Spatiotemporal patterns of putaminal dopamine processing in Parkinson’s disease: A multi-tracer positron emission tomography study
Alterations in different aspects of dopamine processing may exhibit different progressive behaviours throughout the course of Parkinson’s disease. We used a novel data-driven multivariate approach to quantify and compare spatiotemporal patterns related to different aspects of dopamine processing fro...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-01-01
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| Series: | NeuroImage: Clinical |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213158222003114 |
| _version_ | 1797991734974611456 |
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| author | Jessie Fanglu Fu Tilman Wegener Ivan S. Klyuzhin Julia G. Mannheim Martin J. McKeown A. Jon Stoessl Vesna Sossi |
| author_facet | Jessie Fanglu Fu Tilman Wegener Ivan S. Klyuzhin Julia G. Mannheim Martin J. McKeown A. Jon Stoessl Vesna Sossi |
| author_sort | Jessie Fanglu Fu |
| collection | DOAJ |
| description | Alterations in different aspects of dopamine processing may exhibit different progressive behaviours throughout the course of Parkinson’s disease. We used a novel data-driven multivariate approach to quantify and compare spatiotemporal patterns related to different aspects of dopamine processing from cross-sectional Parkinson’s subjects obtained with: 1) 69 [11C]±dihydrotetrabenazine (DTBZ) scans, most closely related to dopaminergic denervation; 2) 73 [11C]d-threo-methylphenidate (MP) scans, marker of dopamine transporter density; 3) 50 6-[18F]fluoro-l-DOPA (FD) scans, marker of dopamine synthesis and storage. The anterior-posterior gradient in the putamen was identified as the most salient feature associated with disease progression, however the temporal progression of the spatial gradient was different for the three tracers. The expression of the anterior-posterior gradient was the highest for FD at disease onset compared to that of DTBZ and MP (P = 0.018 and P = 0.047 respectively), but decreased faster (P = 0.006) compared to that of DTBZ. The gradient expression for MP was initially similar but decreased faster (P = 0.015) compared to that for DTBZ. These results reflected unique temporal behaviours of regulatory mechanisms related to dopamine synthesis (FD) and reuptake (MP). While the relative early disease upregulation of dopamine synthesis in the anterior putamen prevalent likely extends to approximately 10 years after symptom onset, the presumed downregulation of dopamine transporter density may play a compensatory role in the prodromal/earliest disease stages only. |
| first_indexed | 2024-04-11T08:56:03Z |
| format | Article |
| id | doaj.art-2e3a0b586e1c4056a425c646d5f9a745 |
| institution | Directory Open Access Journal |
| issn | 2213-1582 |
| language | English |
| last_indexed | 2024-04-11T08:56:03Z |
| publishDate | 2022-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | NeuroImage: Clinical |
| spelling | doaj.art-2e3a0b586e1c4056a425c646d5f9a7452022-12-22T04:33:17ZengElsevierNeuroImage: Clinical2213-15822022-01-0136103246Spatiotemporal patterns of putaminal dopamine processing in Parkinson’s disease: A multi-tracer positron emission tomography studyJessie Fanglu Fu0Tilman Wegener1Ivan S. Klyuzhin2Julia G. Mannheim3Martin J. McKeown4A. Jon Stoessl5Vesna Sossi6Department of Physics and Astronomy, University of British Columbia, Vancouver, BC, Canada; Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, USA; Corresponding author at: Athinoula A. Martinos Center for Biomedical Imaging, 149 Thirteenth Street, Charlestown, MA 02129, USA.Department of Physics and Astronomy, University of British Columbia, Vancouver, BC, Canada; Department of Medical Engineering, University of Luebeck, Luebeck, GermanyDivision of Neurology, Department of Medicine, University of British Columbia, Vancouver, BC, CanadaDepartment of Physics and Astronomy, University of British Columbia, Vancouver, BC, Canada; Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard-Karls University Tuebingen, Tuebingen, Germany; Cluster of Excellence iFIT (EXC 2180) “Image Guided and Functionally Instructed Tumor Therapies”, University of Tuebingen, Tuebingen, GermanyDivision of Neurology, Department of Medicine, University of British Columbia, Vancouver, BC, Canada; Djavad Mowafaghian Centre for Brain Health, Pacific Parkinson's Research Centre, University of British Columbia & Vancouver Coastal Health, Vancouver, BC, CanadaDivision of Neurology, Department of Medicine, University of British Columbia, Vancouver, BC, Canada; Djavad Mowafaghian Centre for Brain Health, Pacific Parkinson's Research Centre, University of British Columbia & Vancouver Coastal Health, Vancouver, BC, CanadaDepartment of Physics and Astronomy, University of British Columbia, Vancouver, BC, Canada; Djavad Mowafaghian Centre for Brain Health, Pacific Parkinson's Research Centre, University of British Columbia & Vancouver Coastal Health, Vancouver, BC, CanadaAlterations in different aspects of dopamine processing may exhibit different progressive behaviours throughout the course of Parkinson’s disease. We used a novel data-driven multivariate approach to quantify and compare spatiotemporal patterns related to different aspects of dopamine processing from cross-sectional Parkinson’s subjects obtained with: 1) 69 [11C]±dihydrotetrabenazine (DTBZ) scans, most closely related to dopaminergic denervation; 2) 73 [11C]d-threo-methylphenidate (MP) scans, marker of dopamine transporter density; 3) 50 6-[18F]fluoro-l-DOPA (FD) scans, marker of dopamine synthesis and storage. The anterior-posterior gradient in the putamen was identified as the most salient feature associated with disease progression, however the temporal progression of the spatial gradient was different for the three tracers. The expression of the anterior-posterior gradient was the highest for FD at disease onset compared to that of DTBZ and MP (P = 0.018 and P = 0.047 respectively), but decreased faster (P = 0.006) compared to that of DTBZ. The gradient expression for MP was initially similar but decreased faster (P = 0.015) compared to that for DTBZ. These results reflected unique temporal behaviours of regulatory mechanisms related to dopamine synthesis (FD) and reuptake (MP). While the relative early disease upregulation of dopamine synthesis in the anterior putamen prevalent likely extends to approximately 10 years after symptom onset, the presumed downregulation of dopamine transporter density may play a compensatory role in the prodromal/earliest disease stages only.http://www.sciencedirect.com/science/article/pii/S2213158222003114Parkinson’s diseasePETStriatal dopamine processingMultivariate analysisSpatiotemporal patterns |
| spellingShingle | Jessie Fanglu Fu Tilman Wegener Ivan S. Klyuzhin Julia G. Mannheim Martin J. McKeown A. Jon Stoessl Vesna Sossi Spatiotemporal patterns of putaminal dopamine processing in Parkinson’s disease: A multi-tracer positron emission tomography study NeuroImage: Clinical Parkinson’s disease PET Striatal dopamine processing Multivariate analysis Spatiotemporal patterns |
| title | Spatiotemporal patterns of putaminal dopamine processing in Parkinson’s disease: A multi-tracer positron emission tomography study |
| title_full | Spatiotemporal patterns of putaminal dopamine processing in Parkinson’s disease: A multi-tracer positron emission tomography study |
| title_fullStr | Spatiotemporal patterns of putaminal dopamine processing in Parkinson’s disease: A multi-tracer positron emission tomography study |
| title_full_unstemmed | Spatiotemporal patterns of putaminal dopamine processing in Parkinson’s disease: A multi-tracer positron emission tomography study |
| title_short | Spatiotemporal patterns of putaminal dopamine processing in Parkinson’s disease: A multi-tracer positron emission tomography study |
| title_sort | spatiotemporal patterns of putaminal dopamine processing in parkinson s disease a multi tracer positron emission tomography study |
| topic | Parkinson’s disease PET Striatal dopamine processing Multivariate analysis Spatiotemporal patterns |
| url | http://www.sciencedirect.com/science/article/pii/S2213158222003114 |
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