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AJNR. American Journal of Neuroradiology Jul 2018
Topics: Animals; Crush Injuries; Gadolinium DTPA; Rats; Sciatic Nerve
PubMed: 29700050
DOI: 10.3174/ajnr.A5661 -
Investigative Radiology Oct 2022Using a murine model of multiple sclerosis, we previously showed that repeated administration of gadopentetate dimeglumine led to retention of gadolinium (Gd) within...
OBJECTIVES
Using a murine model of multiple sclerosis, we previously showed that repeated administration of gadopentetate dimeglumine led to retention of gadolinium (Gd) within cerebellar structures and that this process was enhanced with inflammation. This study aimed to compare the kinetics and retention profiles of Gd in inflamed and healthy brains after application of the macrocyclic Gd-based contrast agent (GBCA) gadobutrol or the linear GBCA gadopentetate. Moreover, potential Gd-induced neurotoxicity was investigated in living hippocampal slices ex vivo.
MATERIALS AND METHODS
Mice at peak of experimental autoimmune encephalomyelitis (EAE; n = 29) and healthy control mice (HC; n = 24) were exposed to a cumulative dose of 20 mmol/kg bodyweight of either gadopentetate dimeglumine or gadobutrol (8 injections of 2.5 mmol/kg over 10 days). Magnetic resonance imaging (7 T) was performed at baseline as well as at day 1, 10, and 40 post final injection (pfi) of GBCAs. Mice were sacrificed after magnetic resonance imaging and brain and blood Gd content was assessed by laser ablation-inductively coupled plasma (ICP)-mass spectrometry (MS) and ICP-MS, respectively. In addition, using chronic organotypic hippocampal slice cultures, Gd-induced neurotoxicity was addressed in living brain tissue ex vivo, both under control or inflammatory (tumor necrosis factor α [TNF-α] at 50 ng/μL) conditions.
RESULTS
Neuroinflammation promoted a significant decrease in T1 relaxation times after multiple injections of both GBCAs as shown by quantitative T1 mapping of EAE brains compared with HC. This corresponded to higher Gd retention within the EAE brains at 1, 10, and 40 days pfi as determined by laser ablation-ICP-MS. In inflamed cerebellum, in particular in the deep cerebellar nuclei (CN), elevated Gd retention was observed until day 40 after last gadopentetate application (CN: EAE vs HC, 55.06 ± 0.16 μM vs 30.44 ± 4.43 μM). In contrast, gadobutrol application led to a rather diffuse Gd content in the inflamed brains, which strongly diminished until day 40 (CN: EAE vs HC, 0.38 ± 0.08 μM vs 0.17 ± 0.03 μM). The analysis of cytotoxic effects of both GBCAs using living brain tissue revealed an elevated cell death rate after incubation with gadopentetate but not gadobutrol at 50 mM. The cytotoxic effect due to gadopentetate increased in the presence of the inflammatory mediator TNF-α (with vs without TNF-α, 3.15% ± 1.18% vs 2.17% ± 1.14%; P = 0.0345).
CONCLUSIONS
In the EAE model, neuroinflammation promoted increased Gd retention in the brain for both GBCAs. Whereas in the inflamed brains, efficient clearance of macrocyclic gadobutrol during the investigated time period was observed, the Gd retention after application of linear gadopentetate persisted over the entire observational period. Gadopentetate but not gadubutrol appeared to be neurotoxic in an ex vivo paradigm of neuronal inflammation.
Topics: Animals; Brain; Chelating Agents; Contrast Media; Gadolinium; Gadolinium DTPA; Inflammation; Magnetic Resonance Imaging; Mice; Organometallic Compounds; Tumor Necrosis Factor-alpha
PubMed: 35467573
DOI: 10.1097/RLI.0000000000000884 -
Magnetic Resonance in Medical Sciences... Mar 2022Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA; Gadoxetic acid; Gadoxetate disodium) is a hepatocyte-specific MR contrast agent. It acts as an... (Review)
Review
Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA; Gadoxetic acid; Gadoxetate disodium) is a hepatocyte-specific MR contrast agent. It acts as an extracellular contrast agent in the early phase after intravenous injection, and then is taken up by hepatocytes later. Using this contrast agent, we can evaluate the hemodynamics of the liver and liver tumors, and can therefore improve the detection and characterization of hepatocellular carcinoma (HCC). Gd-EOB-DTPA helps in the more accurate detection of hypervascular HCC than by other agents. In addition, Gd-EOB-DTPA can detect hypovascular HCC, which is an early stage of the multi-stage carcinogenesis, with a low signal in the hepatobiliary phase. In addition to tumor detection and characterization, Gd-EOB-DTPA contrast-enhanced MR imaging can be applied for liver function evaluation and prognoses evaluation. Thus, Gd-EOB-DTPA plays an important role in the diagnosis of HCC. However, we have to employ optimal imaging techniques to improve the diagnostic ability. In this review, we aimed to discuss the characteristics of the contrast media, optimal imaging techniques, diagnosis, and applications.
Topics: Carcinoma, Hepatocellular; Contrast Media; Gadolinium DTPA; Humans; Liver Neoplasms; Magnetic Resonance Imaging
PubMed: 34421091
DOI: 10.2463/mrms.rev.2021-0031 -
Korean Journal of Radiology Jan 2019Gadolinium-based contrast agents (GBCAs) are commonly used for enhancement in MR imaging and have long been considered safe when administered at recommended doses.... (Review)
Review
Gadolinium-based contrast agents (GBCAs) are commonly used for enhancement in MR imaging and have long been considered safe when administered at recommended doses. However, since the report that nephrogenic systemic fibrosis is linked to the use of GBCAs in subjects with severe renal diseases, accumulating evidence has suggested that GBCAs are not cleared entirely from our bodies; some GBCAs are deposited in our tissues, including the brain. GBCA deposition in the brain is mostly linked to the specific chelate structure of the GBCA: linear GBCAs were responsible for brain deposition in almost all reported studies. This review aimed to summarize the current knowledge about GBCA brain deposition and discuss its clinical implications.
Topics: Brain; Contrast Media; Gadolinium; Gadolinium DTPA; Humans; Magnetic Resonance Imaging
PubMed: 30627029
DOI: 10.3348/kjr.2018.0356 -
The British Journal of Radiology Dec 2022Contrast-enhanced MRI could be useful to guide high-intensity focused ultrasound treatment (HIFU), but the effects of HIFU on gadolinium-based agents is not known. Here,...
OBJECTIVE
Contrast-enhanced MRI could be useful to guide high-intensity focused ultrasound treatment (HIFU), but the effects of HIFU on gadolinium-based agents is not known. Here, we tested in vitro the stability of gadoteridol and gadobenate dimeglumine, two widely used MR contrast agents, after exposure to HIFU at power levels typically applied in the clinical practice.
METHODS
0.5 M (gadoteridol and gadobenate dimeglumine) and diluted formulations (1:10 gadoteridol in saline) were exposed to different HIFU sequences. Unexposed and exposed solutions were characterized by high-performance liquid chromatography in terms of concentration of gadolinium complex, free gadolinium and free ligand.
RESULTS
Gadoteridol formulation after treatment showed concentrations of the complex not significantly different from control. Free Gd and/or free ligand concentrations in the order of 0.002/0.004% w/w, were observed occasionally without significant correlation with intensity and duration of exposure to HIFU. Gadobenate dimeglumine formulation after treatment showed complex assay content values, by-products (0.24-0.26%) and free BOPTA levels (0.07%) comparable to control sample within the experimental error.
CONCLUSION
In the range of conditions explored, HIFU exposure did not induce significant dissociations of gadoteridol and gadobenate dimeglumine, nor a detectable increase in the concentration of free species.
ADVANCES IN KNOWLEDGE
Our study strengthens the hypothesis that gadolinium-based contrast agents are stable during HIFU treatment for body applications ( thermal ablation of uterine fibroids).
Topics: Humans; Gadolinium; Contrast Media; Gadolinium DTPA; Ligands; Meglumine; Organometallic Compounds; Magnetic Resonance Imaging
PubMed: 36169642
DOI: 10.1259/bjr.20220619 -
BMC Medical Imaging Jun 2023To evaluate the value of MRI T1 mapping with Gd-EOB-DTPA for assessing liver function.
PURPOSE
To evaluate the value of MRI T1 mapping with Gd-EOB-DTPA for assessing liver function.
METHODS
Seventy-two patients who underwent Gd-EOB-DTPA-enhanced MRI for focal liver lesions at Beijing Friendship Hospital from August 2020 to March 2022 were prospectively enrolled, and variable-flip-angle T1 mapping was performed before and 20 min after enhancement. The Child-Pugh (C-P) score and albumin-bilirubin (ALBI) grade of liver function were assessed using the clinical data of the patients. Correlation analysis was used to evaluate the correlation between T1 mapping parameters and liver function grading and laboratory tests. Nonparametric tests were used to compare the differences among different liver function groups. The liver function classification efficiency of each image index was evaluated with receiver operating characteristic (ROC) curves.
RESULTS
T1post was positively correlated with the C-P grade and the ALBI grade (r = 0.717 and r = 0.652). ΔT1 was negatively correlated with the C-P grade and the ALBI grade (r = -0.790 and r = -0.658). T1post and ΔT1 significantly differed among different liver function grades (p < 0.05). For the C-P grade, T1post and ΔT1 were significantly different between each pair of groups (p < 0.05), and ΔT1 had a better diagnostic efficiency than T1post. For the ALBI grade, ΔT1 and T1post were significantly different between the NLF and ALBI1 groups (p < 0.05), and ΔT1 had a better diagnostic efficacy than T1post. T1post significantly differed between the ALBI1 and ALBI2 + 3 groups (p < 0.05), while ΔT1 had a weak ability to differentiate between these two groups.
CONCLUSION
T1post and ΔT1 were strongly correlated with the two liver function grades and can be noninvasive imaging indexes for evaluating liver function.
Topics: Humans; Liver; Contrast Media; Gadolinium DTPA; Magnetic Resonance Imaging
PubMed: 37271809
DOI: 10.1186/s12880-023-01028-z -
Abdominal Radiology (New York) Nov 2020The introduction of hepatobiliary contrast agents, most notably gadoxetic acid (GA), has expanded the role of MRI, allowing not only a morphologic but also a functional... (Review)
Review
The introduction of hepatobiliary contrast agents, most notably gadoxetic acid (GA), has expanded the role of MRI, allowing not only a morphologic but also a functional evaluation of the hepatobiliary system. The mechanism of uptake and excretion of gadoxetic acid via transporters, such as organic anion transporting polypeptides (OATP1,3), multidrug resistance-associated protein 2 (MRP2) and MRP3, has been elucidated in the literature. Furthermore, GA uptake can be estimated on either static images or on dynamic imaging, for example, the hepatic extraction fraction (HEF) and liver perfusion. GA-enhanced MRI has achieved an important role in evaluating morphology and function in chronic liver diseases (CLD), allowing to distinguish between the two subgroups of nonalcoholic fatty liver diseases (NAFLD), simple steatosis and nonalcoholic steatohepatitis (NASH), and help to stage fibrosis and cirrhosis, predict liver transplant graft survival, and preoperatively evaluate the risk of liver failure if major resection is planned. Finally, because of its noninvasive nature, GA-enhanced MRI can be used for long-term follow-up and post-treatment monitoring. This review article aims to describe the current role of GA-enhanced MRI in quantifying liver function in a variety of hepatobiliary disorders.
Topics: Contrast Media; Gadolinium DTPA; Humans; Liver; Liver Neoplasms; Magnetic Resonance Imaging
PubMed: 33034671
DOI: 10.1007/s00261-020-02779-x -
Molecules (Basel, Switzerland) Dec 2021The extracellular class of gadolinium-based contrast agents (GBCAs) is an essential tool for clinical diagnosis and disease management. In order to better understand the... (Review)
Review
The extracellular class of gadolinium-based contrast agents (GBCAs) is an essential tool for clinical diagnosis and disease management. In order to better understand the issues associated with GBCA administration and gadolinium retention and deposition in the human brain, the chemical properties of GBCAs such as relative thermodynamic and kinetic stabilities and their likelihood of forming gadolinium deposits in vivo will be reviewed. The chemical form of gadolinium causing the hyperintensity is an open question. On the basis of estimates of total gadolinium concentration present, it is highly unlikely that the intact chelate is causing the hyperintensities observed in the human brain. Although it is possible that there is a water-soluble form of gadolinium that has high relaxitvity present, our experience indicates that the insoluble gadolinium-based agents/salts could have high relaxivities on the surface of the solid due to higher water access. This review assesses the safety of GBCAs from a chemical point of view based on their thermodynamic and kinetic properties, discusses how these properties influence in vivo behavior, and highlights some clinical implications regarding the development of future imaging agents.
Topics: Animals; Chemical Phenomena; Contrast Media; Gadolinium; Gadolinium DTPA; Humans; Kinetics; Magnetic Resonance Imaging; Molecular Structure; Thermodynamics
PubMed: 35011290
DOI: 10.3390/molecules27010058 -
World Journal of Gastroenterology Sep 2023The liver is one of the organs most commonly involved in metastatic disease, especially due to its unique vascularization. It's well known that liver metastases... (Review)
Review
The liver is one of the organs most commonly involved in metastatic disease, especially due to its unique vascularization. It's well known that liver metastases represent the most common hepatic malignant tumors. From a practical point of view, it's of utmost importance to evaluate the presence of liver metastases when staging oncologic patients, to select the best treatment possible, and finally to predict the overall prognosis. In the past few years, imaging techniques have gained a central role in identifying liver metastases, thanks to ultrasonography, contrast-enhanced computed tomography (CT), and magnetic resonance imaging (MRI). All these techniques, especially CT and MRI, can be considered the non-invasive reference standard techniques for the assessment of liver involvement by metastases. On the other hand, the liver can be affected by different focal lesions, sometimes benign, and sometimes malignant. On these bases, radiologists should face the differential diagnosis between benign and secondary lesions to correctly allocate patients to the best management. Considering the above-mentioned principles, it's extremely important to underline and refresh the broad spectrum of liver metastases features that can occur in everyday clinical practice. This review aims to summarize the most common imaging features of liver metastases, with a special focus on typical and atypical appearance, by using MRI.
Topics: Humans; Contrast Media; Gadolinium DTPA; Liver Neoplasms; Magnetic Resonance Imaging; Liver
PubMed: 37901445
DOI: 10.3748/wjg.v29.i36.5180 -
Radiology Jan 2019
Topics: Gadolinium DTPA; Hepatocytes; Liver; Magnetic Resonance Imaging
PubMed: 30375935
DOI: 10.1148/radiol.2018182251