Administration Of Gadolinium-based Contrast Agents Research Articles

Acute adverse reactions after multiple initially well-tolerated gadolinium-based contrast-enhanced abdomen MRIs in pediatric patients.

Repeated gadolinium-based contrast agent (GBCA)-enhanced MRIs are crucial in the diagnosis and follow-up of oncologic and chronic disorders in pediatric patients. The aim of the study was to evaluate the frequency and severity of adverse reactions to GBCAs in children after a single vs. multiple GBCA-enhanced abdomen MRIs. All pediatric patients with at least one GBCA-enhanced abdominal MRI between 2009 and 2020 were retrospectively evaluated based on adverse reactions reports, according to the classification system of the American College of Radiology and guidelines on contrast agents of the European Society of Urogenital Radiology. A Student´s t-test analysis, a spearman ρ-correlation and a Chi-square test between the reported adverse reactions and the total number of GBCA applications, and the number of each applied GBCA was calculated. A p-value <0.05 was considered significant. Of 623 patients with 964 GBCA-enhanced abdomen MRIs, there were 464 patients with only one and 159 patients with multiple GBCA administrations. Of 964 GBCA doses administrated, two cases with urticaria (mild allergy-like adverse reaction) and one case with vomiting (mild chemotoxic adverse reaction) were recorded (3/964 = 0.31%), but all the reports were in patients with multiple GBCA administration (3/159 = 1.89%). No adverse reactions in patients with a single GBCA administration were observed. The reported adverse reactions correlated significantly with the total number of GBCAs (p<0.001) and the number of each GBCA (p<0.001 or p = 0.002). The independent two-tailed t-tests, and the chi-square test were significant (p<0.001, p = 0.003). GBCA-associated adverse reactions are rare and mostly mild, but initially well-tolerated GBCA could cause adverse reactions due to the increase likelihood of drug hypersensitivity upon repeated GBCA exposure.

The impact of gadolinium-based contrast agents on 1H-magnetic resonance spectroscopy in normal brain area: a preliminary study

Background Giving contrast material before 1H-magnetic resonance spectroscopy (MRS) could enhance the precision of locating the lesion of interest. However, evidence indicates that contrast material might influence the outcomes of MRS. Purpose To verify the effect of gadolinium-based contrast agent (GBCA) on MRS in normal white matter. Material and Methods A total of 34 patients were referred for brain magnetic resonance imaging (MRI) with GBCAs, and they underwent single-volume MRS before and after administering contrast material. Those patients had the MRS voxel placed at the right frontal normal white matter, which remained consistent across all examinations. Measurements were taken for the integral concerning N-acetyl aspartate (NAA), choline (Cho), creatine (Cr and Cr2), and myo-inositol (Ins) in all examinations. Results NAA ( P = 0.0313) and Cho ( P = 0.0094) had a significant decrease in their integral after intravenous GBCA administration. No significant differences were found between the pre- and post-contrast MRS studies for Cr, Cr2, and Ins. Conclusion Intravenous GBCA can alter NAA and Cho integrals in normal white matter. Therefore, brain 1H-MRS should precede intravenous GBCA administration to avoid the potential impact of contrast material on peak integrals.

Loss of aquaporin-4 impairs cerebrospinal fluid solute clearance through cerebrospinal fluid drainage pathways

The aquaporin-4 (AQP4) water channel is essential in neurofluid dynamics. AQP4 loss impairs solute exchange between the cerebrospinal fluid (CSF) and interstitial fluid (ISF). However, whether AQP4 expression affects solute clearance from the CSF space to the extracranial space remains unclear. This study aimed to investigate this using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) following the intrathecal administration of gadolinium-based contrast agents (GBCAs) to AQP4 knockout (KO) rats. AQP4 KO rats showed reduced efflux of intrathecal GBCAs to the extracranial spaces through CSF drainage pathways and increased retention of intrathecal GBCAs in the CSF space compared with the controls. These results suggest that AQP4 loss impairs solute clearance from the CSF space to the extracranial spaces via the CSF drainage pathways. This study revealed a close relationship between AQP4 expression and CSF solute clearance, contributing to a better understanding of the function of AQP4 in neurofluid dynamics.

The GREENWATER study: patients' green sensitivity and potential recovery of injected contrast agents.

The environmental footprint of iodinated contrast agents (ICAs) and gadolinium-based contrast agents (GBCAs) is noteworthy. This study assesses: (1) patients' "green sensitivity" as measured by their acceptance in a sustainability study and (2) the resulting potential reduction of contrast residuals in wastewater. After ethical approval, participants scheduled for administration of ICAs or GBCAs for diagnostic purposes were enrolled in this prospective observational study from July 2022 to October 2023. They were asked to prolong their hospital stay by up to 60 min to collect their first urine in dedicated canisters, thereby measuring the recovery rates of ICAs and GBCAs as found/theoretical ratio of concentrations. Mann-Whitney U, χ2 tests, and multivariable regression analysis were used. Patients scheduled for contrast-enhanced CT or MRI (n = 455) were screened; 422 (92.7%) accepted to participate. We enrolled 212 patients administered with ICAs and 210 administered with GBCAs. The median recovery rate was 51.2% (interquartile range 29.2-77.9%) for ICAs and 12.9% (9.0-19.3%) for GBCAs. At multivariable analysis, a significant effect of patient age (ICAs, p = 0.001; GBCAs, p = 0.014), urine volume (p < 0.001 for both), and time interval from contrast administration to urine collection (p < 0.001 for both) on recovery rates was found for both contrast agents; injected contrast volume (p = 0.046) and saline flushing usage (p = 0.008) showed asignificant effect only for ICAs. The high patient enrollment compliance (93%) and potential recovery rates of 51% (ICAs) and 13% (GBCAs) play in favor of sustainable practices in reducing the environmental footprint of contrast agents. Question How many patients are willing to extend their stay in radiology by up to 60 min to help reduce the environmental impact of contrast agents? Findings Over 90% of screened patients agreed to extend their stay by up to 60 min and collect their urine in dedicated containers. Clinical relevance Patients demonstrated a high willingness to cooperate in reducing the environmental impact of contrast agents, allowing for a potential recovery of approximately 51% for iodinated and 13% for gadolinium-based contrast agents.

Electron microscopy evidence of gadolinium toxicity being mediated through cytoplasmic membrane dysregulation.

Past functional toxicogenomic studies have indicated that genes relevant to membrane lipid synthesis are important for tolerance to the lanthanides. Moreover, previously reported imaging of patient's brains following administration of gadolinium-based contrast agents shows gadolinium lining the vessels of the brain. Taken together, these findings suggest the disruption of cytoplasmic membrane integrity as a mechanism by which lanthanides induce cytotoxicity. In the presented work we used scanning transmission electron microscopy and spatially resolved elemental spectroscopy to image the morphology and composition of gadolinium, europium, and samarium precipitates that formed on the outside of yeast cell membranes. In no sample did we find that the lanthanide contaminant had crossed the cell membrane, even in experiments using yeast mutants with disrupted genes for sphingolipid synthesis-the primary lipids found in yeast cytoplasmic membranes. Rather, we have evidence that lanthanides are co-located with phosphorus outside the yeast cells. These results lead us to hypothesize that the lanthanides scavenge or otherwise form complexes with phosphorus from the sphingophospholipid head groups in the cellular membrane, thereby compromising the structure or function of the membrane, and gaining the ability to disrupt membrane function without entering the cell.

ASNR Statement on Gadolinium-Based Contrast Agent Use in Patients with Chronic Kidney Disease.

Beginning in 2006, neuroradiologists became increasingly aware of the risk of nephrogenic system fibrosis (NSF) when patients suffering from chronic kidney disease (CKD) received gadolinium-based contrast agents (GBCAs) in conjunction with MRI scans. Radiology practices began withholding GBCAs from MRI patients with substantial CKD and instated a variety of safety measures to ensure that these individuals did not inadvertently receive GBCAs. As a result, the worldwide incidence of NSF was dramatically reduced. Since that time, a wealth of research on NSF and its etiology has found few unconfounded cases associated with those GBCAs categorized as Group II agents by the American College of Radiology. In 2023 and 2024, members of the American Society of Neuroradiology (ASNR) Standards and Guidelines Committee reviewed new research evidence on GBCA safety and its relevance to current MRI contrast administration guidelines for patients with CKD. This focused on systematic reviews and meta-analyses conducted during the past five years. Upon consideration of this literature, recommendations for administration of GBCAs to patients with CKD were formulated. For neuroimaging applications, the ASNR recommends that Group II GBCAs no longer be withheld in patients with CKD when these agents are medically indicated for diagnosis. Moreover, if Group II GBCAs are exclusively used in an MRI practice, other safety measures such as checking renal function or querying patients about chronic kidney disease can be discontinued. ACR = American College of Radiology; ASNR = American Society of Neuroradiology; CKD = chronic kidney disease; GBCA = gadolinium-based contrast agent; NSF = nephrogenic systemic fibrosis.

Rapid imaging of intravenous gadolinium-based contrast agent (GBCA) entering ventricular cerebrospinal fluid (CSF) through the choroid plexus in healthy human subjects

BackgroundPathways for intravenously administered gadolinium-based-contrast-agents (GBCAs) entering cerebrospinal-fluid (CSF) circulation in the human brain are not well-understood. The blood-CSF-barrier (BCSFB) in choroid-plexus (CP) has long been hypothesized to be a main entry-point for intravenous-GBCAs into CSF. Most existing studies on this topic were performed in animals and human patients with various diseases. Results in healthy human subjects are limited. Besides, most studies were performed using MRI methods with limited temporal resolution and significant partial-volume effects from blood and CSF.MethodsThis study employs the recently developed dynamic-susceptibility-contrast-in-the-CSF (cDSC) MRI approach to measure GBCA-distribution in the CSF immediately and 4 h after intravenous-GBCA administration in healthy subjects. With a temporal resolution of 10 s, cDSC MRI can track GBCA-induced CSF signal changes during the bolus phase, which has not been investigated previously. It employs a long echo-time (TE = 1347 ms) to suppress tissue and blood signals so that pure CSF signal is detected with minimal partial-volume effects. GBCA concentration in the CSF can be estimated from cDSC MRI. In this study, cDSC and FLAIR MRI were performed immediately and 4 h after intravenous GBCA administration in 25 healthy volunteers (age 48.9 ± 19.5 years; 14 females). Paired t-tests were used to compare pre-GBCA and post-GBCA signal changes, and their correlations with age were evaluated using Pearson-correlation-coefficients.ResultsAt ~ 20 s post-GBCA, GBCA-induced cDSC signal changes were detected in the CSF around CP (ΔS/S = − 2.40 ± 0.30%; P < .001) but not in the rest of lateral ventricle (LV). At 4 h, significant GBCA-induced cDSC signal changes were observed in the entire LV (ΔS/S = − 7.58 ± 3.90%; P = .002). FLAIR MRI showed a similar trend. GBCA-induced CSF signal changes did not correlate with age.ConclusionsThese results provided direct imaging evidence that GBCAs can pass the BCSFB in the CP and enter ventricular CSF immediately after intravenous administration in healthy human brains. Besides, our results in healthy subjects established a basis for clinical studies in brain diseases exploiting GBCA-enhanced MRI to detect BCSFB dysfunction.

Quantitative assessment of gadolinium deposition in dentate nuclei with MR fingerprinting

Gadolinium deposition in the dentate nucleus (DN) has been evaluated by T1-weighted imaging (T1WI) and T1 (R1) mapping, but not MR fingerprinting (MRF). This study investigated associations between T1 and T2 values of DN and gadolinium-based contrast agents (GBCAs) using 2-dimensional MRF. This study included 101 patients. Region of interest analysis was performed for T1 and T2 values of DN on MRF (T1-MRF, T2-MRF) and T1-weighted images (T1WI ratio). T1 and T2 ratios compared to normal cerebellar white matter (T1-MRF ratio, T2-MRF ratio) were calculated. The type of previous GBCA was confirmed in 79 patients, and linear regressions were performed between T1, T2 values and number of GBCAs. Good correlations were observed between T1-MRF and T1WI ratio (ρ=-0.69, P<0.001) and between T1-MRF ratio and T1WI ratio (ρ=-0.76, P<0.001). Mild correlations were observed between T2-MRF and T1WI ratio (ρ=-0.32, P<0.001) and between T2-MRF ratio and T1WI ratio (ρ=-0.44, P<0.001). The number of linear-type GBCAs was associated with T1-MRF (β=-0.62, P<0.001) and T1-MRF ratio (β=-0.54, P<0.001) in univariate linear regression analyses, and with T1-MRF (β=-0.61, P<0.001) and T1-MRF ratio (β=-0.53, P<0.001) in multivariate analysis. The number of linear-type GBCAs was associated with T2-MRF (β=-0.30, P<0.001) and T2-MRF ratio (β=-0.29, P<0.001) in univariate analyses, and with T2-MRF (β=-0.31, P<0.001) and T2-MRF ratio (β=-0.32, P<0.001) in multivariate analyses. No associations were observed between number of macrocyclic GBCAs and T1-MRF (ratio) or T2-MRF (ratio). The number of linear-type GBCA administrations was associated with lower T1 and T2 values (ratios) in DN.

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.

Evaluation of the Contrast Enhancement Performance of Gadopiclenol for Magnetic Resonance Angiography in Healthy Rabbits and Pigs.

Unexpected accumulations of gadolinium in various organs were reported after the administration of gadolinium-based contrast agents, making desirable to reduce the dose while maintaining equivalent diagnostic performance. The aim of this study was to evaluate the contrast enhancement performance of high relaxivity gadopiclenol compared with gadoterate meglumine in abdominal contrast-enhanced magnetic resonance angiography (CE-MRA). In a first study in healthy rabbits, axial 3D gradient echo sequences were applied at 4.7 T to study arterial enhancement as a function of gadopiclenol dose (0.025, 0.05, 0.075, and 0.1 mmol Gd/kg) or gadoterate meglumine at 0.1 mmol Gd/kg (n = 5-6/group). The increase in signal-to-noise ratio (ΔSNR) in the aorta at the first pass was measured and compared. In a second, crossover study in 6 healthy pigs, abdominal CE-MRA sequences were acquired at 3 T with gadopiclenol at 0.05 mmol Gd/kg or gadoterate meglumine at 0.1 mmol Gd/kg at a 1-week interval. Quantitatively on the maximum intensity projection (MIP) images, the mean MIP SNR within the aorta of both groups was compared. Qualitatively, a blinded comparison of the angiograms was performed by an experienced radiologist to determine the preferred contrast agent. In the rabbit, ∆SNR is linearly correlated with the gadopiclenol dose ( P = 0.0010). Compared with gadoterate meglumine 0.1 mmol Gd/kg, an increase in the ∆SNR is observed after 0.05, 0.075, and 0.1 mmol Gd/kg of gadopiclenol (+63% P = 0.0731, +78% P = 0.0081, and +72% P = 0.0773, respectively), whereas at 0.025 mmol Gd/kg, ∆SNR is in the same range as with gadoterate meglumine 0.1 mmol Gd/kg (+15% P > 0.9999). In pigs, contrast enhancement after gadopiclenol at 0.05 mmol/kg is +22% superior to MIP SNR after gadoterate meglumine at 0.1 mmol Gd/kg ( P = 0.3095). Qualitatively, a preference was shown for gadopiclenol images (3/6) over the gadoterate meglumine examinations (1/6), with no preference being shown for the remainder (2/6). First-pass CE-MRA is feasible with gadopiclenol at 0.05 mmol Gd/kg with at least the same arterial signal enhancement and image quality as gadoterate meglumine at 0.1 mmol Gd/kg.

Clinical implementation of a fully automated quantitative perfusion cardiovascular magnetic resonance imaging workflow with a simplified dual-bolus contrast administration scheme

This study clinically implemented a ready-to-use quantitative perfusion (QP) cardiovascular magnetic resonance (QP CMR) workflow, encompassing a simplified dual-bolus gadolinium-based contrast agent (GBCA) administration scheme and fully automated QP image post-processing. Twenty-five patients with suspected obstructive coronary artery disease (CAD) underwent both adenosine stress perfusion CMR and an invasive coronary angiography or coronary computed tomography angiography. The dual-bolus protocol consisted of a pre-bolus (0.0075 mmol/kg GBCA at 0.5 mmol/ml concentration + 20 ml saline) and a main bolus (0.075 mmol/kg GBCA at 0.5 mmol/ml concentration + 20 ml saline) at an infusion rate of 3 ml/s. The arterial input function curves showed excellent quality. Stress MBF ≤ 1.84 ml/g/min accurately detected obstructive CAD (area under the curve 0.79; 95% Confidence Interval: 0.66 to 0.89). Combined visual assessment of color pixel QP maps and conventional perfusion images yielded a diagnostic accuracy of 84%, sensitivity of 70% and specificity of 93%. The proposed easy-to-use dual-bolus QP CMR workflow provides good image quality and holds promise for high accuracy in diagnosis of obstructive CAD. Implementation of this approach has the potential to serve as an alternative to current methods thus increasing the accessibility to offer high-quality QP CMR imaging by a wide range of CMR laboratories.

Deep learning for discrimination of active and inactive lesions in multiple sclerosis using non-contrast FLAIR MRI: A multicenter study

BackgroundWithin the domain of multiple sclerosis (MS), the precise discrimination between active and inactive lesions bears immense significance. Active lesions are enhanced on T1-weighted MRI images after administration of gadolinium-based contrast agents, which brings about associated complexities. This study investigates the potential of deep learning to differentiate between active and inactive lesions in MS using non-contrast FLAIR-type MRI data, presenting a non-invasive alternative to conventional gadolinium-based MRI methods. MethodsThe dataset encompasses 9097 lesion images collected from 130 MS patients across four distinct imaging centers, with post-contrast T1-weighted images as the benchmark reference. We initially identified and labeled the lesions and carefully selected corresponding regions of interest (ROIs). These ROIs were employed as inputs for a convolutional neural network (CNN) to predict lesion status. Also, transfer learning was utilized, incorporating 12 pre-trained CNN models. Subsequently, an ensemble technique was applied to 3 of best models, followed by a systematic comparison of the results. ResultsThrough a 5-fold cross-validation, our custom designed network exhibited an average accuracy of 85 %, a sensitivity of 95 %, a specificity of 75 %, and an AUC value of 0.90. Among the pre-trained models, ResNet50 emerged as the most effective, achieving a specificity of 58 %, an accuracy of 75 %, a sensitivity of 91 %, and an AUC value of 0.81. Our comprehensive evaluations encompassed the receiver operating characteristic curve, precision-recall curve, and confusion matrix analyses. ConclusionThe findings underscore the efficacy of the proposed CNN, trained on FLAIR MRI data ROIs, in accurately discerning active and inactive lesions without reliance on contrast agents. Our multicenter study of 130 patients with diverse imaging devices outperforms the other single-center studies, achieving superior sensitivity and specificity. Unlike studies using multiple modalities, our exclusive use of FLAIR images streamlines the process, and our streamlined approach, excluding conventional pre-processing, demonstrates efficiency. The external validation conducted on diverse datasets, coupled with the analysis of dilated masks, underscores the adaptability and efficacy of our custom CNN model in discerning between active and inactive lesions.

Gadolinium Contrast Agent Deposition in Children.

Over the past few years, a large number of studies have evidenced increased signal intensity in the deep brain nuclei on unenhanced T1-MRI images achieved by the application of gadolinium-based contrast agents (GBCAs). The deposition of gadolinium in the brain, bone, and other tissues following administration of GBCAs has also been confirmed in histological studies in rodents and in necropsy studies in adults and children. Given the distinct physiological characteristics of children, this review focuses on examining the current research on gadolinium deposition in children, particularly studies utilizing novel methods and technologies. Furthermore, the article compares safety research findings of linear GBCAs and macrocyclic GBCAs in children, with the aim of offering clinicians practical guidance based on the most recent research outcomes. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY: Stage 2.

An update on susceptibility-weighted imaging in brain gliomas.

Susceptibility-weighted imaging (SWI) has become a standard component of most brain MRI protocols. While traditionally used for detecting and characterising brain hemorrhages typically associated with stroke or trauma, SWI has also shown promising results in glioma assessment. Numerous studies have highlighted SWI's role in differentiating gliomas from other brain lesions, such as primary central nervous system lymphomas or metastases. Additionally, SWI aids radiologists in non-invasively grading gliomas and predicting their phenotypic profiles. Various researchers have suggested incorporating SWI as an adjunct sequence for predicting treatment response and for post-treatment monitoring. A significant focus of these studies is on the detection of intratumoural susceptibility signals (ITSSs) in gliomas, which are indicative of microhemorrhages and vessels within the tumour. The quantity, distribution, and characteristics of these ITSSs can provide radiologists with more precise information for evaluating and characterising gliomas. Furthermore, the potential benefits and added value of performing SWI after the administration of gadolinium-based contrast agents (GBCAs) have been explored. This review offers a comprehensive, educational, and practical overview of the potential applications and future directions of SWI in the context of glioma assessment. CLINICAL RELEVANCE STATEMENT: SWI has proven effective in evaluating gliomas, especially through assessing intratumoural susceptibility signal changes, and is becoming a promising, easily integrated tool in MRI protocols for both pre- and post-treatment assessments. KEY POINTS: • Susceptibility-weighted imaging is the most sensitive sequence for detecting blood and calcium inside brain lesions. • This sequence, acquired with and without gadolinium, helps with glioma diagnosis, characterisation, and grading through the detection of intratumoural susceptibility signals. • There are ongoing challenges that must be faced to clarify the role of susceptibility-weighted imaging for glioma assessment.

Contrast Media-driven Anthropogenic Gadolinium: Knowns and Unknowns.

Gadolinium-based contrast agents (GBCAs) have augmented the capabilities of MRI, which has led to their widespread and increasing use in radiology practice. GBCAs are introduced into the environment through disposal of unused product and elimination after intravenous injection, both primarily via liquid dispersion into the environment. This human introduction of gadolinium into the environment, referred to as anthropogenic gadolinium, is associated with the detection of gadolinium in water systems, raising concerns for potential adverse impact and prompting certain mitigation actions. This article summarizes the existing knowledge and problem scope, conveys the relevant underlying chemical principles of chelate dissociation, and offers an inferred perspective that the magnitude of the problem is most unlikely to cause human harm. The merits and limitations regarding possible mitigation tactics, such as collecting urine after GBCA administration, use of lower-dose high-relaxivity macrocyclic GBCAs, and the option for virtual contrast-enhanced examinations, will be discussed. Finally, the potential for monitoring gadolinium uptake in bone will be presented, and recommendations for future research will be offered. © RSNA, 2024 See also the article by Ibrahim et al in this issue. See also the article by McKee et al in this issue.

Magnetic resonance lymphangiography: Establishing normal

BackgroundDespite an increased interest in visualizing the lymphatic vessels with magnetic resonance lymphangiography (MRL), little literature is available describing their appearance in nonlymphedematous individuals. To determine lymphatic abnormalities, an understanding of how healthy lymphatic vessels appear and behave needs to be established. Therefore, in this study, MRL of individuals without a history of lymphatic disease was performed. MethodsA total of 25 individuals (15 women) underwent MRL of their lower limbs using a 3.0 T Philips magnetic resonance imaging scanner (Philips Medical Systems). The first nine participants were recruited to establish the concentration of gadolinium-based contrast agent (GBCA) to administer, with the remainder imaged before and after interdigital forefoot GBCA injections at the optimized dose. Outcomes, including lymphatic vessel diameter, tortuosity, and frequency of drainage via particular drainage routes, were recorded. ResultsHealthy lymphatic vessels following the anteromedial pathway were routinely observed in post-contrast T1-weighted images (average tortuosity, 1.09 ± 0.03), with an average of 2.16 ± 0.93 lymphatic vessels with a diameter of 2.47 ± 0.50 mm crossing the anterior ankle. In six limbs, vessels following the anterolateral pathways were observed. No vessels traversing the posterior of the legs were seen. In a subset of 10 vessels, the lymphatic signal, measured at the ankle, peaked 29 minutes, 50 seconds ± 9 minutes, 29 seconds after GBCA administration. No lymphatic vessels were observed in T2-weighted images. ConclusionsContrast-enhanced MRL reliably depicts the lymphatic vessels in the legs of healthy controls. Following interdigital contrast injection, anteromedial drainage appears dominant. Quantitative measures related to lymphatic vessel size, tortuosity, and drainage rate are readily obtainable and could be beneficial for detecting even subtle lymphatic impairment.

Automatic Active Lesion Tracking in Multiple Sclerosis Using Unsupervised Machine Learning.

Identifying active lesions in magnetic resonance imaging (MRI) is crucial for the diagnosis and treatment planning of multiple sclerosis (MS). Active lesions on MRI are identified following the administration of Gadolinium-based contrast agents (GBCAs). However, recent studies have reported that repeated administration of GBCA results in the accumulation of Gd in tissues. In addition, GBCA administration increases health care costs. Thus, reducing or eliminating GBCA administration for active lesion detection is important for improved patient safety and reduced healthcare costs. Current state-of-the-art methods for identifying active lesions in brain MRI without GBCA administration utilize data-intensive deep learning methods. To implement nonlinear dimensionality reduction (NLDR) methods, locally linear embedding (LLE) and isometric feature mapping (Isomap), which are less data-intensive, for automatically identifying active lesions on brain MRI in MS patients, without the administration of contrast agents. Fluid-attenuated inversion recovery (FLAIR), T2-weighted, proton density-weighted, and pre- and post-contrast T1-weighted images were included in the multiparametric MRI dataset used in this study. Subtracted pre- and post-contrast T1-weighted images were labeled by experts as active lesions (ground truth). Unsupervised methods, LLE and Isomap, were used to reconstruct multiparametric brain MR images into a single embedded image. Active lesions were identified on the embedded images and compared with ground truth lesions. The performance of NLDR methods was evaluated by calculating the Dice similarity (DS) index between the observed and identified active lesions in embedded images. LLE and Isomap, were applied to 40 MS patients, achieving median DS scores of 0.74 ± 0.1 and 0.78 ± 0.09, respectively, outperforming current state-of-the-art methods. NLDR methods, Isomap and LLE, are viable options for the identification of active MS lesions on non-contrast images, and potentially could be used as a clinical decision tool.

Low-dose GBCA administration for brain tumour dynamic contrast enhanced MRI: a feasibility study

A key limitation of current dynamic contrast enhanced (DCE) MRI techniques is the requirement for full-dose gadolinium-based contrast agent (GBCA) administration. The purpose of this feasibility study was to develop and assess a new low GBCA dose protocol for deriving high-spatial resolution kinetic parameters from brain DCE-MRI. Nineteen patients with intracranial skull base tumours were prospectively imaged at 1.5 T using a single-injection, fixed-volume low GBCA dose, dual temporal resolution interleaved DCE-MRI acquisition. The accuracy of kinetic parameters (ve, Ktrans, vp) derived using this new low GBCA dose technique was evaluated through both Monte-Carlo simulations (mean percent deviation, PD, of measured from true values) and an in vivo study incorporating comparison with a conventional full-dose GBCA protocol and correlation with histopathological data. The mean PD of data from the interleaved high-temporal-high-spatial resolution approach outperformed use of high-spatial, low temporal resolution datasets alone (p < 0.0001, t-test). Kinetic parameters derived using the low-dose interleaved protocol correlated significantly with parameters derived from a full-dose acquisition (p < 0.001) and demonstrated a significant association with tissue markers of microvessel density (p < 0.05). Our results suggest accurate high-spatial resolution kinetic parameter mapping is feasible with significantly reduced GBCA dose.

Effects of Gadolinium Retention in the Brains of Type 2 Diabetic Rats after Repeated Administration of Gadolinium-Based MRI Contrast Agents on Neurobiology and NLRP3 Inflammasome Activation.

The neurotoxic potential of gadolinium (Gd)-based contrast agents (GBCAs) retention in the brains of patients with type 2 diabetes mellitus (T2DM) is unclear. To determine the deposition and clearance of GBCAs in T2DM rats and the mechanism by which Gd enhances nucleotide-binding oligomerization domain-3 (NLRP3) inflammasome activation. Cross-sectional, prospective. 104 T2DM male Wistar rats. 9.4-T, T1-weighted fast spin echo sequence. T2DM (male Wistar rats, n = 52) and control group (healthy, male Wistar rats, n = 52) rats received saline, gadodiamide, Gd-diethylenetriaminepentaacetic acid, and gadoterate meglumine for four consecutive days per week for 7 weeks. The distribution and clearance of Gd in the certain brain were assessed by MRI (T1 signal intensity and relaxation rate R1, on the last day of each week), inductively coupled plasma mass-spectroscopy, ultraperformance liquid chromatography mass spectrometry, and transmission electron microscopy. Behavioral tests, histopathological features, and the effects of GBCAs on neuroinflammation were also analyzed. One-way analysis of variance, bonferroni method, and unpaired t-test. A P-value <0.05 was considered statistically significant. The movement distance and appearance time in the open field test of the T2DM rats in the gadodiamide group were significantly shorter than in the other groups. Furthermore, the expression of NLRP3, Pro-Caspase-1, interleukin-1β (IL-1β), and apoptosis-associated speck-like protein containing a CARD protein in neurons was significantly higher in the gadodiamide group than in the saline group, as shown by Western blot. Gadodiamide also induced differentiation of microglia into M1 type, decreased the neuronal mitochondrial membrane potential, and significantly increased neuronal apoptosis from flow cytometry. T2DM may affect both the deposition and clearance of GBCAs in the brain. Informed by the T2DM model, gadodiamide could mediate the neuroinflammatory response by NLRP3 inflammasome activation. 1 TECHNICAL EFFICACY: Stage 1.

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.