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多次静脉注射线性钆基造影剂后犬脑内的钆沉积。

Gadolinium deposition in the brain of dogs after multiple intravenous administrations of linear gadolinium based contrast agents.

机构信息

Diagnostic Imaging Research Unit (DIRU), Clinic for Diagnostic Imaging, Department of Clinical Diagnostics and Services, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland.

Institute of Inorganic and Analytical Chemistry, University of Münster, Münster, Germany.

出版信息

PLoS One. 2020 Feb 3;15(2):e0227649. doi: 10.1371/journal.pone.0227649. eCollection 2020.


DOI:10.1371/journal.pone.0227649
PMID:32012163
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6996830/
Abstract

OBJECTIVE: To determine the effect of a linear gadolinium-based contrast agent (GBCA) on the signal intensity (SI) of the deep cerebellar nuclei (DCN) in a retrospective clinical study on dogs after multiple magnetic resonance (MR) examinations with intravenous injections of gadodiamide and LA-ICP-MS analysis of a canine cerebellum after gadodiamide administration. ANIMALS: 15 client-owned dogs of different breeds and additionally 1 research beagle dog cadaver. PROCEDURES: In the retrospective study part, 15 dogs who underwent multiple consecutive MR imaging examinations with intravenous injection of linear GBCA gadodiamide were analyzed. SI ratio differences on unenhanced T1-weighted MR images before and after gadodiamide injections was calculated by subtracting SI ratios between DCN and pons of the first examination from the ratio of the last examination. Additionally, 1 research beagle dog cadaver was used for LA-ICP-MS (Laser ablation inductively coupled plasma mass spectrometry) analysis of gadolinium in the cerebellum as an add-on to another animal study. Descriptive and non-parametrical statistical analysis was performed and a p-value of < 0.05 was considered significant. RESULTS: No statistically significant differences of SI ratios, between DCN and pons, were detectable based on unenhanced T1-weighted MR images. LA-ICP-MS analyses showed between 1.5 to 2.5 μg gadolinium/g tissue in the cerebellum of the examined dog, 35 months after the last of 3 MRI examination with gadodiamide (two examinations at a dose of 1 x 0.1mmol/kg, last examination at a dose of 3 x 0.05mmol/kg). CONCLUSION AND CLINICAL RELEVANCE: Although the retrospective MRI study did not indicate any visible effect of SI increase after multiple gadodiamide exposures, further studies based on LA-ICP-MS showed that the optical threshold was not reached for a potential visible effect. Gadolinium was detectable at a level of 1.5 to 2.5 μg gadolinium/g tissue by using LA-ICP-MS in the cerebellum 35 months after last MRI examination. The general importance of gadolinium retention of subvisible contents requires further investigation.

摘要

目的:通过对使用静脉注射钆喷酸葡胺多次磁共振成像(MR)检查的犬进行回顾性临床研究,以及对给予钆喷酸葡胺后犬小脑进行激光烧蚀电感耦合等离子体质谱(LA-ICP-MS)分析,确定一种线性钆基造影剂(GBCA)对小脑深部核(DCN)信号强度(SI)的影响。

动物:15 只不同品种的患犬,另外 1 只研究用比格犬尸体。

程序:在回顾性研究部分,分析了 15 只接受多次连续静脉注射线性 GBCA 钆喷酸葡胺的 MR 成像检查的犬。通过从最后一次检查的比值中减去第一次检查时 DCN 和脑桥之间的 SI 比值,计算增强前和增强后 T1 加权 MR 图像上 DCN 和脑桥之间的 SI 比值差异。此外,使用 1 只研究用比格犬尸体进行小脑内镧系元素(LA)-ICP-MS(激光烧蚀电感耦合等离子体质谱)分析,作为另一项动物研究的补充。进行描述性和非参数统计分析,p 值<0.05 认为具有统计学意义。

结果:基于增强前 T1 加权 MR 图像,DCN 和脑桥之间的 SI 比值无统计学显著差异。LA-ICP-MS 分析显示,在接受 3 次 MRI 检查(2 次剂量为 1 x 0.1mmol/kg,最后 1 次剂量为 3 x 0.05mmol/kg)后 35 个月,检查犬小脑内的组织中含有 1.5 至 2.5μg 镧系元素/g 组织。

结论和临床相关性:尽管回顾性 MRI 研究未显示多次使用钆喷酸葡胺后 SI 增加的可见影响,但基于 LA-ICP-MS 的进一步研究表明,尚未达到潜在可见影响的光学阈值。使用 LA-ICP-MS 在最后一次 MRI 检查后 35 个月时,小脑内可检测到 1.5 至 2.5μg/g 组织的镧系元素。需要进一步研究亚可见含量的镧系元素保留对整体的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3240/6996830/54f274221af4/pone.0227649.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3240/6996830/b22cfd3ccae2/pone.0227649.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3240/6996830/54f274221af4/pone.0227649.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3240/6996830/b22cfd3ccae2/pone.0227649.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3240/6996830/54f274221af4/pone.0227649.g002.jpg

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Gadolinium deposition in the brain of dogs after multiple intravenous administrations of linear gadolinium based contrast agents.

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引用本文的文献

[1]
Gadolinium: pharmacokinetics and toxicity in humans and laboratory animals following contrast agent administration.

Arch Toxicol. 2022-2

[2]
Musculoskeletal magnetic resonance imaging in the DE50-MD dog model of Duchenne muscular dystrophy.

Neuromuscul Disord. 2021-8

本文引用的文献

[1]
Gadolinium Deposition in the Brain in a Large Animal Model: Comparison of Linear and Macrocyclic Gadolinium-Based Contrast Agents.

Invest Radiol. 2019-9

[2]
Increased Retention of Gadolinium in the Inflamed Brain After Repeated Administration of Gadopentetate Dimeglumine: A Proof-of-Concept Study in Mice Combining ICP-MS and Micro- and Nano-SR-XRF.

Invest Radiol. 2019-10

[3]
Gadolinium retention in gliomas and adjacent normal brain tissue: association with tumor contrast enhancement and linear/macrocyclic agents.

Neuroradiology. 2019-5

[4]
Gadolinium in human brain sections and colocalization with other elements.

Neurol Neuroimmunol Neuroinflamm. 2018-10-19

[5]
Standardized assessment of the signal intensity increase on unenhanced T1-weighted images in the brain: the European Gadolinium Retention Evaluation Consortium (GREC) Task Force position statement.

Eur Radiol. 2018-11-9

[6]
One-year Retention of Gadolinium in the Brain: Comparison of Gadodiamide and Gadoterate Meglumine in a Rodent Model.

Radiology. 2018-5-22

[7]
High Signal Intensity in the Dentate Nucleus and Globus Pallidus on Unenhanced T1-Weighted MR Images: Comparison between Gadobutrol and Linear Gadolinium-Based Contrast Agents.

AJNR Am J Neuroradiol. 2018-2-1

[8]
Gadolinium Accumulation in the Deep Cerebellar Nuclei and Globus Pallidus After Exposure to Linear but Not Macrocyclic Gadolinium-Based Contrast Agents in a Retrospective Pig Study With High Similarity to Clinical Conditions.

Invest Radiol. 2018-5

[9]
Gadolinium deposition in the paediatric brain: T1-weighted hyperintensity within the dentate nucleus following repeated gadolinium-based contrast agent administration.

Clin Radiol. 2018-3

[10]
Spatially resolved quantification of gadolinium deposited in the brain of a patient treated with gadolinium-based contrast agents.

J Trace Elem Med Biol. 2017-10-13

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