Department of Physics and Astronomy, University of British Columbia, Vancouver, BC, Canada; Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, USA.
Department of Physics and Astronomy, University of British Columbia, Vancouver, BC, Canada; Department of Medical Engineering, University of Luebeck, Luebeck, Germany.
Neuroimage Clin. 2022;36:103246. doi: 10.1016/j.nicl.2022.103246. Epub 2022 Oct 25.
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 [C]±dihydrotetrabenazine (DTBZ) scans, most closely related to dopaminergic denervation; 2) 73 [C]d-threo-methylphenidate (MP) scans, marker of dopamine transporter density; 3) 50 6-[F]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.
多巴胺处理的不同方面的改变可能在帕金森病的病程中表现出不同的进行性行为。我们使用了一种新的数据驱动的多变量方法来量化和比较来自横断面帕金森病患者的不同方面的多巴胺处理的时空模式，这些患者接受了以下三种方法的检查：1）69 [C]±二氢四苯并嗪（DTBZ）扫描，与多巴胺能神经支配最密切相关；2）73 [C]d-threo-甲基苯丙胺（MP）扫描，多巴胺转运体密度的标志物；3）50 6-[F]氟-L-多巴（FD）扫描，多巴胺合成和储存的标志物。壳核的前后梯度被确定为与疾病进展最相关的最显著特征，但三种示踪剂的时空梯度的时间进展不同。与 DTBZ 和 MP 相比，FD 在疾病发作时表现出最高的前后梯度表达（P=0.018 和 P=0.047），但下降更快（P=0.006）。MP 的梯度表达最初相似，但下降更快（P=0.015）与 DTBZ 相比。这些结果反映了与多巴胺合成（FD）和再摄取（MP）相关的调节机制的独特时间行为。虽然在症状出现后大约 10 年内，前壳核中多巴胺合成的相对早期疾病上调可能会扩展，但多巴胺转运体密度的假定下调可能仅在前驱期/最早疾病阶段发挥代偿作用。
