From the University of Washington, Seattle, WA.
Clin Nucl Med. 2015 Mar;40(3):191-4. doi: 10.1097/RLU.0000000000000638.
Differential vulnerabilities of subregional dopamine neurons have been suggested in movement disorders such as idiopathic Parkinson disease. In this study, we examined dopamine transporter (DaT) density in the striatum versus midbrain (MB) in patients with nigrostriatal denervation.
Brain SPECT was performed in 39 patients with parkinsonian syndrome (age 61 ± 15 years, 18 male patients) 4 hours after IV injection of 3 to 5 mCi 123I ioflupane using SPECT-CT acquisition. Images were reconstructed using OSEM with resolution recovery and correction for scatter and attenuation based on a low-dose CT. Peak pixel counts within the caudate head (CA), mid putamen (PT), and MB localized by sagittal CT, as well as averaged counts around the calcarine fissure as reference, were determined by region-of-interest analysis. Semiquantitative DaT values were expressed as CA, PT, or MB uptake relative to the reference. We then assessed the relationship between the MB measurements and independent clinical evaluation of motor symptoms in these patients.
Averaged striatal DaT values for both hemispheres ranged from 1.67 to 6.59 for CA, 1.50 to 5.33 for PT, and 1.08 to 2.24 for MB. Within the high striatal DaT group (mean, 4.76 [SD, 0.55]) and low DaT group (mean, 2.71 [SD, 0.58]; dichotomy defined as a threshold of 4), mean DaT values in MB were 1.68 (SD, 0.32) and 1.53 (SD, 0.29), respectively, indicating nonsignificant 9% decrease (P > 0.15) in comparison to 43% decrease in the averaged striatal uptake. Within the high striatal DaT group, Pearson correlations between DaT values of CA and PT versus MB were highly significant at 0.81 and 0.82 (P ≤ 0.001), respectively, but those correlations were not significant, 0.35 (P > 0.05) and 0.06 (P > 0.75), in the low striatal DaT group. Midbrain uptake measurements did not correlate with motor symptoms (bradykinesia, tremor, rigidity, and postural instability).
These findings indicate that reductions in DaT values in the striatum and MB are not necessarily simultaneous with the process of nigrostriatal denervation, and correlation of DaT values among CA/PT and MB becomes weaker as the denervation becomes more severe. Differential regional DaT loss may indicate differential vulnerability of DaT-containing neurons in these structures or could be in part related to tracer binding to non-DaT targets.
在特发性帕金森病等运动障碍中，已经提出了亚区多巴胺神经元的不同脆弱性。在这项研究中，我们检查了黑质纹状体投射（nigrostriatal）缺失患者纹状体与中脑（midbrain，MB）之间的多巴胺转运蛋白（dopamine transporter，DaT）密度。
39 例帕金森综合征患者（年龄 61±15 岁，男性 18 例）在静脉注射 3 至 5mCi 123I 碘氟潘后 4 小时进行脑 SPECT 检查。使用 SPECT-CT 采集，通过具有分辨率恢复的 OSEM 进行图像重建，并基于低剂量 CT 校正散射和衰减。通过感兴趣区域分析确定由矢状 CT 定位的尾状核头部（caudate head，CA）、中脑壳核（mid putamen，PT）和 MB 中的最大像素计数，以及作为参考的环槽周围的平均计数。DaT 值的半定量表示为 CA、PT 或 MB 与参考的摄取比值。然后，我们评估了 MB 测量值与这些患者独立运动症状临床评估之间的关系。
双侧半球的平均纹状体 DaT 值范围为 CA 为 1.67 至 6.59，PT 为 1.50 至 5.33，MB 为 1.08 至 2.24。在高纹状体 DaT 组（平均值 4.76[SD，0.55]）和低 DaT 组（平均值 2.71[SD，0.58]；二分类定义为 4 的阈值）中，MB 的平均 DaT 值分别为 1.68（SD，0.32）和 1.53（SD，0.29），表明与纹状体摄取的 43%下降相比，MB 的摄取下降了 9%（P＞0.15）。在高纹状体 DaT 组中，CA 和 PT 与 MB 的 DaT 值之间的 Pearson 相关性分别为 0.81 和 0.82（P≤0.001），高度显著，但在低纹状体 DaT 组中，这些相关性不显著，分别为 0.35（P＞0.05）和 0.06（P＞0.75）。MB 摄取测量值与运动症状（运动迟缓、震颤、僵硬和姿势不稳）无相关性。
这些发现表明，纹状体和 MB 中的 DaT 值减少不一定与黑质纹状体投射缺失同时发生，随着去神经支配的加重，CA/PT 和 MB 之间的 DaT 值相关性变弱。DaT 含量的区域差异损失可能表明这些结构中 DaT 神经元的不同脆弱性，或者在一定程度上与示踪剂与非 DaT 靶标结合有关。
