Artzi Moran, Even-Sapir Einat, Lerman Shacham Hedva, Thaler Avner, Urterger Avi Orr, Bressman Susan, Marder Karen, Hendler Talma, Giladi Nir, Ben Bashat Dafna, Mirelman Anat
Functional Brain Center, The Wohl Institute for Advanced Imaging, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
PLoS One. 2017 Apr 13;12(4):e0175424. doi: 10.1371/journal.pone.0175424. eCollection 2017.
Identification of early changes in Dopamine-Transporter (DaT) SPECT imaging expected in the prodromal phase of Parkinson's disease (PD), are usually overlooked. Carriers of the G2019S LRRK2 mutation are known to be at high risk for developing PD, compared to non-carriers. In this work we aimed to study early changes in Dopamine uptake in non-manifesting PD carriers (NMC) of the G2019S LRRK2 mutation using quantitative DaT-SPECT analysis and to examine the potential for early prediction of PD. Eighty Ashkenazi-Jewish subjects were included in this study: eighteen patients with PD; thirty-one NMC and thirty-one non-manifesting non-carriers (NMNC). All subjects underwent a through clinical assessment including evaluation of motor, olfactory, affective and non-motor symptoms and DaT-SPECT imaging. A population based DaT-SPECT template was created based on the NMNC cohort, and data driven volumes-of-interest (VOIs) were defined. Comparisons between groups were performed based on VOIs and voxel-wise analysis. The striatum area of all three cohorts was segmented into four VOIs, corresponding to the right/left dorsal and ventral striatum. Significant differences in clinical measures were found between patients with PD and non-manifesting subjects with no differences between NMC and NMNC. Significantly lower uptake (p<0.001) was detected in the right and left dorsal striatum in the PD group (2.2±0.3, 2.3±0.4) compared to the NMC (4.2±0.6, 4.3±0.5) and NMNC (4.5±0.6, 4.6±0.6), and significantly (p = 0.05) lower uptake in the right dorsal striatum in the NMC group compared to NMNC. Converging results were obtained using voxel-wise analysis. Two NMC participants, who later phenoconverted into PD, demonstrated reduced uptake mainly in the dorsal striatum. No significant correlations were found between the DaT-SPECT uptake in the different VOIs and clinical and behavioral assessments in the non-manifesting groups. This study shows the clinical value of quantitative assessment of DaT-SPECT imaging and the potential for predicting PD by detection of dopamine depletion, already at the pre-symptomatic stage. Clinical registration numbers: NCT01089270 and NCT01089283.
帕金森病（PD）前驱期多巴胺转运体（DaT）单光子发射计算机断层扫描（SPECT）成像的早期变化通常被忽视。与非携带者相比，已知携带G2019S LRRK2突变的个体患PD的风险很高。在这项研究中，我们旨在使用定量DaT-SPECT分析研究G2019S LRRK2突变的未表现出症状的PD携带者（NMC）中多巴胺摄取的早期变化，并检验早期预测PD的可能性。本研究纳入了80名阿什肯纳兹犹太受试者：18名PD患者；31名NMC和31名未表现出症状的非携带者（NMNC）。所有受试者均接受了全面的临床评估，包括运动、嗅觉、情感和非运动症状评估以及DaT-SPECT成像。基于NMNC队列创建了一个基于人群的DaT-SPECT模板，并定义了数据驱动的感兴趣区（VOI）。基于VOI和体素分析进行组间比较。所有三个队列的纹状体区域被分割为四个VOI，分别对应右/左背侧和腹侧纹状体。PD患者与未表现出症状的受试者之间在临床指标上存在显著差异，而NMC和NMNC之间没有差异。与NMC（4.2±0.6，4.3±0.5）和NMNC（4.5±0.6，4.6±0.6）相比，PD组左右背侧纹状体的摄取显著降低（p<0.001）（2.2±0.3，2.3±0.4），并且NMC组右背侧纹状体的摄取显著低于NMNC（p = 0.05）。使用体素分析也得到了一致的结果。两名后来转化为PD的NMC参与者主要在背侧纹状体表现出摄取减少。在未表现出症状的组中，不同VOI的DaT-SPECT摄取与临床和行为评估之间未发现显著相关性。本研究显示了DaT-SPECT成像定量评估的临床价值以及在症状前阶段通过检测多巴胺耗竭来预测PD的可能性。临床注册号：NCT01089270和NCT01089283。
