Department of Mechanical and Aerospace Engineering, University of Florida, Gainesville, FL 32611, USA.
J Neurosci Methods. 2012 Jul 30;209(1):62-73. doi: 10.1016/j.jneumeth.2012.05.024. Epub 2012 Jun 8.
Convection-enhanced delivery (CED) shows promise in treating neurological diseases due to its ability to circumvent the blood-brain barrier (BBB) and deliver therapeutics directly to the parenchyma of the central nervous system (CNS). Such a drug delivery method may be useful in treating CNS disorders involving the hippocampus such as temporal lobe epilepsy and gliomas; however, the influence of anatomical structures on infusate distribution is not fully understood. As a surrogate for therapeutic agents, we used gadolinium-labeled-albumin (Gd-albumin) tagged with Evans Blue dye to observe the time dependence of CED infusate distributions into the rat dorsal and ventral hippocampus in vivo with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). For finer anatomical detail, final distribution volumes (V(d)) of the infusate were observed with high-resolution T(1)-weighted MR imaging and light microscopy of fixed brain sections. Dynamic images demonstrated that Gd-albumin preferentially distributed within the hippocampus along neuroanatomical structures with less fluid resistance and less penetration was observed in dense cell layers. Furthermore, significant leakage into adjacent cerebrospinal fluid (CSF) spaces such as the hippocampal fissure, velum interpositum and midbrain cistern occurred toward the end of infusion. V(d) increased linearly with infusion volume (V(i)) at a mean V(d)/V(i) ratio of 5.51 ± 0.55 for the dorsal hippocampus infusion and 5.30 ± 0.83 for the ventral hippocampus infusion. This study demonstrated the significant effects of tissue structure and CSF space boundaries on infusate distribution during CED.
脑室内输注（CED）因其能够绕过血脑屏障（BBB）并将治疗剂直接递送至中枢神经系统（CNS）实质而在治疗神经疾病方面显示出前景。这种药物递送方法可能在治疗涉及海马体的 CNS 疾病（如颞叶癫痫和神经胶质瘤）方面有用；然而，解剖结构对输注物分布的影响尚未完全了解。作为治疗剂的替代品，我们使用钆标记白蛋白（Gd-albumin）标记 Evans Blue 染料，并用动态对比增强磁共振成像（DCE-MRI）观察CED 输注物在体内向大鼠背侧和腹侧海马体的时间依赖性分布。为了获得更精细的解剖细节，我们用高分辨率 T1 加权磁共振成像和固定脑切片的光显微镜观察最终输注物的分布体积（V(d)）。动态图像表明，Gd-albumin 优先沿着具有较小流体阻力和较少穿透性的神经解剖结构分布在海马体中。此外，在输注结束时，观察到明显的渗漏到相邻的脑脊液（CSF）空间，如海马裂、中间帆池和中脑池。V(d) 随输注量（V(i)）呈线性增加，背侧海马体输注的平均 V(d)/V(i) 比为 5.51±0.55，腹侧海马体输注的平均 V(d)/V(i) 比为 5.30±0.83。这项研究表明，在 CED 期间，组织结构和 CSF 空间边界对输注物分布有显著影响。
