Injection Of Gadolinium-based Contrast Agent Research Articles

Different Glymphatic Kinetics in Spontaneous Intracranial Hypotension.

The glymphatic (glia-lymphatic) system is a paravascular pathway for the clearance of waste metabolites including amyloid β from the brain. Serial T1 relaxation time measurements after the intrathecal injection of gadolinium-based contrast agents facilitate the analysis of the temporal dynamics that may be different in patients with spontaneous intracranial hypotension (SIH) and those without SIH. 3D T1-weighted magnetization-prepared 2 rapid gradient echo sequences were acquired in 4 patients with SIH with proved CSF leaks and 12 patients without SIH before, 2-4, 6-8, and 24-48 hours after intrathecal gadobutrol injection. MR scans were warped to the Montreal Neurological Institute space and serial scans were coregistered. T1 relaxation times were measured in predefined ROIs including the subarachnoid space, cortex, white matter, and cervical lymph nodes. In the subarachnoid space and cortex, T1 relaxation times decreased after 2-4 and 6-8 hours before they increased again. In contrast, in the white matter of the temporal lobe T1 relaxation time still decreased after 24-48 hours. There was a striking difference in patients with SIH who did not show a clear contrast distribution within the brain parenchyma. T1 relaxation time curves are compatible with a convective flow driven by arterial pulsations via paravascular spaces surrounding penetrating arteries into the brain's interstitial fluid in the deep white matter. Different curves in patients with SIH and those without SIH indicate that the CSF pressure also impacts the temporal kinetics of the glymphatic system.

Deposition of Gadolinium in the Central and Peripheral Nervous Systems and Its Effects on Sensory, Cognitive, and Athletic Implications after Multiple Injections of Gadolinium-Based Contrast Agents in Rats.

After repeat administration of gadolinium-based contrast agents (GBCAs), the association between gadolinium retention in the central and peripheral nervous systems and the main manifestations of myelopathy and progressive neurologic symptoms remains unclear. We investigated the effects of the repeat administration of GBCAs on gadolinium retention in the central and peripheral nervous systems and the sensory, cognitive, and athletic implications. Forty-eight male Wistar rats (6 weeks of age) were randomly divided into 4 experimental groups (12 rats in each group): the gadodiamide group (linear and nonionic GBCAs), the gadopentetate dimeglumine group (linear and ionic GBCAs), the gadoterate meglumine group (macrocyclic and ionic GBCAs), and the control group (0.9% saline solution). The brains of the rats were scanned using 9.4T MRI. Sensory behavioral tests were performed to assess the effect of GBCAs on pain sensitivity function. Gadolinium deposition in the brain, spinal cord, and peripheral nerves was determined by inductively coupled plasma mass-spectrometry. Transmission electron microscopy was used to observe the microscopic distribution of gadolinium after deposition in the spinal cord. The histopathologic features in the spinal cord were analyzed by H&E staining, Nissl staining, glial fibrillary acidic protein staining, and neuron-specific enolase staining after administration of GBCAs. All GBCAs resulted in gadolinium deposition in the central and peripheral nerve tissues, with the highest deposition in the sciatic nerve tissue (mean, 62.86 [SD, 12.56] nmol/g). Decreased muscle power, impairment of spatial cognitive function power, and pain hypersensitivity to thermal and mechanical stimuli were observed after exposure to gadodiamide. At the spinal cord, transmission electron microscopy found that the region of gadolinium depositions had a spheric structure similar to "sea urchins" and was mainly located near the vascular basement membrane. Multiple injections of GBCAs caused gadolinium deposition in the brain, spinal cord, and peripheral nerves, especially in the spinal cords of the gadodiamide group. Gadodiamide led to pain hypersensitivity and decreased muscle power and cognitive ability. For the patients who are hypersensitive to pain and need multiple MRI examinations, we recommend using macrocyclic GBCAs and the lowest dose possible.

Fat-signal suppression in breast diffusion-weighted imaging: the Good, the Bad, and the Ugly.

Fat-signal suppression is essential for breast diffusion magnetic resonance imaging (or diffusion-weighted MRI, DWI) as the very low diffusion coefficient of fat tends to decrease absolute diffusion coefficient (ADC) values. Among several methods, the STIR (short-tau inversion recovery) method is a popular approach, but signal suppression/attenuation is not specific to fat contrary to other methods such as SPAIR (spectral adiabatic (or attenuated) inversion recovery). This article focuses on those two techniques to illustrate the importance of appropriate fat suppression in breast DWI, briefly presenting the pros and cons of both approaches. We show here through simulation and data acquired in a dedicated breast DWI phantom made of vials with water and various concentrations of polyvinylpyrrolidone (PVP) how ADC values obtained with STIR DWI may be biased toward tissue componentswith the longest T1 values: ADC values obtained with STIR fat suppression may be over/underestimated depending on the T1 and ADC profile within tissues. This bias is also illustrated in twoclinical examples. Fat-specific methods should be preferred over STIR for fat-signal suppression in breast DWI, such as SPAIR which also provides a higher sensitivity than STIR for lesion detection. One should remain aware, however, that efficient fat-signal suppression with SPAIR requires good B0 shimming to avoid ADC underestimation from residual fat contamination. The spectral adiabatic (or attenuated) inversion recovery (SPAIR) method should be preferred over short-tau inversion recovery (STIR) for fat suppression in breast DWI. Fat-signal suppression is essential for breast DWI; the SPAIR method is recommended. Short-tau inversion recovery (STIR)is not specific to fat; as a result, SNR is decreased and ADC values may be over- or underestimated. The STIR fat-suppression method must not be used after the injection of gadolinium-based contrast agents.

The effect of time-delayed contrast-enhanced scanning in determining the gross tumor target volume of large-volume brain metastases

Background and PurposeTo assess the variation of large-volume brain metastases (BMs) boundaries and shapes using enhanced magnetic resonance (MR) scanning with different delay times and to provide a basis for determining the gross tumor target volume (GTV) for radiotherapy of BMs. Materials and MethodsWe prospectively enrolled 155 patients initially diagnosed with BMs (561 lesions > 1 cm). Contrast-enhanced (CE) T1-weighted imaging scans were performed 1, 3, 5, 10, 18, and 20 min after gadolinium-based contrast agent injection and GTVs were determined as GTV-1min, GTV-3min, GTV-5min, GTV-10min, GTV-18min, and GTV-20min, respectively, which were subsequently fused in different phases. Fusion of the six GTVs was defined as GTV-total, which was set as the reference GTV. The volume, shape, and signal intensity of the GTVs and brain white matter (BWM) were compared at different delay times. ResultsGTV-3min, GTV-5min, GTV-10min, GTV-18min, and GTV-20min volumes increased by 2.2 %, 3.8 %, 6.5 %, 9.5 %, and 10.6 %, respectively (P < 0.05) compared with GTV-1min. Compared with GTV-total, GTV-1min, GTV-3min, GTV-5min, GTV-10min, GTV-18min, and GTV-20min volumes reduced by 25.4 %, 22.1 %, 18.7 %, 15.0 %, 11.2 %, and 10.3 %, respectively (P < 0.05). Compared with GTV-total, 29 (51.8 %) fused GTVs had a volume reduction rate < 5 %, 45 (80.4 %) had a Dice similarity coefficient > 0.95, and all contained GTV-10min, GTV-18min or GTV-20min. The signal intensity ratio between the GTV and BWM peaked at 5 min (0.351 ± 0.24). ConclusionEnhanced MR scans with different delay times show significant differences in the boundaries and shapes of large-volume BMs, and time-delayed multi-phase CE scanning should be used in GTV determination, with time phases ≥ 10 min being mandatory.

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

PurposeThe 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.Materials and methodsNinety-eight participants (aged 14–84 years) were scanned 4 h 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.ResultsA 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.ConclusionThe 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.

Human brain clearance imaging: Pathways taken by magnetic resonance imaging contrast agents after administration in cerebrospinal fluid and blood.

Over the last decade, it has become evident that cerebrospinal fluid (CSF) plays a pivotal role in brain solute clearance through perivascular pathways and interactions between the brain and meningeal lymphatic vessels. Whereas most of this fundamental knowledge was gained from rodent models, human brain clearance imaging has provided important insights into the human system and highlighted the existence of important interspecies differences. Current gold standard techniques for human brain clearance imaging involve the injection of gadolinium-based contrast agents and monitoring their distribution and clearance over a period from a few hours up to 2 days. With both intrathecal and intravenous injections being used, which each have their own specific routes of distribution and thus clearance of contrast agent, a clear understanding of the kinetics associated with both approaches, and especially the differences between them, is needed to properly interpret the results. Because it is known that intrathecally injected contrast agent reaches the blood, albeit in small concentrations, and that similarly some of the intravenously injected agent can be detected in CSF, both pathways are connected and will, in theory, reach the same compartments. However, because of clear differences in relative enhancement patterns, both injection approaches will result in varying sensitivities for assessment of different subparts of the brain clearance system. In this opinion review article, the "EU Joint Programme - Neurodegenerative Disease Research (JPND)" consortium on human brain clearance imaging provides an overview of contrast agent pharmacokinetics in vivo following intrathecal and intravenous injections and what typical concentrations and concentration-time curves should be expected. This can be the basis for optimizing and interpreting contrast-enhanced MRI for brain clearance imaging. Furthermore, this can shed light on how molecules may exchange between blood, brain, and CSF.

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.

Brain Tumor Imaging without Gadolinium-based Contrast Agents: Feasible or Fantasy?

Gadolinium-based contrast agents (GBCAs) form the cornerstone of current primary brain tumor MRI protocols at all stages of the patient journey. Though an imperfect measure of tumor grade, GBCAs are repeatedly used for diagnosis and monitoring. In practice, however, radiologists will encounter situations where GBCA injection is not needed or of doubtful benefit. Reducing GBCA administration could improve the patient burden of (repeated) imaging (especially in vulnerable patient groups, such as children), minimize risks of putative side effects, and benefit costs, logistics, and the environmental footprint. On the basis of the current literature, imaging strategies to reduce GBCA exposure for pediatric and adult patients with primary brain tumors will be reviewed. Early postoperative MRI and fixed-interval imaging of gliomas are examples of GBCA exposure with uncertain survival benefits. Half-dose GBCAs for gliomas and T2-weighted imaging alone for meningiomas are among options to reduce GBCA use. While most imaging guidelines recommend using GBCAs at all stages of diagnosis and treatment, non-contrast-enhanced sequences, such as the arterial spin labeling, have shown a great potential. Artificial intelligence methods to generate synthetic postcontrast images from decreased-dose or non-GBCA scans have shown promise to replace GBCA-dependent approaches. This review is focused on pediatric and adult gliomas and meningiomas. Special attention is paid to the quality and real-life applicability of the reviewed literature.

Near-cure in patients with Gadolinium deposition disease undergoing intravenous DTPA chelation.

To demonstrate and evaluate factors contributing to near-cures in patients with Gadolinium Deposition Disease (GDD) undergoing intravenous (IV) DTPA chelation. Patients who had undergone or are currently undergoing DTPA chelation for GDD were included in this report based on their medical records that showed their perceived improvement was at least 80% back to normal. A survey was developed that included factors commonly reported by patients treated in one clinic to determine if these 'near-cured' (pre-MRI baseline health) individuals possessed certain factors and lacked others. The anonymized survey was emailed to these individuals by the principal treating physician, the only investigator not blinded to the subjects. This report describes clinical documentation of patient status and their underlying factors in individuals treated by the primary author, and no research was performed. The survey was sent to sixteen individuals; Fourteen patients completed it (10 females; 41.1 ± 11.2y/o). The most common factor was the administration of ≤5 lifetime doses of a Gadolinium-Based Contrast Agents (GBCA) (12/14). Unconfounded agents triggering GDD were seen in nine subjects. Most subjects (12/14) initiated chelation in the first year after the causative GBCA, and most (11/14) underwent ≤10 chelations with DTPA. Good healthcare status prior to MRI was observed in 5 subjects. The majority (11/14) described their immune status as strong. Severe physical disability prior to chelation was seen in 1. Subjects with GDD can experience near-cure with IV DTPA chelation. Factors surveyed that predict near-cure include the start of chelation in the first year, few GBCA administrations, and good health status before MRI with GBCA injection. Nonetheless, a few patients with predictors of less successful outcomes still experienced near-cure.

Smart forecasting of artifacts in contrast-enhanced breast MRI before contrast agent administration

ObjectivesTo evaluate whether artifacts on contrast-enhanced (CE) breast MRI maximum intensity projections (MIPs) might already be forecast before gadolinium-based contrast agent (GBCA) administration during an ongoing examination by analyzing the unenhanced T1-weighted images acquired before the GBCA injection.Materials and methodsThis IRB-approved retrospective analysis consisted of n = 2884 breast CE MRI examinations after intravenous administration of GBCA, acquired with n = 4 different MRI devices at different field strengths (1.5 T/3 T) during clinical routine. CE-derived subtraction MIPs were used to conduct a multi-class multi-reader evaluation of the presence and severity of artifacts with three independent readers. An ensemble classifier (EC) of five DenseNet models was used to predict artifacts for the post-contrast subtraction MIPs, giving as the input source only the pre-contrast T1-weighted sequence. Thus, the acquisition directly preceded the GBCA injection. The area under ROC (AuROC) and diagnostics accuracy scores were used to assess the performance of the neural network in an independent holdout test set (n = 285).ResultsAfter majority voting, potentially significant artifacts were detected in 53.6% (n = 1521) of all breast MRI examinations (age 49.6 ± 12.6 years). In the holdout test set (mean age 49.7 ± 11.8 years), at a specificity level of 89%, the EC could forecast around one-third of artifacts (sensitivity 31%) before GBCA administration, with an AuROC = 0.66.ConclusionThis study demonstrates the capability of a neural network to forecast the occurrence of artifacts on CE subtraction data before the GBCA administration. If confirmed in larger studies, this might enable a workflow-blended approach to prevent breast MRI artifacts by implementing in-scan personalized predictive algorithms.Clinical relevance statementSome artifacts in contrast-enhanced breast MRI maximum intensity projections might be predictable before gadolinium-based contrast agent injection using a neural network.Key Points• Potentially significant artifacts can be observed in a relevant proportion of breast MRI subtraction sequences after gadolinium-based contrast agent administration (GBCA).• Forecasting the occurrence of such artifacts in subtraction maximum intensity projections before GBCA administration for individual patients was feasible at 89% specificity, which allowed correctly predicting one in three future artifacts.• Further research is necessary to investigate the clinical value of such smart personalized imaging approaches.

Delayed Gadolinium Leakage in Ocular Structures on Brain MR Imaging: Prevalence and Associated Factors.

Gadolinium leakage in ocular structures (GLOS) is characterized by hyperintense signal in the chambers of the eye on FLAIR and has been reported in association with blood-ocular barrier breakdown in patients with ischemic strokes. The underlying mechanism of GLOS remains poorly understood; however, some studies suggest it may be part of a physiologic excretion pathway of gadolinium. This study aimed to determine the prevalence of GLOS in an unselected patient population. A retrospective analysis was conducted on 439 patients who underwent brain MR imaging within 7 days of receiving a gadolinium-based contrast agent injection for a prior MR imaging study. Clinical, imaging, and laboratory data were collected. Descriptive and logistic regression analyses were performed. GLOS was observed in 26 of 439 patients (6%). The occurrence of GLOS varied with time, with 3 (12%), 14 (54%), 8 (31%), and 1 (4%) patient showing GLOS within 24, 25-72, 73-120, and >120 hours after gadolinium-based contrast agent injection, respectively. Patients with GLOS were older (median age: 72 versus 55 years, P = .001) and had higher median serum creatinine levels (73 versus 64 µmol/L, P = .005) and a lower median estimated glomerular filtration rate (84 versus 101 mL/min/1.73 m2, P < .001). A shorter median time interval between gadolinium-based contrast agent injection and the index brain MR imaging was observed in the group positive for GLOS (62 versus 91 hours, P = .003). Multivariable regression analysis identified the estimated glomerular filtration rate (OR = 0.970; 95% CI, 0.049-0.992; P = .008) and time interval since gadolinium-based contrast agent injection (OR = 0.987; 95% CI, 0.977-0.997; P = .012) as independent factors associated with GLOS. GLOS was observed in only a small percentage of patients receiving gadolinium-based contrast agent within 7 days before brain MR imaging. This phenomenon was noted in patients with normal findings on brain MR imaging and those with various CNS pathologies, and it was associated with lower estimated glomerular filtration rates and shorter time intervals after gadolinium-based contrast agent injection. While GLOS may be a physiologic gadolinium-based contrast agent excretion pathway, the presence of ocular disease was not formally evaluated in the included population. Awareness of GLOS is nonetheless useful for appropriate radiologic interpretation.

Elemental Bioimaging of Sheep Bone and Articular Cartilage After Single Application of Gadolinium-Based Contrast Agents.

Gadolinium-based contrast agents (GBCAs) are applied to enhance magnetic resonance imaging. Gadolinium (Gd), a rare earth metal, is used in a chelated form when administered as GBCA to patients. There is an ongoing scientific debate about the clinical significance of Gd retention in tissues after administration of GBCAs. It is known that bone serves as Gd reservoir, but only sparse information on localization of Gd in bone is available. The aim of this study was to compare Gd tissue concentration and spatial distribution in femoral epiphysis and diaphysis 10 weeks after single-dose injection of linear and macrocyclic GBCAs in a large animal model. In this prospective animal study, Swiss-Alpine sheep (n = 36; age range, 4-10 years) received a single injection (0.1 mmol/kg) of macrocyclic (gadobutrol, gadoteridol, and gadoterate meglumine), linear (gadodiamide and gadobenate dimeglumine) GBCAs, or saline. Ten weeks after injection, sheep were killed, and femur heads and shafts were harvested. Gadolinium spatial distribution was determined in 1 sample of each treatment group by laser ablation-inductively coupled plasma-mass spectrometry. All bone specimens were analyzed histopathologically. Injection of GBCAs in female Swiss-Alpine sheep (n = 36) resulted in Gd localization at the endosteal and periosteal surface and in a subset of GBCAs additionally at the cement lines and the bone cartilage junction. No histopathological alterations were observed in the investigated tissue specimens. Ten weeks after single injection of a clinically relevant dose in adult sheep, both linear species of GBCA resulted in considerably higher accumulation than macrocyclic GBCAs. Gadolinium deposits were restricted to distinct bone and cartilage compartments, such as in bone linings, cement lines, and bone cartilage junctions. Tissue histology remained unaffected.

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.

Is non-contrast MRI sufficient to detect meningioma residue after surgery?

BackgroundContrast-enhanced magnetic resonance imaging (MRI) is the imaging modality routinely used to follow up patients who have undergone surgical resection of brain meningiomas. There are growing concerns about the massive use of gadolinium-based contrast agents (GBCA). Our aim was to evaluate the performance of a new imaging protocol, performed without GBCA injection, in the detection of tumoral residue or local recurrence after surgery of parafalcine and convexity meningiomas. Materials and methodsOnly adult patients with a documented resected parafalcine or convexity meningioma were included. We performed a dedicated MRI protocol that included non-contrast and post-contrast sequences. The presence or absence of residue on the unenhanced sequences was independently recorded by three observers: first blindly, then in comparison with a baseline enhanced MRI examination. ResultsA total of 51 patients were included. 37 of them featured a tumor residue on the reference enhanced sequence. Overall, an average of 32 of 37 (87%) residues were identified on the unenhanced sequences that were blindly reviewed; and more than 34 of 37 (93%) were identified with the help of the comparative baseline enhanced examination, with a high sensitivity. The missed cases were related to small residues. ConclusionUnenhanced MRI sequences are highly sensitive and specific in identifying a tumor residue or a local recurrence in the post operative follow up of brain meningiomas. Sensitivity is even higher with the help of a comparative baseline enhanced MRI examination, whatever the strength of magnetic field.

Gadolinium K-edge angiography with a spectral photon counting CT in atherosclerotic rabbits

PurposeThe purpose of this study was to investigate the feasibility of gadolinium-K-edge-angiography (angio-Gd-K-edge) with gadolinium-based contrast agents (GBCAs) as obtained with spectral photon counting CT (SPCCT) in atherosclerotic rabbits. Materials and methodsSeven atherosclerotic rabbits underwent angio-SPCCT acquisitions with two GBCAs, with similar intravenous injection protocol. Conventional and angio-Gd-K-edge images were reconstructed with the same parameters. Regions of interest were traced in different locations of the aorta and its branches. Hounsfield unit values, Gd concentrations, signal-to-noise (SNR) and contrast-to-noise (CNR) were calculated and compared. The maximum diameter and the diameter of the aorta in regard to atherosclerotic plaques were measured by two observers. Images were subjectively evaluated regarding vessels’ enhancement, artefacts, border sharpness and overall image quality. ResultsIn the analyzable six rabbits, Gd-K-edge allowed visualization of target vessels and no other structures. HU values and Gd concentrations were greatest in the largest artery (descending aorta, 5.6 ± 0.8 [SD] mm), and lowest in the smallest (renal arteries, 2.1 ± 0.3 mm). While greater for conventional images, CNR and SNR were satisfactory for both images (all P < 0.001). For one observer there were no statistically significant differences in either maximum or plaque-diameters (P = 0.45 and all P > 0.05 in post-hoc analysis, respectively). For the second observer, there were no significant differences for images reconstructed with the same parameters (all P < 0.05). All subjective criteria scored higher for conventional images compared to K-edge (all P < 0.01), with the highest scores for enhancement (4.3–4.4 vs. 3.1–3.4). ConclusionWith SPCCT, angio-Gd-K-edge after injection of GBCAs in atherosclerotic rabbits is feasible and allows for angiography-like visualization of small arteries and for the reliable measurement of their diameters.

Elemental bioimaging and transcriptomics reveal unchanged gene expression in mouse cerebellum following a single injection of Gadolinium-based contrast agents

Gadolinium (Gd) deposition in the brain, first and foremost in the dentate nucleus in the cerebellum, following contrast enhanced MRI, rose awareness of potential adverse effects of gadolinium-based contrast agent (GBCA) administration. According to previous in vitro experiments, a conceivable side-effect of Gd deposition could be an alteration of gene expression. In the current study, we aimed to investigate the influence of GBCA administration on gene expression in the cerebellum of mice using a combination of elemental bioimaging and transcriptomics. In this prospective animal study, three groups of eight mice each were intravenously injected with either linear GBCA gadodiamide, macrocyclic GBCA gadoterate (1 mmol GBCA/kg body weight) or saline (NaCl 0.9%). Animals were euthanized four weeks after injection. Subsequently, Gd quantification via laser ablation-ICP-MS and whole genome gene expression analysis of the cerebellum were performed. Four weeks after single application of GBCAs to 24–31 days old female mice, traces of Gd were detectable in the cerebellum for both, the linear and macrocyclic group. Subsequent transcriptome analysis by RNA sequencing using principal component analysis did not reveal treatment-related clustering. Also differential expression analysis did not reveal any significantly differentially expressed genes between treatments.

Impact of gadodiamide (Omniscan) on a beef liver catalase ex vivo model

Gadolinium is used in Magnetic Resonance Imaging scans to enhance image quality and allow doctors to more effectively diagnose patients. It is administered to patients through intravenous injection of gadolinium-based contrast agents (GBCAs). Although most of the injected gadolinium is excreted from the body soon after it is administered, studies have shown that some gadolinium remains in the body for extended periods of time. In patients with renal dysfunction, gadolinium retention has been associated with Nephrogenic Systemic Fibrosis, and even in patients with normal kidney function, long-term gadolinium deposits have been observed in the brain following exposure to GBCAs. The specific biochemical effects of gadolinium retention remain largely unknown, but it is possible that gadolinium may impact enzymatic activity. The present experiment investigated the effects of gadodiamide (brand name Omniscan), a common GBCA, on the function of catalase, a crucial biological enzyme that converts hydrogen peroxide into water and oxygen. We exposed beef liver to various concentrations of hydrogen peroxide both with and without gadodiamide, and we determined the Vmax and Km values of the catalase. We found that the presence of gadodiamide did not significantly inhibit catalase, which we hypothesize is due to the chelating agent present in gadodiamide. This work has important implications for understanding the biochemical effects of GBCAs and their potential impact on patient health.

Higher magnetic susceptibility of globus pallidus in patients after macrocyclic GBCAs: assessment using quantitative susceptibility mapping.

As previous studies reported, gadolinium deposits in globus pallidus (GP) and dentate nucleus (DN) after repeated administrations of gadolinium-based contrast agents (GBCAs) and a signal intensity (SI) increase on T1-weighted images were related to linear GBCAs, not macrocyclic GBCAs. To identify whether quantitative susceptibility mapping (QSM) could measure a subtle increase in magnetic susceptibility in DN and GP in patients after repeated administrations of gadoteric acid meglumine (Gd-DOTA). In this study, 50 patients with cerebral tumors who had received at least three injections of Gd-DOTA (GBCA group) and 50 individuals without a history of GBCA injections (non-GBCA group) were included. The image data for QSM and T1-weighted images were reviewed. Spearman rank correlation was used to estimate the associations between the values (magnetic susceptibility of QSM and SI ratios of T1-weighted images) and the number of Gd-DOTA injections. The mean magnetic susceptibility of GP in GBCA group was 0.136 ± 0.031 ppm, which was significantly higher than that in control group (0.114 ± 0.030 ppm) (P = 0.001). In the GBCA group (n = 50), we found a substantial positive correlation between magnetic susceptibility of GP and the number of Gd-DOTA injections according to Spearman rank correlation coefficient (ρ = 0.673, P = 0.0001). There was a modest but significant correlation between magnetic susceptibility of DN and the number of Gd-DOTA injections (ρ = 0.311, P = 0.028). In comparison to the control group, the magnetic susceptibility of GP in the GBCA group was significantly higher and had a substantial positive association with the number of Gd-DOTA injections.

Gadolinium Distribution in the Kidney, Liver, and Heart of Wistar Rats after Administration of Gadolinium-Based Contrast Agents

Magnetic resonance imaging (MRI) is an established non-invasive and non-destructive medical imaging modality for the assessment of various organ systems in the human body. Gadolinium-Based Contrast Agent (GBCA) enhanced and improved images from MRI and was believed to be entirely excreted through urine in normal kidney function within 24 hours after injection. Previous studies identified gadolinium accumulations in the brain, bones, and skin of animals. This study evaluated gadolinium retention in normal kidneys, Liver, and heart of Wistar rats after administration of GBCAs in male Wistar rats. Twenty-five male Wistar rats of ages ≥ 5 weeks or ≤ 6 weeks in 4 experimental and 1 control groups were studied. Ethical considerations were obtained from the Institutional Review Board (IRB) of the Nigerian Institute of Medical Research (NIMR), Nigeria. Samples in experimental groups each administered 2.5 mls of 4 different GBCAs, and the control group same per day of saline intravenously through the lateral tail for five days a week and continued for 4 weeks. The kidney, Liver, and Heart tissues of these samples were harvested 4 weeks after the last injection and sent for spectrometry evaluation. Samples in the control group had no gadolinium accumulation. Groups administered gadopentetate dimeglumine, and gadodiamide had greater cardiac metrics (0.397 and 0.390). The higher renal metric was experienced by samples that received dotarem and cyclolux (0.397 and 0.377), though the sample exposed to cyclolux reported more Liver metric (0.407) than other concentrations. Wistar rats’ Kidneys, Liver, and Heart retained gadolinium weeks after injection of GBCAs. Keywords: Dotarem and Cyclolux, Gadolinium, Gadodiamide, Gadopentetate dimenglumine, Magnetic resonance imaging.