelet-aided parametric imaging with cerebellum as reference region. We assessed test-retest performance using estimates of reliability and repeatability. Regions for primary analysis were caudate, putamen, ventral striatum, and substantia nigra. Exploratory analysis was performed for functional subdivisions of the striatum. We also compared the more vs. less-affected side. Results. [18F]FE-PE2I showed absolute variability estimates of 5.3–7.6% in striatal regions and 11% in substantia nigra, and ICCs of 0.74—0.97 (median: 0.91). The absolute variability for functional striatal subdivisions was 6.0–9.6% and ICCs of 0.76–0.91 (median: 0.91). The less affected substantia nigra exhibited greater consistency than the more affected side. According to power calculations based on the current sample size, DAT changes of 5–11% in the striatum and 28% in the substantia nigra can be detected with a power of 0.8 (p<0.0125).Conclusion. DAT-PET measurements with [18F]FE-PE2I in PD patients showed good repeatability and reliability. The slightly lower reliability in the substantia nigra in patients may be explained by lower DAT density and smaller anatomical size. Power calculations suggest that [18F]FE-PE2I PET of DAT is a suitable disease progression marker in PD. Trial registration number: EudraCT 2017-003327-29 Keywords: reliability, test-retest, [18F]FE-PE2I, dopamine transporter, Parkinson’s disease

scholarly journals Reliability of Dopamine Transporter PET Measurements with [18F]FE-PE2I in patients with Parkinson´s Disease

2020 ◽  
Author(s):  
Vera S. Kerstens ◽  
Patrik Fazio ◽  
Mathias Sundgren ◽  
Granville J. Matheson ◽  
Erika Franzén ◽  
...  
Keyword(s):  
Substantia Nigra ◽  
Dopamine Transporter ◽  
Radioligand Binding ◽  
Binding Potential ◽  
Primary Analysis ◽  
Yahr Stage ◽  
Measurement Variability ◽  
Power Calculations ◽  
Affected Side ◽  
Registration Number

Abstract Background. Reliable quantification of dopamine transporter (DAT), a biomarker for Parkinson’s disease (PD), is essential for diagnostic purposes as well as for evaluation of potential disease-modifying treatment. Due to degeneration of dopaminergic neurons and thus lower expected radioligand binding to DAT, higher measurement variability in PD patients might be expected than earlier reproducibility results in healthy controls. Therefore, we aimed to examine the test-retest properties of [18F]FE-PE2I-PET in PD patients. Methods. Nine patients with PD (Hoehn & Yahr stage < 3) were included (men/women: 6/3; mean age 65.2±6.8y). Each patient underwent two [18F]FE-PE2I-PET measurements within 7–28 days. The outcome measure was non-displaceable binding potential generated using wavelet-aided parametric imaging with cerebellum as reference region. We assessed test-retest performance using estimates of reliability and repeatability. Regions for primary analysis were caudate, putamen, ventral striatum, and substantia nigra. Exploratory analysis was performed for functional subdivisions of the striatum. We also compared the more vs. less-affected side.Results. [18F]FE-PE2I showed absolute variability estimates of 5.3–7.6% in striatal regions and 11% in substantia nigra, and ICCs of 0.74—0.97 (median: 0.91). The absolute variability for functional striatal subdivisions was 6.0–9.6% and ICCs of 0.76–0.91 (median: 0.91). The less affected substantia nigra exhibited greater consistency than the more affected side. According to power calculations based on the current sample size, DAT changes of 5–11% in the striatum and 28% in the substantia nigra can be detected with a power of 0.8 (p<0.0125). Conclusion. DAT-PET measurements with [18F]FE-PE2I in PD patients showed good repeatability and reliability. The slightly lower reliability in the substantia nigra in patients may be explained by lower DAT density and smaller anatomical size. Power calculations suggest that [18F]FE-PE2I PET is a suitable marker for longitudinal DAT decline in PD.Trial registration number: EudraCT 2017-003327-29

scholarly journals Relationship between neuromelanin and dopamine terminals within the Parkinson’s nigrostriatal system

Brain ◽  
2019 ◽  
Vol 142 (7) ◽  
pp. 2023-2036 ◽  
Author(s):  
Antonio Martín-Bastida ◽  
Nicholas P Lao-Kaim ◽  
Andreas Antonios Roussakis ◽  
Graham E Searle ◽  
Yue Xing ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Dopamine Transporter ◽  
Substantia Nigra Pars Compacta ◽  
Control Group ◽  
Post Mortem ◽  
Significant Relationships ◽  
Affected Side

Abstract Parkinson’s disease is characterized by the progressive loss of pigmented dopaminergic neurons in the substantia nigra and associated striatal deafferentation. Neuromelanin content is thought to reflect the loss of pigmented neurons, but available data characterizing its relationship with striatal dopaminergic integrity are not comprehensive or consistent, and predominantly involve heterogeneous samples. In this cross-sectional study, we used neuromelanin-sensitive MRI and the highly specific dopamine transporter PET radioligand, 11C-PE2I, to assess the association between neuromelanin-containing cell levels in the substantia nigra pars compacta and nigrostriatal terminal density in vivo, in 30 patients with bilateral Parkinson’s disease. Fifteen healthy control subjects also underwent neuromelanin-sensitive imaging. We used a novel approach taking into account the anatomical and functional subdivision of substantia nigra into dorsal and ventral tiers and striatal nuclei into pre- and post-commissural subregions, in accordance with previous animal and post-mortem studies, and consider the clinically asymmetric disease presentation. In vivo, Parkinson’s disease subjects displayed reduced neuromelanin levels in the ventral (−30 ± 28%) and dorsal tiers (−21 ± 24%) as compared to the control group [F(1,43) = 11.95, P = 0.001]. Within the Parkinson’s disease group, nigral pigmentation was lower in the ventral tier as compared to the dorsal tier [F(1,29) = 36.19, P < 0.001] and lower in the clinically-defined most affected side [F(1,29) = 4.85, P = 0.036]. Similarly, lower dopamine transporter density was observed in the ventral tier [F(1,29) = 76.39, P < 0.001] and clinically-defined most affected side [F(1,29) = 4.21, P = 0.049]. Despite similar patterns, regression analysis showed no significant association between nigral pigmentation and nigral dopamine transporter density. However, for the clinically-defined most affected side, significant relationships were observed between pigmentation of the ventral nigral tier with striatal dopamine transporter binding in pre-commissural and post-commissural striatal subregions known to receive nigrostriatal projections from this tier, while the dorsal tier correlated with striatal projection sites in the pre-commissural striatum (P < 0.05, Benjamini-Hochberg corrected). In contrast, there were no statistically significant relationships between these two measures in the clinically-defined least affected side. These findings provide important insights into the topography of nigrostriatal neurodegeneration in Parkinson’s disease, indicating that the characteristics of disease progression may fundamentally differ across hemispheres and support post-mortem data showing asynchrony in the loss of neuromelanin-containing versus tyrosine hydroxylase positive nigral cells.

Dopamine transporter messenger RNA in Parkinson's disease and control substantia nigra neurons

1994 ◽  
Vol 35 (4) ◽  
pp. 494-498 ◽  
Author(s):  
George R. Uhl ◽  
Donna Walther ◽  
Deborah Mash ◽  
Baptiste Faucheux ◽  
France Javoy-Agid
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Dopamine Transporter ◽  
Messenger Rna ◽  
And Control

scholarly journals VMAT2 availability in Parkinson’s disease with probable REM sleep behaviour disorder

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Mikaeel Valli ◽  
Sang Soo Cho ◽  
Carme Uribe ◽  
Mario Masellis ◽  
Robert Chen ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Rem Sleep ◽  
Radioligand Binding ◽  
Striatal Dopamine ◽  
Behaviour Disorder ◽  
Group Condition ◽  
Sleep Behaviour ◽  
Rem Sleep Behaviour Disorder

AbstractREM sleep behaviour disorder (RBD) can be an early non-motor symptom of Parkinson’s disease (PD) with pathology involving mainly the pontine nuclei. Beyond the brainstem, it is unclear if RBD patients comorbid with PD have more affected striatal dopamine denervation compared to PD patients unaffected by RBD (PD-RBD−). To elucidate this, we evaluated the availability of vesicular monoamine transporter 2 (VMAT2), an index of nigrostriatal dopamine innervation, in 15 PD patients with probable RBD (PD-RBD+), 15 PD-RBD−, and 15 age-matched healthy controls (HC) using [11C]DTBZ PET imaging. This technique measured VMAT2 availability within striatal regions of interest (ROI). A mixed effect model was used to compare the radioligand binding of VMAT2 between the three groups for each striatal ROI, while co-varying for sex, cognitive function and depression scores. Multiple regressions were also computed to predict clinical measures from group condition and VMAT2 binding within all ROIs explored. We observed a significant main effect of group condition on VMAT2 availability within the caudate, putamen, ventral striatum, globus pallidus, substantia nigra, and subthalamus. Specifically, our results revealed that PD-RBD+ had lower VMAT2 availability compared to HC in all these regions except for the subthalamus and substantia nigra, while PD-RBD− was significantly lower than HC in all these regions. PD-RBD− showed a negative relationship between motor severity and VMAT2 availability within the left caudate. Our findings reflect that both PD patient subgroups had similar denervation within the nigrostriatal pathway. There were no significant interactions detected between radioligand binding and clinical scores in PD-RBD+. Taken together, VMAT2 and striatal dopamine denervation in general may not be a significant contributor to the pathophysiology of RBD in PD patients. Future studies are encouraged to explore other underlying neural chemistry mechanisms contributing to RBD in PD patients.

Hyperechogenicity of substantia nigra in Parkinson's disease – Searching for genetic predictors

2008 ◽  
Vol 35 (S 01) ◽  
Author(s):  
C Funke ◽  
A Soehn ◽  
C Schulte ◽  
M Bonin ◽  
C Klein ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Genetic Predictors
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