Where does the gadolinium go? A review into the excretion and retention of intravenous gadolinium.

Gadolinium-based contrast agents (GBCAs) are commonly used in medical imaging. Most intravenously (IV) administered gadolinium is excreted via the kidneys, and pathological retention in renal failure leading to nephrogenic systemic fibrosis (NSF) is well described. More recently, retention of gadolinium in the body in the absence of renal disease has been identified, with unknown clinical consequences. Many patients are aware of this, either through the media or via comprehensive consent documentation. Some internet sites, without hard evidence, have suggested a constellation of possible symptoms associated with GBCA retention. Recent experience with patients ascribing symptoms to a contrast-enhanced MRI examination prompted this review of the fate of injected GBCA after MRI study, and of information available to patients online regarding gadolinium retention.

Utility of Gadolinium Use in the Imaging Follow-Up of Nonenhancing Primary Brain Neoplasms in Children.

Background and purpose Gadolinium-based contrast agents (GBCAs) have been administered clinically since 1988. They are remarkably well tolerated by children and result in dose-dependent tissue deposition, even in patients with normal renal function. No adverse effects of gadolinium deposition in patients with normal renal function have been established. Given the uncertain effects of gadolinium deposition, we sought to analyze gadolinium use in the imaging follow-up of nonenhancing primary brain neoplasms in children. Materials and methods This retrospective, institutional review board-approved and Health Insurance Portability and Accountability Act-compliant study evaluated pediatric patients who received GBCA in the routine evaluation of brain neoplasms. This special subset included 30 patients (<18 years old) with initially nonenhancing primary intracranial neoplasms who received treatment and follow-up at our institution. Patient data included sex, age from diagnosis to most recent imaging follow-up, number of contrast-enhanced magnetic resonance imaging (MRI) follow-up exams, and histopathology from a biopsy or resection. Results The group had an expected variety of tumors, including low-grade astrocytomas, dysembryoplastic neuroepithelial tumors, oligodendrogliomas, and teratomas. Half of our patients had tumors of unknown histopathology that were not biopsied or resected. The median age at diagnosis was 8.9 years, the median of four follow-up MRIs per patient, and the median follow-up time of four years. Only one of the 30 patients developed an enhancing focus on follow-up MRI that remained stable and asymptomatic over two years and did not require surgical intervention. Conclusion Judicious use of GBCA in children, especially when numerous exams over many years are anticipated, is advised given the data regarding soft-tissue deposition. Preliminary results suggest that it may be feasible to omit GBCA from routine follow-ups of initially nonenhancing brain neoplasms.

Crown Ether-Immobilized Cellulose Acetate Membranes for the Retention of Gd (III).

This study presents a new, revolutionary, and easy method of separating Gd (III). For this purpose, a cellulose acetate membrane surface was modified in three steps, as follows: firstly, with aminopropyl triethoxysylene; then with glutaraldehyde; and at the end, by immobilization of crown ethers. The obtained membranes were characterized by Fourier transform infrared spectroscopy (FT-IR) and X-ray photoelectron spectroscopy (XPS), through which the synthesis of membranes with Gd (III) separation properties is demonstrated. In addition, for the Gd (III) separating process, a gadolinium nitrate solution, with applications of moderator poison in nuclear reactors, was used. The membranes retention performance has been demonstrated by inductively coupled plasma mass spectrometry (ICP-MS), showing a separation efficiency of up to 91%, compared with the initial feed solution.

Dentate Nucleus Signal Intensity Changes in Children with Adrenoleukodystrophy in Comparison to Primary Brain Tumor with and without Radiotherapy after Gadobutrol Administration.

BACKGROUND AND PURPOSE: To determine whether cerebral adrenoleukodystrophy (cALD) or brain irradiation in patients with primary brain tumor affects T1-weighted imaging (T1WI) signal intensity (SI) of the dentate nucleus (DN) in a pediatric cohort who had received consecutive macrocyclic gadolinium-based contrast agent (mcGBCA) gadobutrol. METHODS: This study included 97 pediatric patients who underwent mcGBCA-enhanced MRI from 2010 to 2020 (29 children with primary brain tumors without brain radiation therapy [mcGBCA group-1], 33 children with primary brain tumors and radiation treatment [mcGBCA group-2], 35 children with cALD [mcGBCA group-3], and 97 sex-/age-matched control subjects [subgroups matched to each of the three subject groups] without GBCA administration). The DN-to-middle cerebellar peduncle (MCP) SI ratios on T1WI were then determined. A paired t-test was performed to compare SI ratios between children exposed to mcGBCA in each group and control subjects. The relationships between SI ratios and confounding variables were analyzed utilizing the Pearson correlation analysis. RESULTS: The DN-to-MCP SI ratio was significantly higher of mcGBCA group-2 (1.046±.071) or mcGBCA group-3 (.972±.038) than in the control group-2 (.983±.041, P<.001) and control group-3 (.937±.051, P = .002), respectively, but no significant difference of the SI ratio was noted between mcGBCA group-1 (.984±.032) and control-group-1 (.982±.035, P = .860). No significant correlation was noted between SI ratio values and the cumulative dose or number of mcGBCA administrations, age, or the elapsed time between the MRI examinations (all P>.05). CONCLUSIONS: Hyperintense T1WI signal in the DN may be seen in children with brain tumors undergoing brain irradiation, as well as in children with cALD.

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

PURPOSE: To quantitate gadolinium deposits in gliomas and adjacent normal brain specimens, and to evaluate their association with tumor contrast enhancement and the type of gadolinium-based contrast agent (GBCA) used. METHODS: A total of 69 patients with primary glioma who underwent contrast-enhanced magnetic resonance imaging (MRI) prior to surgery were included in this retrospective study. Gadolinium was measured from histologically viable tumor, normal brain, and necrosis within the sample, when available, using inductively coupled plasma mass spectrometry (ICP-MS). Tumor contrast enhancement was categorized as none, minimal, or noticeable. Differences in gadolinium deposits by contrast enhancement and GBCA type were assessed. RESULTS: Seven patients received linear GBCA and 62 macrocyclic, respectively. At the time of surgery, gadolinium deposits were detected in 39 out of 69 (57%) tumor samples, 8 out of 13 (62%) normal brain, and 12 out of 14 (86%) necrotic specimens. Gadolinium was detected in both enhancing and non-enhancing tumors, but was greatest in gliomas with noticeable enhancement (p = 0.02). Administration of linear agents gadodiamide and gadopentetate dimeglumine resulted in significantly higher tumor gadolinium relative to macrocyclic gadoterate meglumine (p < 0.01 and p < 0.05, respectively). Normal brain and necrosis also showed higher gadolinium after exposure to linear gadodiamide (both p < 0.05). In multivariate regression, GBCA type (linear/macrocyclic) was the most powerful predictor of tumor gadolinium retention (p < 0.001). CONCLUSION: Gadolinium can be detected in both enhancing and non-enhancing gliomas, neighboring normal brain, and necrosis. Gadolinium retention is higher after exposure to linear GBCAs compared with the macrocyclic gadoterate meglumine.

LA-ICP-MS/MS improves limits of detection in elemental bioimaging of gadolinium deposition originating from MRI contrast agents in skin and brain tissues.

A novel analytical method to detect the retention of gadolinium from contrast agents for magnetic resonance imaging (MRI) in tissue samples of patients is presented. It is based on laser ablation - inductively coupled plasma - triple quadrupole - mass spectrometry (LA-ICP-MS/MS). Both Gd and P were monitored with a mass shift of +16, corresponding to mono-oxygenated species, as well as Zn, Ca, and Fe on-mass. This method resulted in a significantly reduced background and improved limits of detection not only for phosphorus, but also for gadolinium. These improvements were essential to perform elemental bioimaging with improved resolution of 5 µm x 5 µm, allowing the detection of small Gd deposits in fibrotic skin and brain tumour tissue with diameters of approximately 50 µm. Detailed analyses of these regions revealed that most Gd was accompanied with P and Ca, indicating co-precipitation.

Gadolinium-based contrast agents induce gadolinium deposits in cerebral vessel walls, while the neuropil is not affected: an autopsy study.

Recent studies showed gadolinium depositions following serial administrations of gadolinium-based contrast agents (GBCAs) for magnetic resonance imaging examinations in various parts of the brain with the dentate nucleus (DN) being most affected. Even though no clinical correlates of the deposits are known yet, an intensive debate developed if this might be harmful. The aim of the current study was to specify the gadolinium distribution in brain tissue of patients who received serial injections of GBCAs in the low-µm range and to explore any potential pathological tissue changes caused by gadolinium deposits. Thirteen autopsy cases-eight receiving GBCA administrations, five serving as controls-were identified and analyzed. For all patients, total gadolinium quantification after acidic digestion by means of inductively coupled plasma-mass spectrometry (ICP-MS) was performed. Six cases were utilized for the spatially resolved quantification of gadolinium within the cerebellum and the basal ganglia by means of high-resolution laser ablation (LA)-ICP-MS. Histopathological and immunohistochemical examinations were performed to determine tissue reactions. LA-ICP-MS revealed gadolinium depositions in the walls of small blood vessels of the DN in all GBCA exposed patients, while no gadolinium was found in the control group. Additionally, the detection of phosphorus and metals like copper, zinc and iron provides evidence that transmetalation reactions might have occurred. No significant pathological changes of the brain tissue in the vicinity of the DN with respect to micro-/astrogliosis and neuronal loss were found in any of the patients. This notably holds true even for a patient who died from nephrogenic systemic fibrosis exhibiting extremely high gadolinium concentrations within the DN. The findings show that gadolinium depositions in the brain are restricted to blood vessel walls, while the neuropil is spared and apparent cellular reactions are absent.

Confirming improved detection of gadolinium in bone using in vivo XRF.

The safety of using Gd in MRI contrast agents has recently been questioned, due to recent evidence of the retention of Gd in individuals with healthy renal function. Bone has proven to be a storage site for Gd, as unusually high concentrations have been measured in femoral heads of patients undergoing hip replacement surgery, as well as in autopsy samples. All previous measurements of Gd in bone have been invasive and required the bone to be removed from the body. X-ray fluorescence (XRF) offers a non-invasive and non-destructive method for carrying out in vivo measurements of Gd in humans. An updated XRF system provides improved detection limits in a short measurement time of 30-min. A new four-detector system and higher activity Cd-109 excitation source of 5GBq results in minimum detection limits (MDLs) of 1.64-1.72µgGd/g plaster for an average overlaying tissue thickness of the tibia. These levels are well within the range of previous in vitro Gd measurements. Additional validation through comparison with ICP-MS measurements has confirmed the ability of the XRF system for detecting Gd further, proving it is a feasible system to carry out human measurements.