目的通过MRI观察豚鼠鼓膜穿刺听泡内注射钆喷酸葡胺后内耳增强显影的特征,观察不同时间点造影剂在内耳的分布,找出内耳增强显影的最佳时间,同时了解钆喷酸葡胺在内耳的药代动力学特点,探讨在现有实验条件下内、外淋巴区分显影的可行性。方法65只豚鼠随机数字表法分为13组,每组5只。豚鼠鼓膜穿刺听泡内注射生理盐水稀释8倍的钆喷酸葡胺,分别在注射前、注射后0.5、1、2、4、6、8、10、12、24、48、72及96h行内耳MRI扫描(3D—T1FSE序列)。使用e—Film软件对内耳各部位MRI图像灰度值进行提取,应用体外试验获得的灰度值一造影剂浓度关系将灰度值转化成浓度。分别测量注射前、注射后1d及7d豚鼠左耳(生理盐水)和右耳(稀释造影剂)的听性脑干反应(ABR)阈值并进行对比。结果注射后6h为造影剂扩散至全内耳并达到较好显影条件的时间点,也即造影剂在内耳各部分达到较高浓度的时间,此时造影剂在前庭、底转鼓阶、底转前庭阶、第二转、第三转、顶转的浓度分别为589.29、552.54、570.17、255.08、107.09、139.18μmol/L;造影剂选择性进入外淋巴,未见内淋巴增强显影。造影剂注射后1d及7d豚鼠左、右耳ABR阈值相比,差异无统计学意义(P值均〉0.05)。结论豚鼠听泡内注射钆喷酸葡胺后6h为MRI内耳增强显影的最佳观察时间。造影剂可选择性显影外淋巴,对豚鼠ABR阈值无明显影响。通过MRI可以间接研究钆喷酸葡胺在内耳的代谢特点。
Objective To observe the distribution of Gd-DTPA in the inner ear of guinea pig by MRI at different time points after intratympanic administration, explore the optical time for observing the whole inner ear. To study the pharmacokinetic feature of Gd-DTPA in the inner ear, and find out whether discrimination of endolymph and perilymph can be obtained under current conditions. Methods Sixty-five guinea pigs were randomly divided into 13 groups, after diluted Gd-DTPA intratympanic injection, each group of guinea pigs were scanned through MRI (3D-T1 FSE sequence) at different time points (0 h, 0. 5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 10 h, 12 h, 24 h, 48 h, 72 h, 96 h). Pixel intensity values of some locations in the inner ear were analyzed using e-Film software, then pixel intensity was converted into concentration using the results of previous in-vitro study. ABR thresholds of bilateral ears before, 1 d and 7 d after intratympanic injection were compared. Results Six hours after transtympanic Gd-DTPA injection was the time point when contrast agent was distributed all over the inner ear, and reached a high concentration: 589. 29, 552. 54, 570. 17, 255.08, 107. 09 and 139. 18 Ixmol/L in the vestibule, scala vestibuli and scala tympani of basal turn, the 2n~1, the 3ra and the apical turn individually, that was also the optimal time for observing the whole inner ear by MRI. Perilymph appeared to be preferentially enhanced relative to the endolymph, resulting in a distinction between the scalaes of the inner ear. There was no significant difference between the experimental ear( diluted GD-DTPA injected ear) and contrast ear(physiological saline injected ear) on 1 d and 7 d. Conclusions The best time getting MRI imaging after intratympanic diluted GD-DTPA injection is 6 h. After diluted agent injection perilymph can be enhanced so as to be differentiated with endolymph by MRI, diluted agent have no obvious effect on the ABR threshold. The pharmacokinetic feature of Gd-DTPA in the inner can be studied using MR