Dynamic contrast-enhanced MRI of Gd-albumin delivery to the rat hippocampus in vivo by convection-enhanced delivery.
Dynamic contrast-enhanced MRI of Gd-albumin delivery to the rat hippocampus in vivo by convection-enhanced delivery.
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DOI：
10.1016/j.jneumeth.2012.05.024
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发表时间：
2012-07-30
影响因子：
3
通讯作者：
Sarntinoranont M
中科院分区：
文献类型：
--
作者：
Kim JH;Astary GW;Nobrega TL;Kantorovich S;Carney PR;Mareci TH;Sarntinoranont M
对流增强输送（CED）由于其能够绕过血脑屏障（BBB）并将治疗药物直接输送到中枢神经系统（CNS）的实质，在治疗神经系统疾病方面显示出前景。这种给药方法可能有助于治疗涉及海马的中枢神经系统疾病，如颞叶癫痫和胶质瘤；然而，解剖结构对输液分布的影响尚不完全清楚。作为治疗药物的替代，我们使用Evans蓝染料标记的钆白蛋白（Gd-albumin），通过动态对比增强磁共振成像（DCE-MRI）观察CED在体内大鼠海马背侧和腹侧灌注分布的时间依赖性。为了获得更精细的解剖细节，通过高分辨率t1加权MR成像和固定脑切片的光学显微镜观察灌注物的最终分布体积（Vd）。动态图像显示，gd -白蛋白优先沿神经解剖结构分布在海马内，在致密细胞层中观察到较少的流体阻力和较少的穿透。此外，在输注结束时，邻近的脑脊液（CSF）间隙（如海马裂缝、间膜和中脑池）发生了明显的渗漏。Vd随注射量（Vi）线性增加，海马背侧注射Vd/Vi平均为5.51±0.55，海马腹侧注射Vd/Vi平均为5.30±0.83。本研究表明，组织结构和脑脊液空间边界对脑积水分布有显著影响。
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 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 (Vd) of the infusate were observed with high-resolution T1-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. Vd increased linearly with infusion volume (Vi) at a mean Vd/Vi 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.
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影响因子：
3
作者：
Astary, Garrett W.;Kantorovich, Svetlana;Carney, Paul R.;Mareci, Thomas H.;Sarntinoranont, Malisa
通讯作者：
Sarntinoranont, Malisa
影响因子：
2.8
作者：
Foley, Conor P.;Nishimura, Nozomi;Olbricht, William L.
通讯作者：
Olbricht, William L.
影响因子：
15.9
作者：
Inoue, Tomoo;Yamashita, Yoji;Tominaga, Teiji
通讯作者：
Tominaga, Teiji
影响因子：
3.2
作者：
Kim, Jung Hwan;Mareci, Thomas H.;Sarntinoranont, Malisa
通讯作者：
Sarntinoranont, Malisa
影响因子：
12.4
作者：
Cunningham, Janet;Pivirotto, Philip;Bankiewicz, Krystof S.
通讯作者：
Bankiewicz, Krystof S.