The purpose of this manuscript is to review the successive regulatory actions and decisions following the initial publication by Kanda and colleagues in 2014 regarding gadolinium retention in the human brain after multiple gadolinium-based contrast agents (GBCAs) administrations.
Materials and Methods
Starting from 2014, the actions and decisions made by all regulatory authorities were collected and summarized region by region. Volumes of GBCA sales in 2018 per region and main countries are also presented as an indicator of patients’ exposure to those products.
All regulatory authorities agreed on the absence of evidence of any harmful effect of gadolinium retention in humans. However, based on the same amount of preclinical and clinical evidence available in adults and children, regulatory authorities used different approaches resulting in different actions and decisions regarding the labeling and market authorizations of GBCAs, as well as the specific actions requested to the manufacturers.
The manufacturers of GBCAs had to face different situations according to the countries, due to the different positions and expectations from regulatory agencies. They have adapted their responses to the different positions of the regulatory agencies and conducted specific preclinical and clinical investigations to provide the expected evidence. It is also their responsibility to continuously monitor the benefit-risk balance of the products and to propose risk minimization measures to the regulatory agencies.
The advent of computed tomography (CT) has revolutionized radiology, and this revolution is still going on. Starting as a pure head scanner, modern CT systems are now able to perform whole-body examinations within a couple of seconds in isotropic resolution, single-rotation whole-organ perfusion, and temporal resolution to fulfill the needs of cardiac CT. Because of the increasing number of CT examinations in all age groups and overall medical-driven radiation exposure, dose reduction remains a hot topic. Although fast gantry rotation, broad detector arrays, and different dual-energy solutions were main topics in the past years, new techniques such as photon counting detectors, powerful x-ray tubes for low-kV scanning, automated image preprocessing, and machine learning algorithms have moved into focus today.
The aim of this article is to give an overview of the technical specifications of up-to-date available CT systems and recent hardware and software innovations for CT systems in the near future.
The aim of this study was to compare the risk of hypersensitivity reactions to iopromide after intra-arterial (IA) administration and intravenous (IV) administration.
Materials and Methods
Four observational studies were pooled. Almost half of the study population (48.1%) was from Europe, and one quarter each from China (27.6%) and other Asia countries (24.1%). All patients received iopromide either intra-arterially or intravenously for angiographic procedures (mostly cardio-angiography) or contrast-enhanced computed tomography. A nested case-control analysis, including a multivariable logistic regression model, was performed. Cases were defined by patients with a typical and unequivocal hypersensitivity (assumed non–IgE-mediated) reaction; controls were patients without any recorded reaction. The primary target variable is the odds ratio of having a hypersensitivity reaction after IA versus IV administration.
A total of 133,331 patients met the inclusion criteria, 105,460 and 27,871 patients received iopromide IV or IA, respectively. Hypersensitivity reactions were recorded for 822 patients, and 132,509 patients served as controls.
Major risk factors for hypersensitivity reactions were method of injection (IV vs IA), age (18 to <50 years vs ≥65 years), history of allergy or previous contrast media reaction (all P < 0.001), and asthma (P = 0.005).
A total of 766 patients (0.7%) and 56 patients (0.2%) were recorded with hypersensitivity reactions after IV or IA administration, respectively (P < 0.0001).
Adjusted odds ratio (IA vs IV) was 0.23 (95% confidence interval, 0.16–0.32) for all countries together: for China only, 0.22 (0.11–0.44); for all countries without China, 0.36 (0.25–0.53).
Most frequent reactions were erythema/urticaria/rash, pruritus, and cough/sneezing.
Hypersensitivity reactions to iopromide were significantly less frequently recorded after IA administrations. This could be related to the delayed and diluted arrival of iopromide to the lungs.
The aim of this study was to compare image quality, conspicuity, and endoleak detection between single-energy low-kV images (SEIs) and dual-energy low-keV virtual monoenergetic images (VMIs+) in computed tomography angiography of the aorta after endovascular repair.
Materials and Methods
An abdominal aortic aneurysm phantom simulating 36 endoleaks (2 densities; diameters: 2, 4, and 6 mm) in a medium- and large-sized patient was used. Each size was scanned using single-energy at 80 kVp (A) and 100 kVp (B), and dual-energy at 80/Sn150kVp for the medium (C) and 90/Sn150kVp for the large size (D). VMIs+ at 40 keV and 50 keV were reconstructed from protocols C and D. Radiation dose was 3 mGy for the medium and 6 mGy for the large size. Objective image quality and normalized noise power spectrum were determined. Subjective image quality, conspicuity, and sensitivity for endoleaks were independently assessed by 6 radiologists. Sensitivity was compared using Marascuilo procedure and Fisher exact test. Conspicuities were compared using Wilcoxon-matched pairs test, analysis of variance, and Tukey test.
The contrast-to-noise-ratio of the aorta was significantly higher for VMI+ compared with SEI (P < 0.001). Noise power spectrum showed a higher noise magnitude and coarser texture in VMI+. Subjective image quality and overall conspicuity was lower for VMI+ compared with SEI (P < 0.05). Sensitivity for endoleaks was overall higher in the medium phantom for SEI (60.9% for A, 62.2% for B) compared with VMI+ (54.2% for C, 49.3% for D) with significant differences between protocols B and D (P < 0.05). In the large phantom, there was no significant difference in sensitivity among protocols (P = 0.79), with highest rates for protocols B (31.4%) and C (31.7%).
Our study indicates that low-keV VMI+ results in improved contrast-to-noise-ratio of the aorta, whereas noise properties, subjective image quality, conspicuity, and sensitivity for endoleaks were overall superior for SEI.
The use of artificial intelligence (AI) is a powerful tool for image analysis that is increasingly being evaluated by radiology professionals. However, due to the fact that these methods have been developed for the analysis of nonmedical image data and data structure in radiology departments is not “AI ready”, implementing AI in radiology is not straightforward. The purpose of this review is to guide the reader through the pipeline of an AI project for automated image analysis in radiology and thereby encourage its implementation in radiology departments. At the same time, this review aims to enable readers to critically appraise articles on AI-based software in radiology.
Being administered intravenously, the tissue that gadolinium-based contrast agents (GBCAs) for magnetic resonance imaging mostly encounter is blood. Herein, it has been investigated how much Gd is internalized by cellular blood components upon the in vitro incubation of GBCAs in human blood or upon intravenous administration of GBCAs to healthy mice. We report results that show how the superb sensitivity of inductively coupled plasma–mass spectrometry (ICP-MS) allows the detection of very tiny amounts of GBCAs entering red blood cells (RBCs) and white blood cells (WBCs). This finding may introduce new insights in the complex matter relative to excretion and retention pathway of administered GBCAs.
Materials and Methods
The study was tackled by 2 independent approaches. First, human blood was incubated in vitro with 5 mM of GBCAs (gadoteridol, gadobenate dimeglumine, gadodiamide, and gadopentetate dimeglumine) for variable times (30 minutes, 1 hour, 2 hours, and 3 hours) at 37°C. Then, blood cell components were isolated by using the Ficoll Histopaque method, washed 3 times, mineralized, and analyzed by ICP-MS for total Gd quantification. Furthermore, blood components derived from human blood incubated with gadodiamide or gadoteridol underwent UPLC-MS (ultra performance liquid chromatography–mass spectrometry) analysis for determination of the amount of intact Gd-DTPA-BMA and Gd-HPDO3A. Second, the distribution of Gd in the blood components of healthy CD-1 mice was administered intravenously with a single dose (1.2 mmol/kg) of gadodiamide or gadoteridol. Blood samples were separated and processed at different time points (24 hours, 48 hours, 96 hours, and 10 days after GBCA administration). As for human blood, ICP-MS quantification of total Gd and UPLC-MS determination of the amount of intact GBCAs were carried out.
The amount of Gd taken up by RBCs and WBCs was well detectable by ICP-MS. The GBCAs seem to be able to cross the membrane by diffusion (RBCs) or, possibly, by macropinocytosis (WBCs). Ex vivo studies allowed it to be established that the structure of the different GBCAs were not relevant to determine the amount of Gd internalized in the cells. Although the amount of Gd steadily decreases over time in gadoteridol-labeled cells, in the case of gadodiamide, the amount of Gd in the cells does not decrease (even 10 days after the administration of the GBCA). Moreover, while gadoteridol maintains its structural integrity upon cellular uptake, in the case of gadodiamide, the amount of intact complex markedly decreases over time.
The detection of significant amounts of Gd in RBCs and WBCs indicates that GBCAs can cross blood cell membranes. This finding may play a role in our understanding of the processes that are at the basis of Gd retention in the tissues of patients who have received the administration of GBCAs.