Intravenous Gadolinium-based Contrast Agents Research Articles

Assessment of first-time and repeated acute adverse reactions to Gadolinium-based contrast agents in MRI: A retrospective study

PurposeTo identify gadolinium-based contrast agents (GBCAs)-related and patient-related risk factors for acute adverse reactions (AARs), and to examine the incidence and severity of repeated AARs. MethodsThis study retrospectively evaluated all intravenous GBCA injections in MRI studies at a single institution from January 2012 to September 2019. First-time AARs in patients without a past history of AARs and risk factors were assessed using multivariable regression models with generalized estimating equations. For patients with a past history of AAR(s), we evaluated the incidence of repeated AARs using the Fisher’s exact test, as well as the severity of these repeated AARs. ResultsFirst-time AARs occurred in 129 of 41,827 GBCA injections (0.31 %; 0.70 % of 18,431 patients). With gadoterate meglumine as the reference, the odds ratio (OR) for allergic-like reactions to three GBCAs ranged from 3.27 to 8.03 (p = 0.012 to <0.001). For chemotoxic reactions, the OR was 3.75 (p = 0.001) for gadoteridol. Outpatients had a lower OR for chemotoxic reactions, while higher ORs were observed in head/neck and breast MRI (p < 0.05). The OR for age was 0.99 (p < 0.05). Patients with a past history of AAR(s) had a 3.6 % incidence of mild repeated AARs for all GBCA, significantly higher than the 0.31 % in first-time AARs (p < 0.001). No effectiveness was found for steroid premedication. ConclusionThe occurrence of first-time AARs was related to the GBCA used and other factors. The incidence of repeated AARs was higher than first-time AARs, though all were mild in severity.

Imaging evaluation and volumetric measurement of the space surrounding the diploic veins.

The diploic veins have been suggested to be involved in the excretion of cerebrospinal fluid and intracranial waste products; however, to date, there have been no reports evaluating the space surrounding the diploic veins. Therefore, we aimed to visualize the distribution of gadolinium-based contrast agent (GBCA) in the space surrounding the diploic veins and to evaluate the spatial characteristics. Ninety-eight participants (aged 14-84years) were scanned 4h after intravenous GBCA injection at Nagoya University Hospital between April 2021 and December 2022. The volume of the space surrounding the diploic veins where the GBCA was distributed was measured using contrast-enhanced T1-weighted images with the application of three-axis motion-sensitized driven equilibrium. The parasagittal dura (PSD) volume adjacent to the superior sagittal sinus was also measured using the same images. Both volumes were corrected for intracranial volume. The correlation between age and the corrected volume was examined using Spearman's rank correlation coefficient; the relationship between the corrected volume and sex was assessed using the Mann-Whitney U test. A significant weak negative correlation was observed between the volume of the space surrounding the diploic veins and age (r = -0.330, p < 0.001). Furthermore, there was a significant weak positive correlation between the PSD volume and age (r = 0.385, p < 0.001). Both volumes were significantly greater in men than in women. There was no correlation between the volume of the space surrounding the diploic veins and the volume of the PSD. The volume of the space surrounding the diploic veins was measurable and, in contrast to the volume of the PSD, was greater in younger participants. This space may be related to intracranial excretory mechanisms and immune responses during youth, requiring further research.

Prediction of the Risk of Malignancy of Adnexal Masses during Pregnancy Comparing Subjective Assessment and Non-Contrast MRI Score (NCMS) in Radiologists with Different Expertise.

Ovarian cancer represents 7% of all cancers in pregnant women. Characterising an ovarian mass during pregnancy is essential to avoid unnecessary treatment and, if treatment is required, to plan it accordingly. Although ultrasonography (US) is the first-line modality to characterise adnexal masses, MRI is indicated when adnexal masses are indeterminate at the US examination. An MRI risk stratification system has been proposed to assign a malignancy probability based on the adnexal lesion's MRI, but features of the scoring system require the administration of intravenous gadolinium-based contrast agents, a method that might have a limited use in pregnant women. The non-contrast MRI score (NCMS) has been used and evaluated in non-pregnant women to characterise adnexal masses indeterminate at the US examination. Therefore, we evaluated the diagnostic accuracy of the NCMS in pregnant women, analysing 20 cases referred to our specialised institution. We also evaluated the diagnostic agreement between two radiologists with different expertise. The two readers classified ovarian masses as benign or malignant using both subjective assessment (SA), based on the interpretive evaluation of imaging findings derived from personal experience, and the NCMS, which includes five categories where 4 and 5 indicate a high probability of a malignant mass. The expert radiologist correctly classified 90% of the diagnoses, using both SA and the NCMS, relying on a sensitivity of 85.7% and a specificity of 92.3%, with a false positive rate of 7.7% and a false negative rate of 14.3%. The non-expert radiologist correctly identified patients at a lower rate, especially using the SA. The analysis of the inter-observer agreement showed a K = 0.47 (95% CI: 0.48-0.94) for the SA (agreement in 71.4% of cases) and a K = 0.8 (95% CI: 0.77-1.00) for the NCMS (agreement in 90% of cases). Although in pregnant patients, non-contrast MRI is used, our results support the use of a quantitative score, i.e., the NCMS, as an accurate tool. This procedure may help less experienced radiologists to reduce the rate of false negatives or positives, especially in centres not specialised in gynaecological imaging, making the MRI interpretation easier and more accurate for radiologists who are not experts in the field, either.

Breast Imaging and Intervention during Pregnancy and Lactation.

Physiologic changes that occur in the breast during pregnancy and lactation create challenges for breast cancer screening and diagnosis. Despite these challenges, imaging evaluation should not be deferred, because delayed diagnosis of pregnancy-associated breast cancer contributes to poor outcomes. Both screening and diagnostic imaging can be safely performed using protocols based on age, breast cancer risk, and whether the patient is pregnant or lactating. US is the preferred initial imaging modality for the evaluation of clinical symptoms in pregnant women, followed by mammography if the US findings are suspicious for malignancy or do not show the cause of the clinical symptom. Breast MRI is not recommended during pregnancy because of the use of intravenous gadolinium-based contrast agents. Diagnostic imaging for lactating women is the same as that for nonpregnant nonlactating individuals, beginning with US for patients younger than 30 years old and mammography followed by US for patients aged 30 years and older. MRI can be performed for high-risk screening and local-regional staging in lactating women. The radiologist may encounter a wide variety of breast abnormalities, some specific to pregnancy and lactation, including normal physiologic changes, benign disorders, and malignant neoplasms. Although most masses encountered are benign, biopsy should be performed if the imaging characteristics are suspicious for cancer or if the finding does not resolve after a short period of clinical follow-up. Knowledge of the expected imaging appearance of physiologic changes and common benign conditions of pregnancy and lactation is critical for differentiating these findings from pregnancy-associated breast cancer. ©RSNA, 2023 Online supplemental material is available for this article. Quiz questions for this article are available through the Online Learning Center.

Noninvasive investigations of human glymphatic dynamics in a diseased model.

To explore human glymphatic dynamics in a diseased model via a noninvasive technique. Patients with reversible vasoconstriction syndrome (RCVS) presenting with blood-brain barrier disruption, i.e., para-arterial gadolinium leakage on 3-T 3-dimensional isotropic contrast-enhanced T2-fluid-attenuated inversion recovery (CE-T2-FLAIR) magnetic resonance imaging (MRI), were prospectively enrolled. Consecutive 9-min-CE-T2-FLAIR for 5-6 times (early panel) after intravenous gadolinium-based contrast agent (GBCA) administration and one time-varying deferred scan of noncontrast T2-FLAIR (delayed panel) were performed. In Bundle 1, we measured the calibrated signal intensities (cSIs) of 10 different anatomical locations. In Bundle 2, brain-wide measurements of para-arterial glymphatic volumes, means, and medians of the signal intensities were conducted. We defined mean (mCoIs) or median (mnCoIs) concentration indices as products of volumes and signal intensities. Eleven subjects were analyzed. The cSIs demonstrated early increase (9min) in perineural spaces: (cranial nerve [CN] V, p = 0.008; CN VII + VII, p = 0.003), choroid plexus (p = 0.003), white matter (p = 0.004) and parasagittal dura (p = 0.004). The volumes, mCoIs, and mnCoIs demonstrated increasing rates of enhancement after 9 to 18min and decreasing rates after 45 to 54min. The GBCA was transported centrifugally and completely removed within 961-1086min after administration. The exogenous GBCA leaked into the para-arterial glymphatics could be completely cleared around 961 to 1086min after administration in a human model of BBB disruption. The tracer enhancement started variously in different intracranial regions but was eventually cleared centrifugally to brain convexity, probably towards glymphatic-meningeal lymphatics exits. Glymphatic clearance time intervals and the centrifugal directions assessed by a noninvasive approach may have implications for clinical glymphatic evaluation in the near future. • This study aimed to investigate the human glymphatic dynamics in a noninvasive diseased model. • The intracranial MR-detectable gadolinium-based contrast agents were removed centrifugally within 961 to 1086min. • The glymphatic dynamics was demonstrable by enhancing MRI in an in vivo diseased model noninvasively.

Diagnostic utility of contrast-enhanced FLAIR MRI in imaging of demyelinating and infectious brain lesions

BackgroundContrast-enhanced MRI is frequently used as a baseline modality and indispensable tool for early diagnosis and follow-up of different brain lesions. Herein, we aimed to evaluate the diagnostic impact of contrast-enhanced FLAIR compared to the widely used post-contrast T1W sequence in terms of demyelinating and infectious brain lesions detection in clinical practice and explore its value in monitoring disease activity for selecting appropriate therapy. MR Imaging was performed using 1.5 Tesla device. Both T1W and FLAIR sequences were obtained prior to and after administration of intravenous gadolinium-based contrast agent. Both qualitative and quantitative approaches were used for image analysis by two independent radiologists.ResultsSixty patients were prospectively enrolled in this study. Our participants were subdivided into two categories, either demyelinating (45 multiple sclerosis) or infectious lesions (13 meningitis/meningoencephalitis and 2 pyogenic abscess). By comparing the two post-contrast sequences, CE-FLAIR revealed greater enhancement in 38 cases (63.34%), equal enhancement in 17 cases (28.33%) and less enhancement in 5 cases (8.33%). For lesion conspicuity: good delineation observed in (61.67%), fair delineation in (25%) and no delineation in (13.33%). Lesion-to-background contrast ratio was statistically significant in CE-FLAIR with excellent inter-class correlation.ConclusionCE-FLAIR should be added in conjunction with or as a superior alternative to conventional CE-T1W sequence to optimize lesion detection and improve diagnostic reliability particularly in demyelinating and infectious lesions.

Histopathologic Validation of Stress T1 Mapping in Myocardial Ischemia: Another Step toward Clinical Translation?

Histopathologic Validation of Stress T1 Mapping in Myocardial Ischemia: Another Step toward Clinical Translation?

The relationship of apparent diffusion coefficient values of renal cell carcinoma before and after cryotherapy ablation

IntroductionThe diagnosis of renal cell carcinoma (RCC) is increasing due to incidental findings with more frequent use of cross-sectional imaging. Therefore improvements to diagnostic and follow up imaging techniques is necessary. MRI diffusion weighted imaging (DWI) is a recognised method of measuring the diffusion of water within lesions using the apparent diffusion coefficient (ADC), and may have a role in monitoring the efficacy of cryotherapy ablation of RCC. MethodsA retrospective cohort study of 50 patients was approved to investigate if the ADC value can determine the success of cryotherapy ablation treatment for RCC. DWI was performed at a single centre using 1.5 T MRI before and after cryotherapy ablation to the RCC. The control group was considered as the unaffected kidney. The ADC value of the RCC tumour and normal kidney tissue prior to and after cryotherapy ablation was measured, and compared to the result of the MRI. ResultsA statistically significant change in the ADC values was observed, pre ablation (1.562 × 10¯mm2/sec) to the post ablation (1.126 × 10¯³mm2/sec), p < 0.0005. There was no statistical significance in any of the other outcomes measured. ConclusionAlthough a change of ADC value occurred this is likely due to cryotherapy ablation causing coagulative necrosis at the site, and does not determine the success of the cryotherapy ablation. This can be considered a feasibility study for future research. Implications for practiceDWI is a quick addition to routine protocols, does not require intravenous gadolinium based contrast agent, and provides qualitative and quantitative data. Further research is required to establish the role of ADC for treatment monitoring.

Incidental findings involving the temporomandibular joint on computed tomography and magnetic resonance imaging.

The temporomandibular joint (TMJ) is frequently imaged in head and neck computed tomography (CT) and magnetic resonance imaging (MRI) studies. Depending on the indication for the study, an abnormality of the TMJ may be an incidental finding. These findings encompass both intra- and extra-articular disorders. They may also be related to local, regional or systemic conditions. Familiarity with these findings along with pertinent clinical information helps narrow the list of differential diagnoses. While definitive diagnosis may not be immediately apparent, a systematic approach contributes to improved discussions between clinicians and radiologists and better patient management.

Neurologic Effects of Gadolinium Retention in the Brain after Gadolinium-based Contrast Agent Administration.

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.

Short tau inversion recovery (STIR) after intravenous contrast agent administration obscures bone marrow edema-like signal on forefoot MRI

ObjectiveShort tau or short TI inversion recovery (STIR) MRI sequences are considered a robust fat suppression technique. However, STIR also suppresses signals from other tissues with similar T1 relaxation times. This study investigates the in vivo effect of intravenous gadolinium-based T1-shortening contrast agent on STIR signal.Materials and methodsInstitutional board approval and informed consent was obtained. MRI examinations (1.5-T or 3-T) of 31 prospectively included patients were analyzed by two readers. Signal intensity of degenerative bone marrow edema-like signal at the Lisfranc joint on precontrast STIR images and on STIR images acquired after intravenous contrast agent administration (gadoteric acid, gadolinium: 0.5 mmol/ml, 15 ml) was measured. The medial cuneiform bone without observable bone marrow edema-like signal was considered a healthy tissue and served as a reference. Relative changes in signal intensity between precontrast and postcontrast images were calculated for the two tissues. Wilcoxon signed-rank test served for statistical analyses.ResultsIn bone marrow edema-like signal, both readers observed a median signal change of -35% (interquartile range (IQR) 24) and -34% (IQR 21), respectively, on postcontrast STIR images compared to precontrast STIR. In healthy tissue, the signal remained constant on postcontrast STIR images (median change -2%, IQR 15, and 0%, IQR 17) respectively. For both readers, postcontrast signal change in bone marrow edema-like signal differed from that in healthy tissue (p < 0.001).ConclusionIntravenous gadolinium-based contrast agent causes a significant reduction of signal intensity in bone marrow edema-like signal on routine STIR images. Thus, pathological MRI findings may be obscured.

Neonatal body magnetic resonance imaging: preparation, performance and optimization

Performing and optimizing MRI of the chest, abdomen and pelvis in neonates and young infants can be challenging. This is a result of several factors, including patient size, desire to avoid or minimize sedation/general anesthesia, and the relative rarity of these examinations. However, with proper preparation and protocol optimization, high-quality diagnostic images can be acquired that can aid in diagnosis and patient management. In addition, numerous special considerations arise when performing body MRI in neonates compared to older pediatric patients. This review article provides an update on the performance and optimization of MRI of the body in neonates and infants. Furthermore, the authors present common indications for neonatal body MRI and discuss the use of intravenous gadolinium-based contrast agents in this vulnerable patient population.

Limited Utility of Gadolinium Contrast Administration in Routine Multiple Sclerosis Surveillance.

Assess the incidence of enhancing lesions on follow-up MRIs in patients with multiple sclerosis (MS) to determine the utility of intravenous, gadolinium-based contrast agent (IV-GBCA) use in routine follow-up imaging. We retrospectively identified head MRIs associated with an MS diagnosis acquired between January 1, 2015and January 10, 2018. Final reports were reviewed to determine the presence of (1) a new or larger lesion, (2) at least one enhancing lesion, and (3) if at least one enhancing lesion was new or larger on Fluid-Attenuation Inversion Recovery (FLAIR). For MRIs with at least one enhancing lesion, but no new or larger enhancing lesions, reports and images of the preceding MRI were reviewed. A total of 1,805 MRIs performed on 920 patients were included. 354/1,805 (20%) MRIs reported new or enlarging lesions. 138/1,805 (8%) MRIs reported at least one enhancing lesion. Of these, 117/138 (85%) reported at least one enhancing lesion that was new or larger. In the remaining 21 MRIs which contained an enhancing lesion but none of the enhancing lesions were reported as new or enlarging, at least one enhancing lesion was present on preceding MRI. Enhancing lesions are uncommon on follow-up MRIs in MS patients. Our data suggest that new enhancing lesions are not present on a follow-up MRI when two conditions are met: (1) preceding MRI does not demonstrate any enhancing lesions and (2) there is no interval change of the lesions on the current 3D-T2-FLAIR sequence compared to the preceding 3D-T2-FLAIR sequence. IV-GBCA should be reserved for instances when temporal knowledge of lesion formation is needed.

Differentiating epidural fibrosis from disc herniation on contrast-enhanced and unenhanced MRI in the postoperative lumbar spine.

To determine diagnostic confidence and inter-observer/intra-observer agreement in differentiating epidural fibrosis from disc herniation and lumbar spinal stenosis parameters on magnetic resonance images (MRI) in postoperative lumbar spines with (Gad-MRI) and without (unenhanced MRI) intravenous gadolinium-based contrast agent. N = 124 lumbar spine MRI examinations of four groups were included: 1-6months, 7-18months, 19-36months, more than 37months between lumbar spine surgery and imaging. Two radiologists evaluated Gad-MRI and unenhanced MRI: diagnostic confidence was determined as confident or unconfident. Inter-observer and intra-observer agreement were assessed in differentiating epidural fibrosis from disc herniation and for lumbar spinal stenosis parameters on MRI. Fisher's exact test and Cohen's kappa served for statistics. Diagnostic confidence in differentiating epidural fibrosis from disc herniation was significantly higher on Gad-MR images compared with unenhanced MRI at 1-18months for observer 1 and at 1-6months postoperatively for observer 2 (p values: 0.01-0.025). Inter-observer agreement at 1-6months postoperatively for identification of epidural fibrosis was higher on Gad-MRI (kappa values: 0.53 versus 0.24). Inter-observer and intra-observer agreement for identification of disc herniation and for assessment of lumbar spinal stenosis parameters revealed inconsistent data, without a trend for higher inter-observer or intra-observer agreement on Gad-MRI compared with unenhanced MRI (kappa values: 0.17-0.75). Gad-MR images compared with unenhanced MRI improved diagnostic confidence and agreement in differentiating epidural fibrosis from disc herniation for both observers in the first 6months and for one observer in the first 18months after lumbar spine surgery. After 18months, Gad-MR images compared with unenhanced MRI did neither improve confidence nor agreement.

Two Non-gadolinium-based, Innovative Approaches to Preoperative Lymphangiography.

Summary:Most magnetic resonance lymphangiography techniques employ intravenous gadolinium-based contrast agents, which carry a US Food and Drug Administration warning about gadolinium retention in the body when used intravenously. Because of this, there may be reluctance to perform intradermal injections of gadolinium-based contrast agents in patients with obstructed lymphatic drainage due to concerns about gadolinium retention in the skin and soft tissues and potential-related toxicity. The aim of this study was to show proof of concept of 2 preoperative lymphangiographic techniques that do not use gadolinium-based contrast agents. One technique used contrast-enhanced ultrasound with intradermal injections of microbubbles (Lumason) in a patient with stage 3, nonpitting left upper extremity edema. Another technique used magnetic resonance imaging with intradermal injections of 0.03 mg/mL or 0.003% ferumoxytol (Feraheme) in a patient with stage 3, nonpitting right lower extremity edema. Both contrast-enhanced ultrasound with microbubbles and magnetic resonance lymphangiogram with ferumoxytol were able to identify candidates for lymphovenous bypass surgery. These candidates were not identified by conventional indocyanine green injections. The authors conclude that (1) low-dose ferumoxytol is a potentially effective non-gadolinium–based contrast alternative to gadolinium-based contrast agent in magnetic resonance lymphangiography and (2) contrast-enhanced ultrasound can identify candidate lymphatic vessels for anastomosis.

Safety of Gadolinium-Based Contrast Agents in Patients with Stage 4 and 5 Chronic Kidney Disease: a Radiologist's Perspective.

Gadolinium-based contrast agents (GBCAs) have been used for contrast-enhanced magnetic resonance imaging (MRI) since 1988 with >450 million intravenous GBCA doses administered worldwide and overall have had an excellent safety record (1,2). Numerous studies have demonstrated the benefit of GBCAs for a variety of diagnostic indications including improving sensitivity and specificity for malignancy, demyelination, central nervous system malignancy, and infection (3⇓⇓⇓–7). Initially, it was thought that GBCAs would be safer than iodinated contrast media for patients with kidney disease because they are less nephrotoxic at clinically administered doses (8). Although some case reports have linked AKI to GBCA administration, most cases involve patients with advanced renal disease or diabetes and with doses that exceed US Food and Drug Administration (FDA) recommendations (8). The safety of GBCAs in patients with kidney disease came into question in 2006 when a strong association was found between the use of GBCAs in patients with severe kidney disease and the development of nephrogenic systemic fibrosis (NSF) (9⇓–11). NSF results in fibrosis of the skin and internal organs and can be fatal. A conclusive mechanism of causation for NSF has not been determined. Several mouse models of NSF have been developed to investigate the underlying pathophysiology; however, they tend to use doses which are higher than those approved by the FDA and older linear agents (12⇓–14). A confounding issue is that many people with severe kidney disease received multiple exposures to GBCAs and did not develop NSF. Conversely, patients with only one administration of a GBCA have developed NSF (15,16). It is unclear if this could at least partially relate to interspecies differences. Multiple factors may contribute, most notably patient-specific risk factors and the stability of the GBCA, which is …

Intravenous gadolinium-based hepatocyte-specific contrast agents (HSCAs) for contrast-enhanced liver magnetic resonance imaging in pediatric patients: what the radiologist should know.

Hepatocyte-specific contrast agents (HSCAs) are a group of intravenous gadolinium-based MRI contrast agents that can be used to characterize hepatobiliary pathology. The mechanism by which these agents are taken up by hepatocytes and partially excreted into the biliary tree improves characterization of hepatic lesions and biliary abnormalities relative to conventional extracellular gadolinium-based contrast agents (GBCAs). This manuscript presents an overview of HSCA use in pediatric patients with the intent to provide radiologists a guide for clinical use. We review available HSCAs and discuss dosing and age specifications for use in children. We also review various hepatic and biliary indications for HSCA use in children, with emphasis on the imaging characteristics distinct to HSCAs, as well as discussion of pitfalls one can encounter when imaging with HSCAs. Given the growing concern regarding gadolinium deposition in soft tissues and brain, we also discuss safety of HSCA use in children.

Acute Adverse Events Following Gadolinium-based Contrast Agent Administration: A Single-Center Retrospective Study of 281 945 Injections.

Background Acute allergic-like and physiologic reactions occur following administration of gadolinium-based contrast agents (GBCAs) for MRI examinations. Because these reactions are uncommon, it is challenging to compare reaction rates between GBCAs and to determine risk factors. Purpose To compare reaction rates between the four GBCAs gadodiamide, gadobutrol, gadobenate dimeglumine, and gadoterate meglumine, and to determine potential risk factors for reactions. Materials and Methods This retrospective study identified all intravenous GBCA injections for MRI examinations performed at a single institution from June 1, 2009, to May 9, 2017. Reactions were identified by reviewing records from the MRI technologist, MRI nursing staff, radiologist, emergency department, and provider. Reactions were classified as allergic-like or physiologic and as mild, moderate, or severe by using American College of Radiology criteria. GBCA reaction rates and other potential risk factors were examined by using multivariable regression models with generalized estimating equations. Results Analysis included a total of 158 100 patients (median age, 55 years [interquartile range, 40-67 years], 51% women) who received a total of 281 945 GBCA injections (140 645 gadodiamide, 94 109 gadobutrol, 39 138 gadobenate, and 8053 gadoterate). At multivariate analysis, gadobenate or gadobutrol had higher rates of allergic-like reactions compared with gadodiamide (gadobenate: odds ratio [OR], 3.9 [95% confidence interval {CI}: 3.0, 5.1]; P < .001; gadobutrol: OR, 2.3 [95% CI: 1.8, 2.9]; P < .001) or gadoterate (gadobenate: OR, 4.8 [95% CI: 1.0, 23]; P = .049; gadobutrol: OR, 2.8 [95% CI: 0.6, 14]; P = .20). Physiologic reactions were more frequently observed with gadoterate (OR, 7.7 [95% CI: 2.3, 25; P = .001), gadobenate (OR, 1.8 [95% CI: 1.3, 2.5; P < .001), and gadobutrol (OR, 1.6 [95% CI: 1.3, 2.1; P < .001) administration compared with gadodiamide. Six severe allergic-like reactions (three gadobutrol, three gadobenate) occurred requiring hospitalization. Patient age (P values .025 to < .001), sex (P < .001), location (P = .006), and MRI type (P = .003 and P = .006) were associated with acute reactions. Conclusion Gadobenate and gadobutrol are associated with higher rates of allergic-like reactions compared with gadodiamide or gadoterate, and gadoterate, gadobenate, and gadobutrol are associated with higher rates of physiologic reactions compared with gadodiamide. Patient sex, age, location, and MRI type correlate with acute reaction rates. © RSNA, 2019 Online supplemental material is available for this article.

Usefulness of diffusion-weighted MRI in the initial assessment of osseous sarcomas in children and adolescents.

Concern regarding gadolinium deposition in the brain after repeated administration of intravenous gadolinium-based contrast agents has prompted evaluation of imaging alternatives. The study purpose was to determine if magnetic resonance imaging (MRI) using conventional sequences with diffusion-weighted imaging (DWI) instead of gadolinium-based contrast-enhanced MRI is valid for local staging and guiding biopsies in osseous sarcomas. Initial pretreatment MRI with DWI and gadolinium-based contrast-enhanced images in patients ≤ 18years with histopathologically proven osseous sarcomas were included. Two radiologists blinded to collated demographic and clinical data, independently reviewed conventional/DWI and conventional/gadolinium-based contrast-enhanced MRI then conventional sequences alone, recording tumor size, skip lesions, necrosis, neurovascular invasion, enlarged lymph nodes and diffusion restriction. Discrepancies were resolved by a third reader. A single reader measured apparent diffusion coefficient (ADC) values in non-necrotic tumors, then correlated minimum ADC values -- with and without normalization to skeletal muscle -- with relative enhancement. Twenty-one patients (mean age: 11.3±4.2years, 15 [71%] females) had 14 osteosarcomas and 7 Ewing sarcomas, 50% centered in the femur. Conventional/DWI versus conventional/gadolinium-based contrast-enhanced MRI showed agreement for tumor size estimation with significant associations for necrosis (P=0.021), neurovascular involvement (P<0.001) and enlarged lymph nodes (P=0.005). Diagnostic accuracy of conventional/DWI is comparable to conventional/gadolinium-based contrast-enhanced MRI and superior to conventional sequences alone. Comparison between minimum ADC values and relative enhancement showed no correlation (P>0.05). Significant associations of key imaging features in the initial assessment of osseous sarcomas support DWI as an alternative to gadolinium-based contrast-enhanced MRI. The lack of association between ADC values and relative enhancement suggests that they measure independent constructs, DWI dependent upon tumor cellularity and perfusion.

Glymphatic Pathway of Gadolinium-Based Contrast Agents Through the Brain: Overlooked and Misinterpreted.

The "glymphatic system" (GS), a brain-wide network of cerebrospinal fluid microcirculation, supplies a pathway through and out of the central nervous system (CNS); malfunction of the system is implicated in a variety of neurological disorders. In this exploratory study, we analyzed the potential of a new imaging approach that we coined delayed T2-weighted gadolinium-enhanced imaging to visualize the GS in vivo. Heavily T2-weighted fluid-attenuated inversion recovery (hT2w-FLAIR) magnetic resonance imaging was obtained before, and 3 hours and 24 hours after intravenous gadolinium-based contrast agent (GBCA) application in 33 neurologically healthy patients and 7 patients with an impaired blood-brain barrier (BBB) due to cerebral metastases. Signal intensity (SI) was determined in various cerebral fluid spaces, and white matter hyperintensities were quantified by applying the Fazekas scoring system. Delayed hT2w-FLAIR showed GBCA entry into the CNS via the choroid plexus and the ciliary body, with GBCA drainage along perineural sheaths of cranial nerves and along perivascular spaces of penetrating cortical arteries. In all patients and all sites, a significant SI increase was found for the 3 hours and 24 hours time points compared with baseline. Although no significant difference in SI was found between neurologically healthy patients and patients with an impaired BBB, a significant positive correlation between Fazekas scoring system and SI increase in the perivascular spaces 3 hours post injection was shown. Delayed T2-weighted gadolinium-enhanced imaging can visualize the GBCA pathway into and through the GS. Presence of GBCAs within the GS might be regarded as part of the natural excretion process and should not be mixed up with gadolinium deposition. Rather, the correlation found between deep white matter hyperintensities, an imaging sign of vascular dementia, and GS functioning demonstrated feasibility to exploit the pathway of GBCAs through the GS for diagnostic purposes.