Department of Neurosurgery, University of California San Francisco, 1855 Folsom Street, MCB 226, San Francisco, CA 94103, USA.
Neuroimage. 2011 Jan;54 Suppl 1:S196-203. doi: 10.1016/j.neuroimage.2009.08.069. Epub 2009 Sep 15.
Optimal results in the direct brain delivery of brain therapeutics such as growth factors or viral vector into primate brain depend on reproducible distribution throughout the target region. In the present study, we retrospectively analyzed MRI of 25 convection-enhanced delivery (CED) infusions with MRI contrast into the putamen of non-human primates (NHP). Infused volume (V(i)) was compared to total volume of distribution (V(d)) versus V(d) within the target putamen. Excellent distribution of contrast agent within the putamen was obtained in eight cases that were used to define an optimal target volume or "green" zone. Partial or poor distribution with leakage into adjacent anatomical structures was noted in 17 cases, defining "blue" and "red" zones, respectively. Quantitative containment (99±1%) of infused gadoteridol within the putamen was obtained when the cannula was placed in the green zone, 87±3% in the blue zone and 49±0.05% in the red zone. These results were used to determine a set of 3D stereotactic coordinates that define an optimal site for putaminal infusions in NHP and human putamen. We conclude that cannula placement and definition of optimal (green zone) stereotactic coordinates have important implications in ensuring effective delivery of therapeutics into the putamen utilizing routine stereotactic MRI localization procedures and should be considered when local therapies such as gene transfer or protein administration are being translated into clinical therapy.
在灵长类动物大脑中直接输送脑治疗药物（如生长因子或病毒载体）以达到最佳效果，取决于在目标区域内可重复的分布。在本研究中，我们回顾性分析了 25 例非人类灵长类动物（NHP）纹状体磁共振对比增强递送（CED）输注的 MRI。将注入体积（V(i)）与分布的总体积（V(d)）与目标纹状体中的 V(d)进行比较。在 8 例获得良好分布的情况下，获得了出色的对比剂在纹状体中的分布，这些病例被用来定义一个最佳的目标体积或“绿色”区域。在 17 例部分或分布不良且有渗漏到相邻解剖结构的情况下，分别定义了“蓝色”和“红色”区域。当导管放置在绿色区域时，可在纹状体中获得 99±1%的注入钆特醇的定量包含，在蓝色区域中获得 87±3%，在红色区域中获得 49±0.05%。这些结果被用来确定一组 3D 立体定向坐标，定义了 NHP 和人类纹状体中进行纹状体输注的最佳部位。我们得出结论，导管放置和最佳（绿色区域）立体定向坐标的定义对于利用常规立体定向 MRI 定位程序确保将治疗药物有效输送到纹状体具有重要意义，并且在将基因转移或蛋白质给药等局部治疗转化为临床治疗时应考虑这些因素。
