钆喷酸葡胺多次注射后大鼠深部脑核团中长期滞留的钆对代谢的影响。

Effect of Long-Term Retention of Gadolinium on Metabolism of Deep Cerebellar Nuclei After Repeated Injections of Gadodiamide in Rats.

机构信息

From the Center of Molecular Biophysics, CNRS UPR4301, Orléans.

Department of Research and Innovation, Imaging and Biological Research Division, Roissy CDG, France.

出版信息

Invest Radiol. 2020 Feb;55(2):120-128. doi: 10.1097/RLI.0000000000000621.

DOI:10.1097/RLI.0000000000000621

PMID:31876627

Abstract

OBJECTIVES

The aim of this study was to determine potential metabolism and histological modifications due to gadolinium retention within deep cerebellar nuclei (DCN) after linear gadolinium-based contrast agent injection (gadodiamide) in rats at 1 year after the last injection.

MATERIALS AND METHODS

Twenty female rats received 20 doses of gadodiamide (0.6 mmol of gadolinium per kilogram each) over 5 weeks. They were followed at 1 week (M0), 6 weeks (M1), and 54 to 55 weeks (M13) postinjections to evaluate hypersignal on unenhanced T1-weighted magnetic resonance imaging and metabolic alterations by H magnetic resonance spectroscopy (H-MRS). At 1 year postinjections, brains were sampled to determine the localization of gadolinium within cerebellum by laser ablation inductively coupled mass spectroscopy and to evaluate morphological changes by semiquantitative immunofluorescence analysis.

RESULTS

There is a significant increase of the ratio DCN/brainstem for the gadodiamide group at M0 (+7.2% vs control group = 0.989 ± 0.01), M1 (+7.6% vs control group = 1.002 ± 0.018), and it lasted up to M13 (+4.7% vs control group = 0.9862 ± 0.008). No variation among metabolic markers (cellular homeostasis [creatine, choline, taurine], excitatory neurotransmitter [glutamate], and metabolites specific to a cellular compartment [N-acetyl aspartate for neurons and myo-inositol for glial cells]) were detected by H-MRS between gadodiamide and saline groups at M0, M1, and M13. At M13, laser ablation inductively coupled mass spectroscopy demonstrated that long-term gadolinium retention occurred preferentially in DCN. No histological abnormalities (including analysis of astrocytes, neurons, and microglial cells) were found in the rostral part of DCN.

CONCLUSIONS

Repeated administration of gadodiamide lead to a retention of gadolinium preferentially within DCN at 1 year postinjections. This retention did not lead to any detectable changes of the measured metabolic biomarkers nor histological alterations.

摘要

目的

本研究旨在确定在最后一次注射后 1 年，大鼠接受线性钆基造影剂（钆喷酸葡胺）注射后，由于深脑核（DCN）内的钆蓄积而导致的潜在代谢和组织学改变。

材料和方法

20 只雌性大鼠在 5 周内接受 20 次钆喷酸葡胺（每公斤 0.6 毫摩尔的钆）注射。在注射后 1 周（M0）、6 周（M1）和 54 至 55 周（M13）时进行评估，以评估未增强 T1 加权磁共振成像上的高信号和磁共振波谱（H-MRS）的代谢改变。在注射后 1 年，通过激光烧蚀电感耦合质谱法确定小脑内的钆定位，并通过半定量免疫荧光分析评估形态变化。

结果

M0（+7.2%对对照组=0.989±0.01）、M1（+7.6%对对照组=1.002±0.018）时，DCN/脑干比值显著增加，且持续至 M13（+4.7%对对照组=0.9862±0.008）。在 M0、M1 和 M13 时，H-MRS 未检测到代谢标志物（细胞内稳态[肌酸、胆碱、牛磺酸]、兴奋性神经递质[谷氨酸]和细胞内特定代谢物[神经元的 N-乙酰天冬氨酸和神经胶质细胞的肌醇]）在钆喷酸葡胺和生理盐水组之间有变化。在 M13 时，激光烧蚀电感耦合质谱法表明，长期的钆蓄积主要发生在 DCN 中。在 DCN 的前半部分未发现组织学异常（包括星形胶质细胞、神经元和小胶质细胞的分析）。