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Background Safety concerns caused by gadolinium retention call for the development of high-relaxivity gadolinium-based contrast agents (GBCAs) allowing minimal dosing. Purpose To investigate brain gadolinium retention in healthy rats after exposure to gadopiclenol (Elucirem, Guerbet; macrocyclic GBCA) compared with gadobutrol (Gadovist or Gadavist, Bayer; macrocyclic GBCA) and gadodiamide (Omniscan, GE Healthcare; linear GBCA) over 1 year. Materials and Methods In this study conducted between May 2018 and April 2020, 9-week-old healthy Sprague Dawley rats received five injections of either gadopiclenol, gadobutrol, or gadodiamide (2.4 mmol of gadolinium per kilogram of body weight for each), or saline (control animals) over a period of 5 weeks. Rats were randomly assigned to different groups (six female and six male rats per group). MRI examinations were performed before euthanasia at 1, 3, 5, or 12 months after the last injection. Brains were sampled to determine the total gadolinium content via inductively coupled plasma mass spectrometry (ICP-MS), to characterize gadolinium species with size exclusion chromatography (SEC)-ICP-MS, and to perform elemental mapping with laser ablation (LA)-ICP-MS. Mann-Whitney tests were performed on pairwise comparisons of the same time points. Results For both macrocyclic agents, no T1 signal hyperintensities were observed in the cerebellum, and approximately 80% of gadolinium washout was found between 1 month (gadobutrol, 0.30 nmol/g; gadopiclenol, 0.37 nmol/g) and 12 months (gadobutrol, 0.062 nmol/g; gadopiclenol, 0.078 nmol/g). After 12 months, only low-molecular-weight gadolinium species were detected in the soluble fraction. Gadodiamide led to significantly higher gadolinium concentrations after 1 month in the cerebellum (gadodiamide, 2.65 nmol/g

Background To improve myocardial delayed enhancement (MDE) CT, a deep learning (DL)-based post hoc denoising method supervised with averaged MDE CT data was developed. Purpose To assess the image quality of denoised MDE CT images and evaluate their diagnostic performance by using late gadolinium enhancement (LGE) MRI as a reference. Materials and methods MDE CT data obtained by averaging three acquisitions with a single breath hold 5 minutes after the contrast material injection in patients from July 2020 to October 2021 were retrospectively reviewed. Preaveraged images obtained in 100 patients as inputs and averaged images as ground truths were used to supervise a residual dense network (RDN). The original single-shot image, standard averaged image, RDN-denoised original (DL

International audience; Background: Cardiac MRI features are not well-defined in immune checkpoint inhibitor (ICI)-induced myocarditis (ICI-M), a severe complication of ICI therapy in patients with cancer.Purpose: To analyze the cardiac MRI features of ICI-M and to explore their prognostic value in major adverse cardiovascular events (MACE).Materials and Methods: In this retrospective study from May 2017 to January 2020, cardiac MRI findings (including late gadolinium enhancement [LGE], T1 and T2 mapping, and extracellular volume fraction [ECV] z scores) of patients with ICI-M were compared with those of patients with cancer scheduled to receive ICI therapy (pre-ICI group) and patients with viral myocarditis. As a secondary objective, the potential value of cardiac MRI for predicting MACE in patients with ICI-M by using Cox proportional hazards models was explored.Results: Thirty-three patients with ICI-M (mean age +/- standard deviation, 68 years +/- 14; 23 men) were compared with 21 patients scheduled to receive to ICI therapy (mean age, 65 years +/- 14; 14 men) and 85 patients with viral myocarditis (mean age, 32 years +/- 13; 67 men). Compared with the pre-ICI group, patients with ICI-M showed higher global native T1, ECV, and T2 z scores (0.03 +/- 0.85 vs 1.79 +/- 1.93 [P < .001]; 1.34 +/- 0.57 vs 2.59 +/- 1.97 [P = .03]; and -0.76 +/- 1.41 vs 0.88 +/- 1.96 [P = .002], respectively), and LGE was more frequently observed (27 of 33 patients [82%] vs two of 21 [10%]; P < .001). LGE was less frequent in patients with ICI-M than those with viral myocarditis (27 of 33 patients [82%] vs 85 of 85 [100%]; P < .001) but was more likely to involve the septal segments (16 of 33 patients [48%] vs 25 of 85 [29%]; P < .001) and midwall layer (11 of 33 patients [33%] vs two of 85 [2%]; P < .001). Septal LGE was the only cardiac MRI predictor of MACE at 1 year even after adjustment for peak troponin (adjusted hazard ratio, 2.7 [95% CI: 1.1, 6.7]; P = .03).Conclusion: Cardiac MRI features of immune checkpoint inhibitor (ICI)-induced myocarditis (ICI-M) seem to differ from those in patients scheduled to receive ICIs and patients with viral myocarditis. Septal late gadolinium enhancement might be a predictor of major cardiovascular events in patients with ICI-M.

Background With the widespread use of gadolinium-based contrast agents (GBCAs), the incidence of allergic-like hypersensitivity reactions (HSRs) to GBCAs is increasing. Research on the incidence and risk factors for HSRs to GBCAs is needed for their safe use. Purpose To determine the incidence of acute and delayed reactions to GBCAs and to discuss the risk factors and strategies for the prevention of HSRs to GBCAs. Materials and Methods All cases of HSRs to contrast media that occurred at the Seoul National University Hospital from July 1, 2012, to June 30, 2020, were assessed. Information including age, sex, GBCA type, onset, and severity of HSRs was retrospectively analyzed. Results Among the 331070 cases of GBCA exposure in 154539 patients, 1304 cases of HSRs (0.4%) were reported. Acute HSRs accounted for 1178 cases (0.4%), while 126 cases (0.04%) were delayed HSRs. While both premedication (odds ratio [OR] = 0.7

BACKGROUND: Concerns over the neurotoxic potential of retained gadolinium in brain tissues after intravenous gadolinium-based contrast agent (GBCA) administration have led to pronounced worldwide use changes, yet the clinical sequelae of gadolinium retention remain undefined. PURPOSE: To assess clinical and neurologic effects and potential neurotoxicity of gadolinium retention in rats after administration of various GBCAs. MATERIALS AND METHODS: From March 2017 through July 2018, 183 male Wistar rats received 20 intravenous injections of 2.5 mmol per kilogram of body weight (80 human equivalent doses) of various GBCAs (gadodiamide, gadobenate, gadopentetate, gadoxetate, gadobutrol, gadoterate, and gadoteridol) or saline over 4 weeks. Rats were evaluated 6 and 34 weeks after injection with five behavioral tests, and inductively coupled plasma mass spectrometry, transmission electron microscopy, and histopathology were performed on urine, serum, cerebrospinal fluid (CSF), basal ganglia, dentate nucleus, and kidney samples. Dunnett post hoc test and Wilcoxon rank sum test were used to compare differences between treatment groups. RESULTS: No evidence of differences in any behavioral test was observed between GBCA-exposed rats and control animals at either 6 or 34 weeks (P = .08 to P = .99). Gadolinium concentrations in both neuroanatomic locations were higher in linear GBCA-exposed rats than macrocyclic GBCA-exposed rats at 6 and 34 weeks (P < .001). Gadolinium clearance over time varied among GBCAs, with gadobutrol having the largest clearance (median: 62% for basal ganglia, 70% for dentate) and gadodiamide having no substantial clearance. At 34 weeks, gadolinium was largely cleared from the CSF and serum of gadodiamide-, gadobenate-, gadoterate-, and gadobutrol-exposed rats, especially for the macrocyclic agents (range: 70%–98% removal for CSF, 34%–94% removal for serum), and was nearly completely removed from urine (range: 96%–99% removal). Transmission electron microscopy was used to detect gadolinium foci in linear GBCA-exposed brain tissue, but no histopathologic differences were observed for any GBCA. CONCLUSION: In this rat model, no clinical evidence of neurotoxicity was observed after exposure to linear and macrocyclic gadolinium-based contrast agents at supradiagnostic doses. © RSNA, 2022 Online supplemental material is available for this article.

In this article, members of the American College of Radiology Committee on Drugs and Contrast Media propose a new term for symptoms reported after intravascular exposure to gadolinium-based contrast agents-Symptoms Associated with Gadolinium Exposure, or SAGE. This term is advocated in lieu of other proposed nomenclature that presumes a causal relationship that has not yet been scientifically verified. The purpose of this new term, SAGE, is to assist researchers and clinical providers in describing such symptoms without prematurely causally attributing them to a disease and to standardize reporting of these symptoms to allow for coherent interpretation of related studies.

Repeated injection of gadolinium-based contrast agents did not cause any motor or behavioral changes, whether the agents were linear or macrocyclic.

A 66-year-old male patient with end-stage chronic kidney disease undergoing maintenance dialysis and with a history of group I intravenous gadolinium-based contrast media (GBCM) administration presented with clinical and pathologic findings consistent with nephrogenic systemic fibrosis. A summary of the evidence and recommendations for use of intravenous GBCM in patients with kidney disease is presented. © RSNA, 2021.

Background There are limited data on the pattern and severity of myocardial injury in patients with COVID-19 vaccination-associated myocarditis. Purpose To describe myocardial injury following COVID-19 vaccination and to compare these findings to other causes of myocarditis. Materials and Methods In this retrospective cohort study, consecutive adult patients with myocarditis with at least one T1-based and at least one T2-based abnormality at cardiac MRI performed at a tertiary referral hospital from December 2019 to November 2021 were included. Patients were classified into one of three groups: myocarditis following COVID-19 vaccination, myocarditis following COVID-19 illness, and other myocarditis not associated with COVID-19 vaccination or illness. Results Of the 92 included patients, 21 (23%) had myocarditis following COVID-19 vaccination (mean age, 31 years ± 14 [SD]; 17 men; messenger RNA-1273 in 12 [57%] and BNT162b2 in nine [43%]). Ten of 92 (11%) patients had myocarditis following COVID-19 illness (mean age, 51 years ± 14; three men) and 61 of 92 (66%) patients had other myocarditis (mean age, 44 years ± 18; 36 men). MRI findings in the 21 patients with vaccine-associated myocarditis included late gadolinium enhancement (LGE) in 17 patients (81%) and left ventricular dysfunction in six (29%). Compared with other causes of myocarditis, patients with vaccine-associated myocarditis had a higher left ventricular ejection fraction and less extensive LGE, even after controlling for age, sex, and time from symptom onset to MRI. The most frequent location of LGE in all groups was subepicardial at the basal inferolateral wall, although septal involvement was less common in vaccine-associated myocarditis. At short-term follow-up (median, 22 days [IQR, 7-48 days]), all patients with vaccine-associated myocarditis were asymptomatic with no adverse events. Conclusion Cardiac MRI demonstrated a similar pattern of myocardial injury in vaccine-associated myocarditis compared with other causes, although abnormalities were less severe, with less frequent septal involvement and no adverse events over the short-term follow-up. © RSNA, 2022

BACKGROUND: The immuno-metabolic interplay has gained interest for determining and targeting immunosuppressive tumor micro-environments that remain a barrier to current immuno-oncologic therapies in hepatocellular carcinoma. PURPOSE: To develop molecular MRI tools to reveal resistance mechanisms to immuno-oncologic therapies caused by the immuno-metabolic interplay in a translational liver cancer model. MATERIALS AND METHODS: A total of 21 VX2 liver tumor–bearing New Zealand white rabbits were used between October 2018 and February 2020. Rabbits were divided into three groups. Group A (n = 3) underwent intra-arterial infusion of gadolinium 160 ((160)Gd)–labeled anti–human leukocyte antigen–DR isotope (HLA-DR) antibodies to detect antigen-presenting immune cells. Group B (n = 3) received rhodamine-conjugated superparamagnetic iron oxide nanoparticles (SPIONs) intravenously to detect macrophages. These six rabbits underwent 3-T MRI, including T1- and T2-weighted imaging, before and 24 hours after contrast material administration. Group C (n = 15) underwent extracellular pH mapping with use of MR spectroscopy. Of those 15 rabbits, six underwent conventional transarterial chemoembolization (TACE), four underwent conventional TACE with extracellular pH– buffering bicarbonate, and five served as untreated controls. MRI signal intensity distribution was validated by using immunohistochemistry staining of HLA-DR and CD11b, Prussian blue iron staining, fluorescence microscopy of rhodamine, and imaging mass cytometry (IMC) of gadolinium. Statistical analysis included Mann-Whitney U and Kruskal-Wallis tests. RESULTS: T1-weighted MRI with (160)Gd-labeled antibodies revealed localized peritumoral ring enhancement, which corresponded to gadolinium distribution detected with IMC. T2-weighted MRI with SPIONs showed curvilinear signal intensity representing selective peritumoral deposition in macrophages. Extracellular pH–specific MR spectroscopy of untreated liver tumors showed acidosis (mean extracellular pH, 6.78 ± 0.09) compared with liver parenchyma (mean extracellular pH, 7.18 ± 0.03) (P = .008) and peritumoral immune cell exclusion. Normalization of tumor extracellular pH (mean, 6.96 ± 0.05; P = .02) using bicarbonate during TACE increased peri- and intratumoral immune cell infiltration (P = .002). CONCLUSION: MRI in a rabbit liver tumor model was used to visualize resistance mechanisms mediated by the immuno-metabolic interplay that inform susceptibility and response to immuno-oncologic therapies, providing a therapeutic strategy to restore immune permissiveness in liver cancer.

Background Increased cerebral signal intensity (SI) has been reported in patients undergoing MRI with gadolinium-based contrast agents (GBCAs). Published data on gadobenate dimeglumine have been somewhat contradictory. Purpose To evaluate the relationship between dosage of gadobenate dimeglumine and SI change at MRI following multiple gadobenate dimeglumine administrations. Materials and Methods In this retrospective study, patients referred for clinically indicated brain MRI from January 2006 through May 2016 were evaluated for inclusion. Eligible patients were between 18 and 90 years old at their baseline brain MRI and had never received a GBCA, had undergone three or more MRI examinations with gadobenate dimeglumine, and had the baseline scan and another brain MRI scan available for comparison. The primary group consisted of patients with four or fewer supratentorial lesions smaller than 3 cm who underwent axial T1-weighted MRI at 1.5 T. One patient had also undergone prior radiation therapy. The secondary group consisted of patients with a history of brain radiation therapy or craniotomy who underwent 1.5-T and 3-T same-plane T1-weighted MRI (in any order). The SI for up to eight brain MRI examinations per patient was measured, and relative SI changes from baseline to interval scans were calculated. A subgroup analysis was performed to assess the gadobenate dimeglumine washout since the last gadolinium exposure. All patients had normal renal and liver functions. Linear mixed regression analyses were performed for variables with P < .05. Results In 43 patients (14 men, 29 women; median age, 49 years; age range, 25-73 years), the dentate nucleus (DN)-to-middle cerebral peduncle (MCP) SI ratio showed a mean increase of 6.7% ± 3.9 in the primary group and 4.0% ± 2.7 in the secondary group (both P < .001) following the administration of 134 mL ± 141 gadobenate dimeglumine over 55 months ± 35.2. The DN/MCP SI ratio increased linearly with the amount of gadobenate dimeglumine, with a mean increase of 0.015% ± 0.004 per 1 mL of gadobenate dimeglumine (R2 = 0.3, P < .001). Conclusion In patients receiving multiple doses of gadobenate dimeglumine, a linear relationship existed between gadobenate dimeglumine administrations and an increase in the dentate nucleus-to-middle cerebral peduncle signal intensity ratio at MRI. © RSNA, 2020 See also the editorial by McDonald and Kallmes in this issue.

BACKGROUND: The value of native myocardial T1 mapping and extracellular volume (ECV) fraction in patients who have hypertrophic cardiomyopathy (HCM) but no late gadolinium enhancement (LGE) and no hemodynamic obstruction are currently unknown. PURPOSE: To evaluate myocardial fibrosis in patients with nonobstructive HCM and no LGE by using native myocardial T1 mapping and ECV fraction and to study their relationships to left ventricular (LV) function and LV hypertrophy. MATERIALS AND METHODS: Patients with HCM who underwent cardiac MRI between 2012 and 2015 were retrospectively evaluated. Patients were included if they had no LGE at MRI, LV ejection fraction greater than or equal to 45%, and no LV outflow tract obstruction. Healthy participants had similar age and sex distribution. Native myocardial T1 and ECV were measured with MRI. RESULTS: A total of 258 patients with HCM (mean age ± standard deviation, 49 years ± 15; 74% men) and 122 healthy participants (mean age, 50 years ± 14; 76% men) were evaluated. Native myocardial T1 was longer and ECV fraction was higher in the patients with HCM relative to the healthy participants (mean native T1, 950 msec ± 48 vs 913 msec ± 46; mean ECV, 24.5% ± 2.8 vs 23.0% ± 2.7; both P < .001). Maximum T1 and ECV values correlated strongly with LV mass index for the entire patient cohort with HCM (both r = 0.86; P < .001) and for the subgroups (r = 0.86 and 0.85 for interventricular septal group and r = 0.88 and 0.86 for apical group; all P < .001). CONCLUSION: Prolonged myocardial T1 and elevated extracellular volume in hypertrophic cardiomyopathy suggests diffuse myocardial fibrosis, even in the absence of regionally apparent late gadolinium enhancement and hemodynamic obstruction, and is associated with left ventricular hypertrophy. © RSNA, 2019 See also the editorial by Bluemke and Lima in this issue.

BACKGROUND: Gadolinium retention after repeated gadolinium-based contrast agent (GBCA) exposure has been reported in subcortical gray matter. However, gadolinium retention in the cerebral cortex has not been systematically investigated. PURPOSE: To determine whether and where gadolinium is retained in rat and human cerebral cortex. MATERIALS AND METHODS: The cerebral cortex in Sprague-Dawley rats treated with gadopentetate dimeglumine (three doses over 4 weeks; cumulative gadolinium dose, 7.2 mmol per kilogram of body weight; n = 6) or saline (n = 6) was examined with antemortem MRI. Two human donors with repeated GBCA exposure (three and 15 doses; 1 and 5 months after exposure), including gadopentetate dimeglumine, and two GBCA-naive donors were also evaluated. Elemental brain maps (gadolinium, phosphorus, zinc, copper, iron) for rat and human brains were constructed by using laser ablation inductively coupled plasma mass spectrometry. RESULTS: Gadopentetate dimeglumine–treated rats showed region-, subregion-, and layer-specific gadolinium retention in the neocortex (anterior cingulate cortex: mean gadolinium concentration, 0.28 µg ∙ g(−1) ± 0.04 [standard error of the mean]) that was comparable (P > .05) to retention in the allocortex (mean gadolinium concentration, 0.33 µg ∙ g(−1) ± 0.04 in piriform cortex, 0.24 µg ∙ g(−1) ± 0.04 in dentate gyrus, 0.17 µg ∙ g(−1) ± 0.04 in hippocampus) and subcortical structures (0.47 µg ∙ g(−1) ± 0.10 in facial nucleus, 0.39 µg ∙ g(−1) ± 0.10 in choroid plexus, 0.29 µg ∙ g(−1) ± 0.05 in caudate-putamen, 0.26 µg ∙ g(−1) ± 0.05 in reticular nucleus of the thalamus, 0.24 µg ∙ g(−1) ± 0.04 in vestibular nucleus) and significantly greater than that in the cerebellum (0.17 µg ∙ g(−1) ± 0.03, P = .01) and white matter tracts (anterior commissure: 0.05 µg ∙ g(−1) ± 0.01, P = .002; corpus callosum: 0.05 µg ∙ g(−1) ± 0.02, P = .001; cranial nerve: 0.02 µg ∙ g(−1) ± 0.01, P = .004). Retained gadolinium colocalized with parenchymal iron. T1-weighted MRI signal intensification was not observed. Gadolinium retention was detected in the cerebral cortex, pia mater, and pia-ensheathed leptomeningeal vessels in two GBCA-exposed human brains but not in two GBCA-naive human brains. CONCLUSION: Repeated gadopentetate dimeglumine exposure is associated with gadolinium retention in specific regions, subregions, and layers of cerebral cortex that are critical for higher cognition, affect, and behavior regulation, sensorimotor coordination, and executive function. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Kanal in this issue.

Background Detection of cerebral lesions at MRI may benefit from a chemically stable and more sensitively detected gadolinium-based contrast agent (GBCA). Gadopiclenol, a macrocyclic GBCA with at least twofold higher relaxivity, is currently undergoing clinical trials in humans. Purpose To determine the relationship between MRI contrast enhancement and the injected dose of gadopiclenol in a glioma rat model compared with those of conventional GBCA at label dose. Materials and Methods Between April and July 2012, 32 rats implanted with C6 glioma received two intravenous injections at a 24-hour interval. The injections were randomly selected among five doses of gadopiclenol (0.025, 0.05, 0.075, 0.1, and 0.2 mmol/kg) and three reference GBCAs (gadoterate meglumine, gadobutrol, and gadobenate dimeglumine) at 0.1 mmol/kg. MRI tumor enhancement was assessed on T1-weighted images before and up to 30 minutes after injection. Two blinded radiologists visually and qualitatively scored contrast enhancement, border delineation, and visualization of tumor morphology. Quantitatively, variations in contrast-to-noise ratio (ΔCNR) between tumor and contralateral parenchyma were calculated at each time point and were compared for each treatment at 5 minutes by using a mixed model after normality test. Results A total of 24 rats underwent the complete protocol (

BackgroundThe safety of gadolinium-based contrast agent (GBCA) exposure during pregnancy has not been established, and the use of GBCAs during pregnancy is not recommended unless it is essential to the health of the woman or fetus.PurposeTo examine the prevalence of GBCA exposure in a large sample of pregnancies resulting in a live birth.Materials and MethodsThe Sentinel Distributed Database was used to retrospectively identify U.S. pregnancies that resulted in live births between 2006 and 2017 from 16 data partners. The main outcome was the prevalence of MRI procedures with and without GBCAs, sorted by anatomic location and trimester, among pregnant and matched comparator women.ResultsAmong 4 692 744 pregnancies resulting in a live birth, we identified 6879 exposures to GBCAs in 5457 pregnancies, representing one contrast-enhanced MRI examination per 860 pregnancies (0.12% of all pregnancies). Most contrast-enhanced MRI examinations were performed in the head (

Background Despite advances in immunomodulatory agents, most current therapies for multiple sclerosis target lymphocytes or lymphocytic function. However, therapy response may be less than optimal due to demyelination and axonal damage caused by myeloid cells. Purpose To determine if myeloperoxidase (MPO) molecular MRI can evaluate whether combination therapy targeting both lymphoid and myeloid inflammation can improve autoimmune neuroinflammation compared with either drug alone, even at suboptimal doses. Materials and Methods Four groups of 94 female mice (8-10 weeks old) were induced with experimental autoimmune encephalomyelitis (EAE) from August 2, 2016, to March 30, 2018, and divided into saline control (n = 22), 4-aminobenzoic acid hydrazide (ABAH) therapy group (n = 19), glatiramer acetate (GA) therapy group (n = 22), and combination therapy group (n = 31). Mice were administered suboptimal doses of ABAH, an irreversible inhibitor of MPO; GA, a first-line multiple sclerosis drug; both ABAH and GA; or saline (control). Mice were imaged with bis-5-hydroxytryptamide-diethylenetriaminepentaacetate gadolinium (hereafter, MPO-Gd) MRI. One-way analysis of variance, two-way analysis of variance, Kurskal-Wallis, and log-rank tests were used. P < .05 was considered to indicate statistical significance. Results The combination-treated group showed delayed disease onset (day 11.3 vs day 9.8 for ABAH, day 10.4 for GA, day 9.9 for control; P < .05) and reduced disease severity (clinical score during the acute exacerbation period of 1.8 vs 3.8 for ABAH, 3.1 for GA, 3.9 for control; P < .05). The combination-treated group demonstrated fewer MPO-positive lesions (30.2 vs 73.7 for ABAH, 64.8 for GA, 67.2 for control; P < .05), smaller MPO-positive lesion volume (16.7 mm3 vs 65.2 mm3 for ABAH, 69.9 mm3 for GA, 66.0 mm3 for control; P < .05), and lower intensity of MPO-Gd lesion activation ratio (0.7 vs 1.9 for ABAH, 3.2 for GA, 2.3 for control; P < .05). Reduced disease severity in the combination group was confirmed at histopathologic analysis, where MPO expression (1779 vs 2673 for ABAH, 2898 for GA; P < .05) and demyelination (5.3% vs 9.0% for ABAH, 10.6% for GA; P < .05) were ameliorated. Conclusion Myeloperoxidase molecular MRI can track the treatment response from immunomodulatory drugs even if the drug does not directly target myeloperoxidase, and establishes that combination therapy targeting both myeloid and lymphocytic inflammation is effective for murine autoimmune neuroinflammation, even at suboptimal doses. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Walczak in this issue.

Background Linear gadolinium-based contrast agents (GBCAs) are known to be retained at higher levels of gadolinium than macro-cyclic GBCAs. However, very little is known regarding their relative elimination rates and retained fraction of injected gadolinium. Purpose To quantify and compare gadolinium retention and elimination rates in human brain tissue, skin, and bone obtained from cadavers exposed to single-agent administration of either gadoteridol (macrocyclic GBCA) or gadobenate dimeglumine (linear GBCA). Materials and Methods Autopsy cases from August 2014 to July 2019 of patients exposed to a single type of GBCA, either gadoteridol or gadobenate dimeglumine, either single or multiple doses, were included. Gadolinium levels in the brain, skin, and bone were analyzed with inductively coupled plasma mass spectrometry. Linear regression was used to compare gadolinium retention between agents and estimate elimination rates of the retained gadolinium using the time between last injection and death. Results Twenty-eight cadavers with gadoteridol exposure and nine with gadobenate dimeglumine exposure were identified (22 men; age range, 19-83 years). The median gadolinium retention of gadobenate dimeglumine was 3.0-6.5 times higher than that of gadoteridol in the brain (P < .02), 4.4 times higher in bone (P = .002), and 2.9 times higher in skin (P = .05). Gadolinium retention in the globus pallidus (GP), dentate nucleus (DN), white matter (WM), bone, and skin decreased with time elapsed from last administration to death in both the gadobenate dimeglumine (GP: -3% per twofold increase in time, P = .69; DN: -2%, P = .83; WM: -20%, P = .01; bone: -22%, P = .07; skin: -47%, P < .001) and gadoteridol (GP: -17%, P = .11; DN: -16%, P = .15; WM: -30%, P < .001; bone: -11%, P = .16; skin: -24%, P = .01) groups (P values for elimination are compared with a null hypothesis of no elimination). Conclusion The linear agent gadobenate dimeglumine retains several-fold higher levels of gadolinium in the brain and bone compared with the macrocyclic agent gadoteridol. Nonzero elimination of retained gadolinium was detected in the white matter and skin for both agents. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Tweedle in this issue.

Background Electrophysiology studies have demonstrated that left atrial late gadolinium enhancement (LGE) is associated with the chronicity of atrial fibrillation (AF). To date, cardiac MRI has been used to assess the extent of atrial LGE but not the distribution pattern of LGE in the left atrium. Purpose To determine whether the MRI pattern of left atrial fibrosis is associated with the chronicity of AF. Materials and Methods This retrospective study included patients with AF who underwent LGE MRI between June 2017 and May 2018. The presence of left atrial LGE was assessed at nine left atrial segments; the extent was determined by the number of segments involved. According to the chronicity of AF, patients were separated into paroxysmal AF (PAF) and persistent AF (PeAF) groups. The location and extent of left atrial LGE were compared between PAF and PeAF by using the χ2 test and logistic regression analysis. Results Of the 195 patients (mean age, 55 years ± 10 [standard deviation], 161 men), 74 (38%) had PAF and 121 (62%) had PeAF. Of all patients, 114 (58.4%) had at least one left atrial LGE segment. The mean number of LGE segments was higher (1.4 ± 1.1 vs 0.6 ± 0.7, P = .002) in the PeAF group than in the PAF group. The incidence of LGE at the left inferior pulmonary vein (LIPV) antrum was higher in the PeAF group than in the PAF group (39.2% [29 of 74] vs 7.4% [nine of 121]; P < .001). In multivariable analysis, LGE at the LIPV antrum was independently associated with PeAF (odds ratio = 4.2; 95% confidence interval: 1.7, 10.5; P < .001). Conclusion The presence of fibrosis assessed with late gadolinium enhancement MRI of the left inferior pulmonary vein antrum was associated with persistent atrial fibrillation. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Almeida in this issue.

Background Administration of a gadolinium-based contrast material is widely considered obligatory for follow-up imaging of patients with multiple sclerosis (MS). However, advances in MRI have substantially improved the sensitivity for detecting new or enlarged lesions in MS. Purpose To investigate whether the use of contrast material has an effect on the detection of new or enlarged MS lesions and, consequently, the assessment of interval progression. Materials and Methods In this retrospective study based on a local prospective observational cohort, 507 follow-up MR images obtained in 359 patients with MS (mean age, 38.2 years ± 10.3; 246 women, 113 men) were evaluated. With use of subtraction maps, nonenhanced images (double inversion recovery [DIR], fluid-attenuated inversion recovery [FLAIR]) and contrast material-enhanced (gadoterate meglumine, 0.1 mmol/kg) T1-weighted images were separately assessed for new or enlarged lesions in independent readings by two readers blinded to each other's findings and to clinical information. Primary outcome was the percentage of new or enlarged lesions detected only on contrast-enhanced T1-weighted images and the assessment of interval progression. Interval progression was defined as at least one new or unequivocally enlarged lesion on follow-up MR images. Results Of 507 follow-up images, 264 showed interval progression, with a total of 1992 new or enlarged and 207 contrast-enhancing lesions. Four of these lesions (on three MR images) were retrospectively detected on only the nonenhanced images, corresponding to 1.9% (four of 207) of the enhancing and 0.2% (four of 1992) of all new or enlarged lesions. Nine enhancing lesions were not detected on FLAIR-based subtraction maps (nine of 1442, 0.6%). In none of the 507 images did the contrast-enhanced sequences reveal interval progression that was missed in the readouts of the nonenhanced sequences, with use of either DIR- or FLAIR-based subtraction maps. Interrater agreement was high for all three measures, with intraclass correlation coefficients of 0.91 with FLAIR, 0.94 with DIR, and 0.99 with contrast-enhanced T1-weighted imaging. Conclusion At 3.0 T, use of a gadolinium-based contrast agent at follow-up MRI did not change the diagnosis of interval disease progression in patients with multiple sclerosis. © RSNA, 2019 See also the editorial by Saindane in this issue.

Gadolinium-based contrast agents (GBCAs) have revolutionized MRI, enabling physicians to obtain crucial life-saving medical information that often cannot be obtained with other imaging modalities. Since initial approval in 1988, over 450 million intravenous GBCA doses have been administered worldwide, with an extremely favorable pharmacologic safety profile; however, recent information has raised new concerns over the safety of GBCAs. Mounting evidence has shown there is long-term retention of gadolinium in human tissues. Further, a small subset of patients have attributed a constellation of symptoms to GBCA exposure, although the association of these symptoms with GBCA administration or gadolinium retention has not been proven by scientific investigation. Despite evidence that macrocyclic GBCAs show less gadolinium retention than linear GBCAs, the safety implications of gadolinium retention are unknown. The mechanism and chemical forms of gadolinium retention, as well as the biologic activity and clinical importance of these retained gadolinium species, remain poorly understood and underscore the need for additional research. In February 2018, an international meeting was held in Bethesda, Md, at the National Institutes of Health to discuss the current literature and knowledge gaps about gadolinium retention, to prioritize future research initiatives to better understand this phenomenon, and to foster collaborative standardized studies. The greatest priorities are to determine (a) if gadolinium retention adversely affects the function of human tissues, (b) if retention is causally associated with short- or long-term clinical manifestations of disease, and (c) if vulnerable populations, such as children, are at greater risk for experiencing clinical disease. The purpose of the research roadmap is to highlight important information that is not known and to identify and prioritize needed research. ©RSNA, 2018 Online supplemental material is available for this article .

Purpose To determine whether treatment affects MRI signal intensity in pediatric patients with primary brain tumors independent of the administration of macrocyclic gadolinium-based contrast agents (GBCAs). Materials and Methods This retrospective, single-center study included 78 patients (mean age, 7.7 years ± 5.4) with primary brain tumors who underwent macrocyclic GBCA-enhanced MRI from 2015 to 2018. Three groups were compared: (a) patients who had undergone radiation therapy (37 patients, 26 of whom had undergone concurrent chemotherapy), (b) patients who had undergone chemotherapy only (17 patients), and (c) patients who had received no treatment ("no-treatment group," 24 patients). The signal intensity in the globus pallidus (GP), thalamus, dentate nucleus (DN), and pons was measured on unenhanced T1-weighted images. GP-to-thalamus and DN-to-pons signal intensity ratios were compared among groups with analysis of variance by using the Kruskal-Wallis test, followed by post hoc pairwise tests with Tukey adjustment, and were analyzed relative to group, total cumulative doses of GBCA, age, and sex with multivariable linear models. Results The mean number of GBCA-enhanced MRI examinations in the radiation therapy, chemotherapy-only, and no-treatment groups was 7.11, 7.29, and 4.96, respectively (P.01 for the radiation therapy and chemotherapy groups compared with the no-treatment group). The DN-to-pons ratio in the radiation therapy group was higher than that in both the no-treatment group and the chemotherapy-only group (P.01 for both). There was no significant difference in the DN-to-pons ratios between the chemotherapy-only group and the no-treatment group (P = .99). The GP-to-thalamus ratios did not differ among all three groups (P = .09). There was no dose-dependent effect of GBCA on the DN-to-pons and GP-to-thalamus ratios when adjusting for the effects of treatment (P = .21 and P = .38, respectively). Conclusion Brain irradiation contributes to a higher dentate nucleus signal intensity in pediatric patients with brain tumor independent of the administration of macrocyclic gadolinium-based contrast agents. © RSNA, 2018.