Gadolinium Deposition Research Articles

Medication-induced changes on magnetic resonance imaging of the brain.

In this review the authors focus on abnormal brain magnetic resonance imaging caused by drugs given to patients in any age group for any disease. The review includes viral infections with fever in children/infections in general, epilepsy, psychiatric diseases, multiple sclerosis, neoplasms, bone marrow/organ transplantations, total parenteral nutrition, vaccinations, oral contraceptives and other prothrombotic drugs, and gadolinium deposition. Knowledge of patients' diseases and medications they receive is crucial to establish the correct diagnosis. The absence of these data in a referral for a brain MRI scan can result in completely wrong suspicions and unleash unnecessary, complicated, time-consuming and expensive diagnostics, causing additional stress in patients and their guardians.

Quantitative assessment of gadolinium deposition in dentate nuclei with MR fingerprinting

Gadolinium deposition in the dentate nucleus (DN) has been evaluated by T1-weighted imaging (T1WI) and T1 (R1) mapping, but not MR fingerprinting (MRF). This study investigated associations between T1 and T2 values of DN and gadolinium-based contrast agents (GBCAs) using 2-dimensional MRF. This study included 101 patients. Region of interest analysis was performed for T1 and T2 values of DN on MRF (T1-MRF, T2-MRF) and T1-weighted images (T1WI ratio). T1 and T2 ratios compared to normal cerebellar white matter (T1-MRF ratio, T2-MRF ratio) were calculated. The type of previous GBCA was confirmed in 79 patients, and linear regressions were performed between T1, T2 values and number of GBCAs. Good correlations were observed between T1-MRF and T1WI ratio (ρ=-0.69, P<0.001) and between T1-MRF ratio and T1WI ratio (ρ=-0.76, P<0.001). Mild correlations were observed between T2-MRF and T1WI ratio (ρ=-0.32, P<0.001) and between T2-MRF ratio and T1WI ratio (ρ=-0.44, P<0.001). The number of linear-type GBCAs was associated with T1-MRF (β=-0.62, P<0.001) and T1-MRF ratio (β=-0.54, P<0.001) in univariate linear regression analyses, and with T1-MRF (β=-0.61, P<0.001) and T1-MRF ratio (β=-0.53, P<0.001) in multivariate analysis. The number of linear-type GBCAs was associated with T2-MRF (β=-0.30, P<0.001) and T2-MRF ratio (β=-0.29, P<0.001) in univariate analyses, and with T2-MRF (β=-0.31, P<0.001) and T2-MRF ratio (β=-0.32, P<0.001) in multivariate analyses. No associations were observed between number of macrocyclic GBCAs and T1-MRF (ratio) or T2-MRF (ratio). The number of linear-type GBCA administrations was associated with lower T1 and T2 values (ratios) in DN.

The effect of iron status on gadolinium deposition in the rat brain: mechanistic implications.

Introduction: Sites associated with gadolinium (Gd) deposition in the brain (e.g., the globus pallidus) are known to contain high concentrations of ferric iron. There is considerable debate over the mechanism of Gd deposition in the brain. The role of iron transport mechanisms in Gd deposition has not been determined. Thus, we seek to identify if Gd deposition can be controlled by modifying iron exposure. Methods: Female Sprague-Dawley rats were given diets with controlled iron levels at 2-6ppm, 6ppt (20g/kg Fe carbonyl) or 48ppm for 3weeks to induce iron deficiency, overload or normalcy. They were kept on those diets while receiving a cumulative 10mmol/kg dose of gadodiamide intravenously over 2weeks, then left to washout gadodiamide for 3days or 3weeks before tissues were harvested. Gd concentrations in tissues were analyzed by ICP-MS. Results: There were no significant effect of dietary iron and total Gd concentrations in the organs, but there was a significant effect of iron status on Gd distribution in the brain. For the 3-week washout cohort, there was a non-significant trend of increasing total brain deposition and decreasing dietary iron, and about 4-fold more Gd in the olfactory bulbs of the low iron group compared to the other groups. Significant brain accumulation was observed in the low iron group total brain Gd in the 3-week washout group relative to the 3-day washout group and no accumulation was observed in other tissues. There was a strong negative correlation between femur Gd concentrations and concentrations in other organs when stratifying by dietary iron. Discussion: Gd brain deposition from linear Gd-based contrast agents (GBCAs) are dependent upon iron status, likely through variable transferrin saturation. This iron dependence appears to be associated with redistribution of peripheral deposited Gd (e.g., in the bone) into the brain.

Differences in hypersensitivity reactions and gadolinium deposition disease/symptoms associated with gadolinium exposure to gadolinium-based contrast agents: new insights based on global databases VigiBase, FAERS, and IQVIA-MIDAS

BackgroundHypersensitivity reactions (HSRs) can occur unexpectedly and be life-threatening when gadolinium-based contrast agents (GBCAs) are used. Gadolinium deposition disease (GDD) and symptoms associated with gadolinium exposure (SAGE) have been controversial for a long time. However, similar studies are currently incomplete or outdated. Therefore, comparing the safety of different GBCAs in terms of HSRs and GDD/SAGE using the latest post-marketing safety data should yield further insights into safely using GBCAs.MethodsThe safety differences between all GBCAs to GDD and the spectrum of GBCA-related HSRs were all compared and analyzed by using the World Health Organization database VigiBase and the FDA Adverse Event Reporting System (FAERS) database in this study. A further analysis of SAGE was also conducted using FAERS data. The lower limit of the reporting odds ratio (ROR) 95% confidence interval was used for signal detection. Moreover, the frequency of HSRs was calculated by dividing the number of reports in VigiBase by the total sales volume (measured in millions) from 2008 to 2022 in the IQVIA Multinational Integrated Data Analysis System. All adverse events were standardized using the Medical Dictionary for Drug Regulatory Activities (MedDRA) 26.0.ResultsThis study shows that all GBCAs have the potential to induce HSRs, with nonionic linear GBCAs exhibiting a comparatively lower signal. According to standardized MedDRA query stratification analysis, gadobutrol had a greater ROR025 for angioedema. The ROR025 of gadobenate dimeglumine and gadoteridol is larger for anaphylactic/anaphylactoid shock conditions. Regarding severe cutaneous adverse reactions, only gadoversetamide and gadodiamide showed signals in FAERS and VigiBase. There were also differences in the frequency of HSRs between regions. Regarding GDD, gadoterate meglumine, and gadoteridol had a lower ROR025. An analysis of the 29 preferred terms linked to SAGE indicated that special consideration should be given to the risk of skin induration associated with gadoversetamide, gadopentetate dimeglumine, gadobenate dimeglumine, gadodiamide, and gadoteridol. Additionally, gadodiamide and gadoteridol pose a greater risk of skin tightness compared to other GBCAs.ConclusionsThe risk differences among GBCAs using data from several sources were compared in this study. However, as a hypothesis-generating method, a clear causal relationship would require further research and validation.

Deposition of Gadolinium in the Central and Peripheral Nervous Systems and Its Effects on Sensory, Cognitive, and Athletic Implications after Multiple Injections of Gadolinium-Based Contrast Agents in Rats.

After repeat administration of gadolinium-based contrast agents (GBCAs), the association between gadolinium retention in the central and peripheral nervous systems and the main manifestations of myelopathy and progressive neurologic symptoms remains unclear. We investigated the effects of the repeat administration of GBCAs on gadolinium retention in the central and peripheral nervous systems and the sensory, cognitive, and athletic implications. Forty-eight male Wistar rats (6 weeks of age) were randomly divided into 4 experimental groups (12 rats in each group): the gadodiamide group (linear and nonionic GBCAs), the gadopentetate dimeglumine group (linear and ionic GBCAs), the gadoterate meglumine group (macrocyclic and ionic GBCAs), and the control group (0.9% saline solution). The brains of the rats were scanned using 9.4T MRI. Sensory behavioral tests were performed to assess the effect of GBCAs on pain sensitivity function. Gadolinium deposition in the brain, spinal cord, and peripheral nerves was determined by inductively coupled plasma mass-spectrometry. Transmission electron microscopy was used to observe the microscopic distribution of gadolinium after deposition in the spinal cord. The histopathologic features in the spinal cord were analyzed by H&E staining, Nissl staining, glial fibrillary acidic protein staining, and neuron-specific enolase staining after administration of GBCAs. All GBCAs resulted in gadolinium deposition in the central and peripheral nerve tissues, with the highest deposition in the sciatic nerve tissue (mean, 62.86 [SD, 12.56] nmol/g). Decreased muscle power, impairment of spatial cognitive function power, and pain hypersensitivity to thermal and mechanical stimuli were observed after exposure to gadodiamide. At the spinal cord, transmission electron microscopy found that the region of gadolinium depositions had a spheric structure similar to "sea urchins" and was mainly located near the vascular basement membrane. Multiple injections of GBCAs caused gadolinium deposition in the brain, spinal cord, and peripheral nerves, especially in the spinal cords of the gadodiamide group. Gadodiamide led to pain hypersensitivity and decreased muscle power and cognitive ability. For the patients who are hypersensitive to pain and need multiple MRI examinations, we recommend using macrocyclic GBCAs and the lowest dose possible.

Non-contrast MRI Surveillance of Craniopharyngiomas using a balanced steady state free precession (bSSFP) sequence.

Contrast-enhanced MRI (CEMRI) is a commonly used imaging modality for craniopharyngioma surveillance; however, it carries risks such as allergic reaction and gadolinium deposition. This study evaluates the efficacy of non-contrast enhanced MRI (NCMRI) with a balanced steady state free precession (bSSFP) sequence compared with CEMRI T1-weighted imaging for craniopharyngioma surveillance. 29 craniopharyngioma patients (16 female/13 male, mean age=21.5± 4.3 years) with CEMRIs including a bSSFP sequence were evaluated. For each patient, 2 blinded neuroradiologists compared the dimensions of residual craniopharyngioma on noncontrast and contrast-enhanced sequences. Tumor volume and solid/cystic component measurements were evaluated using paired t-tests. Diagnostic confidence levels for NC-and CE evaluations were measured using a 3-point scale (2=confident,1=adequate,0=unsure). Analyses of tumor involvement of cranial nerves and adjacent vasculature and diagnostic confidence were performed using Fisher's exact and chi-square tests. No significant difference was observed between residual tumor volumes in both studies (18.86±21.67 cm3 vs 17.64±23.85 cm3, p=0.55) and measurements of dominant solid component volume, number of cystic components, and largest cystic component volume (2.71±3.47 cm3 vs 3.95±5.51 cm3, p=0.10; 2.5±1.5 vs 2.9±1.5, p=0.10; 7.61±13.41 vs 6.84±13.37 cm3, p=0.22, respectively). Tumoral involvement of cranial nerves II (p=0.64), III (p=0.42), and adjacent vasculature (p=0.05) showed no significant differences in detection. Diagnostic confidence was comparable evaluating cranial nerve II, vascular structures, and third ventricle (p>0.05) involvement. Higher levels of confidence were observed with bSSFP sequences for detection of cranial nerve III involvement (p=0.0001) and with ce-T1W for cavernous sinus involvement (p=0.02). NCMRI techniques using a bSSFP sequence provides similar characterization of craniopharyngiomas as contrast enhanced techniques. 3D DRIVE, 3-dimensional driven equilibrium; ACA, anterior cerebral artery; bSSFP, balanced steady-state free precession; ce-T1W, contrast-enhanced T1-weighted imaging; CN, cranial nerve; GTR, gross total resection; STR, subtotal resection.

Contrast-Enhanced Ultrasound (CEUS) for Evaluating Indeterminate Liver Lesions During Pregnancy: A Case Report

We report a case of a 34-year-old woman diagnosed with HER2-positive breast cancer at 12 weeks of pregnancy. The oncology team opted for neoadjuvant chemotherapy while continuing the pregnancy. To exclude metastatic liver disease, CT was not feasible due to radiation risks, and liver MRI was avoided due to concerns about gadolinium deposition in the fetal basal ganglia.

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.

Temporal Assessment of Gadolinium Deposition and T1 Signal Intensity Changes in Rat Kidney with Single and Multiple Doses of Injection: An Experimental Study.

Gadolinium deposition in biological tissues was first reported in patients with renal failure. We aimed to investigate gadolinium deposition in the rat kidney after exposure to single and multiple doses of gadolinium and evaluate deposition for 1- and 3-month periods. We also aimed to determine any correlation between the amount of deposition and T1-weighted image intensity. Seventy rats (5 animals per group) were included in the sample, and 9 groups received a single dose (0.3, 0.6, and 1.2 mmol/kg) of gadolinium, and 1 group for each dose was sacrificed at the end of the first day, week, and month. Four groups received weekly doses (0.3 and 0.6 mmol/kg) and were sacrificed at the end of 6 and 12 weeks. Measurement of T1 intensities was carried out with postinjection images before sacrifice, and deposition was determined using inductively coupled plasma mass spectrometry. The number of injections was associated with increased gadolinium deposition (P <.001) in the kidney. After the weekly injections, the deposited gadolinium levels did not significantly difer between the low and medium doses at the end of the sixth week (P=.067). There was no agreement between the observers regarding the measurement of T1 signal intensity in both single-dose and multidose experiments (P=.263 and P=.307, respectively). Deposition was dose dependent in the postinjection stage in contrast to the late stage in which deposition was not associated with dose or number of injections until the 12th week. T1 signal intensity measurement is unreliable for assessing deposition in the rat kidney.

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

ObjectivesTo 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. MethodsAdult 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. ResultsThe 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. ConclusionsLF aggravated gadolinium deposition in the liver and DCN after administration of GD. However, no significant acute histological alterations were observed due to gadolinium deposition.

Synthesis of gadolinium-enhanced glioma images on multisequence magnetic resonance images using contrastive learning.

Gadolinium-based contrast agents are commonly used in brain magnetic resonance imaging (MRI), however, they cannot be used by patients with allergic reactions or poor renal function. For long-term follow-up patients, gadolinium deposition in the body can cause nephrogenic systemic fibrosis and other potentialrisks. Developing a new method of enhanced image synthesis based on the advantages of multisequence MRI has important clinical value for these patients. In this paper, an end-to-end synthesis model structure similarity index measure (SSIM)-based Dual Constrastive Learning with Attention (SDACL) based on contrastive learning is proposed to synthesize contrast-enhanced T1 (T1ce) using three unenhanced MRI images of T1, T2, and Flair in patients withglioma. The model uses the attention-dilation generator to enlarge the receptive field by expanding the residual blocks and to strengthen the feature representation and context learning of multisequence MRI. To enhance the detail and texture performance of the imaged tumor area, a comprehensive loss function combining patch-level contrast loss and structural similarity loss is created, which can effectively suppress noise and ensure the consistency of synthesized images and real images. The normalized root-mean-square error (NRMSE), peak signal-to-noise ratio (PSNR), and SSIM of the model on the independent test set are 0.307 0.12, 23.337 3.21, and 0.881 0.05,respectively. Results show this method can be used for the multisequence synthesis of T1ce images, which can provide valuable information for clinical diagnosis.

Near-cure in patients with Gadolinium deposition disease undergoing intravenous DTPA chelation.

To demonstrate and evaluate factors contributing to near-cures in patients with Gadolinium Deposition Disease (GDD) undergoing intravenous (IV) DTPA chelation. Patients who had undergone or are currently undergoing DTPA chelation for GDD were included in this report based on their medical records that showed their perceived improvement was at least 80% back to normal. A survey was developed that included factors commonly reported by patients treated in one clinic to determine if these 'near-cured' (pre-MRI baseline health) individuals possessed certain factors and lacked others. The anonymized survey was emailed to these individuals by the principal treating physician, the only investigator not blinded to the subjects. This report describes clinical documentation of patient status and their underlying factors in individuals treated by the primary author, and no research was performed. The survey was sent to sixteen individuals; Fourteen patients completed it (10 females; 41.1 ± 11.2y/o). The most common factor was the administration of ≤5 lifetime doses of a Gadolinium-Based Contrast Agents (GBCA) (12/14). Unconfounded agents triggering GDD were seen in nine subjects. Most subjects (12/14) initiated chelation in the first year after the causative GBCA, and most (11/14) underwent ≤10 chelations with DTPA. Good healthcare status prior to MRI was observed in 5 subjects. The majority (11/14) described their immune status as strong. Severe physical disability prior to chelation was seen in 1. Subjects with GDD can experience near-cure with IV DTPA chelation. Factors surveyed that predict near-cure include the start of chelation in the first year, few GBCA administrations, and good health status before MRI with GBCA injection. Nonetheless, a few patients with predictors of less successful outcomes still experienced near-cure.

Gadolinium Effects on Liposome Fluidity and Size Depend on the Headgroup and Side Chain Structure of Key Mammalian Brain Lipids.

The lanthanide metal gadolinium has been used in the healthcare industry as a paramagnetic contrast agent for years. Gadolinium deposition in brain tissue and kidneys has been reported following gadolinium-based contrast agent administration to patients undergoing MRI. This study demonstrates the detrimental effects of gadolinium exposure at the level of the cell membrane. Biophysical analysis using fluorescence spectroscopy and dynamic light scattering illustrates differential interactions of gadolinium ions with key classes of brain membrane lipids, including phosphatidylcholines and sphingomyelins, as well as brain polar extracts and biomimetic brain model membranes. Electrostatic attraction to negatively charged lipids like phosphatidylserine facilitates metal complexation but zwitterionic phosphatidylcholine and sphingomyelin interaction was also significant, leading to membrane rigidification and increases in liposome size. Effects were stronger for fully saturated over monounsaturated acyl chains. The metal targets key lipid classes of brain membranes and these biophysical changes could be very detrimental in biological membranes, suggesting that the potential negative impact of gadolinium contrast agents will require more scientific attention.

Accuracy of Noncontrast T2 SPACE in Active MS Cord Lesion Detection.

The diagnosis of active MS lesions is often based on postgadolinium T1-weighted MR imaging. Recent studies suggest a risk of IV gadolinium to patients, predominantly based on gadolinium deposition in tissue. Noncontrast sequences have shown promise in MS diagnosis, but none differentiate acute from chronic MS lesions. We hypothesized that 3D T2 sampling perfection with application-optimized contrasts by using different flip angle evolution (SPACE) MR imaging can help detect and differentiate active-versus-chronic MS lesions without the need for IV contrast. In this single-center retrospective study, 340 spinal MR imaging cases of MS were collected in a 24-month period. Two senior neuroradiologists blindly and independently reviewed postcontrast T1-weighted sagittal and T2-SPACE sagittal images for the presence of MS lesions, associated cord expansion/atrophy on T2-SPACE, and enhancement on postcontrast T1WI. Discrepancies were resolved by consensus between the readers. Sensitivity, specificity, and accuracy of T2-SPACE compared with postcontrast T1WI were computed, and interobserver agreement was calculated. The sensitivity of lesion detection on T2-SPACE was 85.71%, 95% CI, 63.66%-96.95%; with a specificity of 93.52%, 95% CI, 90.06%-96.05%; and an accuracy of 92.99%, 95% CI, 89.58%-95.56. Additionally, 16/21 (84.2%) acute enhancing cord lesions showed cord expansion on T2-SPACE. The interobserver agreement was 92%. Our study shows that T2-SPACE facilitates noncontrast detection of acute MS lesions with high accuracy compared with postcontrast T1WI and with high interobserver agreement. The lack of gadolinium use provides an advantage, bypassing any potential adverse effects of repetitive contrast administration.

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

PurposeTo 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. MethodsOne 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. ResultsThe 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. ConclusionMeasurements 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.

Reducing Gadolinium Contrast With Artificial Intelligence.

Gadolinium contrast is an important agent in magnetic resonance imaging (MRI), particularly in neuroimaging where it can help identify blood-brain barrier breakdown from an inflammatory, infectious, or neoplastic process. However, gadolinium contrast has several drawbacks, including nephrogenic systemic fibrosis, gadolinium deposition in the brain and bones, and allergic-like reactions. As computer hardware and technology continues to evolve, machine learning has become a possible solution for eliminating or reducing the dose of gadolinium contrast. This review summarizes the clinical uses of gadolinium contrast, the risks of gadolinium contrast, and state-of-the-art machine learning methods that have been applied to reduce or eliminate gadolinium contrast administration, as well as their current limitations, with a focus on neuroimaging applications. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 1.

Update on Gadolinium-Based Contrast Agent Safety, From the AJR Special Series on Contrast Media.

Since its introduction more than 35 years ago, gadolinium-enhanced MRI has fundamentally changed medical practice. Although extraordinarily safe, gadolinium-based contrast agents (GBCAs) may have side effects. Four distinct safety considerations include acute allergiclike reactions, nephrogenic systemic fibrosis (NSF), gadolinium deposition, and symptoms associated with gadolinium exposure. Acute reactions after GBCA administration are uncommon-far less than with iodinated contrast agents-and, although rare, serious reactions can occur. NSF is a rare but serious sclerodermalike condition occurring in patients with kidney failure after exposure to American College of Radiology (ACR) group I GBCAs. Group II and III GBCAs are considered lower risk, and, through their use, NSF has largely been eliminated. Unrelated to NSF, retention of trace amounts of gadolinium in the brain and other organs has been recognized for over a decade. Deposition occurs with all agents, although linear agents appear to deposit more than macrocyclic agents. Importantly, to date, no data show any adverse biologic or clinical effects from gadolinium deposition, even with normal kidney function. This article summarizes the latest safety evidence of commercially available GBCAs with a focus on new agents, discusses updates to the ACR NSF GBCA safety classifications, and describes approaches for strengthening the evidence needed for regulatory decisions.

Using the non-distortion IVIM to reduce the need for contrast agents in nasopharyngeal MRI

BackgroundPatients with nasopharyngeal carcinoma (NPC) who undergo longitudinal follow-up contrast-enhanced MRI are at risk of developing gadolinium deposition in their neural tissue, which may potentially harm them. Therefore, for these patients, a non-contrast-enhanced method is potentially beneficial as an alternative approach to predict enhancement in T1-weighted imaging (CE-T1WI). The traditional intravoxel incoherent motion (IVIM) is one of the non-contrast-enhanced methods; however, the severe distortion and signal loss limit its application in patients with NPC. The present study aimed to investigate whether non-distortion IVIM could reduce the need of CE-T1WI in the follow-up of patients with NPC. MethodsThe patients with NPC underwent Turbo Spin-echo MVXD diffusion-weighted imaging-based IVIM (non-distortion IVIM) from November 2021 to May 2022. Firstly, thirty patients with NPC were underwent both non-distortion IVIM and traditional IVIM. The distortion rate (DR) of the non-distortion IVIM was compared with the traditional IVIM. Then, twenty-one NPC patients with tumors (areas >50mm2) were included and correlation coefficient analysis was used to assess the relationship between their non-distortion IVIM and CE-T1WI. Linear regression analysis was performed to determine whether non-distortion IVIM predictors could predict CE-T1WI. ResultsThe correlation was observed between the parameter f of the non-distortion IVIM and the enhancement ratio of CE-T1WI (r = 0.543, P = 0.011). Moreover, the linear regression analysis revealed that f was an independent IVIM predictor of CE-T1WI in patients with NPC (P = 0.011). The DR of the non-distortion IVIM was significantly smaller than that of the traditional IVIM (0.12 ± 0.05 vs 0.48 ± 0.16, P < 0.001). ConclusionsIn patients with NPC, non-distortion IVIM showed potential clinical benefits to reduce the need for contrast agents, and it can independently predict the enhancement ratio.

Uptake of Gadolinium-Based Contrast Agents by Blood Cells During Contrast-Enhanced MRI Examination.

Gadolinium-based contrast agents (GBCAs) are routinely used in magnetic resonance imaging (MRI) examinations. However, there is limited knowledge about the interaction with and distribution of the drug in human cells. This lack of knowledge is surprising, given that the first interaction of the drug occurs with blood cells. Moreover, recent studies reported gadolinium (Gd) deposition within organs, such as the brain. Hence, this study is aiming to determine the uptake of GBCA in blood cells of patients undergoing contrast-enhanced MRI (ce-MRI) examination. Human blood was exposed to either gadoterate meglumine (Gd-DOTA) or Eu-DOTA in vitro or was collected from patients undergoing ce-MRI with Gd-DOTA. Uptake of contrast agents (CAs) by blood cells was quantified by Gd measurements using single-cell inductively coupled plasma mass spectrometry (SC-ICP-MS) or, to confirm Gd-DOTA uptake, by a complementary method using Eu-DOTA by time-resolved fluorescence spectroscopy, respectively. Uptake of Gd-DOTA or Eu-DOTA into white blood cells (WBCs) ex vivo was detectable by SC-ICP-MS and time-resolved fluorescence spectroscopy. The intracellular concentrations were estimated to be in the range of 1-3 μM. However, no CA uptake into erythrocytes was detected with either method. In total, 42 patients between 30 and 84 years old (24 men, 18 women) were enrolled. White blood cells' uptake of Gd was measured by SC-ICP-MS. Isolated WBCs from patients who underwent ce-MRI examination showed substantial Gd uptake; however, the studied patient group showed an inhomogeneous distribution of Gd uptake. Measurements immediately after MRI examination indicated 21-444 attogram/WBC, corresponding to an intracellular Gd concentration in the range from 0.2 to 5.5 μM. This study confirms the ex vivo uptake of GBCA by WBCs and provides the first evidence that GBCA is indeed taken up by WBCs in vivo by patients undergoing ce-MRI examination. However, the observed Gd uptake in WBCs does not follow a log-normal distribution commonly observed in the fields of environmental studies, biology, and medicine. Whether cellular uptake of GBCA is linked to the observed deposition of Gd remains unclear. Therefore, studying the interaction between GBCA and human cells may clarify crucial questions about the effects of Gd on patients after MRI examinations.

Elemental Bioimaging of Sheep Bone and Articular Cartilage After Single Application of Gadolinium-Based Contrast Agents.

Gadolinium-based contrast agents (GBCAs) are applied to enhance magnetic resonance imaging. Gadolinium (Gd), a rare earth metal, is used in a chelated form when administered as GBCA to patients. There is an ongoing scientific debate about the clinical significance of Gd retention in tissues after administration of GBCAs. It is known that bone serves as Gd reservoir, but only sparse information on localization of Gd in bone is available. The aim of this study was to compare Gd tissue concentration and spatial distribution in femoral epiphysis and diaphysis 10 weeks after single-dose injection of linear and macrocyclic GBCAs in a large animal model. In this prospective animal study, Swiss-Alpine sheep (n = 36; age range, 4-10 years) received a single injection (0.1 mmol/kg) of macrocyclic (gadobutrol, gadoteridol, and gadoterate meglumine), linear (gadodiamide and gadobenate dimeglumine) GBCAs, or saline. Ten weeks after injection, sheep were killed, and femur heads and shafts were harvested. Gadolinium spatial distribution was determined in 1 sample of each treatment group by laser ablation-inductively coupled plasma-mass spectrometry. All bone specimens were analyzed histopathologically. Injection of GBCAs in female Swiss-Alpine sheep (n = 36) resulted in Gd localization at the endosteal and periosteal surface and in a subset of GBCAs additionally at the cement lines and the bone cartilage junction. No histopathological alterations were observed in the investigated tissue specimens. Ten weeks after single injection of a clinically relevant dose in adult sheep, both linear species of GBCA resulted in considerably higher accumulation than macrocyclic GBCAs. Gadolinium deposits were restricted to distinct bone and cartilage compartments, such as in bone linings, cement lines, and bone cartilage junctions. Tissue histology remained unaffected.