Regional convection-enhanced delivery of gadolinium-labeled albumin in the rat hippocampus in vivo
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- 作者：Garrett W. Astary ; Svetlana Kantorovich ; Paul R. Carney ; Thomas H. Mareci ; Malisa Sarntinoranont
- 关键词：Convection-enhanced delivery ; Magnetic resonance imaging ; Contrast agent ; Gd-albumin ; Rat hippocampus
- 刊名：Journal of Neuroscience Methods
- 出版年：2010
- 出版时间：15 March 2010
- 年：2010
- 卷：187
- 期：1
- 页码：129-137
- 全文大小：1482 K
文摘
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 (Vi = 5 μl) 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 T. 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.