From the Departments of Radiology (R.J.M., J.S.M., D.F.K., K.R.T., E.E.W., L.J.E.), Neurosurgery (D.F.K.), and Laboratory Medicine and Pathology (M.E.J., D.L.M.), College of Medicine, Mayo Clinic, 200 First St SW, Rochester, MN 55905.
Radiology. 2015 Jun;275(3):772-82. doi: 10.1148/radiol.15150025. Epub 2015 Mar 5.
PURPOSE: To determine if repeated intravenous exposures to gadolinium-based contrast agents (GBCAs) are associated with neuronal tissue deposition. MATERIALS AND METHODS: In this institutional review board-approved single-center study, signal intensities from T1-weighted magnetic resonance (MR) images and postmortem neuronal tissue samples from 13 patients who underwent at least four GBCA-enhanced brain MR examinations between 2000 and 2014 (contrast group) were compared with those from 10 patients who did not receive GBCA (control group). Antemortem consent was obtained from all study participants. Neuronal tissues from the dentate nuclei, pons, globus pallidus, and thalamus of these 23 deceased patients were harvested and analyzed with inductively coupled plasma mass spectrometry (ICP-MS), transmission electron microscopy, and light microscopy to quantify, localize, and assess the effects of gadolinium deposition. Associations between cumulative gadolinium dose, changes in T1-weighted MR signal intensity, and ICP-MS-derived tissue gadolinium concentrations were examined by using the Spearman rank correlation coefficient (ρ). RESULTS: Compared with neuronal tissues of control patients, all of which demonstrated undetectable levels of gadolinium, neuronal tissues of patients from the contrast group contained 0.1-58.8 μg gadolinium per gram of tissue, in a significant dose-dependent relationship that correlated with signal intensity changes on precontrast T1-weighted MR images (ρ = 0.49-0.93). All patients in the contrast group had relatively normal renal function at the time of MR examination. Gadolinium deposition in the capillary endothelium and neural interstitium was observed only in the contrast group. CONCLUSION: Intravenous GBCA exposure is associated with neuronal tissue deposition in the setting of relatively normal renal function. Additional studies are needed to investigate the clinical significance of these findings and the generalizability to other GBCAs. Online supplemental material is available for this article.
目的：确定重复静脉内接触钆基对比剂（GBCA）是否与神经元组织沉积有关。
材料和方法：在这项经过机构审查委员会批准的单中心研究中，比较了 2000 年至 2014 年间至少接受过 4 次 GBCA 增强脑磁共振检查的 13 名患者（对比组）的 T1 加权磁共振（MR）图像信号强度和死后神经元组织样本与未接受 GBCA 的 10 名患者（对照组）的信号强度。所有研究参与者均获得了生前同意。从这 23 名已故患者的齿状核、脑桥、苍白球和丘脑采集神经元组织，并进行电感耦合等离子体质谱（ICP-MS）、透射电子显微镜和光镜分析，以定量、定位和评估钆沉积的影响。使用 Spearman 秩相关系数（ρ）检查累积钆剂量、T1 加权 MR 信号强度变化与 ICP-MS 衍生的组织钆浓度之间的关系。
结果：与对照组患者的神经元组织相比，所有对照组患者的神经元组织均未检测到钆，而对比组患者的神经元组织中每克组织含有 0.1-58.8μg 的钆，呈显著剂量依赖性关系，与增强前 T1 加权 MR 图像上的信号强度变化相关（ρ=0.49-0.93）。在进行 MR 检查时，对比组的所有患者均具有相对正常的肾功能。仅在对比组中观察到毛细血管内皮和神经间质中的钆沉积。
结论：在肾功能相对正常的情况下，静脉内 GBCA 暴露与神经元组织沉积有关。需要进一步的研究来调查这些发现的临床意义以及对其他 GBCA 的普遍性。本文提供了在线补充材料。
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