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Background: The neurotoxic potential of gadolinium (Gd)-based contrast agents (GBCAs) retention in the brains of patients with type 2 diabetes mellitus (T2DM) is unclear., Purpose: 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., Study Type: Cross-sectional, prospective., Animal Model: 104 T2DM male Wistar rats., Field Strength/sequence: 9.4-T, T1-weighted fast spin echo sequence., Assessment: 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., Statistical Tests: One-way analysis of variance, bonferroni method, and unpaired t-test. A P-value <0.05 was considered statistically significant., Results: 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., Data Conclusion: 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., Level of Evidence: 1 TECHNICAL EFFICACY: Stage 1., (© 2024 International Society for Magnetic Resonance in Medicine.)

Background: Implantable cardioverter-defibrillator (ICD) intervention is an established prophylactic measure. Identifying high-benefit patients poses challenges., Purpose: To assess the prognostic value of cardiac magnetic resonance imaging (MRI) parameters including myocardial deformation for risk stratification of ICD intervention in non-ischemic cardiomyopathy (NICM) while accounting for competing mortality risk., Study Type: Retrospective and prospective., Population: One hundred and fifty-nine NICM patients eligible for primary ICD (117 male, 54 ± 13 years) and 49 control subjects (38 male, 53 ± 5 years)., Field Strength/sequence: Balanced steady state free precession (bSSFP) and three-dimensional phase-sensitive inversion-recovery late gadolinium enhancement (LGE) sequences at 1.5 T or 3 T., Assessment: Patients underwent MRI before ICD implantation and were followed up. Functional parameters, left ventricular global radial, circumferential and longitudinal strain, right ventricular free wall longitudinal strain (RV FWLS) and left atrial strain were measured (Circle, cvi42). LGE presence was assessed visually. The primary endpoint was appropriate ICD intervention. Models were developed to determine outcome, with and without accounting for competing risk (non-sudden cardiac death), and compared to a baseline model including LGE and clinical features., Statistical Tests: Wilcoxon non-parametric test, Cox's proportional hazards regression, Fine-Gray competing risk model, and cumulative incidence functions. Harrell's c statistic was used for model selection. A P value <0.05 was considered statistically significant., Results: Follow-up duration was 1176 ± 960 days (median: 896). Twenty-six patients (16%) met the primary endpoint. RV FWLS demonstrated a significant difference between patients with and without events (-12.5% ± 5 vs. -16.4% ± 5.5). Univariable analyses showed LGE and RV FWLS were significantly associated with outcome (LGE: hazard ratio [HR] = 3.69, 95% CI = 1.28-10.62; RV FWLS: HR = 2.04, 95% CI = 1.30-3.22). RV FWLS significantly improved the prognostic value of baseline model and remained significant in multivariable analysis, accounting for competing risk (HR = 1.73, 95% CI = 1.12-2.66)., Data Conclusions: In NICM, RV FWLS may provide additional predictive value for predicting appropriate ICD intervention., Level of Evidence: 2 TECHNICAL EFFICACY: Stage 5., (© 2024 International Society for Magnetic Resonance in Medicine.)

This study examined the influence of growth temperature and dopant concentration on the properties of Gd- and Ni-doped zinc oxide nanorods (ZnO NRs). ZnO seed layers were deposited on glass substrates using a sol-gel and dip-coating approach. Gd- and Ni-doped ZnO NRs were hydrothermally grown on the seed layers at different temperatures such as 75, 90, and 105°C for a constant growth time of 5 h. The crystal structure, optical, surface morphology views, and electrical properties of the NRs were extensively investigated by x-ray diffraction (XRD), scanning electron microscopy (SEM), UV-visible spectroscopy, and four probe experimental methods. The XRD analysis confirmed the successful substitution of Zn 2+ ions by Gd 3+ and Ni 2+ within the ZnO main matrices. The reordering of hexagonal structures with varied electronegativity, ionic radius dimensions, and valence electron states of Gd and Ni dopants affected seriously the fundamental characteristic features of NRs. The SEM images showed that the ZnO NRs grown at 90°C possessed a more favorable surface morphology and well-defined hexagonal shape compared with those grown at other growth temperatures. Higher dopant concentration led to an increase in NR diameter but a decrease in density depending on the increase in the space between the NRs. Additionally, the optical transmittance was found to generally enhance with increasing dopant concentration. The results obtained highlighted the interplay between growth temperature, dopant type and concentration in tailoring the structural, morphological, and optical properties of Gd- and Ni-doped ZnO NRs, paving the way for the development of optimized nanomaterials for various applications. RESEARCH HIGHLIGHTS: The XRD analysis confirmed the successful substitution of Zn 2+ ions by Gd 3+ and Ni 2+ within the ZnO main matrices. The SEM images showed that the ZnO NRs grown at 90°C possessed a more favorable surface morphology and well-defined hexagonal shape compared with those grown at other growth temperatures. The optical transmittance was found to generally enhance with increasing dopant concentration. The results obtained highlighted the interplay between growth temperature, dopant type and concentration in tailoring the structural, morphological, and optical properties of Gd- and Ni-doped ZnO NRs, paving the way for the development of optimized nanomaterials for various applications., (© 2024 The Author(s). Microscopy Research and Technique published by Wiley Periodicals LLC.)

Objectives: This study aims to generate post-contrast MR images reducing the exposure of gadolinium-based contrast agents (GBCAs) for brainstem glioma (BSG) detection, simultaneously delineating the BSG lesion, and providing high-resolution contrast information., Methods: A retrospective cohort of 30 patients diagnosed with brainstem glioma was included. Multi-contrast images, including pre-contrast T1 weighted (pre-T1w), T2 weighted (T2w), arterial spin labeling (ASL) and post-contrast T1w images, were collected. A multi-task generative model was developed to synthesize post-contrast T1w images and simultaneously segment BSG masks from the multi-contrast inputs. Performance evaluation was conducted using peak signal-to-noise ratio (PSNR), structural similarity index (SSIM), and mean absolute error (MAE) metrics. A perceptual study was also undertaken to assess diagnostic quality., Results: The proposed model achieved SSIM of 0.86 ± 0.04, PSNR of 26.33 ± 0.05 and MAE of 57.20 ± 20.50 for post-contrast T1w image synthesis. Automated delineation of the BSG lesions achieved Dice similarity coefficient (DSC) score of 0.88 ± 0.27., Conclusions: The proposed model can synthesize high-quality post-contrast T1w images and accurately segment the BSG region, yielding satisfactory DSC scores., Clinical Relevance Statement: The synthesized post-contrast MR image presented in this study has the potential to reduce the usage of gadolinium-based contrast agents, which may pose risks to patients. Moreover, the automated segmentation method proposed in this paper aids radiologists in accurately identifying the brainstem glioma lesion, facilitating the diagnostic process., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: To compare the repeatability and interrelation of various late gadolinium enhancement (LGE) assessment techniques for monitoring fibrotic changes in myocarditis follow-up., Materials and Methods: LGE extent change between baseline and 3-month cardiovascular magnetic resonance (CMR) was compared in patients with acute myocarditis using the full width at half maximum (FWHM), gray-scale thresholds at 5 and 6 standard deviations (SD5 and SD6), visual assessment with threshold (VAT) and full manual (FM) techniques. In addition, visual presence score (VPS), visual transmurality score (VTS), and a simplified visual change score (VCS) were assessed. Intraclass-correlation (ICC) was used to evaluate repeatability, and methods were compared using Spearman's correlation., Results: Forty-seven patients (38 male, median age: 27 [IQR: 21; 38] years) were included. LGE extent change differed among quantitative techniques (p < 0.01), with variability in the proportion of patients showing LGE change during follow-up (FWHM: 62%, SD5: 74%, SD6: 66%, VAT: 43%, FM: 60%, VPS: 53%, VTS: 77%, VCS: 89%). Repeatability was highest with FWHM (ICC: 0.97) and lowest with SD5 (ICC: 0.89). Semiquantitative scoring had slightly lower values (VPS ICC: 0.81; VTS ICC: 0.71). VCS repeatability was excellent (ICC: 0.93). VPS and VTS correlated with quantitative techniques, while VCS was positively associated with VPS, VTS, VAT, and FM, but not with FWHM, SD5, and SD6., Conclusion: FWHM offers the least observer-dependent LGE follow-up after myocarditis. VPS, VTS, and VCS are practical alternatives, showing reliable correlations with quantitative methods. Classification of patients exhibiting either stable or changing LGE relies on the assessment technique., Clinical Relevance Statement: This study shows that LGE monitoring in myocarditis is technique-dependent; the FWHM method yields the most consistent fibrotic tracking results, with scoring-based techniques as reliable alternatives., Key Points: Recognition of fibrotic changes during myocarditis follow-up is significantly influenced by the choice of the quantification technique employed. The FWHM technique ensures highly repeatable tracking of myocarditis-related LGE changes. Segment-based visual scoring and the simplified visual change score offer practical, reproducible alternatives in resource-limited settings., (© 2024. The Author(s).)

Gadolinium (Gd) is a rare earth element (REE) used in the formulation of contrast agents for Magnetic Resonance Imaging (MRI) due to its paramagnetic properties. The growth in population and the improved quality of the healthcare systems over the last years, has promoted the use of MRI as an effective diagnostic tool thus increasing the consumption of gadolinium and its release into the wastewater treatment network. Therefore, the tracking and quantification of this metal in sewage treatment plants and water bodies, is of paramount importance since there are currently no specific rare earth treatment technologies installed in WWTPs, and consequently gadolinium is finally discharged into the environment. In this work, the presence of gadolinium and all other rare earth elements was monitored during a year in three WWTPs in northern Spain (Vuelta Ostrera and San Román in Cantabria and Galindo in País Vasco). These WWTPs are located close to urban centres with hospitals where MRI tests are performed. By tracing Gd throughout the wastewater treatment facilities, its presence was confirmed in water streams, in the order of ng per litter, and in sludge and ashes, in the order of mg per kilogram. A significant human influence was observed, with Gd anomaly values between 3.14 and 79.2 and anthropogenic Gd percentages above 90 %. The presence of Gd in water streams is affected by the sampling period due to the variations of the activity periods of the hospitals nearby the treatment plants. On the contrary, its content in sludge and ashes remains almost constant along the year. The concentration of this metal found in the ashes opens the door to its possible recovery together with other critical raw materials in the context of the circular economy., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ma.-Fresnedo San-Roman reports financial support, article publishing charges, equipment, drugs, or supplies, travel, and writing assistance were provided by University of Cantabria. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: To develop a gadolinium-free MRI-based diagnosis prediction decision tree (DPDT) for adult-type diffuse gliomas and to assess the added value of gadolinium-based contrast agent (GBCA) enhanced images., Materials and Methods: This study included preoperative grade 2-4 adult-type diffuse gliomas (World Health Organization 2021) scanned between 2010 and 2021. The DPDT, incorporating eleven GBCA-free MRI features, was developed using 18% of the dataset based on consensus readings. Diagnosis predictions involved grade (grade 2 vs. grade 3/4) and molecular status (isocitrate dehydrogenase (IDH) and 1p/19q). GBCA-free diagnosis was predicted using DPDT, while GBCA-enhanced diagnosis included post-contrast images. The accuracy of these predictions was assessed by three raters with varying experience levels in neuroradiology using the test dataset. Agreement analyses were applied to evaluate the prediction performance/reproducibility., Results: The test dataset included 303 patients (age (SD): 56.7 (14.2) years, female/male: 114/189, low-grade/high-grade: 54/249, IDH-mutant/wildtype: 82/221, 1p/19q-codeleted/intact: 34/269). Per-rater GBCA-free predictions achieved ≥ 0.85 (95%-CI: 0.80-0.88) accuracy for grade and ≥ 0.75 (95%-CI: 0.70-0.80) for molecular status, while GBCA-enhanced predictions reached ≥ 0.87 (95%-CI: 0.82-0.90) and ≥ 0.77 (95%-CI: 0.71-0.81), respectively. No accuracy difference was observed between GBCA-free and GBCA-enhanced predictions. Group inter-rater agreement was moderate for GBCA-free (0.56 (95%-CI: 0.46-0.66)) and substantial for GBCA-enhanced grade prediction (0.68 (95%-CI: 0.58-0.78), p = 0.008), while substantial for both GBCA-free (0.75 (95%-CI: 0.69-0.80) and GBCA-enhanced (0.77 (95%-CI: 0.71-0.82), p = 0.51) molecular status predictions., Conclusion: The proposed GBCA-free diagnosis prediction decision tree performed well, with GBCA-enhanced images adding little to the preoperative diagnostic accuracy of adult-type diffuse gliomas., Key Points: Question Given health and environmental concerns, is there a gadolinium-free imaging protocol to preoperatively evaluate gliomas comparable to the gadolinium-enhanced standard practice? Findings The proposed gadolinium-free diagnosis prediction decision tree for adult-type diffuse gliomas performed well, and gadolinium-enhanced MRI demonstrated only limited improvement in diagnostic accuracy. Clinical relevance Even inexperienced raters effectively classified adult-type diffuse gliomas using the gadolinium-free diagnosis prediction decision tree, which, until further validation, can be used alongside gadolinium-enhanced images to respect standard practice, despite this study showing that gadolinium-enhanced images hardly improved diagnostic accuracy., (© 2024. The Author(s).)

The glymphatic pathway was defined in rodents as a network of perivascular spaces (PVSs) that facilitates organized distribution of cerebrospinal fluid (CSF) into the brain parenchyma. To date, perivascular CSF and cerebral interstitial fluid exchange has not been shown in humans. Using intrathecal gadolinium contrast-enhanced MRI, we show that contrast-enhanced CSF moves through the PVS into the parenchyma, supporting the existence of a glymphatic pathway in humans., Competing Interests: Competing interests statement:The authors declare no competing interest.

Due to the widespread application in medicine and industry of anthropogenic gadolinium (Gd anth ), the widespread of Gd anomaly in surface water has leading to disruption of the natural Gd geochemical cycle. However, challenges related to the identification and quantification of Gd anth , assessment of its impacts on marine ecosystems, and exploration of strategies for mitigating its adverse effects still exist. Meanwhile, as the major source of the Gd anth , the environmental geochemical behavior of Gd-based contrast agents (GBCAs), which are used in medical diagnostics in magnetic resonance imaging (MRI), are still poorly understood. In this review, we 1) analyzed Gd anomalies in samples from published literature worldwide, confirmed their prevalence (81.25% for sea and lake water, 72.73% for river water), 2) demonstrated that the third-order polynomial method is the preferred approach for the detection of Gd anth in surface seawater, 3) outlined the species and applications of Gd anth and its impacts on marine environment, 4) explored the process of GBCAs influx into the ocean and demonstrated the concentration of Gd anth in coral samples was mainly affected by terrestrial input GBCAs (63.75%) through Pearson correlation analysis and principle component analysis, 5) proposed effective management strategies for GBCAs at all stages from production to release into the ocean, 6) formulated an expectation for future research on marine Gd anth ., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: The pragmatic role of dynamic contrast-enhanced magnetic resonance lymphangiography (DCMRL) needs to be evaluated and compared across distinct lymphatic disorders. We aimed to evaluate the performance of DCMRL for identifying the underlying causes of lymphatic disorders and to define the potential benefit of DCMRL for planning lymphatic interventions., Methods: Patients who underwent DCMRL between August 2017 and July 2022 were included in this retrospective analysis. DCMRL was performed with intranodal injection of a gadolinium-based contrast medium through inguinal lymph nodes under local anesthesia. Technical success of DCMRL and feasibility of percutaneous embolization were assessed based on the lymphatic anatomy visualized by DCMRL. Based on the underlying causes, clinical outcomes were evaluated and compared., Results: Seventy consecutive patients were included. The indications were traumatic chylothorax (n = 42), traumatic chylous ascites (n = 11), and nontraumatic lymphatic leak (n = 17). The technical success rate of DCMRL was the highest in association with nontraumatic lymphatic disorders (94.1% [16/17]), followed by traumatic chylothorax (92.9% [39/42]) and traumatic chylous ascites (81.8% [9/11]). Thirty-one (47.7%) patients among 65 patients who underwent technically successful DCMRL had feasible anatomy for intervention. Clinical success was achieved in 90.3% (28/31) of patients with feasible anatomy for radiologic intervention, while 62.5% (10/16) of patients with anatomical challenges showed improvement. Most patients with traumatic chylothorax showed improvement (92.9% [39/42]), whereas only 23.5% (4/17) of patients with nontraumatic lymphatic disorders showed clinical improvement., Conclusion: DCMRL can help identify the underlying causes of lymphatic disorders. The performance of DCMRL and clinical outcomes vary based on the underlying cause. The feasibility of lymphatic intervention can be determined using DCMRL, which can help in predicting clinical outcomes., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

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., (© The Author(s) 2024. Published by Oxford University Press.)

We identified inconsistencies in the pituitary MRI ordering practices at our pediatric institution. We used an interdepartmental collaboration to develop a pituitary MRI ordering guide based on available evidence and local expertise. The initiative has led to an improvement in the appropriate use of intravenous gadolinium-based contrast agents for pediatric pituitary MRI studies., (© 2024 by American Journal of Neuroradiology.)

Competing Interests: Dr Graziani participated in advisory board of Takeda, Sanofi, Amicus Therapeutics; received investigator-initiated research grant from Takeda; received speaker’s fees from Takeda, Sanofi, Alnylam; and travel support from Pfizer, Takeda. Dr Pieroni is speaker and received advisory board fees from Sanofi Genzyme, Pfizer, and Bristol Myers Squibb. Dr Cappelli received consultant fees from Pfizer, Alnylam, Novonordisk, Amicus, Astra Zeneca, Daichi-Sankio, and Bridgebio. Dr Limongelli received advisory board fees from Chiesi Global Rare Disease; and unrestricted grant from Genzyme, Amicus, Takeda. Dr Olivotto received grants from Bristol Myers Squibb, Cytokinetics, Amicus, Chiesi, Shire, Genzyme; and advisory board/speaker’s fees from Bristol Myers Squibb, Cytokinetics, Amicus, Chiesi, Shire, Genzyme, Edgewise, Tenaya, Edgewise, and Lexeo. Dr Biagini received speaker’s fees: Amicus, Genzyme, and Takeda.

Background: Dark-blood late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) has better correlation with bipolar voltage (BiV) to define ablation scar in the left atrium (LA) compared to conventional bright-blood LGE CMR., Objectives: This study sought to determine the optimal signal intensity threshold of dark-blood LGE CMR to identify LA ablation scar., Methods: In 54 patients scheduled for atrial fibrillation ablation, image intensity ratios (IIRs) were derived from preprocedural dark-blood LGE CMR. In 26 patients without previous ablation, the upper limit of normal was derived from the 95th and 98th percentiles of pooled IIR values. In 28 patients with previous atrial fibrillation ablation, BiV was compared with the corresponding IIR. Receiver-operating characteristics analyses were employed to determine the optimal IIR threshold (ie, the point with the smallest distance to the upper left corner of the receiver-operating characteristics) for LA ablation scar (BiV ≤0.15 mV)., Results: Upper limit of normal corresponded to IIR values 1.16 and 1.21, yielding low sensitivities of 0.32 and 0.09 to detect LA ablation scar. Receiver-operating characteristics analysis of IIR and BiV comparison achieved a median area under the curve of 0.77. Median optimal IIR threshold for LA ablation scar was 1.09, with an average sensitivity of 0.73, specificity of 0.75, and accuracy of 0.71. Median IIR thresholds of 1.00 and 1.10 corresponded to 80% sensitivity and 80% specificity, respectively. There was considerable interpatient variability: optimal IIR thresholds per patient ranged from 1.01 to 1.22., Conclusions: The optimal IIR threshold to identify LA ablation scar by dark-blood LGE CMR is 1.09. Because of interpatient variability, the investigators recommend using a lower (1.00) and upper (1.10) threshold to prevent over- or underestimation of ablation scar., Competing Interests: Funding Support and Author Disclosures This work was supported by the Netherlands Heart Foundation (grant CVON2014-09, RACE V [Reappraisal of Atrial Fibrillation: Interaction Between Hypercoagulability, Electrical Remodeling, and Vascular Destabilisation in the Progression of AF], and grant 01-002-2022-0118, EmbRACE [Electro-Molecular Basis and the Therapeutic Management of Atrial Cardiomyopathy, Fibrillation and Associated Outcomes]), the European Union (grant 860974, ITN Network Personalize AF [Personalized Therapies for Atrial Fibrillation: A Translational Network]; grant 965286, MAESTRIA [Machine Learning Artificial Intelligence Early Detection Stroke Atrial Fibrillation]; and grant 952166, REPAIR [Restoring Cardiac Mechanical Function by Polymeric Artificial Muscular Tissue]). Dr Wildberger has received institutional grants via Clinical Trial Center Maastricht from Bard, Bayer, Boston, Brainlab, GE, Gleamer, Philips, and Siemens; and has received speaker fees via Maastricht UMC+ for serving on the Speakers Bureaus of Bayer and Siemens. Dr Schotten has received consulting fees or honoraria from Università della Svizzera Italiana, Roche Diagnostics, EP Solutions Inc , Johnson & Johnson Medical Limited, and Bayer Healthcare; and is cofounder and shareholder of YourRhythmics BV, a spin-off company of the University Maastricht. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The synthesis and characterization of a novel trinuclear rhodamine-Gd(III) complex, along with two analogous mononuclear rhodamine-Gd(III) complexes, are reported. All complexes displayed good selectivity in a human glioma cell line (T98G) when compared to a glial cell line (SVG p12), with low cytotoxicities. Superior tumor cell uptake for these Gd(III) complexes was observed at lower incubation concentrations compared to previously-reported delocalized lipophilic cations such as a rhodamine-lanthanoid(III) probe and Gd(III)-arylphosphonium complexes, with ca. 150 % and 250 % increases in Gd uptake, respectively., (© 2024 The Author(s). Chemistry - A European Journal published by Wiley-VCH GmbH.)

Purpose: To investigate whether deep cervical lymph node (DCLN) ligation alters intracranial cerebrospinal fluid (CSF) tracer dynamics and outflow using a rat model with intrathecal dynamic contrast-enhanced (DCE) MRI., Methods: Six bilateral DCLN-ligated and six sham-operated rats were subjected to DCE MRI with Gd-BTDO3A, and dynamic T1-weighted images were acquired. ROIs were collected from the CSF at the C1 level (CSF&#95;C1), CSF between the olfactory bulbs (CSF&#95;OB), CSF at the pituitary recess (CSF&#95;PitR), and CSF at the pineal recess (CSF&#95;PinR), upper nasal turbinate (UNT), olfactory bulbs, cerebrum, and the jugular region. Time-intensity curves were evaluated, and the maximum slope, peak timing, peak signal ratio, and elimination half-life for the four CSF ROIs and UNT were calculated and compared., Results: Delayed tracer arrival in the rostral CSF space and the nasal cavity with tracer retention in the ventral CSF space were observed in the ligation group. The maximum slopes were smaller in the ligation group at UNT (sham: 0.075 ± 0.0061, ligation: 0.044 ± 0.0086/min, P = 0.011). A significant difference was not detected in peak timings. The peak signal ratio values were lower in the ligation group at UNT (sham: 2.12 ± 0.19, ligation: 1.72 ± 0.11, P = 0.011). The elimination half-life was delayed in the ligation group at CSF&#95;C1 (sham: 30.5 ± 2.70, ligation: 44.4 ± 12.6 min, P = 0.043), CSF&#95;OB (sham: 30.2 ± 2.67, ligation: 44.8 ± 7.47 min, P = 0.021), and CSF&#95;PitR (sham: 30.2 ± 2.49, ligation: 41.3 ± 7.57 min, P = 0.021)., Conclusion: The DCLN ligation in rats blocked CSF outflow into the nasal cavity and caused CSF retention.

Background: Gadolinium (Gd) is an increasingly found lanthanide element in soil; thus, understanding its impact on plant physiology, biochemistry, and molecular responses is crucial. Here, we aimed to provide a comprehensive understanding of Gd (150 mg kg - 1 ) impacts on guar (Cyamopsis tetragonoloba L.) plant yield and metabolism and whether the symbiotic relationship with arbuscular mycorrhizal fungi (AMF) can mitigate Gd toxicity of soil contamination., Results: AMF treatment improved mineral nutrient uptake and seed yield by 38-41% under Gd stress compared to non-inoculated stressed plants. Metabolic analysis unveiled the defense mechanisms adopted by AMF-treated plants, revealing carbon and nitrogen metabolism adaptations to withstand Gd contamination. This included an increase in the synthesis of primary metabolites, such as total sugar (+ 39% compared to control), soluble sugars (+ 29%), starch (+ 30%), and some main amino acids like proline (+ 57%) and phenylalanine (+ 87%) in the seeds of AMF-treated plants grown under Gd contamination. Furthermore, fatty acid and organic acid profile changes were accompanied by the production of secondary metabolites, including tocopherols, polyamines, phenolic acids, flavones, and anthocyanins., Conclusions: Overall, the coordinated synthesis of these compounds underscores the intricate regulatory mechanisms underlying plant-AMF interactions and highlights the potential of AMF to modulate plant secondary metabolism for enhanced Gd stress tolerance., (© 2024. The Author(s).)

Background: Atrial fibrillation (AF) increases stroke and mortality in patients with hypertrophic cardiomyopathy (HCM). Cardiac MRI (CMR) is increasingly used to detect late gadolinium enhancement (LGE) as a reliable indicator of left ventricular fibrosis, a potential predisposing factor of AF. Our research explored the correlation between left ventricular LGE and AF prevalence in HCM., Methods: This retrospective study involved 351 HCM patients who underwent CMR. LGE percentages (0%, 1-5%, 6-14%, ≥15%) on CMR were compared with AF prevalence in HCM patients. Demographic, comorbidity, and imaging data were analyzed using appropriate univariate and multivariate analyses assessing for significant differences in AF prevalence. The predetermined significance level was p < 0.05., Results: CMR demonstrated increased LGE in those with AF (p = 0.004). Increased LGE correlated with increased AF rates: 27.6% (0% LGE), 38.5% (1-5% LGE), 44.4% (6-14% LGE), and 54.7% (≥15% LGE) (p = 0.101, p = 0.043, p = 0.002, respectively, vs. 0% LGE). Adjusted for age, differences persisted and were most evident for LGE >15% (p = 0.001). Multivariate analysis, factoring age, gender, BMI, RVSP, and LVEF, supported LGE (odds ratio of 1.20, p = 0.036) and LAVI (odds ratio 1.05, 1.02-1.07, p < 0.001) as predictive markers for AF prevalence., Conclusions: Our study suggests a correlation between ventricular LGE and AF in patients with HCM. LGE exceeding 15% was associated with a significant increase in AF prevalence. These patients may require more frequent AF monitoring., Competing Interests: Declaration of competing interest This study was supported by a grant from the DeVos Foundation to the Cardiovascular Research Program of the Heart and Vascular Institute, Corewell Health West. The authors report no relationships that could be construed as a conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The accumulation of trace metals in the environmental compartments of coastal rivers is a global and complex environmental issue, requiring multiple tools to constrain the various anthropogenic sources and biogeochemical processes affecting the water quality of these environments. The Valao fluvio-estuarine system (Rio de Janeiro, Brazil) presents a challenging case of a coastal river contaminated by both modern and historical anthropogenic metal sources, located in the land and in the intra-estuary, continuously mixed by tidal cycles. This study employed a combination of spatial distribution analysis of trace metals including gadolinium (Gd), zinc (Zn) isotopic analyses, and X-ray absorption spectroscopy (XAS) to distinguish between these sources. The concentrations of metals in both dissolved (water samples) and surficial sediment compartments (Suspended Particulate Matter and sediment samples) display an overall enrichment trend from upstream to downstream. Multivariate statistical analysis allows to discriminate geogenic elements derived from watershed geology (Ti, K, and Mg) vs anthropogenic contaminants from urban runoff and domestic sewage discharges (Cu, Cr, Pb, Zn, and Gd); and legacy metal contaminants (Zn and Cd) remobilized from ancient metallurgical wastes and transported upstream in the estuary during tidal cycles. The anthropogenic Gd concentration in the dissolved compartment increases along the watercourse, highlighting continuous ongoing sewage discharge. Zinc solid speciation also indicates that Zn contribution from legacy metallurgy waste is primarily associated with sulfide-Zn and Zn-phyllosilicate in the outlet estuary, while in upstream sediments of fluvio-estuarine system, Zn is found bound to organic matter. Zinc isotope systematically reveals a progressive downstream shift to heavier isotope compositions. Upstream, the relatively pristine site and the urbanized section of the river exhibit a relatively uniform δ 66/64 Zn value (+0.20 ± 0.07 ‰) in suspended particulate matter (SPM) and surficial sediments. These results indicate that domestic sewage discharges contribute to Zn enrichment in sediments of the Valao fluvio-estuarine system but without modifying its isotope signature in sediments. The sediment of the downstream estuarine section shows a heavier δ 66/64 Zn value (+0.48 ± 0.08 ‰), indicating the strong influence of the intra-estuarine source identified as the historical metallurgic contamination. An integrated view of the geochemical tracers allows thus inferring that the untreated sewage and legacy metallurgical contamination are the primary sources of anthropogenic Zn contamination. It highlights the progressive mixing along the estuarine gradient under tidal dynamics. The influence of the former source continuously expands from the headland towards the estuary., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. Jeremie garnier reports financial support was provided by National Council for Scientific and Technological Development. Jeremie garnier reports was provided by Coordination of Higher Education Personnel Improvement. Jeremie garnier reports a relationship with National Council for Scientific and Technological Development that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Accurate diagnosis of liver fibrosis is crucial for preventing cirrhosis and liver tumors. Liver fibrosis is driven by activated hepatic stellate cells (HSCs) with elevated CD44 expression. We developed hyaluronic acid (HA)-coated gadolinium-based nanoprobes to specifically target CD44 for diagnosing liver fibrosis using T1-weighted magnetic resonance imaging (MRI)., Materials and Methods: NaGdF 4 nanoparticles (NPs) were synthesized via thermal decomposition and modified with polyethylene glycol (PEG) to obtain non-targeting NaGdF 4 @PEG NPs. These were subsequently coated with HA to target HSCs, resulting in liver fibrosis-targeting NaGdF 4 @PEG@HA nanoprobes. Characterization includedd transmission electron microscopy and X-ray diffraction. Cell viability was assessed using the Cell Counting Kit-8 (CCK-8). Internalization of NaGdF 4 @PEG@HA nanoprobes by mouse HSCs JS1 cells via ligand-receptor interaction was observed using flow cytometry and confocal laser scanning microscopy (CLSM). Liver fibrosis was induced in C57BL/6 mice using a methionine-choline deficient (MCD) diet. MRI performance and nanoprobe distribution in fibrotic and normal livers were analyzed using a GE Discovery 3.0T MR 750 scanner., Results: NaGdF 4 @PEG@HA nanoprobes exhibited homogeneous morphology, low toxicity, and a high T1 relaxation rate (7.645 mM⁻¹s⁻¹). CLSM and flow cytometry demonstrated effective phagocytosis of NaGdF 4 @PEG@HA nanoprobes by JS1 cells compared to NaGdF 4 @PEG. MRI scans revealed higher T1 signals in fibrotic livers compared to normal livers after injection of NaGdF 4 @PEG@HA. NaGdF 4 @PEG@HA demonstrated higher targeting ability in fibrotic mice., Conclusions: NaGdF 4 @PEG@HA nanoprobes effectively target HSCs with high T1 relaxation rate, facilitating efficient MRI diagnosis of liver fibrosis., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Early stage hepatocellular carcinoma (HCC) presents a formidable challenge in clinical settings due to its asymptomatic progression and the limitations of current imaging techniques in detecting micro-HCC lesions. Addressing this critical issue, we introduce a novel ultrathin gadolinium-oxide (Gd-oxide) nanosheet-based platform with heightened sensitivity for high-field MRI and as a therapeutic agent for HCC. Synthesized via a digestive ripening process, these Gd-oxide nanosheets exhibit an exceptional acid-responsive profile. The integration of the ultrathin Gd-oxide with an acid-responsive polymer creates an ultrasensitive high-field MRI probe, enabling the visualization of submillimeter-sized tumors with superior sensitivity. Our research underscores the ultrasensitive probe's efficacy in the treatment of orthotopic HCC. Notably, the ultrasensitive probe functions dually as a companion diagnostic tool, facilitating simultaneous imaging and therapy with real-time treatment monitoring capabilities. In conclusion, this study showcases an innovative companion diagnostic tool that holds promise for the early detection and effective treatment of micro-HCC.

Competing Interests: Funding Support and Author Disclosures Dr Nazarian is funded by the National Institute of Health grant R01HL142893. Dr Xu is funded by American Heart Association grant 23POST909139. Dr Nazarian receives research funding from Biosense Webster and ADAS software. Dr Marchlinski has served as consultant for Abbott Medical, Biosense Webster, Biotronik, and Medtronic Inc. The University of Pennsylvania Conflict of Interest Committee manages all commercial arrangements. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

The study shows that the addition of gadolinium ions has a significant impact on the structure, morphology, and adsorption properties of Ni-Co spinel ferrite that was synthesized by the sol-gel auto-combustion method. The research also indicates that the higher the Gd content, the greater the increase in the lattice parameter, which suggests that Gd 3+ ions uniformly replaced the octahedral Fe 3+ ions. The morphology and chemical composition of Gd-doped Ni-Co ferrites have been studied using SEM and EDS. Gd adding to the NiCoFe matrix increases the BET surface area by 50% (from 48 to 72 m 2 /g) and promotes the formation of mesopores with an average radius from 3.9 to 4.9 nm. The pH PZC values of Gd-doped ferrites are in the range of 7.22-7.39, which means that the ferrite surface will acquire a positive charge at natural pH, so this will promote the adsorption of Congo red anionic dye through electrostatic interaction forces. Langmuir, Freundlich, and Dubinin-Radushkevich models were used to explain the mechanism of CR adsorption on the Ni 0.5 Co 0.5 Gd x Fe 2-x O 4 adsorbent surface. The ionic-covalent parameter has been estimated to describe the surface acid-base properties. Overall, this study highlights the potential of Gd 3+ doping as a promising approach for enhancing the adsorption properties of nickel-cobalt ferrites., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: 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., Materials and Methods: Ninety-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., Results: 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., Conclusion: 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., (© 2024. The Author(s).)

Objectives: 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)., Materials and Methods: 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., Results: 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)., Conclusions: 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., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: To evaluate the differences between audio-vestibular function testing and inner ear gadolinium magnetic resonance imaging (MRI) in distinguishing definite Ménière disease (DMD) and probable Ménière disease (PMD), and to provide a reference for early clinical diagnosis and intervention., Methods: A total of 116 patients diagnosed with DMD (n = 80) and PMD (n = 36) were enrolled. The differences in the results of pure tone audiometry, caloric test, and tympanic injection of gadolinium for contrast-enhanced MRI between the two groups were compared and analyzed. Parameters that could differentiate between the two conditions were identified, and the sensitivity and specificity and the area under the curve (AUC) of individual and combined indices in the differential diagnosis of DMD and PMD were evaluated., Results: The hearing threshold and hearing asymmetry rate of the DMD group were significantly higher than those of the PMD group (p < 0.001), 98.8% and 30.6%, respectively. The abnormal rates of canal paresis (CP) and severity of endolymphatic hydrops in the DMD group were higher than those in the PMD group (p < 0.05). When combined with high-frequency hearing thresholds, hearing asymmetry, hearing curve type, endolymphatic hydrops, and abnormal CP, the diagnostic accuracy of DMD was improved compared to using high-frequency alone (p < 0.05)., Conclusion: This study showed that PMD and DMD may represent two different stages in the development of MD disease. The comprehensive assessment of audio-vestibular function testing and inner ear MRI proves beneficial for early diagnosis, potentially contributing to the preservation of inner ear function., Competing Interests: Conflict of interest statement: The authors have no relevant financial or nonfinancial interests to disclose., (Copyright © 2024, Otology & Neurotology, Inc.)

Objectives: To evaluate the diagnostic performance and reliability of MRI descriptors used for the detection of Ménière's disease (MD) on delayed post-gadolinium MRI. To determine which combination of descriptors should be optimally applied and whether analysis of the vestibular aqueduct (VA) contributes to the diagnosis., Materials and Methods: This retrospective single centre case-control study evaluated delayed post-gadolinium MRI of patients with Ménièriform symptoms examined consecutively between Dec 2017 and March 2023. Two observers evaluated 17 MRI descriptors of MD and quantified perilymphatic enhancement (PLE) in the cochlea. Definite MD ears according to the 2015 Barany Society criteria were compared to control ears. Cohen's kappa and diagnostic odds ratio (DORs) were calculated for each descriptor. Forward stepwise logistic regression determined which combination of MRI descriptors would best predict MD ears, and the area under the receiver operating characteristic curve for this model was measured., Results: A total of 227 patients (mean age 48.3 ± 14.6, 99 men) with 96 definite MD and 78 control ears were evaluated. The presence of saccular abnormality (absent, as large as or confluent with the utricle) performed best with a DOR of 292.6 (95% confidence interval (CI), 38.305-2235.058). All VA descriptors demonstrated excellent reliability and with DORs of 7.761 (95% CI, 3.517-17.125) to 18.1 (95% CI, 8.445-39.170). Combining these saccular abnormalities with asymmetric cochlear PLE and an incompletely visualised VA correctly classified 90.2% of cases (sensitivity 84.4%, specificity 97.4%, AUC 0.938)., Conclusion: Either absent, enlarged or confluent saccules are the best predictors of MD. Incomplete visualisation of the VA adds value to the diagnosis., Clinical Relevance Statement: A number of different MRI descriptors have been proposed for the diagnosis of Ménière's disease, but by establishing the optimally performing MRI features and highlighting new useful descriptors, there is an opportunity to improve the diagnostic performance of Ménière's disease imaging., Key Points: • A comprehensive range of existing and novel vestibular aqueduct delayed post-gadolinium MRI descriptors were compared for their diagnostic performance in Ménière's disease. • Saccular abnormality (absent, confluent with or larger than the utricle) is a reliable descriptor and is the optimal individual MRI predictor of Ménière's disease. • The presence of this saccule descriptor or asymmetric perilymphatic enhancement and incomplete vestibular aqueduct visualisation will optimise the MRI diagnosis of Ménière's disease., (© 2024. Crown.)

Objectives: To develop and share a deep learning method that can accurately identify optimal inversion time (TI) from multi-vendor, multi-institutional and multi-field strength inversion scout (TI scout) sequences for late gadolinium enhancement cardiac MRI., Materials and Methods: Retrospective multicentre study conducted on 1136 1.5-T and 3-T cardiac MRI examinations from four centres and three scanner vendors. Deep learning models, comprising a convolutional neural network (CNN) that provides input to a long short-term memory (LSTM) network, were trained on TI scout pixel data from centres 1 to 3 to identify optimal TI, using ground truth annotations by two readers. Accuracy within 50 ms, mean absolute error (MAE), Lin's concordance coefficient (LCCC) and reduced major axis regression (RMAR) were used to select the best model from validation results, and applied to holdout test data. Robustness of the best-performing model was also tested on imaging data from centre 4., Results: The best model (SE-ResNet18-LSTM) produced accuracy of 96.1%, MAE 22.9 ms and LCCC 0.47 compared to ground truth on the holdout test set and accuracy of 97.3%, MAE 15.2 ms and LCCC 0.64 when tested on unseen external (centre 4) data. Differences in vendor performance were observed, with greatest accuracy for the most commonly represented vendor in the training data., Conclusion: A deep learning model was developed that can identify optimal inversion time from TI scout images on multi-vendor data with high accuracy, including on previously unseen external data. We make this model available to the scientific community for further assessment or development., Clinical Relevance Statement: A robust automated inversion time selection tool for late gadolinium-enhanced imaging allows for reproducible and efficient cross-vendor inversion time selection., Key Points: • A model comprising convolutional and recurrent neural networks was developed to extract optimal TI from TI scout images. • Model accuracy within 50 ms of ground truth on multi-vendor holdout and external data of 96.1% and 97.3% respectively was achieved. • This model could improve workflow efficiency and standardise optimal TI selection for consistent LGE imaging., (© 2024. The Author(s).)

In the diagnosis of migraine, which is a neurovascular disease, gadolinium-based contrast agents (GBCAs) are used to rule out more serious conditions. On the other hand, it remains unclear as a scientific gap whether GBCAs may trigger migraine-related pain. The aim of this study was to investigate the effect of GBCAs on mechanical and thermal pain behaviour in a nitroglycerin (NTG)-induced migraine model in mice. NTG (10 mg/kg) was administered intraperitoneally to adult (6-8weeks old) BALB/c mice 2 h before behavioral tests 5 times every other day on days 1st, 3rd, 5th and 9th to induce migraine model (N = 50). As GBCAs, gadobenate dimeglumine (linear-ionic), Gadodiamide (linear-nonionic), and gadobutrol (macrocyclic-nonionic) were delivered intravenously through the tail vein of mice for 5 days on test days. Mechanical pain threshold (plantar and facial withdrawal threshold) was evaluated by plantar von Frey and periorbital von Frey tests on days 1st, 5th, and 9th, and thermal pain threshold (latency) was evaluated by hot plate and cold plate tests on days 3rd and 7th. There was a statistically significant increase in mechanical and thermal hyperalgesia in NTG administered groups compared to the control group. Gadodiamide, gadobutrol and gadobenate dimeglumine administration significantly decreased latency, paw and facial withdrawal threshold (0.18 ± 0.05, 0.17 ± 0.07, 0.16 ± 0.09; 9th day values respectively) compared to NTG group (0.27 ± 0.05). The results of this in vivo study show that GBCAs produce effects that may trigger migraine attacks in migraine. It is recommended that these effects be further investigated and supported by further clinical studies., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Since its introduction more than 35 years ago, gadolinium-enhanced MRI has fundamentally changed medical practice. Although extraordinarily safe, gadolinium-based contrast agents (GBCAs) may have side effects. Four distinct safety considerations include acute allergiclike reactions, nephrogenic systemic fibrosis (NSF), gadolinium deposition, and symptoms associated with gadolinium exposure. Acute reactions after GBCA administration are uncommon-far less than with iodinated contrast agents-and, although rare, serious reactions can occur. NSF is a rare but serious sclerodermalike condition occurring in patients with kidney failure after exposure to American College of Radiology (ACR) group I GBCAs. Group II and III GBCAs are considered lower risk, and, through their use, NSF has largely been eliminated. Unrelated to NSF, retention of trace amounts of gadolinium in the brain and other organs has been recognized for over a decade. Deposition occurs with all agents, although linear agents appear to deposit more than macrocyclic agents. Importantly, to date, no data show any adverse biologic or clinical effects from gadolinium deposition, even with normal kidney function. This article summarizes the latest safety evidence of commercially available GBCAs with a focus on new agents, discusses updates to the ACR NSF GBCA safety classifications, and describes approaches for strengthening the evidence needed for regulatory decisions.

Background: Late gadolinium enhancement (LGE) cardiac MRI is the method of choice in revealing the presence of myocardial scarring, but its availability remains limited in clinical practice., Purpose: To assess myocardial scarring in patients with autoimmune rheumatic diseases (ARDs) using contrast-free cardiac MRI with a radiomics model., Study Type: Retrospective., Population: One hundred ninety-two patients (mean age, 41 years ± 15, 62 men) with or without ARDs, grouped into a training set of 153 patients and a testing set of 39 patients., Field Strength/sequence: 3.0 T/ cine imaging with a balanced steady-state free precession sequence, T1 mapping with a modified Look-Locker inversion recovery sequence, and LGE imaging with a phase-sensitive inversion recovery gradient echo sequence., Assessment: LGE assessment was the reference standard for identifying myocardial scarring. Based on motion features extracted from cine images and tissue characterization features extracted from native T1 maps, a fully automated radiomics model with T1, cine MRI, or combined inputs was developed., Statistical Tests: Logistic regression model was used to detect myocardial scarring using contrast-free cardiac MRI parameters. Receiver operating characteristic curves were analyzed to assess the accuracy, sensitivity, and specificity in detecting myocardial scarring. Sensitivities of the models were further assessed in patients with various myocardial scarring proportions. Z-statistic and dice coefficient were assessed to compare the performance. P-values <0.05 were considered significant., Results: The multivariable regression model exhibited an accuracy of 85.3%, a sensitivity of 93.5%, and a specificity of 50.0%. The radiomics model with T1 and cine MRI input exhibited an accuracy of 75.7%, a sensitivity of 60.9%, and a specificity of 85.5%. Moreover, the radiomics model showed a sensitivity of 90.9% among patients with >25% myocardial scarring., Data Conclusions: The proposed radiomics model allowed for the identification of myocardial scarring similar to LGE, but on contrast-free cardiac MRI in patients with ARDs., Evidence Level: 3 TECHNICAL EFFICACY: Stage 1., (© 2023 International Society for Magnetic Resonance in Medicine.)

Background: First-pass perfusion cardiac MR imaging could reflect pulmonary hemodynamics. However, the clinical value of pulmonary transit time (PTT) derived from first-pass perfusion MRI in light-chain (AL) amyloidosis requires further evaluation., Purpose: To assess the clinical and prognostic value of PTT in patients with AL amyloidosis., Study Type: Prospective observational study., Population: 226 biopsy-proven systemic AL amyloidosis patients (age 58.62 ± 10.10 years, 135 males) and 43 healthy controls (age 42 ± 16.2 years, 20 males)., Field Strength/sequence: SSFP cine and phase sensitive inversion recovery late gadolinium enhancement (LGE) sequences, and multislice first-pass myocardial perfusion imaging with a saturation recovery turbo fast low-angle shot (SR-TurboFLASH) pulse sequence at 3.0T., Assessment: PTT was measured as the time interval between the peaks of right and left ventricular cavity arterial input function curves on first-pass perfusion MR images., Statistical Tests: Independent-sample t test, Mann-Whitney U test, Chi-square test, Fisher's exact test, analysis of variance, or Kruskal-Wallis test, as appropriate; univariable and multivariable Cox proportional hazards models and Kaplan-Meier curves, area under receiver operating characteristic curve were used to determine statistical significance., Results: PTT could differentiate AL amyloidosis patients with (N = 188) and without (N = 38) cardiac involvement (area under the curve [AUC] = 0.839). During a median follow-up of 35 months, 160 patients (70.8%) demonstrated all-cause mortality. After adjustments for clinical (Hazard ratio [HR] 1.061, confidence interval [CI]: 1.021-1.102), biochemical (HR 1.055, CI: 1.014-1.097), cardiac MRI-derived (HR 1.077, CI: 1.034-1.123), and therapeutic (HR 1.063, CI: 1.024-1.103) factors, PTT predicted mortality independently in patients with AL amyloidosis. Finally, PTT could identify worse outcomes in patients demonstrating New York Heart Association class III, Mayo 2004 stage III, and transmural LGE pattern., Data Conclusion: PTT may serve as a new imaging predictor of cardiac involvement and prognosis in AL amyloidosis., Level of Evidence: 2 TECHNICAL EFFICACY: Stage 2., (© 2023 International Society for Magnetic Resonance in Medicine.)

We investigated whether magnetic resonance imaging can visualize the distribution in the vitreous cavity via eye drops of ophthalmic solutions, gadolinium-based contrast agent, and 17 O-water, and to clarify the usefulness of ultra-heavily T2-weighted sequences in the research of intraocular distribution. Five different solutions (V-ROHTO, TRAVATANZ, gadobutrol, H 2 17 O, and saline) were administered to excised pig eye specimens. The samples were scanned using T1 mapping, T2 mapping, 3D T2-weighted (echo times (TE): 500, 3200, and 4500 ms), a half-Fourier single-shot turbo-spin echo sequence (HASTE; TE: 440 and 3000 ms), and 3D-real inversion-recovery before eye drops administration. Subsequently, we used a plastic dropper to drop a 0.5 mL solution each, and images were obtained up to 26 h later. Temporal changes in the T1 and T2 values of the anterior chamber and vitreous cavity were compared. The other sequences were evaluated by determining temporal signal changes as signal intensity ratio (SIR) compared to "No drop." The T1 and T2 values of samples treated with gadobutrol and H 2 17 O decreased over time. The SIR of samples treated with gadobutrol and H 2 17 O showed remarkable changes in the 3D T2-weighted images, whereas no remarkable temporal changes were observed in the other solutions. Longer TEs resulted in remarkable changes. We demonstrated that visualization of distribution in the vitreous cavity via eye drops could be achieved with excised pig eyes using gadobutrol and H 2 17 O, but not with ophthalmic solutions. Ultra-heavily T2-weighted sequences may be promising for the early and highly sensitive visualization of the intraocular distribution of eye drops., (© 2024. The Author(s).)

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) has highly heterogeneous clinical presentations, in which encephalitis is an important phenotype. Moreover, MOGAD has been reported to exhibit diverse imaging findings. However, there have been no previous reports of cases with perivascular radial gadolinium enhancement in periventricular regions, commonly reported in autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy. In this paper, we present two cases of MOGAD with this MRI feature, both of which underwent brain biopsy for the lesions. Brain biopsies revealed perivenous demyelination and inflammation consistent with acute disseminated encephalomyelitis (ADEM), with pronounced axonal damage in Case 1 and minimal axonal involvement in Case 2. Case 1 exhibited more severe cerebral atrophy than Case 2, correlating with the extent of axonal damage. Through these cases, we highlight the heterogeneity of radiological manifestations of MOGAD, expanding the spectrum beyond previously defined MRI patterns. Furthermore, histopathological analysis revealed distinct axonal involvement as a potential prognostic marker of brain atrophy. These observations emphasize the importance of considering MOGAD in the differential diagnosis, even in cases with atypical imaging findings, and highlight the significance of brain biopsy in guiding both diagnosis and prognosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Shimizu, Beck, Murayama, Hoshi, Sumikura, Higashida, Fukasaka, Shimada, Nagashima, Fujioka, Hatayama, Okuno, Mochizuki and Sakaguchi.)

Introduction: Sites associated with gadolinium (Gd) deposition in the brain (e.g., the globus pallidus) are known to contain high concentrations of ferric iron. There is considerable debate over the mechanism of Gd deposition in the brain. The role of iron transport mechanisms in Gd deposition has not been determined. Thus, we seek to identify if Gd deposition can be controlled by modifying iron exposure. Methods: Female Sprague-Dawley rats were given diets with controlled iron levels at 2-6 ppm, 6 ppt (20 g/kg Fe carbonyl) or 48 ppm for 3 weeks to induce iron deficiency, overload or normalcy. They were kept on those diets while receiving a cumulative 10 mmol/kg dose of gadodiamide intravenously over 2 weeks, then left to washout gadodiamide for 3 days or 3 weeks before tissues were harvested. Gd concentrations in tissues were analyzed by ICP-MS. Results: There were no significant effect of dietary iron and total Gd concentrations in the organs, but there was a significant effect of iron status on Gd distribution in the brain. For the 3-week washout cohort, there was a non-significant trend of increasing total brain deposition and decreasing dietary iron, and about 4-fold more Gd in the olfactory bulbs of the low iron group compared to the other groups. Significant brain accumulation was observed in the low iron group total brain Gd in the 3-week washout group relative to the 3-day washout group and no accumulation was observed in other tissues. There was a strong negative correlation between femur Gd concentrations and concentrations in other organs when stratifying by dietary iron. Discussion: Gd brain deposition from linear Gd-based contrast agents (GBCAs) are dependent upon iron status, likely through variable transferrin saturation. This iron dependence appears to be associated with redistribution of peripheral deposited Gd (e.g., in the bone) into the brain., Competing Interests: Author JPP is employed by Pfizer. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Prybylski, Jastrzemski and Jay.)

Background: Gadolinium Leakage into Ocular Structures (GLOS) is common following acute cerebrovascular events. The objective of this study was to investigate the occurrence of GLOS in an acute traumatic brain injury (TBI) cohort without acute cerebrovascular injury and to explore associated factors., Methods: Enrolled acute TBI patients had a baseline MRI ≤48 h of injury (TP1) and follow-up MRI ≤72 h after baseline (TP2). Vitreous chamber enhancement and signal intensity ratios (SIRs) were calculated using pre- and post-contrast Fluid Attenuated Inversion Recovery (FLAIR). White matter hyperintensities (WMHs) were assessed using the Fazekas scale., Results: Of the 128 TBI patients included, median age was 47 years, 70% male, and 66% presented with Glasgow Coma Scale of 15. No GLOS was detected at TP1 but was present in 23% of patients at TP2. GLOS+ patients were older (68 years [56-76] vs 39 years [27-53], p < 0.001), more likely to report falls as injury mechanism (62% vs 36%, p = 0.006), report history of hypertension (41% vs 19%, p = 0.025), and had a higher burden of WMHs (59% vs 14% with a total Fazekas ≥2, p < 0.001). Quantitative SIRs confirmed qualitative assessments: GLOS+ patients had higher SIRs at TP2 (0.43 vs 0.22, p < 0.001). Age (OR 3.28, 95%CI [1.88-5.71], p < 0.001) and prior TBI history (OR 4.99, 95%CI [1.46-17.06], p = 0.010) were independent predictors of GLOS. When age was removed, total Fazekas score (OR 2.53, 95%CI [1.60-4.00], p < 0.001) was an independent predictor of GLOS., Conclusions: GLOS is primarily associated with age and may serve as another imaging marker of chronic vascular disease., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier B.V.)

Gadolinium-based contrast agents are increasingly used in clinical practice. While these pharmaceuticals are verified causal agents in nephrogenic systemic fibrosis, there is a growing body of literature supporting their role as causal agents in symptoms associated with gadolinium exposure after intravenous use and encephalopathy following intrathecal administration. Gadolinium-based contrast agents are multidentate organic ligands that strongly bind the metal ion to reduce the toxicity of the metal. The notion that cationic gadolinium dissociates from these chelates and causes the disease is prevalent among patients and providers. We hypothesize that non-ligand-bound (soluble) gadolinium will be exceedingly low in patients. Soluble, ionic gadolinium is not likely to be the initial step in mediating any disease. The Kidney Institute of New Mexico was the first to identify gadolinium-rich nanoparticles in skin and kidney tissues from magnetic resonance imaging contrast agents in rodents. In 2023, they found similar nanoparticles in the kidney cells of humans with normal renal function, likely from contrast agents. We suspect these nanoparticles are the mediators of chronic toxicity from magnetic resonance imaging contrast agents. This article explores associations between gadolinium contrast and adverse health outcomes supported by clinical reports and rodent models., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Cunningham, Kirk, Hong, Yang, Howard, Brearley, Sáenz-Trevizo, Krawchuck, Watt, Henderson, Dokladny, DeAguero, Escobar and Wagner.)

Late gadolinium enhancement (LGE) is a widely used magnetic resonance imaging method for assessing cardiac disease. However, the relationship between different LGE signal thresholds and microscopic tissue staining images is unclear. In this study, we performed cardiovascular MRI on myocardial infarction (MI) model rats and evaluated the relationship between LGE with different signal thresholding methods and tissue staining images. We prepared 16 rats that underwent MRI 14-18 days following a surgery to create an MI model. We captured cine and LGE images of the cardiac short-axis and longitudinal two- and four-chamber views. The mean ± 2SD, ± 3SD, and ± 5SD of the pixel values in the non-infarcted area were defined as the LGE area. We compared areas of Sirius red staining, determined by the color tone, with their respective LGE areas at end-diastole and end-systole. We observed that the LGE area calculated as the mean ± 2SD of the non-infarcted area at end-diastole demonstrated a significant positive correlation with the area of Sirius red staining (Pearson's correlation coefficient in both: 0.81 [p < 0.01]). Therefore, the LGE area calculated as the mean ± 2SD of the non-infarcted area at end-diastole best reflected the MI area in tissue staining., (© 2024. The Author(s).)

Objective: Blood-labyrinthine barrier leakage has been reported in sudden sensorineural hearing loss (SSNHL). We compared immediate post-contrast 3D heavily T2-weighted fluid-attenuated inversion recovery (FLAIR), T1 spin echo (SE), and 3D T1 gradient echo (GRE) sequences, and heavily T2-weighted FLAIR (hvT2F) with and without deep learning-based reconstruction (DLR) in detecting perilymphatic enhancement., Methods: Fifty-four patients with unilateral SSNHL who underwent ear MRI with three sequences were included. We compared asymmetry scores, confidence scores, and detection rates of perilymphatic enhancement among the three sequences and obtained 3D hvT2F with DLR from 35 patients. The above parameters and subjective image quality between 3D hvT2F with and without DLR were compared., Results: Asymmetry scores and detection rate of 3D hvT2F were significantly higher than 3D GRE T1 and SE T1 (respectively, 1.37, 0.11, 0.19; p < 0.001). Asymmetry scores significantly increased with DLR compared to 3D hvT2F for experienced and inexperienced readers (respectively, 1.77 vs. 1.40, p = 0.036; 1.49 vs. 1.03, p = 0.012). The detection rate significantly increased only for the latter (57.1% vs. 31.4%, p = 0.022). Patients with perilymphatic enhancement had significantly higher air conduction thresholds on initial (77.96 vs. 57.79, p = 0.002) and 5 days after presentation (63.38 vs. 41.85, p = 0.019)., Conclusion: 3D hvT2F significantly increased the detectability of perilymphatic enhancement compared to 3D GRE T1 and SE T1. DLR further improved the conspicuity of perilymphatic enhancement in 3D hvT2F. 3D hvT2F and DLR are useful for evaluating blood-labyrinthine barrier leakage; furthermore, they might provide prognostic value in the early post-treatment period., Clinical Relevance Statement: Ten-minute post-contrast 3D heavily T2-weighed FLAIR imaging is a potentially efficacious sequence in demonstrating perilymphatic enhancement in patients with sudden sensorineural hearing loss and may be further improved by deep learning-based reconstruction., Key Points: • 3D heavily T2-weighted FLAIR (3D hvT2F) is a sequence sensitive in detecting low concentrations of contrast in the perilymphatic space. • 3D hvT2F sequences properly demonstrated perilymphatic enhancement in sudden sensorineural hearing loss compared to T1 sequences and were further improved by deep learning-based reconstruction (DLR). • 3D hvT2F and DLR are efficacious sequences in detecting blood-labyrinthine barrier leakage and with potential prognostic information., (© 2024. The Author(s), under exclusive licence to European Society of Radiology.)

Importance: Understanding the association between clinically defined relapses and radiological activity in multiple sclerosis (MS) is essential for patient treatment and therapeutic development., Objective: To investigate clinical events identified as relapses but not associated with new T2 lesions or gadolinium-enhanced T1 lesions on brain and spinal cord magnetic resonance imaging (MRI)., Design, Setting, and Participants: This multicenter observational cohort study was conducted between January 2015 and June 2023. Data were extracted on June 8, 2023, from the French MS registry. All clinical events reported as relapses in patients with relapsing-remitting MS were included if brain and spinal cord MRI was performed within 12 and 24 months before the event, respectively, and 50 days thereafter with gadolinium injection., Exposures: Events were classified as relapses with active MRI (RAM) if a new T2 lesion or gadolinium-enhanced T1 lesion appeared on brain or spinal cord MRI or as acute clinical events with stable MRI (ACES) otherwise., Main Outcomes and Measures: Factors associated with ACES were investigated; patients with ACES and RAM were compared regarding Expanded Disability Status Scale (EDSS) course, relapse rate, confirmed disability accrual (CDA), relapse-associated worsening (RAW), progression independent of relapse activity (PIRA), and transition to secondary progressive (SP) MS, and ACES and RAM rates under each disease-modifying therapy (DMT) were estimated., Results: Among 31 885 clinical events, 637 in 608 patients (493 [77.4%] female; mean [SD] age, 35.8 [10.7] years) were included. ACES accounted for 166 (26.1%) events and were more likely in patients receiving highly effective DMTs, those with longer disease duration (odds ratio [OR], 1.04; 95% CI, 1.01-1.07), or those presenting with fatigue (OR, 2.14; 95% CI, 1.15-3.96). ACES were associated with significant EDSS score increases, lower than those found for RAM. Before the index event, patients with ACES experienced significantly higher rates of relapse (relative rate [RR], 1.21; 95% CI, 1.01-1.46), CDA (hazard ratio [HR], 1.54; 95% CI, 1.13-2.11), and RAW (HR, 1.72; 95% CI, 1.20-2.45). Patients with ACES were at significantly greater risk of SP transition (HR, 2.58; 95% CI, 1.02-6.51). Although RAM rate decreased with DMTs according to their expected efficacy, ACES rate was stable across DMTs., Conclusions and Relevance: The findings in this study introduce the concept of ACES in MS, which accounted for one-fourth of clinical events identified as relapses.

Purpose: To compare DSC-MRI using Gadolinium (GBCA) and Ferumoxytol (FBCA) in high-grade glioma at 3T and 7T MRI field strengths. We hypothesized that using FBCA at 7T would enhance the performance of DSC, as measured by contrast-to-noise ratio (CNR)., Methods: Ten patients (13 lesions) were assigned to 3T (6 patients, 6 lesions) or 7T (4 patients, 7 lesions). All lesions received 0.1 mmol/kg of GBCA on day 1. Ten lesions (4 at 3T and 6 at 7T) received a lower dose (0.6 mg/kg) of FBCA, followed by a higher dose (1.0-1.2 mg/kg), while 3 lesions (2 at 3T and 1 at 7T) received only a higher dose on Day 2. CBV maps with leakage correction for GBCA but not for FBCA were generated. The CNR and normalized CBV (nCBV) were analyzed on enhancing and non-enhancing high T2W lesions., Results: Regardless of FBCA dose, GBCA showed higher CNR than FBCA at 7T, which was significant for high-dose FBCA ( p < .05). Comparable CNR between GBCA and high-dose FBCA was observed at 3T. There was a trend toward higher CNR for FBCA at 3T than 7T. GBCA also showed nCBV twice that of FBCA at both MRI field strengths with significance at 7T., Conclusion: GBCA demonstrated higher image conspicuity, as measured by CNR, than FBCA on 7T. The stronger T2* weighting realized with higher magnetic field strength, combined with FBCA, likely results in more signal loss rather than enhanced performance on DSC. However, at clinical 3T, both GBCA and FBCA, particularly a dosage of 1.0-1.2 mg/kg (optimal for perfusion imaging), yielded comparable CNR., Competing Interests: Declaration of conflicting interestThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: reports article publishing charges were provided by National Institutes of Health (NIH) grant [K08CA237809], and financial support was provided by The Jonathan D. Lewis Foundation. reports financial support was provided by National Institutes of Health (NIH) grant [NS53468], the Walter S. and Lucienne Driskill Foundation, and AMAG Pharmaceuticals Inc. The other author(s) received no financial support for the research, authorship, and/or publication of this article.

Background: Microvascular scarring compromises the functionality of the endometrium, and vascular flow at the junctional zone (JZ) may be the key to understanding poor reproductive outcomes in women with Asherman syndrome (AS)., Aims: To investigate whether vascular perfusion of the uterus, measured by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is impaired in women with intrauterine adhesions (IUA) and AS., Materials and Methods: A prospective observational cohort pilot study of 23 women with IUA treated with hysteroscopic synecholysis and a control group of two patients with cervix cancer were subject to DCE-MRI with gadolinium to assess uterine vascularity. Twelve regions of interest (ROIs) were allocated on the DCE-MRI image incorporating the JZ, with control ROI placed at the psoas muscle. Individual ROIs were compared to the mean total perfusion (TP) in the same uterus. Pre- and post-operative perfusion analyses were performed on five women. Receiver operator curves (ROC) were used to analyse MRI as a predictor of IUA., Results: There was no significant difference in perfusion; a trend toward reduced perfusion was observed in women with IUA compared to the controls. The ROC was predictive of higher-grade and inoperable IUA., Conclusions: Reduced perfusion on DCE-MRI as assessed by ROC predicted higher-stage AS. The results of this study support further investigation of DCE-MRI as a prognostic tool for AS prior to surgical intervention to assist in providing prognostic guidance for women suffering from AS., (© 2024 The Authors. Australian and New Zealand Journal of Obstetrics and Gynaecology published by John Wiley & Sons Australia, Ltd on behalf of Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)