Gadolinium-based contrast agents (GBCAs) have helped to improve the role of magnetic resonance imaging (MRI) for the diagnosis and treatment of diseases. There are currently nine different commercially available gadolinium-based contrast agents (GBCAs) that can be used for body MRI cases, and which are classifiable according to their structures (cyclic or linear) or biodistribution (extracellular-space agents, target/specific-agents, and blood-pool agents). The aim of this review is to illustrate the commercially available MRI contrast agents, their effect on imaging, and adverse reaction on the body, with the goal to lead to their proper selection in different clinical contexts. When we have to choose between the different GBCAs, we have to consider several factors: (1) safety and clinical impact; (2) biodistribution and diagnostic application; (3) higher relaxivity and better lesion detection; (4) higher stability and lower tissue deposit; (5) gadolinium dose/concentration and lower volume injection; (6) pulse sequences and protocol optimization; (7) higher contrast-to-noise ratio at 3.0 T than at 1.5 T. Knowing the patient\'s clinical information, the relevant GBCAs properties and their effect on body MRI sequences are the key features to perform efficient and high-quality MRI examination.

Gadolinium-based contrast agents (GBCAs) have become a crucial part of MRI acquisitions in neuro-oncology for the detection, characterization and monitoring of brain tumors. However, contrast-enhanced (CE) acquisitions not only raise safety concerns, but also lead to patient discomfort, the need of more skilled manpower and cost increase. Recently, several proposed deep learning works intend to reduce, or even eliminate, the need of GBCAs. This study reviews the published works related to the synthesis of CE images from low-dose and/or their native -non CE- counterparts. The data, type of neural network, and number of input modalities for each method are summarized as well as the evaluation methods. Based on this analysis, we discuss the main issues that these methods need to overcome in order to become suitable for their clinical usage. We also hypothesize some future trends that research on this topic may follow.

Gadolinium-based contrast agents (GBCAs) are widely used in magnetic resonance imaging (MRI) to improve the sensitivity and enhance diagnostic performance. GBCAs are mostly eliminated from the body through the kidney after administration; however small amounts of gadolinium are retained in the brain and other tissues. Although there is increasing concern about the adverse health effects of gadolinium, the cellular effects of GBCAs remains poorly understood. Here, we elucidated the potential cytotoxicity of the GBCAs Omniscan and Gadovist in 12 different cell lines, especially 3T3-L1 adipocyte cell line. Omniscan and Gadovist treatments significantly increased intracellular gadolinium levels in 3T3-L1 cells in a time- and dose-dependent manner. Additionally, Omniscan and Gadovist treatments downregulated the expression of adipocyte differentiation markers, including peroxisome proliferator-activated receptor γ (PPARG), adiponectin (ADIPOQ), and fatty acid-binding protein (FABP4), in 3T3-L1 cells, especially during early differentiation (day 0-2). Moreover, histological analysis using Oil red O staining showed that gadolinium chloride (GdCl3) treatment suppressed lipid droplet accumulation and the expression of adipocyte differentiation markers. Overall, the results showed that Omniscan and Gadovist treatment suppressed adipocyte differentiation in 3T3-L1 cells, contributing to the understanding of the potential toxic effects of GBCA exposure.

OBJECTIVE: Multiple exposures to gadolinium-based contrast agents (GBCAs) is known to be associated with gadolinium deposition in the brain in certain patients. Such deposition has been correlated with specific brain MRI findings, although most available data is in patients with underlying neurologic disorders. We aim to prospectively evaluate brain MRI signal changes as well as neurologic and neuropsychologic testing results in women undergoing screening breast MRI.
METHODS: In this IRB-approved, HIPAA-compliant prospective study, 9 women with 5 or more exposures to linear and/or macrocyclic GBCA due to screening breast MRI underwent noncontrast brain MRI, neurologic exam and neuropsychologic testing. Women with underlying neurologic, psychologic, hepatic or renal disorders were excluded.
RESULTS: The mean total number of GBCA exposures was 8 (standard deviation 2.7), with 63/72 (87%) of the exposures being linear agents. There was no association between brain MRI signal changes and abnormalities on neurologic or neuropsychologic examination. There was no association between total number of GBCA exposures and abnormalities on neurologic or neuropsychologic examination.
CONCLUSIONS: In this prospective exploratory study of 9 women with 5 or more GBCA exposures due to screening breast MRI, there was no association between brain MRI signal changes and clinical abnormalities on neurologic or neuropsychologic examination. While larger studies are needed in this patient population, the lack of clinical impact of multiple GBCA exposures in this study is reassuring.

Over the past five years, several studies have reported deposition and retention of gadolinium in the brain after administration of gadolinium-based contrast agents (GBCAs) during radiological procedures. Patients with renal insufficiency cannot filter gadolinium efficiently; however, gadolinium is also retained in the brain of some adults and pediatrics with no renal impairment. In the literature, data is mostly available from retrospective magnetic resonance imaging (MRI) studies, where gadolinium deposition may be indirectly measured by evaluating changes in T1 signal intensity in the brain tissues, particularly in the deep gray matter such as the dentate nucleus and/or globus pallidus. Many pathological studies have reported a direct correlation between T1 signal changes and gadolinium deposition in human and animal autopsy specimens, which raised concerns on the use of GBCAs, particularly with linear chelators. The association between gadolinium accumulation and occurrence of physical and neurological side effects or neurotoxic damage has not yet been conclusively demonstrated. Studies have also observed that gadolinium is deposited in the extracranial tissues, such as the liver, skin, and bone, of patients with normal kidney function. This narrative review describes the effects of different types of GBCAs in relation to gadolinium deposition, evaluates current evidence on gadolinium deposition in various tissues of the human body, and summarizes the current recommendations regarding the use of GBCAs.

Despite the impressive safety of gadolinium (Gd)-based contrast agents (GBCAs), a small number of patients report the onset of new, severe, ongoing symptoms after even a single exposure-a syndrome termed Gadolinium Deposition Disease (GDD). Mitochondrial dysfunction and oxidative stress have been repeatedly implicated by animal and in vitro studies as mechanisms of Gd/GBCA-related toxicity, and as pathogenic in other diseases with similarities in presentation. Here, we aimed to molecularly characterize and explore potential metabolic associations with GDD symptoms. Detailed clinical phenotypes were systematically obtained for a small cohort of individuals (n = 15) with persistent symptoms attributed to a GBCA-enhanced MRI and consistent with provisional diagnostic criteria for GDD. Global untargeted mass spectroscopy-based metabolomics analyses were performed on plasma samples and examined for relevance with both single marker and pathways approaches. In addition to GDD criteria, frequently reported symptoms resembled those of patients with known mitochondrial-related diseases. Plasma differences compared to a healthy, asymptomatic reference cohort were suggested for 45 of 813 biochemicals. A notable proportion of these are associated with mitochondrial function and related disorders, including nucleotide and energy superpathways, which were over-represented. Although early evidence, coincident clinical and biochemical indications of potential mitochondrial involvement in GDD are remarkable in light of preclinical models showing adverse Gd/GBCA effects on multiple aspects of mitochondrial function. Further research on the potential contributory role of these markers and pathways in persistent symptoms attributed to GBCA exposure is recommended.

Gadolinium-based contrast agents (GBCAs) improve the diagnostic capabilities of magnetic resonance imaging. Although initially believed to be without major adverse effects, GBCA use in patients with severe chronic kidney disease (CKD) was demonstrated to cause nephrogenic systemic fibrosis (NSF). Restrictive policies of GBCA use in CKD and selective use of GBCAs that bind free gadolinium more strongly have resulted in the virtual elimination of NSF cases. Contemporary studies of the use of GBCAs with high binding affinity for free gadolinium in severe CKD demonstrate an absence of NSF. Despite these observations and the limitations of contemporary studies, physicians remain concerned about GBCA use in severe CKD. Concerns of GBCA use in severe CKD are magnified by recent observations demonstrating gadolinium deposition in brain and a possible systemic syndrome attributed to GBCAs. Radiologic advances have resulted in several new imaging modalities that can be used in the severe CKD population and that do not require GBCA administration. In this article, we critically review GBCA use in patients with severe CKD and provide recommendations regarding GBCA use in this population.

Drug biodistribution analyses can be considered a key issue in pharmaceutical discovery and development. Here, mass spectrometric imaging can be employed as a powerful tool to investigate distributions of drug compounds in biologically and medically relevant tissue sections. Both matrix-assisted laser desorption ionization-mass spectrometric imaging as molecular method and laser ablation inductively coupled plasma-mass spectrometric imaging as elemental detection method were applied to determine drug distributions in tissue thin sections. Several mouse organs including the heart, kidney, liver, and brain were analyzed with regard to distribution of Gadovist™, a gadolinium-based contrast agent already approved for clinical investigation. This work demonstrated the successful detection and localization of Gadovist™ in several organs. Furthermore, the results gave evidence that gadolinium-based contrast agents in general can be well analyzed by mass spectrometric imaging methods. In conclusion, the combined application of molecular and elemental mass spectrometry could complement each other and thus confirm analytical results or provide additional information.

Gadolinium-based contrast agents have been considered extremely safe drugs with a low incidence of acute adverse reactions. Most of the reactions are mild and physiologic. However, despite being extremely rare, acute severe adverse reactions, including anaphylaxis, may occur. In this article adverse reactions are discussed with regard to their classification, pathophysiology, symptoms, and risk factors.