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.

Late/delayed gadolinium enhancement in MRI after intravenous administration of extracellular gadolinium-based contrast agents: is it worth waiting?

The acquisition of images minutes or even hours after intravenous extracellular gadolinium-based contrast agents (GBCA) administration ("Late/Delayed Gadolinium Enhancement" imaging; in this review, further termed LGE) has gained significant prominence in recent years in magnetic resonance imaging. The major limitation of LGE is the long examination time; thus, it becomes necessary to understand when it is worth waiting time after the intravenous injection of GBCA and which additional information comes from LGE. LGE can potentially be applied to various anatomical sites, such as heart, arterial vessels, lung, brain, abdomen, breast, and the musculoskeletal system, with different pathophysiological mechanisms. One of the most popular clinical applications of LGE regards the assessment of myocardial tissue thanks to its ability to highlight areas of acute myocardial damage and fibrotic tissues. Other frequently applied clinical contexts involve the study of the urinary tract with magnetic resonance urography and identifying pathological abdominal processes characterized by high fibrous stroma, such as biliary tract tumors, autoimmune pancreatitis, or intestinal fibrosis in Crohn's disease. One of the current areas of heightened research interest revolves around the possibility of non-invasively studying the dynamics of neurofluids in the brain (the glymphatic system), the disruption of which could underlie many neurological disorders.

The role of gadolinium-based contrast agents in magnetic resonance imaging structured reporting and data systems (RADS).

Among the 28 reporting and data systems (RADS) available in the literature, we identified 15 RADS that can be used in Magnetic Resonance Imaging (MRI). Performing examinations without using gadolinium-based contrast agents (GBCA) has benefits, but GBCA administration is often required to achieve an early and accurate diagnosis. The aim of the present review is to summarize the current role of GBCA in MRI RADS. This overview suggests that GBCA are today required in most of the current RADS and are expected to be used in most MRIs performed in patients with cancer. Dynamic contrast enhancement is required for correct scores calculation in PI-RADS and VI-RADS, although scientific evidence may lead in the future to avoid the GBCA administration in these two RADS. In Bone-RADS, contrast enhancement can be required to classify an aggressive lesion. In RADS scoring on whole body-MRI datasets (MET-RADS-P, MY-RADS and ONCO-RADS), in NS-RADS and in Node-RADS, GBCA administration is optional thanks to the intrinsic high contrast resolution of MRI. Future studies are needed to evaluate the impact of the high T1 relaxivity GBCA on the assignment of RADS scores.

Deep Learning Image Reconstruction for CT: Technical Principles and Clinical Prospects.

Filtered back projection (FBP) has been the standard CT image reconstruction method for 4 decades. A simple, fast, and reliable technique, FBP has delivered high-quality images in several clinical applications. However, with faster and more advanced CT scanners, FBP has become increasingly obsolete. Higher image noise and more artifacts are especially noticeable in lower-dose CT imaging using FBP. This performance gap was partly addressed by model-based iterative reconstruction (MBIR). Yet, its "plastic" image appearance and long reconstruction times have limited widespread application. Hybrid iterative reconstruction partially addressed these limitations by blending FBP with MBIR and is currently the state-of-the-art reconstruction technique. In the past 5 years, deep learning reconstruction (DLR) techniques have become increasingly popular. DLR uses artificial intelligence to reconstruct high-quality images from lower-dose CT faster than MBIR. However, the performance of DLR algorithms relies on the quality of data used for model training. Higher-quality training data will become available with photon-counting CT scanners. At the same time, spectral data would greatly benefit from the computational abilities of DLR. This review presents an overview of the principles, technical approaches, and clinical applications of DLR, including metal artifact reduction algorithms. In addition, emerging applications and prospects are discussed.

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.

A systematic review of the incidence of hypersensitivity reactions and post-contrast acute kidney injury after ioversol in more than 57,000 patients: part 1-intravenous administration.

OBJECTIVES: To evaluate the incidence of adverse drug reactions (ADRs), including hypersensitivity reactions (HSRs) and post-contrast acute kidney injury (PC-AKI), after intravenous (IV) administration of ioversol. MATERIALS AND METHODS: A systematic literature search (1980-2021) of studies documenting IV use of ioversol and presence or absence of ADRs, HSRs, or PC-AKI was performed. Key information including patients' characteristics, indication and dose of ioversol, safety outcome incidence, intensity and seriousness were extracted. RESULTS: Thirty-one studies (> 57,000 patients) were selected, including 4 pediatric studies. The incidence of ADRs in adults was reported in 12 studies from ioversol clinical development with a median (range) of 1.65% (0-33.3%), and 3 other studies with an incidence between 0.13 and 0.28%. The incidence of HSRs (reported in 2 studies) ranged from 0.20 to 0.66%, and acute events (4 studies) from 0.23 to 1.80%. Severe reactions were rare with a median (range) of 0 (0-4%), and none were reported among pediatric patients. The incidence of ADRs and HSRs with ioversol, especially those of severe intensity, was among the lowest in studies comparing different iodinated contrast media (ICM) of the same class. PC-AKI incidence was variable (1-42% in 5 studies); however, ioversol exposure per se did not increase the incidence. CONCLUSIONS: When administered by the IV route, ioversol has a good safety profile comparable to that of other ICM within the same class, with a low incidence of severe/serious ADRs overall, and particularly HSRs. PC-AKI incidence does not seem to be increased compared to patients who did not receive ioversol. Further well-designed studies are warranted to confirm these results. KEY POINTS: • Ioversol has a good safety profile in adult and pediatric patients when IV administered. • ADR and HSR incidence with ioversol, especially those of severe intensity, was among the lowest compared to other ICM. • IV administration of ioversol per se did not increase PC-AKI incidence.

A systematic review of the incidence of hypersensitivity reactions and post-contrast acute kidney injury after ioversol: part 2-intra-arterial administration.

OBJECTIVES: To evaluate the incidence of adverse drug reactions (ADRs), including hypersensitivity reactions (HSRs) and post-contrast acute kidney injury (PC-AKI), after intra-arterial (IA) administration of ioversol. METHODS AND MATERIALS: A systematic literature search was performed (1980-2021) and studies documenting IA use of ioversol, and reporting safety outcomes were selected. Key information on study design, patients' characteristics, indication, dose, and type of safety outcome were extracted. RESULTS: Twenty-eight studies (including two pediatric studies) with 8373 patients exposed to IA ioversol were selected. Studies were highly heterogenous in terms of design, PC-AKI definition, and studied population. PC-AKI incidence after coronary angiography was 7.5-21.9% in a general population, 4.0-26.4% in diabetic patients, and 5.5-28.9% in patients with chronic kidney disease (CKD). PC-AKI requiring dialysis was rare and reported mainly in patients with severe CKD. No significant differences in PC-AKI rates were shown in studies comparing different iodinated contrast media (ICM). Based on seven studies of ioversol clinical development, the overall ADR incidence was 1.6%, comparable to that reported with other non-ionic ICM. Pediatric data were scarce with only one study reporting on PC-AKI incidence (12%), and one reporting on ADR incidence (0.09%), both after coronary angiography. CONCLUSIONS: After ioversol IA administration, PC-AKI incidence was highly variable between studies, likely reflecting the heterogeneity of the included study populations, and appeared comparable to that reported with other ICM. The rate of other ADRs appears to be low. Well-designed studies are needed for a better comparison with other ICM. KEY POINTS: • PC-AKI incidence after IA administration of ioversol appears to be comparable to that of other ICM, despite the high variability between studies. • The need for dialysis after IA administration of ioversol is rare. • No obvious difference was found regarding the safety profile of ioversol between IA and IV administration.

The effect of deep learning reconstruction on abdominal CT densitometry and image quality: a systematic review and meta-analysis.

OBJECTIVE: To determine the difference in CT values and image quality of abdominal CT images reconstructed by filtered back-projection (FBP), hybrid iterative reconstruction (IR), and deep learning reconstruction (DLR). METHODS: PubMed and Embase were systematically searched for articles regarding CT densitometry in the abdomen and the image reconstruction techniques FBP, hybrid IR, and DLR. Mean differences in CT values between reconstruction techniques were analyzed. A comparison between signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of FBP, hybrid IR, and DLR was made. A comparison of diagnostic confidence between hybrid IR and DLR was made. RESULTS: Sixteen articles were included, six being suitable for meta-analysis. In the liver, the mean difference between hybrid IR and DLR was - 0.633 HU (p = 0.483, SD ± 0.902 HU). In the spleen, the mean difference between hybrid IR and DLR was - 0.099 HU (p = 0.925, SD ± 1.061 HU). In the pancreas, the mean difference between hybrid IR and DLR was - 1.372 HU (p = 0.353, SD ± 1.476 HU). In 14 articles, CNR was described. In all cases, DLR showed a significantly higher CNR. In 9 articles, SNR was described. In all cases but one, DLR showed a significantly higher SNR. In all cases, DLR showed a significantly higher diagnostic confidence. CONCLUSIONS: There were no significant differences in CT values reconstructed by FBP, hybrid IR, and DLR in abdominal organs. This shows that these reconstruction techniques are consistent in reconstructing CT values. DLR images showed a significantly higher SNR and CNR, compared to FBP and hybrid IR. KEY POINTS: CT values of abdominal CT images are similar between deep learning reconstruction (DLR), filtered back-projection (FBP), and hybrid iterative reconstruction (IR). DLR results in improved image quality in terms of SNR and CNR compared to FBP and hybrid IR images. DLR can thus be safely implemented in the clinical setting resulting in improved image quality without affecting CT values.

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.

Optimal sequences and sequence parameters for GBCA-enhanced MRI of the glymphatic system: a systematic literature review.

BACKGROUND: The glymphatic system (GS) is a recently discovered waste clearance system in the brain. PURPOSE: To evaluate the most promising magnetic resonance imaging (MRI) sequence(s) and the most optimal sequence parameters for glymphatic MRI (gMRI) 4-24 h after administration of gadolinium-based contrast agent (GBCA). MATERIAL AND METHODS: Multiple literature databases were systematically searched for articles regarding gMRI or MRI of the perilymph in the inner ear until 11 May 2020. All relevant MRI sequence parameters were tabulated for qualitative analysis. Their potential was assessed based on detection of low dose GBCA, primarily measured as signal intensity (SI) ratio. RESULTS: Thirty articles were included in the analysis. Three-dimensional fluid attenuated inversion recovery (3D-FLAIR), 3D Real Inversion Recovery (3D-Real IR), and multiple 3D T1-weighted gradient echo sequences were used. In perilymph, 3D-FLAIR with a TE of at least 400 ms yielded the highest SIRs. In the qualitative analysis of inner ear studies using 3D-FLAIR, TR was in the range of 4400-10,000 ms, TI 1500-2600 ms, refocusing flip angle (rFA) (range 120°-180°), and echo train length (ETL) 23-173. In the gMRI studies, quantitative analysis was not possible. In the qualitative analysis, 3D-FLAIR was used in the majority (8/12) of the studies, usually with TR 4800-9000 ms, TI 1650-2500 ms, TE 311-561 ms, rFA 90°-120°, and ETL 167-278. CONCLUSION: Long TE 3D-FLAIR is the most promising sequence for detection of low-dose GBCA in the GS. Clinical and/or phantom studies on other MRI parameters are needed for further optimization of gMRI.

Real-Time Person Identification in a Hospital Setting: A Systematic Review.

In the critical setting of a trauma team activation, team composition is crucial information that should be accessible at a glance. This calls for a technological solution, which are widely available, that allows access to the whereabouts of personnel. This diversity presents decision makers and users with many choices and considerations. The aim of this review is to give a comprehensive overview of available real-time person identification techniques and their respective characteristics. A systematic literature review was performed to create an overview of identification techniques that have been tested in medical settings or already have been implemented in clinical practice. These techniques have been investigated on a total of seven characteristics: costs, usability, accuracy, response time, hygiene, privacy, and user safety. The search was performed on 11 May 2020 in PubMed and the Web of Science Core Collection. PubMed and Web of Science yielded a total n = 265 and n = 228 records, respectively. The review process resulted in n = 23 included records. A total of seven techniques were identified: (a) active and (b) passive Radio-Frequency Identification (RFID) based systems, (c) fingerprint, (d) iris, and (e) facial identification systems and infrared (IR) (f) and ultrasound (US) (g) based systems. Active RFID was largely documented in the included literature. Only a few could be found about the passive systems. Biometric (c, d, and e) technologies were described in a variety of applications. IR and US techniques appeared to be a niche, as they were only spoken of in few (n = 3) studies.

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.