Department of Radiology, Seattle Children's Hospital, University of Washington, 4800 Sand Point Way NE, M/S MA 7.220, Seattle, WA, 98105, USA.
Department of Radiology, University of Washington, Seattle, WA, USA.
Pediatr Radiol. 2020 Mar;50(3):388-396. doi: 10.1007/s00247-019-04535-w. Epub 2020 Jan 27.
BACKGROUND: Retained gadolinium from gadolinium-based contrast agents (GBCAs) used in MR exams has been inferred based on signal changes on serial brain MRI and subsequently demonstrated pathologically in adults. Retention has been similarly inferred in children but pathological demonstration in pediatric patients is limited. The long-term effects of retained gadolinium are unknown but are potentially of greater concern in children given their increased vulnerability from continuing development and their expected longer period of exposure. Several factors can influence gadolinium retention. In adults as well as in children, greater accumulation has been demonstrated based on MR signal changes with linear compared with macrocyclic gadolinium chelates, attributed to lower chelate affinity with linear agents. Effects of age at exposure on retention are unknown, while differences in GBCA washout rates are still under investigation and might affect gadolinium retention relative to time of GBCA administration. OBJECTIVE: The purpose of this study was to confirm whether gadolinium brain deposits are present in pediatric patients who received GBCAs and to quantify the amounts present. MATERIALS AND METHODS: Brain autopsy specimens from 10 pediatric patients between 1 year and 13 years of age who underwent at least one contrast-enhanced MR exam were analyzed for elemental gadolinium using inductively coupled plasma mass spectrometry. Brain samples included white matter, basal ganglia (putamen, globus pallidus), thalamus, dentate nucleus and tumor tissue as available. Type and dose of contrast agent, number and timing of contrast-enhanced MR exams and renal function (estimated glomerular filtration rate [eGFR]) were documented for each child. RESULTS: Patient exposures ranged from 1 dose to 20 doses of GBCAs including both macrocyclic and linear ionic agents. Gadolinium was found to be present in brain tissue in all children and was generally highest in the globus pallidus. Those who received only macrocyclic agents showed lower levels of gadolinium retention. CONCLUSION: This study demonstrates pathological confirmation of gadolinium retention in brain tissue of a series of pediatric patients exposed to GBCAs including not only linear ionic agents but also macrocyclic agents with both nonionic and ionic compounds. The distribution and deposition levels in this small pediatric population are comparable with the findings in adults. While the clinical significance of these deposits remains unknown, at this point it would be prudent to exert caution and avoid unnecessary use of GBCAs in pediatric patients.
背景:在磁共振成像(MRI)检查中使用的基于钆的造影剂(GBCAs)中残留的钆已根据连续脑部 MRI 的信号变化推断出来,随后在成人中通过病理证实。在儿童中也同样推断出了残留,但在儿科患者中病理证实的情况有限。目前尚不清楚长期摄入残留钆的影响,但鉴于儿童在继续发育过程中的脆弱性以及预期的更长暴露时间,这些影响可能更为严重。有几个因素会影响钆的保留。在成人和儿童中,与大环配体相比,线性配体的磁共振信号变化显示出更大的积累,这归因于线性配体与配体的亲和力较低。暴露年龄对保留的影响尚不清楚,而 GBCA 清除率的差异仍在研究中,并且可能会影响相对于 GBCA 给药时间的钆保留。 目的:本研究的目的是确认接受 GBCA 的儿科患者是否存在脑内钆沉积,并定量检测其含量。 材料和方法:对 10 名年龄在 1 至 13 岁之间的儿科患者的脑尸检标本进行了分析,这些患者至少进行了一次对比增强 MRI 检查,使用电感耦合等离子体质谱法检测了元素钆。脑样本包括白质、基底节(苍白球、球状体)、丘脑、齿状核和肿瘤组织(如可获得)。记录了每位患者的造影剂类型和剂量、对比增强 MRI 检查的次数和时间以及肾功能(估算肾小球滤过率[eGFR])。 结果:患者的暴露范围从 1 次剂量到 20 次剂量的 GBCA,包括大环配体和线性离子型药物。在所有患儿的脑组织中均发现了钆的存在,且在苍白球中含量最高。仅接受大环配体的患者显示出较低水平的钆保留。 结论:本研究在一系列接受 GBCA 暴露的儿科患者的脑组织中证实了病理上的钆保留,这些患者不仅接受了线性离子型药物,还接受了具有非离子型和离子型化合物的大环配体药物。在这个小型儿科人群中的分布和沉积水平与成人的发现相似。虽然这些沉积物的临床意义尚不清楚,但目前谨慎起见,应避免在儿科患者中不必要地使用 GBCA。
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