Gadolinium Contrast Agent Deposition in Children.

Over the past few years, a large number of studies have evidenced increased signal intensity in the deep brain nuclei on unenhanced T1-MRI images achieved by the application of gadolinium-based contrast agents (GBCAs). The deposition of gadolinium in the brain, bone, and other tissues following administration of GBCAs has also been confirmed in histological studies in rodents and in necropsy studies in adults and children. Given the distinct physiological characteristics of children, this review focuses on examining the current research on gadolinium deposition in children, particularly studies utilizing novel methods and technologies. Furthermore, the article compares safety research findings of linear GBCAs and macrocyclic GBCAs in children, with the aim of offering clinicians practical guidance based on the most recent research outcomes. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY: Stage 2.

Evaluation of signal intensity changes in dentate nucleus and globus pallidus on magnetic resonance imaging after intrathecal gadolinium-based contrast agent administration.

PURPOSE: Gadolinium deposition has been reported in several normal anatomical structures in the brain after repeated administration of intravenous gadolinium-based contrast agents (GBCAs) used in magnetic resonance imaging (MRI). This study presents preliminary results to see if there is any gadolinium deposition in the dentate nucleus and globus pallidus after using intrathecal GBCAs. METHODS: Between November 2018 and November 2020, 29 patients who underwent intrathecal contrast-enhanced MR cisternography with the suspicion of rhinorrhea were included in this prospective study. In contrast-enhanced MR cisternography, gadoterate meglumine was administered by intrathecal injection at a dose of 1 ml. One month later, patients had a control MRI with 3D T1 SPACE fat-saturated (FS) and susceptibility weighted images (SWI) sequences. The ratio of dentate nucleus signal intensity to middle cerebellar peduncle signal intensity (DN/MCP ratio) and the ratio of globus pallidus signal intensity to thalamus signal intensity (GP/T ratio) were calculated using region of interest (ROI) on pre-contrast and control MRI sequences. RESULTS: There was no significant difference for DN/MCP ratio and GP/T ratio on 3D T1 SPACE FS and SWI sequences after intrathecal GBCAs administration compared to baseline MRI. CONCLUSION: Administration of intrathecal GBCAs did not cause a measurable change in the signal intensity of the dentate nucleus and globus pallidus after a single injection.

Gadolinium deposition in the liver and brain in a rat model with liver fibrosis after intravenous administration of gadoxetate disodium.

Objectives: To investigate gadolinium deposition in the liver and brain in a rat model with liver fibrosis (LF) after intravenous administration of gadoxetate disodium (GD) and the histological effects of gadolinium deposition in the liver and brain. Methods: Adult male Sprague-Dawley rats were randomly assigned to one of the three groups: 1) LF group received intraperitoneal injection of carbon tetrachloride (CCl4) for 9 weeks alone; 2) LF&GD group received CCl4 and intravenous administration of GD (for 5 consecutive days); 3) GD group received olive oil and GD. Seven days after the final injection of GD, the deep cerebellar nuclei (DCN) and liver were excised to determine gadolinium concentrations via inductively coupled plasma mass spectrometry, and histologic staining was performed. Bonferroni's post-hoc test and Wilcoxon rank sum test were used to compare the differences between the three groups. Results: The concentrations of retained gadolinium in the liver in the LF&GD group (2.18 ± 0.44 µg/g) were significantly greater compared to the LF group (0.02 ± 0.01 µg/g, P < 0.001) and GD group (0.37 ± 0.11 µg/g, P < 0.001). Also, the concentrations of retained gadolinium in DCN were increased in the LF&GD group (0.13 ± 0.06 µg/g) compared to the LF group (0.01 ± 0.00 µg/g, P < 0.001) and GD group (0.06 ± 0.02 µg/g, P = 0.019). No histopathological alterations were detected in the liver and DCN between LF&GD group and LF group. Conclusions: LF aggravated gadolinium deposition in the liver and DCN after administration of GD. However, no significant acute histological alterations were observed due to gadolinium deposition.

Data mining and analysis of the adverse events derived signals of 4 gadolinium-based contrast agents based on the US Food and drug administration adverse event reporting system.

BACKGROUND: To detect and analyze risk signals of the drug-related adverse events (AEs) of 4 gadolinium-based contrast agents (GBCAs) (gadopentetate dimeglumine (Gd-DTPA), gadobenate dimeglumine (Gd-BOPTA), gadoteridol (Gd-HP-DO3A), and gadobutrol (Gd-BT-DO3A)) according to the US Food and Drug Administration Adverse Event Reporting System (FAERS) database and ensure the clinical safety. RESEARCH DESIGN AND METHODS: The AEs that are associated with the 4 GBCAs were collected from the FAERS database from 2004Q1 to 2022Q3. The risk signals were mined using reporting odds ratio (ROR) and proportional reporting ratio (PRR). RESULTS: 424 risk signals were excavated, in which 151 risk signals were associated with Gd-DTPA, 93 risk signals were related to Gd-BOPTA, 79 risk signals were relevant to Gd-HP-DO3A, and 101 risk signals were associated with Gd-BT-DO3A. The AE signals involved 20 system organ classes (SOCs). Two of the top four SOCs were identical, namely 'skin and subcutaneous tissue disorders' and 'general disorders and administration site conditions.' CONCLUSIONS: The safety signals of 4 GBCAs were detected, and the SOCs associated with the AEs of the 4 GBCAs were different. Besides, some AEs obtained in this study were not mentioned in the package inserts, which need more attention and research to ensure the clinical safety.

Efficacy of Whole-Blood Model of Gadolinium-Based Contrast Agent Relaxivity in Predicting Vascular MR Signal Intensity In Vivo.

BACKGROUND: Previous in vitro studies have described sub-linear longitudinal and heightened transverse H2 O relaxivities of gadolinium-based contrast agents (GBCAs) in blood due to their extracellular nature. However, in vivo validation is lacking. PURPOSE: Validate theory describing blood behavior of R1 and R2 * in an animal model. STUDY TYPE: Prospective, animal. ANIMAL MODEL: Seven swine (54-65 kg). FIELD STRENGTH/SEQUENCE: 1.5 T; time-resolved 3D spoiled gradient-recalled echo (SPGR) and quantitative Look-Locker and multi-echo fast field echo sequences. ASSESSMENT: Seven swine were each injected three times with 0.1 mmol/kg intravenous doses of one of three GBCAs: gadoteridol, gadobutrol, and gadobenate dimeglumine. Injections were randomized for rate (1, 2, and 3 mL/s) and order, during which time-resolved aortic 3D SPGR imaging was performed concurrently with aortic blood sampling via an indwelling catheter. Time-varying [GBCA] was measured by mass spectrometry of sampled blood. Predicted signal intensity (SI) was determined from a model incorporating sub-linear R1 and R2 * effects (whole-blood model) and simpler models incorporating linear R1 , with and without R2 * effects. Predicted SIs were compared to measured aortic SI. STATISTICAL TESTS: Linear correlation (coefficient of determination, R2 ) and mean errors were compared across the SI prediction models. RESULTS: There was an excellent correlation between predicted and measured SI across all injections and swine when accounting for the non-linear dependence of R1 and high blood R2 * (regression slopes 0.91-1.04, R2 ≥ 0.91). Simplified models (linear R1 with and without R2 * effects) showed poorer correlation (slopes 0.67-0.85 and 0.54-0.64 respectively, both R2 ≥ 0.89) and higher averaged mean absolute and mean square errors (128.4 and 177.4 vs. 42.0, respectively, and 5506 and 11,419 vs. 699, respectively). DATA CONCLUSION: Incorporating sub-linear R1 and high first-pass R2 * effects in arterial blood models allows accurate SPGR SI prediction in an in vivo animal model, and might be utilized when modeling MR blood SI. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 1.

Impairments in sleep and brain molecular clearance in people with cognitive deterioration and biological evidence of AD: a report of four cases.

BACKGROUND: Recent evidence suggests that the failure of the glymphatic system - the brain's waste clearance system, which is active during sleep - plays a key role in the pathophysiology of Alzheimer's Disease (AD). Glymphatic function can be investigated using serial MRIs after intrathecal gadobutrol injection. This technique can reveal the health of the glymphatic system, but has not yet been used in participants with cognitive impairment due to AD. CASE REPORT: This report describes the sleep and gadobutrol tracer clearance patterns of four participants diagnosed with mild to moderate cognitive impairment with evidence of AD pathology (pathological levels of Ab and p-tau in cerebrospinal fluid). We performed polysomnography and MRI studies before tracer injection and MRI scans at 1.5-2 h, 5-6 h, and 48 h after injection. Despite participants reporting no sleep problems, polysomnography revealed that all participants had moderate to severe sleep disturbances, including reduced sleep efficiency during the study and obstructive sleep apnea. Severe side-effects related to tracer administration were observed, impeding the completion of the protocol in two participants. Participants who finished the protocol displayed delayed and persistent tracer enrichment in the cortex and white matter, even 48 h after injection. These outcomes have not been observed in previous studies in participants without AD. CONCLUSION: The findings suggest that brains with sleep impairment and AD pathology have poor glymphatic function, and therefore cannot clear the contrast tracer efficiently. This is likely to have caused the severe side effects in our participants, that have not been reported in healthy individuals. Our results may therefore represent the only available data acquired with this technique in participants with AD pathology.

Exploring Gadolinium-Based Contrast Media for Retrograde Pyelography in the Context of Iodine Allergy.

Iodinated contrast media can rarely cause severe allergic reactions during nonvascular urologic imaging procedures. Alternatives like gadolinium-based contrast may help mitigate this risk in susceptible patients. A 66-year-old woman with a documented iodine allergy presented with an obstructing stone in the right ureter. To avoid the risk of an allergic reaction, the decision was made to use an alternative non-iodinated contrast agent for retrograde pyelography prior to ureteral stent placement. Gadobenate dimeglumine, an MRI contrast agent, was diluted 50:50 with saline and utilized successfully to provide adequate opacification for safe stent placement without adverse reaction. The patient underwent repeat pyelography with gadobenate dimeglumine one month later during ureteroscopy without complication. This case demonstrates that diluted gadobenate can serve as an effective alternative to iodinated contrast media in patients at high risk of reaction to iodine-containing agents. While severe reactions to iodinated contrast are uncommon in nonvascular urologic procedures, they can still occur even with premedication. Gadolinium-based agents have been reported to provide sufficient opacification for most urologic interventions, though inferior radiographically to iodinated contrast. Further study on gadolinium efficacy and safety in this setting is warranted. However the present case supports gadobenate dimeglumine as a viable option for retrograde pyelography when allergy risk precludes iodinated contrast use.

Reliability of signal intensity in the basal ganglia on non-contrast T1-weighted MR scans after repetitive application of a gadolinium-based contrast agent in pediatric neuro-oncology patients.

PURPOSE: To evaluate the reliability of signal intensity (SI) changes in the basal ganglia as a supposed indicator of gadolinium deposition in the brain after repetitive application of gadolinium-based contrast agents (GBCAs) in a pediatric neuro-oncological collective. METHODS: One hundred and eight neuropediatric patients (54 male, 54 female, 0-17 years old), with repetitive GBCA-enhanced cranial MRIs between 2003 and 2017, were retrospectively analyzed. Two radiologists measured SI in the nucleus dentatus (ND), globus pallidus (GP), thalamus (T), and the pons (P). The NDP and GPT ratio were calculated. An intraclass correlation coefficient, and multiple linear regressions with subsequent stepwise backward variable selection were performed to evaluate the influence of gender, patient's age at the first MRI, time interval between the first and last MRI, linear or macrocyclic GBCAs, residual pathology, treatments, and magnet field strengths. RESULTS: The inter-reader agreement was good for GPT and NDP in the whole collective (ICC = 0.837 and ICC = 0.793) and for children >2 years of age (ICC = 0.874 and ICC = 0.790), but poor to moderate for children ≤2 years of age (ICC = 0.397 and ICC = 0.748). The intra-reader agreement was good (ICC = 0.910 and ICC = 0.882). An SI increase was only observed for both readers in GPT (p = 0.003, or p < 0.001). None of the considered cofactors showed a consistent effect on SI changes for either readers or regions. CONCLUSION: Measurements of SI changes in the basal ganglia are not a reliable parameter with which to evaluate or estimate gadolinium deposition in the brain or to identify suspicious influential factors after repeated GBCA applications.

Review of the Efficacy and Safety of Gadopiclenol: A Newly Emerging Gadolinium-Based Contrast Agent.

Gadolinium-based contrast agents (GBCAs) are one of the most commonly used agents in magnetic resonance imaging. Gadopiclenol is a new GBCA aimed at providing improved diagnostic efficacy with a favorable safety profile. The proposed advantages are due to its specific pharmacological properties, one of which is high relaxivity values. The aim of this review is to assess the efficacy, diagnostic accuracy, and safety of gadopiclenol in comparison to other currently used gadolinium-based contrast agents. PubMed and other database systems were used to identify relevant studies. The Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines were followed, resulting in 10 articles that were included in the review. The outcomes were reviewed according to several factors regarding efficacy and accuracy in terms of qualitative and quantitative descriptors relative to properties of enhancement provided by the contrast agent. In terms of safety profile, a number of outcomes were assessed such as the occurrence of serious adverse effects, severe kidney injury, and organ-based contrast retention. Gadopiclenol was found to provide outcomes comparable to other commonly used GBCAs at lower doses with further favorable results at higher doses while maintaining an acceptable safety profile. However, it was found to have high rates of retention within the liver and can cause nonsignificant QT prolongation in healthy individuals, which arguably creates the need for further research regarding more long-term implications of these possible adverse effects.

Ultrasound-guided carotid angioplasty and stenting in a patient with iodinated contrast allergy: A case report.

BACKGROUND: Ischemic stroke is an entity with high incidence, morbidity, and mortality rates. Carotid artery stenosis is an important and independent risk factor for ischemic stroke. The three current approaches for treating carotid artery stenosis are drug treatment, carotid endarterectomy (CEA), carotid angioplasty and stenting (CAS). The approach is chosen based on the degree of stenosis. CEA or CAS could have been chosen for the current patient, who had severe carotid stenosis and an iodinated contrast allergy. After thoroughly communicating with the patient, the patient chose CAS for treatment. Therefore, we performed ultrasound-guided CAS to avoid the use of iodinated contrast. CASE SUMMARY: The main symptoms of the patient were numbness and weakness of the left limb. Computed tomography angiography of the head and neck at another hospital indicated multiple sites of stenosis in the arteries of the head and neck. The patient requested CAS for treatment but was allergic to iodinated contrast media. Thus, routine digital subtraction angiography (DSA) with iodinated contrast could not be used for the procedure. The diagnosis of this patient was as follows: (1) Right parietal lobe cerebral infarction; (2) multiple sites of stenosis in the arteries of the head and neck (severe stenosis of the right internal carotid artery, severe stenosis of the right subclavian artery); (3) right subclavian steal syndrome; and (4) hypertension (stage 3, high risk). The interventions included routine treatment for cerebral infarction, oral administration of clopidogrel (75 mg qd) and aspirin (100 mg qd), ultrasound-guided CAS, and postoperative follow-up. Postoperative color Doppler ultrasound and cerebrovascular magnetic resonance angiography of the carotid artery showed good vascular recovery, and the postoperative follow-up indicated a good prognosis. CONCLUSION: This case study suggests that ultrasound-guided endovascular treatment is a potential option for patients with contraindications to the iodinated contrast agents used in DSA-guided surgery, although excellent surgical operating skills are needed.

Blood-brain barrier water exchange measurements using contrast-enhanced ASL.

A technique for quantifying regional blood-brain barrier (BBB) water exchange rates using contrast-enhanced arterial spin labelling (CE-ASL) is presented and evaluated in simulations and in vivo. The two-compartment ASL model describes the water exchange rate from blood to tissue, k b , but to estimate k b in practice it is necessary to separate the intra- and extravascular signals. This is challenging in standard ASL data owing to the small difference in T 1 values. Here, a gadolinium-based contrast agent is used to increase this T 1 difference and enable the signal components to be disentangled. The optimal post-contrast blood T 1 ( T 1 , b post ) at 3 T was determined in a sensitivity analysis, and the accuracy and precision of the method quantified using Monte Carlo simulations. Proof-of-concept data were acquired in six healthy volunteers (five female, age range 24-46 years). The sensitivity analysis identified the optimal T 1 , b post at 3 T as 0.8 s. Simulations showed that k b could be estimated in individual cortical regions with a relative error ϵ < 1 % and coefficient of variation CoV = 30 %; however, a high dependence on blood T 1 was also observed. In volunteer data, mean parameter values in grey matter were: arterial transit time t A = 1 . 15 ± 0 . 49 s, cerebral blood flow f = 58 . 0 ± 14 . 3 mL blood/min/100 mL tissue and water exchange rate k b = 2 . 32 ± 2 . 49 s-1 . CE-ASL can provide regional BBB water exchange rate estimates; however, the clinical utility of the technique is dependent on the achievable accuracy of measured T 1 values.

Fatal Allergic Reaction to Gadolinium Contrast.

Gadolinium-based contrast agents (GBCA) have been used to enhance the sensitivity and specificity of disease diagnoses. They have excellent safety profiles. However, rare adverse events may happen. We present a case of severe fatal allergic reaction to GBCA in a 35-year-old patient.

Biomonitoring of rare earth elements in Southern Norway: Distribution, fractionation, and accumulation patterns in the marine bivalves Mytilus spp. and Tapes spp.

Growing extraction and usage of rare earth elements and yttrium (REY) for medical and industrial applications has resulted in increased discharges into the marine environment. Using Mytilus spp. Mussels and Tapes spp. clams as bioindicator organisms, we analyzed 15 REY in soft tissues of specimens collected at two potentially polluted sites in Southern Norway: in the vicinity of an industry producing gadolinium-based MRI contrast agents (GBCAs) (Lindesnes) and in an industrially-affected fjord (Porsgrunn). The spatial distribution of REY and shale-normalized fractionation patterns were determined to assess the potential anthropogenic contribution of REY at the sites. At both sites, the REY fractionation pattern in soft tissue was characterized by enrichment of light rare earth elements (LREE) over heavy rare earth elements (HREE), while also displaying negative cerium and small positive gadolinium (Gd) anomalies. LREEs contributed to over 80% of the total REY concentrations, with increasing relative enrichment following higher total REY. Gd anomalies remained conserved in most sites despite significant differences in total REY; however, a high Gd anomaly (Gd/Gd* = 4.4) was found downstream of the GBCA industry spillwater outlet, indicating biotic uptake of excess anthropogenic Gd at this site. Total REY concentrations in clams in Porsgrunn were one order of magnitude higher than in mussels in Lindesnes. This may be attributable to freshwater influences in Porsgrunn, where clams collected closer to the river mouth had significantly higher total REY concentrations. This study constitutes the first assessment of REY concentrations in marine bivalves in Norway and can provide useful information for future biomonitoring studies on REY contamination.

Gadolinium K-edge angiography with a spectral photon counting CT in atherosclerotic rabbits.

PURPOSE: The purpose of this study was to investigate the feasibility of gadolinium-K-edge-angiography (angio-Gd-K-edge) with gadolinium-based contrast agents (GBCAs) as obtained with spectral photon counting CT (SPCCT) in atherosclerotic rabbits. MATERIALS AND METHODS: Seven atherosclerotic rabbits underwent angio-SPCCT acquisitions with two GBCAs, with similar intravenous injection protocol. Conventional and angio-Gd-K-edge images were reconstructed with the same parameters. Regions of interest were traced in different locations of the aorta and its branches. Hounsfield unit values, Gd concentrations, signal-to-noise (SNR) and contrast-to-noise (CNR) were calculated and compared. The maximum diameter and the diameter of the aorta in regard to atherosclerotic plaques were measured by two observers. Images were subjectively evaluated regarding vessels' enhancement, artefacts, border sharpness and overall image quality. RESULTS: In the analyzable six rabbits, Gd-K-edge allowed visualization of target vessels and no other structures. HU values and Gd concentrations were greatest in the largest artery (descending aorta, 5.6 ± 0.8 [SD] mm), and lowest in the smallest (renal arteries, 2.1 ± 0.3 mm). While greater for conventional images, CNR and SNR were satisfactory for both images (all P < 0.001). For one observer there were no statistically significant differences in either maximum or plaque-diameters (P = 0.45 and all P > 0.05 in post-hoc analysis, respectively). For the second observer, there were no significant differences for images reconstructed with the same parameters (all P < 0.05). All subjective criteria scored higher for conventional images compared to K-edge (all P < 0.01), with the highest scores for enhancement (4.3-4.4 vs. 3.1-3.4). CONCLUSION: With SPCCT, angio-Gd-K-edge after injection of GBCAs in atherosclerotic rabbits is feasible and allows for angiography-like visualization of small arteries and for the reliable measurement of their diameters.

Reducing Gadolinium Exposure in Patients Undergoing Monitoring for Meningiomas.

Background Due to the non-malignant and slow-growing nature of many meningiomas, surveillance with serial magnetic resonance imaging (MRI) serves as an acceptable management plan. However, repeated imaging with gold-standard contrast-based studies may lead to contrast-associated adverse effects. Non-gadolinium T2 sequences may serve as a suitable alternative without the risk of adverse effects of contrast. Thus, this study sought to investigate the agreement between post-contrast T1 and non-gadolinium T2 MRI sequences in the measurement of meningioma growth. Methodology The Virginia Commonwealth University School of Medicine (VCU SOM) brain tumor database was used to create a cohort of meningioma patients and determine the number of patients who had T1 post-contrast imaging accompanied by readily measurable imaging from either T2 fast spin echo (FSE) or T2 fluid-attenuated inversion recovery (FLAIR) sequences. Measurements of the largest axial and perpendicular diameters of each tumor were conducted by two independent observers using T1 post-contrast, T2 FSE, and T2 FLAIR imaging series. Lin's concordance correlation coefficient (CCC) was calculated to assess inter-rater reliability between observers and agreement between measurements of tumor diameter among the different imaging sequences. Results In total, 33 patients (average age = 72.1 ± 12.9 years, 90% female) with meningiomas were extracted from our database, with 22 (66.7%) undergoing T1 post-contrast imaging accompanied with readily measurable imaging from T2 FSE and/or T2 FLAIR sequences. The inter-rater reliability between the measurements of T1 axial and perpendicular diameters was 0.96 (95% confidence interval (CI) = 0.92-0.98) and 0.92 (95% CI = 0.83-0.97), respectively. The inter-rater reliability between the measurements of T2 axial perpendicular diameters was 0.93 (95% = CI 0.92-0.97) and 0.89 (95% CI = 0.74-0.95), respectively. The agreements between the measurement of T1 and T2 FSE axial diameter by each observer were 0.97 (95% CI = 0.93-0.98) and 0.92 (95% CI = 0.81-0.97). The agreements between the measurements of T1 and T2 FSE perpendicular diameter measurements by each observer were 0.98 (95% CI = 0.95-0.99) and 0.88 (95% CI = 0.73-0.95). Conclusions Two-thirds of our patients had meningiomas that were readily measurable on either T2 FSE or T2 FLAIR sequences. Additionally, there was excellent inter-rater reliability between the observers in our study as well as an agreement between individual measurements of T1 post-contrast and T2 FSE tumor diameters. These findings suggest that T2 FSE may serve as a safe and similarly effective surveillance method for the long-term management of meningioma patients.

Clinical validation of the basophil activation test in immediate hypersensitivity reactions to gadolinium-based contrast agents.

Gadolinium based contrast agents (GBCAs) are safe compounds globally used in magnetic resonance imaging (MRI). However, in last years it has been detected an increase of immediate hypersensitivity reactions (IHRs) to them. Diagnosis of IHRs to GBCAs is based on clinical symptoms, skin tests (STs) and drug provocation test (DPT). But DPTs are not without risks, thus it is important to implement an in vitro alternative method such as the basophil activation test (BAT). We described the clinical validation of the BAT using ROC curves from a control population formed by 40 healthy individuals without previous reactions to any contrast agents and 5 patients suffering from IHRs to GBCAs. Four patients presented IHRs to gadoteric acid (GA) as the culprit agent and another one to gadobutrol (G). Basophil reactivity was measured in percentage of CD63 expression and in stimulation index (SI). The optimal cut-off with the highest sensitivity (S) and specificity (E) for the GA was of 4.6% at 1:100 dilution (S = 80% and E = 85%; AUC = 0.880, p = 0.006). For the SI with GA, the cut-off of highest sensitivity and specificity was of 2.79 at 1:100 dilution (S = 80% and E = 100%; AUC = 0.920, p = 0.002). Sensitivity did not show differences between STs regarding the BAT (p < 0.05). Moreover, the BAT was able to detect one case with IHR to GA which had negative STs. Therefore, the BAT is a useful method in diagnosis of IHRs to GBCAs.

Relationship between gadolinium-based MRI contrast agent consumption and anthropogenic gadolinium in the influent of a wastewater treatment plant.

Gadolinium-based contrast agents (GBCAs) used in magnetic resonance imaging (MRI) are highly resistant in the environment. They pass through wastewater treatment plants (WWTPs) unhindered escaping degradation. Although GBCAs are subjects of intensive research, we recognized that a quantitative approach to the mass balance of gadolinium, based on known input and output data, is missing. The administered amount of Gd as GBCAs, the number of out- and inpatients and the concentration of rare earth elements (REEs) in wastewater were monitored for 45 days in a medium sized city (ca. 203,000 inhabitants) with two MRI centres. An advection-dispersion type model was established to describe the transport of Gd in the wastewater system. The model calculates with patient locality, excretion kinetics of Gd and the yield of wastewater. The estimated and measured daily amount of anthropogenic gadolinium released to the WWTP were compared. GBCAs (Omniscan and Dotarem) were administered to 1008 patients representing a total of 700 ± 1 g Gd. The amount of total Gd entering the WWTP was 531 ± 2 g, of which the anthropogenic contribution (i.e. GBCAs) was 261 ± 6 g (49 ± 1 % of the total Gd) during the sampling campaign. Local residents and inpatients should fully release Gd in the city, but outpatients only partially. Overall, 37 ± 1 % of the total administered Gd was recovered in the wastewater, so the remaining 63 ± 1 % of administered Gd is expected to be dispensed outside of the sewer system. Our approach enables to better understand the dispersion of GBCAs originated Gd in an urban environment.

Cellular toxicities of gadolinium-based contrast agents used in magnetic resonance imaging.

Contrast agents have been used in magnetic resonance imaging (MRI) as a radiological method. Gadolinium-based contrast agents (GBCAs), because of their paramagnetic characteristics, are the ones mostly used in MRI to increase signal intensity. However, the use of contrast media has raised concerns on cellular toxic risks of these agents. Studies showed the accumulation of gadolinium after injection to humans with or without renal impairment. Also, there are findings obtained under in vitro and/or in vivo conditions that revealed conflicting results for their cytotoxic and genotoxic effects. Some of them declared damage in cells and genetic material; some others did not. Abnormal cell growth and genetic aberration are critical because they may lead to carcinogenesis in somatic cells or may be transferred to the next generations through germ cells. Therefore, understanding the effect of GBCAs on cells is important for their safer usage in clinical administrations to generate high-quality contrast-enhanced magnetic resonance images. Because of all these reasons, cellular toxicities-mainly genotoxic and cytotoxic effects-of GBCAs were reviewed in this paper.

Gadolinium-based contrast agent exposures and physical and cognitive disability in multiple sclerosis.

BACKGROUND AND PURPOSE: The clinical correlation of gadolinium-based contrast agents (GBCAs) has not been well studied in multiple sclerosis (MS). We investigated the extent to which the number of GBCA administrations relates to self-reported disability and performance measures. METHODS: A cohort of MS patients was analyzed in this retrospective observational study. The main outcome was the association between the cumulative number of GBCA exposures (linear or macrocyclic GBCA), Patient-Determined Disease Steps (PDDS), and measures of physical and cognitive performance (walking speed test, manual dexterity test [MDT], and processing speed test [PST]). The analysis was performed first cross-sectionally and then longitudinally. RESULTS: The cross-sectional data included 1059 MS patients with a mean age of 44.0 years (standard deviation = 11.2). While the contrast ratio in globus pallidus weakly correlated with PDDS, MDT, and PST in a univariate correlational analysis (coefficients, 95% confidence interval [CI] = 0.11 [0.04, 0.18], 0.15 [0.08, 0.21], and -0.16 [-0.10, -0.23], respectively), the associations disappeared after covariate adjustment. A significant association was found between number of linear GBCA administrations and PDDS (coefficient [CI] = -0.131 [-0.196, -0.067]), and MDT associated with macrocyclic GBCA administrations (-0.385 [-0.616, -0.154]), but their signs indicated better outcomes in patients with greater GBCA exposures. The longitudinal data showed no significant detrimental effect of macrocyclic GBCA exposures. CONCLUSION: No detrimental effects were observed between GBCA exposure and self-reported disability and standardized objective measures of physical and cognitive performance. While several weak associations were found, they indicated benefit on these measures.

Vestibular paroxysmia entails vestibular nerve function, microstructure and endolymphatic space changes linked to root-entry zone neurovascular compression.

Combining magnetic resonance imaging (MRI) sequences that permit the determination of vestibular nerve angulation (NA = change of nerve caliber or direction), structural nerve integrity via diffusion tensor imaging (DTI), and exclusion of endolymphatic hydrops (ELH) via delayed gadolinium-enhanced MRI of the inner ear (iMRI) could increase the diagnostic accuracy in patients with vestibular paroxysmia (VP). Thirty-six participants were examined, 18 with VP (52.6 ± 18.1 years) and 18 age-matched with normal vestibulocochlear testing (NP 50.3 ± 16.5 years). This study investigated whether (i) NA, (ii) DTI changes, or (iii) ELH occur in VP, and (iv) to what extent said parameters relate. Methods included vestibulocochlear testing and MRI data analyses for neurovascular compression (NVC) and NA verification, DTI and ELS quantification. As a result, (i) NA increased NVC specificity. (ii) DTI structural integrity was reduced on the side affected by VP (p < 0.05). (iii) 61.1% VP showed mild ELH and higher asymmetry indices than NP (p > 0.05). (iv) "Disease duration" and "total number of attacks" correlated with the decreased structural integrity of the affected nerve in DTI (p < 0.001). NVC distance within the nerve's root-entry zone correlated with nerve function (Roh = 0.72, p < 0.001), nerve integrity loss (Roh = - 0.638, p < 0.001), and ELS volume (Roh = - 0.604, p < 0.001) in VP. In conclusion, this study is the first to link eighth cranial nerve function, microstructure, and ELS changes in VP to clinical features and increased vulnerability of NVC in the root-entry zone. Combined MRI with NVC or NA verification, DTI and ELS quantification increased the diagnostic accuracy at group-level but did not suffice to diagnose VP on a single-subject level due to individual variability and lack of diagnostic specificity.