Counter S Allen, Nikkhou-Aski Sahar, Damberg Peter, Berglin Cecilia Engmér, Laurell Göran
*Neurology Department, Harvard University Biological Laboratories, Cambridge, Massachusetts, USA †Karolinska Experimental Research and Imaging Center, Karolinska Universitetssjukhuset Solna ‡Department of Clinical Neuroscience §Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm ||Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
Otol Neurotol. 2017 Aug;38(7):1052-1059. doi: 10.1097/MAO.0000000000001458.
Effective paramagnetic contrast agent for the penetration of the perilymphatic spaces of the scala tympani, scala vestibuli, and scala media of the mouse inner ear can be determined using intravenous injection of various gadolinium (Gd) complexes and ultra-high-field magnetic resonance imaging (MRI) at 9.4 Tesla.
A number of contrast agents have been explored in experimental high-field MRI to determine the most effective Gd complex for ideal signal-to-noise ratio and maximal visualization of the in vivo mammalian inner ear in analyzing the temporal and spatial parameters involved in drug penetration of the blood-perilymph barrier and intrastrial fluid-blood barrier in the mouse model using MRI.
Gadoteric acid (Dotarem), Gadobutrol (Gadovist), Gadodiamide (Omniscan), Gadopent acid (Magnevist), and Mangafodipir (Teslascan) were administered intravenously using the tail vein of 60 Balb/C mice. High-resolution T1 images of drug penetration were acquired with a horizontal 9.4 T Agilent magnet after intravenously injection. Signal intensity was used as a metric of temporal and spatial parameters of drug delivery and penetration of the perilymphatic and endolymphatic spaces.
ANOVA analysis of the area under the curve of intensity enhancement in perilymph revealed a significant difference (p < 0.05) in the scalae uptake using different contrast agents (F (3,25) = 3.54, p = 0.029). The Gadoteric acid complex Dotarem was found to be the most effective Gd compound in terms of rapid, morphological enhancement for analysis of the temporal, and spatial distribution in the perilymphatic space of the inner ear.
Gadoteric acid (Dotarem) demonstrated efficacy as a contrast agent for enhanced visualization of the perilymphatic spaces of the inner ear labyrinthine in the mouse, including the scala tympani and scala vestibuli of the cochlea, and the semicircular canals of the vestibular apparatus. These findings may inform the clinical application of Gd compounds in patients with inner ear fluid disorders and vertigo.
通过静脉注射各种钆（Gd）配合物并使用9.4特斯拉的超高场磁共振成像（MRI），可以确定对小鼠内耳鼓阶、前庭阶和中阶外淋巴间隙具有渗透作用的有效顺磁性造影剂。
在实验性高场MRI中已经探索了多种造影剂，以确定在使用MRI分析小鼠模型中血-外淋巴屏障和内淋巴液-血屏障药物渗透所涉及的时间和空间参数时，哪种Gd配合物对于理想的信噪比和体内哺乳动物内耳的最大可视化最为有效。
通过60只Balb/C小鼠的尾静脉静脉注射钆特酸（多它灵）、钆布醇（加朵唯视）、钆双胺（欧乃影）、钆喷酸（马根维显）和锰福地匹三钠（泰斯拉显）。静脉注射后，使用水平9.4 T安捷伦磁体获取药物渗透的高分辨率T1图像。信号强度用作药物递送以及外淋巴和内淋巴间隙渗透的时间和空间参数的指标。
对外淋巴强度增强曲线下面积的方差分析显示，使用不同造影剂时阶的摄取存在显著差异（p<0.05）（F(3,25)=3.54，p=0.029）。就内耳外淋巴间隙的时间和空间分布分析而言，钆特酸配合物多它灵被发现是最有效的Gd化合物，具有快速的形态增强效果。
钆特酸（多它灵）作为一种造影剂，可有效增强小鼠内耳迷路外淋巴间隙的可视化，包括耳蜗的鼓阶和前庭阶以及前庭装置的半规管。这些发现可能为Gd化合物在患有内耳液紊乱和眩晕的患者中的临床应用提供参考。
