Regional convection-enhanced delivery of gadolinium-labeled albumin in the rat hippocampus in vivo.
Regional convection-enhanced delivery of gadolinium-labeled albumin in the rat hippocampus in vivo.
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DOI：
10.1016/j.jneumeth.2010.01.002
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发表时间：
2010-03-15
影响因子：
3
通讯作者：
Sarntinoranont, Malisa
中科院分区：
文献类型：
--
作者：
Astary, Garrett W.;Kantorovich, Svetlana;Carney, Paul R.;Mareci, Thomas H.;Sarntinoranont, Malisa
对流增强给药（CED）已成为治疗中枢神经系统（CNS）疾病的一种有前途的靶向给药方法，但脑结构对输注物分布的影响尚不清楚。我们已经利用这种方法来研究细胞外运输和分布的海马，一个复杂的结构，易受中枢神经系统疾病的造影剂。磁共振（MR）造影剂二乙烯三胺五乙酸螯合钆标记的白蛋白（Gd-白蛋白），标记与埃文斯蓝染料，直接注入到背侧和腹侧海马的7只雄性Sprague-Dawley大鼠。使用11.1特斯拉的高分辨率T1加权MR成像在体内观察造影剂的最终分布概况，其为CED和有限扩散的产物。致密的细胞层，如齿状回的颗粒细胞层和CA 1的锥体细胞层，似乎是示踪剂运输的障碍。使用半自动分割程序从MR图像确定背侧和腹侧海马输注之间的三维分布形状和体积（Vd）差异（背侧Vd = 23.4 ± 1.8 μl，腹侧Vd = 36.4 ± 5.1 μl）。精细的结构细节的海马获得了组织学分析和荧光成像相结合。本研究表明，CED有可能靶向海马的所有区域，示踪剂分布受输注部位、基础结构和回路以及回流程度的影响。因此，CED结合高分辨率MR成像，可能是一种有用的策略，用于提供治疗影响海马的CNS疾病的治疗。
Convection-enhanced delivery (CED) has emerged as a promising method of targeted drug-delivery for treating central nervous system (CNS) disorders, but the influence of brain structure on infusate distribution is unclear. We have utilized this approach to study extracellular transport and distribution of a contrast agent in the hippocampus, a complex structure susceptible to CNS disorders. The magnetic resonance (MR) contrast agent diethylene triamene penta-acetic acid chelated gadolinium-labeled albumin (Gd-albumin), tagged with Evans blue dye, was directly infused into the dorsal and ventral hippocampus of seven male Sprague-Dawley rats. The final distribution profile of the contrast agent, a product of CED and limited diffusion, was observed in vivo using high-resolution T1-weighted MR imaging at 11.1 Tesla. Dense cell layers, such as the granule cell layer of the dentate gyrus and the pyramidal cell layer of CA1, appeared to be barriers to transport of the tracer. Three-dimensional distribution shape and volume (Vd) differences, between the dorsal and ventral hippocampus infusions, were determined from the MR images using a semi-automatic segmentation routine (Dorsal Vd = 23.4 ± 1.8 μl, Ventral Vd = 36.4 ± 5.1 μl). Finer structural detail of the hippocampus was obtained using a combination of histological analysis and fluorescence imaging. This study demonstrates that CED has the potential to target all regions of the hippocampus and that tracer distribution is influenced by infusion site, underlying structure and circuitry, and extent of backflow. Therefore, CED, combined with high-resolution MR imaging, may be a useful strategy for delivering therapeutics for the treatment of CNS disorders affecting the hippocampus.
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