Ten years of gadolinium retention and deposition: ESMRMB-GREC looks backward and forward.

In 2014, for the first time, visible hyperintensities on unenhanced T1-weighted images in the nucleus dentatus and globus pallidus of the brain were associated with previous Gadolinium-based contrast agent (GBCA) injections and gadolinium deposition in patients with normal renal function. This led to a frenzy of retrospective studies with varying methodologies that the European Society of Magnetic Resonance in Medicine and Biology Gadolinium Research and Educational Committee (ESMRMB-GREC) summarised in 2019. Now, after 10 years, the members of the ESMRMB-GREC look backward and forward and review the current state of knowledge of gadolinium retention and deposition. CLINICAL RELEVANCE STATEMENT: Gadolinium deposition is associated with the use of linear GBCA but no clinical symptoms have been associated with gadolinium deposition. KEY POINTS : • Traces of Gadolinium-based contrast agent-derived gadolinium can be retained in multiple organs for a prolonged time. • Gadolinium deposition is associated with the use of linear Gadolinium-based contrast agents. • No clinical symptoms have been associated with gadolinium deposition.

Use of gadolinium-based contrast agents in multiple sclerosis: a review by the ESMRMB-GREC and ESNR Multiple Sclerosis Working Group.

Magnetic resonance imaging (MRI) is the most sensitive technique for detecting inflammatory demyelinating lesions in multiple sclerosis (MS) and plays a crucial role in diagnosis and monitoring treatment effectiveness, and for predicting the disease course. In clinical practice, detection of MS lesions is mainly based on T2-weighted and contrast-enhanced T1-weighted sequences. Contrast-enhancing lesions (CEL) on T1-weighted sequences are related to (sub)acute inflammation, while new or enlarging T2 lesions reflect the permanent footprint from a previous acute inflammatory demyelinating event. These two types of MRI features provide redundant information, at least in regular monitoring of the disease. Due to the concern of gadolinium deposition after repetitive injections of gadolinium-based contrast agents (GBCAs), scientific organizations and regulatory agencies in Europe and North America have proposed that these contrast agents should be administered only if clinically necessary. In this article, we provide data on the mode of action of GBCAs in MS, the indications of the use of these agents in clinical practice, their value in MS for diagnostic, prognostic, and monitoring purposes, and their use in specific populations (children, pregnant women, and breast-feeders). We discuss imaging strategies that achieve the highest sensitivity for detecting CELs in compliance with the safety regulations established by different regulatory agencies. Finally, we will briefly discuss some alternatives to the use of GBCA for detecting blood-brain barrier disruption in MS lesions. CLINICAL RELEVANCE STATEMENT: Although use of GBCA at diagnostic workup of suspected MS is highly valuable for diagnostic and prognostic purposes, their use in routine monitoring is not mandatory and must be reduced, as detection of disease activity can be based on the identification of new or enlarging lesions on T2-weighted images. KEY POINTS: • Both the EMA and the FDA state that the use of GBCA in medicine should be restricted to clinical scenarios in which the additional information offered by the contrast agent is required. • The use of GBCA is generally recommended in the diagnostic workup in subjects with suspected MS and is generally not necessary for routine monitoring in clinical practice. • Alternative MRI-based approaches for detecting acute focal inflammatory MS lesions are not yet ready to be used in clinical practice.

Waiting times between examinations with intravascularly administered contrast media: a review of contrast media pharmacokinetics and updated ESUR Contrast Media Safety Committee guidelines.

The pharmacokinetics of contrast media (CM) will determine how long safe waiting intervals between successive CT or MRI examinations should be. The Contrast Media Safety Committee has reviewed the data on pharmacokinetics of contrast media to suggest safe waiting intervals between successive contrast-enhanced imaging studies in relation to the renal function of the patient. CLINICAL RELEVANCE STATEMENT: Consider a waiting time between elective contrast-enhanced CT and (coronary) angiography with successive iodine-based contrast media administrations in patients with normal renal function (eGFR > 60 mL/min/1.73 m2) of optimally 12 h (near complete clearance of the previously administered iodine-based contrast media) and minimally 4 h (if clinical indication requires rapid follow-up). KEY POINTS: • Pharmacokinetics of contrast media will guide safe waiting times between successive administrations. • Safe waiting times increase with increasing renal insufficiency. • Iodine-based contrast media influence MRI signal intensities and gadolinium-based contrast agents influence CT attenuation.

Contrast media for hysterosalpingography: systematic search and review providing new guidelines by the Contrast Media Safety Committee of the European Society of Urogenital Radiology.

OBJECTIVES: Hysterosalpingography (HSG) is widely used for evaluating the fallopian tubes; however, controversies regarding the use of water- or oil-based iodine-based contrast media (CM) remain. The aim of this work was (1) to discuss reported pregnancy rates related to the CM type used, (2) to validate the used CM in published literature, (3) to discuss possible complications and side effects of CM in HSG, and (4) to develop guidelines on the use of oil-based CM in HSG. METHODS: A systematic literature search was conducted for original RCT studies or review/meta-analyses on using water-based and oil-based CM in HSG with fertility outcomes and complications. Nine randomized controlled trials (RCTs) and 10 reviews/meta-analyses were analyzed. Grading of the literature was performed based on the Oxford Centre for Evidence-Based Medicine (OCEBM) 2011 classification. RESULTS: An approximately 10% higher pregnancy rate is reported for oil-based CM. Side effects are rare, but oil-based CM have potentially more side effects on the maternal thyroid function and the peritoneum. CONCLUSIONS: 1. HSG with oil-based CM gives approximately 10% higher pregnancy rates. 2. External validity is limited, as in five of nine RCTs, the CM used is no longer on the market. 3. Oil-based CM have potentially more side effects on the maternal thyroid function and on the peritoneum. 4. Guideline: Maternal thyroid function should be tested before HSG with oil-based CM and monitored for 6 months after. CLINICAL RELEVANCE STATEMENT: Oil-based CM is associated with an approximately 10% higher chance of pregnancy compared to water-based CM after HSG. Although side effects are rare, higher iodine concentration and slower clearance of oil-based CM may induce maternal thyroid function disturbance and peritoneal inflammation and granuloma formation. KEY POINTS: • It is unknown which type of contrast medium, oil-based or water-based, is the optimal for HSG. • Oil-based contrast media give a 10% higher chance of pregnancy after HSG, compared to water-based contrast media. • From the safety perspective, oil-based CM can cause thyroid dysfunction and an intra-abdominal inflammatory response in the patient.

Analytical interference of intravascular contrast agents with clinical laboratory tests: a joint guideline by the ESUR Contrast Media Safety Committee and the Preanalytical Phase Working Group of the EFLM Science Committee.

The Contrast Media Safety Committee of the European Society of Urogenital Radiology has, together with the Preanalytical Phase Working Group of the EFLM Science Committee, reviewed the literature and updated its recommendations to increase awareness and provide insight into these interferences.

Visceral adiposity in patients with lipomatous hypertrophy of the interatrial septum.

Lipomatous hypertrophy of the interatrial septum (LHIS) is a benign cardiac mass determined by abnormal deposition of adipose tissue in the interatrial septum. The quantitative relationship between LHIS and visceral adiposity has not been explored to date.In this retrospective study, three groups of consecutive patients undergoing CT imaging were enrolled: L + with LHIS, L- without LHIS, and LO- without both LHIS and history of malignancies. Areas of total adipose tissue (TAT), visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) and LHIS areas were calculated on CT images. The relationship between LHIS and abdominal fat distribution was investigated with linear regression models. Bonferroni correction was applied to account for multiple testing. Statistical significance was set at 5%. In this study we enrolled a total of 175 subjects: 58 (33.14%) with LHIS (L +), 51(29.14%) without LHIS (L-) and 66 (37.71%) without both LHIS and medical history of malignancies (LO-). VAT (coeff: 105.82; 95% CI 59.37-152.27), SAT (coeff: 74.59; 95% CI 31.63-117.54), and TAT (coeff: 190.37; 95% CI 115.02-265.72), were significantly higher in L + patients. Moreover, VAT (coeff: 24.95; 95% CI 6.94-42.96) and TAT (coeff: 36.58; 95% CI 8.75-64.41) were statistically significant linear predictors for LHIS area. Here, we report a novel association between LHIS and visceral adiposity using a quantitative CT-based imaging approach. The results are of great importance also because they might drive early identification of subjects with LHIS at risk for visceral obesity, and trigger lifestyle interventions aimed at weight loss.

Safe use of contrast media in myasthenia gravis: systematic review and updated European Society of Urogenital Radiology Contrast Media Safety Committee guidelines.

OBJECTIVES: It is uncertain whether modern iodine-based or gadolinium-based contrast media (CM) administration can lead to increased symptoms in patients with myasthenia gravis. METHODS: A systematic search in Medline was conducted for studies describing the symptomatology of myasthenia gravis patients before and after receiving intravenous (IV) CM and having a matched control group of myasthenia gravis patients who did not receive IV CM. RESULTS: Three retrospective studies were selected with a total of 374 myasthenia gravis patients who received iodine-based CM and a total of 313 myasthenia gravis patients who underwent unenhanced CT and served as controls. Pooling of the data from the three retrospective studies showed that in 23 of 374 patients, increased symptoms after iodine-based CM administration were described (6.1%). Increased symptomatology also occurred in 11 of 313 patients after unenhanced CT (3.5%). When looking more deeply into the data of the three studies, conflicting results were found, as two articles did not find any relationship between CM and myasthenia gravis symptoms. The remaining study only found a significant increase in symptomatology within 1 day after CT scanning: seven patients (6.3%) in the contrast-enhanced CT group and one patient (0.6%) in the unenhanced CT group (p = 0.01). CONCLUSIONS: There is limited evidence on the relationship between CM and myasthenia gravis symptoms. In the vast majority of myasthenia gravis patients, CM are safe. Probably, in less than 5% of the patients, iodine-based CM administration may lead to increased severity of the symptoms within the first 24 h after administration. CLINICAL RELEVANCE STATEMENT: Be aware that intravenous administration of iodine-based contrast media can lead to an increase of symptoms in patients with myasthenia gravis within the first 24 h. This can probably happen in less than 5% of the patients. KEY POINTS: • It is unclear whether modern contrast media can lead to increased symptoms in myasthenia gravis patients after intravenous administration. • There seems to be a small risk of increased myasthenia gravis symptoms within 24 h after intravenous administration of iodine-based contrast media, probably in less than 5% of the administrations. • Gadolinium-based contrast media are safe for patients with myasthenia gravis.

Analytical interference of intravascular contrast agents with clinical laboratory tests: a joint guideline by the ESUR Contrast Media Safety Committee and the Preanalytical Phase Working Group of the EFLM Science Committee.

The Contrast Media Safety Committee of the European Society of Urogenital Radiology has, together with the Preanalytical Phase Working Group of the EFLM Science Committee, reviewed the literature and updated its recommendations to increase awareness and provide insight into these interferences. CLINICAL RELEVANCE STATEMENT: Contrast Media may interfere with clinical laboratory tests. Awareness of potential interference may prevent unwanted misdiagnosis. KEY POINTS: • Contrast Media may interfere with clinical laboratory tests; therefore awareness of potential interference may prevent unwanted misdiagnosis. • Clinical Laboratory tests should be performed prior to radiological imaging with contrast media or alternatively, blood or urine collection should be delayed, depending on kidney function.

Brain functional connectivity differences between responders and non-responders to sleeve gastrectomy.

PURPOSE: To compare resting-state functional connectivity (RSFC) of obese patients responders or non-responders to sleeve gastrectomy (SG) with a group of obese patients with no past medical history of metabolic or bariatric surgery. METHODS: MR images were acquired at 1.5 Tesla. Resting-state fMRI data were analyzed with statistical significance threshold set at p < 0.05, family-wise error (FWE) corrected. RESULTS: Sixty-two subjects were enrolled: 20 controls (age range 25-64; 14 females), 24 responders (excess weight loss > 50%; age range 23-68; 17 females), and 18 non-responders to sleeve gastrectomy (SG) (excess weight loss < 50%; age range 23-67; 13 females). About within-network RSFC, responders showed significantly lower RSFC with respect to both controls and non-responders in the default mode and frontoparietal networks, positively correlating with psychological scores. Non-responders showed significantly higher (p < 0.05, family-wise error (few) corrected) RSFC in regions of the lateral visual network as compared to controls. Regarding between-network RSFC, responders showed significantly higher anti-correlation between executive control and salience networks (p < 0.05, FWE corrected) with respect to both controls and non-responders. Significant positive correlation (Spearman rho = 0.48, p = 0.0012) was found between % of excess weight loss and executive control-salience network RSFC. CONCLUSION: There are differences in brain functional connectivity in either responders or non-responders patients to SG. The present results offer new insights into the neural correlates of outcome in patients who undergo SG and expand knowledge about neural mechanisms which may be related to surgical response.

Computed tomography density changes of bone metastases after concomitant denosumab.

OBJECTIVE: To evaluate bone density changes at the level of normal trabecular bone and bone metastases (BMs) after denosumab (DM) treatment in oncologic patients. MATERIALS AND METHODS: We retrospectively evaluated 31 consecutive adult patients with histologically confirmed solid tumors with at least one newly diagnosed bone metastatic lesion detected at CT. Patients received treatment with DM, 120 mg subcutaneous every 28 days for at least 6 months. Bone density was determined at the level of BMs and at the level of normal trabecular bone of lumbar vertebrae using a region of interest (ROI)-based approach. RESULTS: A progressive increase in CT bone density was demonstrated at the level of normal trabecular bone at 6 months (18% ± 5%) and 12 months (23% ± 7%) after the treatment begins. BMs showed a significant increase in CT bone density (p < 0.05) as compared to baseline after 6 months (57% ± 15%) and 12 months (1.06 ± 0.25 times higher) after treatment. CONCLUSION: We have found that long-term treatment with DM increases bone density progressively in oncologic patients. This effect can be observed not only at the level of secondary lesions but also at the level of apparently normal trabecular bone and is more pronounced for osteolytic metastases.

Facilitating standardized COVID-19 suspicion prediction based on computed tomography radiomics in a multi-demographic setting.

OBJECTIVE: To develop an automatic COVID-19 Reporting and Data System (CO-RADS)-based classification in a multi-demographic setting. METHODS: This multi-institutional review boards-approved retrospective study included 2720 chest CT scans (mean age, 58 years [range 18-100 years]) from Italian and Russian patients. Three board-certified radiologists from three countries assessed randomly selected subcohorts from each population and provided CO-RADS-based annotations. CT radiomic features were extracted from the selected subcohorts after preprocessing steps like lung lobe segmentation and automatic noise reduction. We compared three machine learning models, logistic regression (LR), multilayer perceptron (MLP), and random forest (RF) for the automated CO-RADS classification. Model evaluation was carried out in two scenarios, first, training on a mixed multi-demographic subcohort and testing on an independent hold-out dataset. In the second scenario, training was done on a single demography and externally validated on the other demography. RESULTS: The overall inter-observer agreement for the CO-RADS scoring between the radiologists was substantial (k = 0.80). Irrespective of the type of validation test scenario, suspected COVID-19 CT scans were identified with an accuracy of 84%. SHapley Additive exPlanations (SHAP) interpretation showed that the "wavelet_(LH)_GLCM_Imc1" feature had a positive impact on COVID prediction both with and without noise reduction. The application of noise reduction improved the overall performance between the classifiers for all types. CONCLUSION: Using an automated model based on the COVID-19 Reporting and Data System (CO-RADS), we achieved clinically acceptable performance in a multi-demographic setting. This approach can serve as a standardized tool for automated COVID-19 assessment. KEYPOINTS: • Automatic CO-RADS scoring of large-scale multi-demographic chest CTs with mean AUC of 0.93 ± 0.04. • Validation procedure resembles TRIPOD 2b and 3 categories, enhancing the quality of experimental design to test the cross-dataset domain shift between institutions aiding clinical integration. • Identification of COVID-19 pneumonia in the presence of community-acquired pneumonia and other comorbidities with an AUC of 0.92.

Intravenous contrast medium extravasation: systematic review and updated ESUR Contrast Media Safety Committee Guidelines.

NEED FOR A REVIEW: Guidelines for management and prevention of contrast media extravasation have not been updated recently. In view of emerging research and changing working practices, this review aims to inform update on the current guidelines. AREAS COVERED: In this paper, we review the literature pertaining to the pathophysiology, diagnosis, risk factors and treatments of contrast media extravasation. A suggested protocol and guidelines are recommended based upon the available literature. KEY POINTS: • Risk of extravasation is dependent on scanning technique and patient risk factors. • Diagnosis is mostly clinical, and outcomes are mostly favourable. • Referral to surgery should be based on clinical severity rather than extravasated volume.

Bilateral MCP Infarct Due to Vertebral Giant Cell Arteritis.

We present the case of an 83-year-old woman with an isolated bilateral middle cerebellar peduncles stroke caused by complete occlusion of the right vertebral artery and focal occlusion of the left vertebral artery due to giant cell arteritis. The diagnosis was achieved by integrating MRI, ultrasound study, laboratory data and subsequent pathology analysis after biopsy of the temporal artery.

Effect of Exposure to Gadodiamide and Brain Irradiation on T1 -Weighted Images and ADC Maps of the Dentate Nucleus.

BACKGROUND: Brain irradiation is considered a cofactor influencing the dentate nucleus (DN) signal intensity (SI) on unenhanced T1 -weighted images in patients exposed to gadolinium-based contrast agents (GBCAs). PURPOSE: To assess the effect of gadodiamide and whole-brain radiation therapy (WBRT) on T1 -weighted images and on apparent diffusion coefficient (ADC) maps of DN. STUDY TYPE: Single-center retrospective. POPULATION: In all, 125 patients who underwent brain MRIs were classified into four groups: 1) patients who did neither receive intravenous GBCAs injections nor irradiation (controls); 2) patients having ≥3 GBCAs-enhanced scans and no WBRT; 3) patients having WBRT and < 3 GBCAs-enhanced scans; and 4) patients having WBRT and ≥ 3 GBCAs-enhanced scans. FIELD STRENGTH/SEQUENCE: 1.5T magnet, echo-planar diffusion weighted imaging (DWI) and unenhanced T1 -weighted sequences. ASSESSMENT: The DN-to-pons SI ratio on unenhanced T1 -weighted images and ADC values of the DN were calculated. Values were compared between groups and relative to the cumulative gadolinium dose and to the time delay after WBRT. STATISTICAL TESTS: Statistical analysis included the Mann-Whitney U-test and Spearman's rank-order correlation. RESULTS: DN ADC values were not significantly different (P = 0.34) between patients exposed to gadodiamide (0.81 ± 0.06) and controls (0.83 ± 0.07). There were no differences in DN ADC values (P = 0.28) and DN-to-pons SI ratios (P = 0.42) between patients exposed to WBRT (ADC values: 0.85 ± 0.09; SI ratio: 1.11 ± 0.10) and controls (ADC values: 0.83 ± 0.06; SI ratio: 1.09 ± 0.06). There was a significant negative correlation between DN ADC values and the time (days) since the end of WBRT (r = - 0.33; 95% confidence interval [CI]: -0.55, -0.06; P < 0.05). DATA CONCLUSION: We did not find changes suggestive of gadolinium-related tissue microstructural damage of the DN. The ADC values of the DN are associated with the time from WBRT. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 5.

Exposure to gadolinium and neurotoxicity: current status of preclinical and clinical studies.

PURPOSE: Gadolinium is a rare-earth lanthanide metal that is known to have a direct neurotoxic effect. The scope of the present review is to summarize the current preclinical and clinical evidence on the association between exposure to gadolinium of the central nervous system and neurotoxicity. METHODS: A literature review was performed by searching for original research papers investigating on gadolinium exposure and neurotoxicity. RESULTS: Gadolinium is neurotoxic through multiple mechanisms, mainly involving Ca++ homeostasis and mitochondrial functions, as shown by preclinical in vitro studies. The available evidence related to the four different classes of gadolinium-based contrast agents commonly applied in clinical practice (i.e., linear and macrocyclic based on ligand structure, and ionic and non-ionic based on their net molecular charge) suggests that serial intravenous injections of gadolinium-based contrast agents and gadolinium brain depositions are not associated to histological changes, as confirmed by preclinical animal and human (MR imaging and autopsy) studies. CONCLUSION: To date, no cause-effect relationship has been demonstrated in patients between brain gadolinium exposure and clinical consequences specific to neurological toxicity.

Within-network brain connectivity in Crohn's disease patients with gadolinium deposition in the cerebellum.

PURPOSE: Patients with Crohn's disease (CD) undergo multiple gadolinium-based contrast agent injections across their lifespan to enhance signal intensity of the intestinal wall and differentiate active from quiescent inflammatory disease. Thus, CD patients are prone to gadolinium accumulation in the brain and represent a non-neurological population to explore gadolinium-related brain toxicity. Possible effects are expected to be greater on the cerebellar network due to the high propensity of the dentate nucleus to accumulate gadolinium. Herein, we provide a whole-brain network analysis of resting-state fMRI dynamics in long-term quiescent CD patients with normal renal function and MRI evidence of gadolinium deposition in the brain. METHODS: Fifteen patients with CD and 16 healthy age- and gender-matched controls were enrolled in this study. Relevant resting-state networks (RSNs) were identified using independent component analysis (ICA) from functional magnetic resonance imaging data. An unpaired two-sample t test (with age and sex as nuisance variables) was used to investigate between different RSNs. Clusters were determined by using threshold-free cluster enhancement and a family-wise error corrected cluster significance threshold of p < 0.05. RESULTS: Patients showed significantly decreased resting-state functional connectivity (p < 0.05, FWE corrected) of several regions of the right frontoparietal (FPR) and the dorsal attention (DAN) RSNs. No differences between the two groups were found in the functional connectivity maps of all the other RSNs, including the cerebellar network. CONCLUSION: Our findings suggest a non-significant impact of gadolinium deposition on within-network cerebellar functional connectivity of long-term quiescent CD patients.

Absence of dentate nucleus resting-state functional connectivity changes in nonneurological patients with gadolinium-related hyperintensity on T1 -weighted images.

BACKGROUND: The dentate nuclei of the cerebellum are the areas where gadolinium predominantly accumulates. It is not yet known whether gadolinium deposition affects brain functions. PURPOSE/HYPOTHESIS: To assess whether gadolinium-dependent high signal intensity of the cerebellum on T1 -weighted images of nonneurological adult patients with Crohn's disease is associated with modifications of resting-state functional connectivity (RSFC) of the cerebellum and dentate nucleus. STUDY TYPE: Observational, cross-sectional. POPULATION: Fifteen patients affected by Crohn's disease were compared with 16 healthy age- and gender-matched control subjects. All participants underwent neurological, neurocognitive-psychological assessment, and blood sampling. FIELD STRENGTH/SEQUENCE: 1.5-T magnet blood oxygenation level-dependent (BOLD) functional MRI. ASSESSMENT: High signal intensity on T1 -weighted images, cerebellum functional connectivity, neurocognitive performance, and blood circulating gadolinium levels. STATISTICAL TESTS: An unpaired two-sample t-test (age and sex were nuisance variables) was used to investigate between-group differences in cerebellar and dentate nucleus functional connectivity. Z-statistical images were set using clusters determined by Z > 2.3 and a familywise error (FWE)-corrected cluster significance threshold of P = 0.05. RESULTS: Dentate nuclei RSFC was not different (P = n.s.) between patients with gadolinium-dependent high signal intensity on T1 -weighted images and controls. Pre- and postcentral gyrus bilaterally and the right supplementary motor cortex showed a decrease of RSFC with the cerebellum hemispheres (P < 0.05 FWE-corrected) and was related to disease duration but not to gadodiamide cumulative doses (P = n.s.). DATA CONCLUSION: Crohn's disease patients with gadolinium-dependent hyperintense dentate nuclei on unenhanced T1 -weighted images do not show dentate nucleus RSFC changes. LEVEL OF EVIDENCE: 2 Technical Efficacy Stage: 5 J. Magn. Reson. Imaging 2019;50:445-455.

Standardized assessment of the signal intensity increase on unenhanced T1-weighted images in the brain: the European Gadolinium Retention Evaluation Consortium (GREC) Task Force position statement.

After the initial report in 2014 on T1-weighted (T1w) hyperintensity of deep brain nuclei following serial injections of linear gadolinium-based contrast agents (GBCAs), a multitude of studies on the potential of the marketed GBCAs to cause T1w hyperintensity in the brain have been published. The vast majority of these studies found a signal intensity (SI) increase for linear GBCAs in the brain-first and foremost in the dentate nucleus-while no SI increase was found for macrocyclic GBCAs. However, the scientific debate about this finding is kept alive by the fact that SI differences do not unequivocally represent the amount of gadolinium retained. Since the study design of the SI measurement in various brain structures is relatively simple, MRI studies investigating gadolinium-dependent T1w hyperintensity are currently conducted at multiple institutions worldwide. However, methodological mistakes may result in flawed conclusions. In this position statement, we assess the methodological basis of the published retrospective studies and define quality standards for future studies to give guidance to the scientific community and to help identify studies with potentially flawed methodology and misleading results. KEY POINTS: • A multitude of studies has been published on the potential of the marketed GBCAs to cause T1w hyperintensity in the brain. • The gadolinium-dependent T1w hyperintensity in the brain depends on patient's history, types of GBCAs used (i.e., linear vs. macrocyclic GBCAs) and MR imaging setup and protocols. • Quality standards for the design of future studies are needed to standardize methodology and avoid potentially misleading results from retrospective studies.