Einleitung: In der prachirurgischen Diagnostik von Epilepsiepatienten muss die Lokalisation des epileptischen Anfallsursprungs bestatigt werden. In dieser Studie soll die tierexperimentell ...vorbeschriebene, fokal erhohte Permeabilitat der Blut-Hirn-Schranke wahrend epileptischer Anfalle mit Hilfe von quantitativer MRT nach iktaler Infusion von Kontrastmittel bei Epilepsiepatienten untersucht und mit Blick auf die prachirurgische Epilepsiediagnostik zur Lokalisation des epileptischen Anfallsursprungs genutzt werden. Methoden: 18 Epilepsiepatienten wurde iktal und interiktal jeweils 7,5 ml Gadolinium-haltiges Kontrastmittel infundiert, bevor sie je einer MRTUntersuchung mit Messung einer quantitativen T1-Sequenz zugefuhrt wurden. Die iktale und interiktale MR-Messungen desselben Patienten hatten dieselbe zeitliche Latenz nach Infusion des Kon trastmittels. Die resultierenden Volumina wurden registriert, mit der Analysesoftware Freesurfer parzelliert und die parzellierten Regionen der postiktal und interiktal akquirierten Volumina statistisch miteinander kontrastiert. Zeitgleich mit der iktalen Infusion des Kontrastmittels wurde das Radiopharmakon zwecks einer iktalen sPEcT-Untersuchung infundiert. Ergebnisse: In 15 von 18 Patienten zeigten sich deutliche Senkungen der T1- Zeit (i. e. 50 bis 200 ms) in kortikalen und subkortikalen Arealen, deren Beteiligung in das epileptische Anfallsgeschehen mit BLick auf andere diagnostische Modalitaten und die Semiologie konkordant erschien. (Siehe Grafik 1 fur drei representative Beispiele.) Der intramodale Vergleich mit Ergebnissen der iktalen SPECT-Untersuchung ergab nicht vollstandig konjunkte aber ebenso valide Ergebnisse. Diskussion: Das beschriebene Verfahren kann am epileptischen Anfallsgeschehen beteiligte Hirnareale zuverlassig identifizieren. Weitere Schritte schliessen den statistischen Vergleich mit den ebenfalls akquirierten MRT-Daten einer Gruppe gesunder Kontrollprobanden ein.
Medical imaging is routine in the diagnosis and staging of a wide range of medical conditions. In particular, magnetic resonance imaging (MRI) is critical for visualizing soft tissue and organs, with ...over 60 million MRI procedures performed each year worldwide. About one-third of these procedures are contrast-enhanced MRI, and gadolinium-based contrast agents (GBCAs) are the mainstream MRI contrast agents used in the clinic. GBCAs have shown efficacy and are safe to use with most patients; however, some GBCAs have a small risk of adverse effects, including nephrogenic systemic fibrosis (NSF), the untreatable condition recently linked to gadolinium (Gd) exposure during MRI with contrast. In addition, Gd deposition in the human brain has been reported following contrast, and this is now under investigation by the US Food and Drug Administration (FDA). To address a perceived need for a Gd-free contrast agent with pharmacokinetic and imaging properties comparable to GBCAs, we have designed and developed zwitterion-coated exceedingly small superparamagnetic iron oxide nanoparticles (ZES-SPIONs) consisting of ∼3-nm inorganic cores and ∼1-nm ultrathin hydrophilic shell. These ZES-SPIONs are free of Gd and show a high T₁ contrast power. We demonstrate the potential of ZES-SPIONs in preclinical MRI and magnetic resonance angiography.
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.
We previously reported the synthesis of gadolinium-based nanoparticles (NPs) denoted AGuIX (activation and guiding of irradiation by X-ray) NPs and demonstrated their potential as an MRI contrast ...agent and their efficacy as radiosensitizing particles during X-ray cancer treatment. Here we focus on the elimination kinetics of AGuIX NPs from the subcellular to whole-organ scale using original and complementary methods such as laser-induced breakdown spectroscopy (LIBS), intravital two-photon microscopy, inductively coupled plasma optical emission spectrometry (ICP-OES), transmission electron microscopy (TEM), and electrospray ionization mass spectrometry (ESI-MS). This combination of techniques allows the exact mechanism of AGuIX NPs elimination to be elucidated, including their retention in proximal tubules and their excretion as degraded or native NPs. Finally, we demonstrated that systemic AGuIX NP administration induced moderate and transient effects on renal function. These results provide useful and promising preclinical information concerning the safety of theranostic AGuIX NPs.
The increasing use of gadolinium-based contrast agents (GBCAs) for magnetic resonance imaging is leading to widespread contamination of freshwater and drinking water systems. Contrary to previous ...assumptions that GBCAs are stable throughout the water cycle, they can degrade. The stability of GBCAs depends largely on their organic ligands, but also on the physicochemical conditions. There is specific concern regarding UV end-of-pipe water treatments, which may degrade GBCAs. Degradation products in drinking water supplies can increase the risk of adverse health effects. This is of particular relevance where the raw water for drinking water production has a higher proportion of recycled wastewater. GBCAs concentrations in aquatic systems, often referred to as anthropogenic gadolinium, are determined using a variety of calculation methods. Where anthropogenic gadolinium concentrations are low, the inconsistent use of these methods results in high discrepancies and high levels of uncertainty. The current COVID-19 crisis will, in the short-term, drastically decrease the input of GBCAs to freshwater systems. Temporal variations in anthropogenic gadolinium concentrations in river water can be used to better understand river-aquifer interactions and groundwater flow velocities. Collecting urine from all patients following MRI examinations could be a way forward to halt the generally increasing concentrations of Gd in drinking water systems and recover this technologically critical element.
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•Rising concentration of gadolinium-based contrast agents (GBCAs) in drinking water.•Stability of GBCAs is determined by their organic ligands.•UV end-of-pipe treatment may enhance the risks posed by GBCAs in drinking water.•Inconsistent use of methods to calculate Gd anomalies and anthropogenic Gd.•Temporal Gd patterns in rivers can improve understanding of subsurface systems.
Gadolinium based contrast agents (GBCA) are used to image patients using magnetic resonance (MR) imaging. In recent years, there has been controversy around gadolinium retention after GBCA ...administration. We sought to evaluate the potential toxicity of gadolinium in the rat brain up to 1-year after repeated gadodiamide dosing and tissue retention kinetics after a single administration. Histopathological and ultrastructural transmission electron microscopy (TEM) analysis revealed no findings in rats administered a cumulative dose of 12 mmol/kg. TEM-energy dispersive X-ray spectroscopy (TEM-EDS) localization of gadolinium in the deep cerebellar nuclei showed ~ 100 nm electron-dense foci in the basal lamina of the vasculature. Laser ablation-ICP-MS (LA-ICP-MS) showed diffuse gadolinium throughout the brain but concentrated in perivascular foci of the DCN and globus pallidus with no observable tissue injury or ultrastructural changes. A single dose of gadodiamide (0.6 mmol/kg) resulted in rapid cerebrospinal fluid (CSF) and blood clearance. Twenty-weeks post administration gadolinium concentrations in brain regions was reduced by 16-72-fold and in the kidney (210-fold), testes (194-fold) skin (44-fold), liver (42-fold), femur (6-fold) and lung (64-fold). Our findings suggest that gadolinium does not lead to histopathological or ultrastructural changes in the brain and demonstrate in detail the kinetics of a human equivalent dose over time in a pre-clinical model.
Gadolinium-based contrast agents (GBCAs) have transformed magnetic resonance imaging (MRI) by facilitating the use of contrast-enhanced MRI to allow vital clinical diagnosis in a plethora of disease ...that would otherwise remain undetected. Although over 500 million doses have been administered worldwide, scientific research has documented the retention of gadolinium in tissues, long after exposure, and the discovery of a GBCA-associated disease termed nephrogenic systemic fibrosis, found in patients with impaired renal function. An understanding of the pharmacokinetics in humans and animals alike are pivotal to the understanding of the distribution and excretion of gadolinium and GBCAs, and ultimately their potential retention. This has been well studied in humans and more so in animals, and recently there has been a particular focus on potential toxicities associated with multiple GBCA administration. The purpose of this review is to highlight what is currently known in the literature regarding the pharmacokinetics of gadolinium in humans and animals, and any toxicity associated with GBCA use.
OBJECTIVERecent studies reported a signal intensity increase in the deep cerebellar nuclei (DCN) on magnetic resonance images caused by gadolinium deposition after the injection of gadolinium-based ...contrast agents (GBCAs). There is an ongoing debate if the propensity of a GBCA to deposit gadolinium is primarily determined by its class as either linear or macrocyclic. In the current study, we aimed to compare the amount and the distribution of retained gadolinium of linear and macrocyclic GBCAs in the DCN after a single injection at a dose comparable to a human patientʼs in a large animal model.
MATERIALS AND METHODSEighteen sheep were randomly assigned in 6 groups of 3 animals, which received a single injection of 0.1 mmol/kg body weight of either the macrocyclic GBCAs gadobutrol, gadoteridol, or gadoterate meglumine; the linear GBCAs gadobenate dimeglumine or gadodiamide; or saline. Animals were euthanized 10 weeks after injection. Local distribution and concentration of gadolinium and colocalization to other metals (iron, zinc, copper) in the DCN was assessed by laser ablation-inductively coupled plasma-mass spectrometry.
RESULTSAverage gadolinium concentration for the macrocyclic GBCAs and the saline group was below the limit of quantification (5.7 ng/g tissue). In contrast, 14 (for gadobenate) and 27 (for gadodiamide) times more gadolinium than the limit of quantification was found for the linear GBCAs gadobenate (mean, 83 ng/g) or gadodiamide (mean, 155 ng/g brain tissue). Gadolinium distribution colocalized with other metals for linear GBCAs and a specific accumulation in the DCN was found.
DISCUSSIONThe current study supports the hypothesis that the amount of gadolinium deposited in the brain is primarily determined by its class as either macrocyclic or linear. The accumulation of gadolinium in the DCN for linear GBCAs explains the hyperintensities in the DCN found in previous patient studies with linear GBCAs.
Nano-theranostic agents play important roles in the development of therapeutic methods for serious diseases. In this study, novel carbon dots (CDs)
L-CD
/
C-CD
were prepared from Gd(
iii
) ...salt/complexes, cationic polymers and citric acid in the hope that they would combine the abilities of gene delivery and multi-modal (MR/FL) imaging. The CDs inherited the properties of good water-solubility and positive charge from their precursor polymers.
In vitro
gene transfection results showed that the CDs have good transfection efficiency and anti-serum ability, especially for
L-CD
, which has 74 times higher transfection efficiency than PEI 25 kDa in the presence of 10% serum. The CDs exhibited bright fluorescence, which was stable for several days under various pH. Confocal laser scanning microscopy revealed that the CDs could image HeLa cells with blue or green fluorescence well, and realize the monitoring of the gene delivery process. Besides, the CDs showed favorable biocompatibility with excellent performance in longitudinal relaxivity rates (
r
1
) of 11.4 mM
−1
s
−1
for
L-CD
and 57.6 mM
−1
s
−1
for
C-CD
, which were about 3-15 times higher than that of the clinical Gd reagent Gd-DTPA (3.75 mM
−1
s
−1
). Furthermore, the CDs could perform
in vivo
tumor-specific MR-imaging more clearly than Gd-DTPA, which is attributed to their suitable particle size and their resulting greater accumulation at tumor site
via
the EPR effect. This study provides a promising strategy for constructing multi-functional CDs for tumor theranostics.
Multi-functional carbon dots with MR/FL dual-imaging and gene delivery abilities were constructed for
in vitro
and
in vivo
applications.
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