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Search Results (238)

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Keywords = gadolinium contrast agent

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23 pages, 3203 KB  
Review
MRI-Derived Evaluation of Liver Function and Its Extension to K-Edge Photon-Counting CT: Focus on Gadolinium-Based Functional Biliary Imaging
by Luigi Asmundo, Ilaria Vicentin, Gaia Ghilardi, Caterina Beatrice Monti, Andrea Vanzulli, Francesco Rizzetto, Leonardo Mariani, Simone Steffani, Leonardo Centonze, Chiara Mazzarelli, Domenico Albano, Stefano Di Sandro and Angelo Vanzulli
Diagnostics 2026, 16(17), 2740; https://doi.org/10.3390/diagnostics16172740 - 26 Aug 2026
Viewed by 192
Abstract
Accurate assessment of liver function is essential in the management of chronic liver disease, hepatobiliary malignancies, and surgical planning. In recent years, hepatobiliary magnetic resonance imaging (MRI) using gadolinium-based contrast agents has evolved from a purely morphological technique into a quantitative functional imaging [...] Read more.
Accurate assessment of liver function is essential in the management of chronic liver disease, hepatobiliary malignancies, and surgical planning. In recent years, hepatobiliary magnetic resonance imaging (MRI) using gadolinium-based contrast agents has evolved from a purely morphological technique into a quantitative functional imaging modality capable of evaluating hepatocyte uptake, biliary excretion, and regional liver function. Quantitative MRI-derived biomarkers, including relative liver enhancement, liver-to-spleen ratio, T1 relaxometry, and pharmacokinetic modeling, have demonstrated significant correlations with established liver function tests and postoperative outcomes. At the same time, the introduction of photon-counting computed tomography (PCCT) and K-edge imaging has opened new perspectives in quantitative imaging. Energy-resolved photon-counting technology has demonstrated gadolinium discrimination and material decomposition under selected experimental conditions, raising the hypothesis that aspects of hepatobiliary contrast distribution might eventually be investigated with computed tomography (CT). However, reliable K-edge detection and quantitative hepatobiliary gadolinium imaging after standard clinical administration have not yet been established in humans. Phantom, simulation, preclinical, and limited non-hepatobiliary human studies have investigated gadolinium K-edge imaging, but direct evidence for functional hepatobiliary PCCT in humans remains lacking. This review aims to provide a comprehensive overview of MRI-derived evaluation of liver function, with particular attention to the experimental evidence exploring whether selected MRI-derived concepts might ultimately be investigated using PCCT and K-edge imaging, highlighting current evidence, technical challenges, translational applications, and future perspectives in precision hepatobiliary diagnostics. Full article
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21 pages, 1516 KB  
Review
Contrast Media-Associated Nephrotoxicity: A Narrative Review of Pathophysiology, Risk Factors, Prevention, and Clinical Management
by Esteban Zavaleta-Monestel, Jeaustin Mora-Jiménez, Kevin Cruz-Mora, Sebastián Arguedas-Chacón, Luis Guillermo Herrera-Jiménez, José Andrés Castro-Gamboa and José Miguel Chaverri-Fernández
Kidney Dial. 2026, 6(3), 54; https://doi.org/10.3390/kidneydial6030054 - 12 Aug 2026
Viewed by 228
Abstract
Background: Contrast media are essential tools in diagnostic and interventional imaging, but their relationship with acute kidney injury remains clinically relevant and conceptually debated. This narrative review aimed to synthesize current evidence on contrast media-associated nephrotoxicity, including terminology, epidemiology, pathophysiology, risk stratification, prevention, [...] Read more.
Background: Contrast media are essential tools in diagnostic and interventional imaging, but their relationship with acute kidney injury remains clinically relevant and conceptually debated. This narrative review aimed to synthesize current evidence on contrast media-associated nephrotoxicity, including terminology, epidemiology, pathophysiology, risk stratification, prevention, pharmacotherapeutic management, and clinical decision-making. Methods: A structured literature search was conducted in major biomedical databases and complemented by international guidelines and consensus statements addressing contrast-associated and contrast-induced acute kidney injury in adults exposed to intravascular contrast media. Discussion: Contemporary evidence emphasizes the distinction between contrast-associated acute kidney injury, which reflects a temporal association after exposure, and contrast-induced acute kidney injury, which implies causality. The renal risk directly attributable to modern intravenous iodinated contrast media appears to have been historically overestimated, although clinically relevant risk persists in vulnerable patients. Proposed mechanisms include renal vasoconstriction, medullary hypoxia, oxidative stress, mitochondrial dysfunction, tubular epithelial injury, endothelial dysfunction, and inflammatory or apoptotic pathways. Preventive strategies should be individualized, with isotonic saline remaining the main intervention when indicated, whereas routine pharmacologic prophylaxis is not supported by consistent clinically meaningful benefit. Conclusions: Renal safety in contrast-enhanced imaging requires a balanced approach that minimizes avoidable kidney injury in high-risk patients without unnecessarily delaying clinically indicated diagnostic or therapeutic procedures. Full article
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25 pages, 2655 KB  
Review
Silver Nanoparticle-Based Hybrid Nanomaterials for Monitoring and Treatment of Hospital Wastewater: Focus on Rare Earth Elements and Radiopharmaceutical Residues from Nuclear Medicine Department
by Alessandro Ovis, Ilaria Maria De Giorgio, Sofia Lemaire, Giovanna Iucci, Chiara Battocchio and Iole Venditti
Appl. Sci. 2026, 16(15), 7720; https://doi.org/10.3390/app16157720 - 3 Aug 2026
Viewed by 277
Abstract
Hospital wastewater has begun to act as an important source of emerging contaminants, including rare earth elements (REEs), mostly lanthanides, and radiopharmaceutical residues originating from diagnostic and therapeutic nuclear medicine procedures. The increasing use of gadolinium-based contrast agents, lutetium-containing therapeutics, technetium-99m tracers, iodine-131, [...] Read more.
Hospital wastewater has begun to act as an important source of emerging contaminants, including rare earth elements (REEs), mostly lanthanides, and radiopharmaceutical residues originating from diagnostic and therapeutic nuclear medicine procedures. The increasing use of gadolinium-based contrast agents, lutetium-containing therapeutics, technetium-99m tracers, iodine-131, yttrium-90, and gallium-68 radiopharmaceuticals has raised growing concerns regarding the release of radioactive and metal-containing compounds into aquatic environments. Conventional wastewater treatment plants are often inefficient in removing these contaminants because of their high chemical stability, low environmental concentrations, and complex aqueous speciation. In this context, hybrid nanomaterials containing silver nanoparticles (AgNPs) have attracted increasing interest for both monitoring and remediation applications. AgNP-based systems exhibit unique plasmonic, catalytic, antimicrobial, and sensing properties that can be exploited in adsorption, photocatalysis, membrane filtration, electrochemical detection, and surface-enhanced Raman spectroscopy (SERS). This review critically analyzes recent advances in hospital wastewater treatment and how hybrid nanomaterials containing silver nanoparticles (AgNPs) are emerging. The review places a particular focus on contamination by REEs and radiopharmaceuticals residues, which to date, as far as we know, remains a challenging and understudied aspect, as reflected by limited publications. Full article
(This article belongs to the Special Issue Environmental Pollution Monitoring and Control)
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15 pages, 2915 KB  
Article
AI-Driven Generation of Post-Contrast T1 and ECV Maps from Native T1 Map in Cardiac MRI
by Young Jung Yang, Ga Hyeon Kim, Yoon-Chul Kim and Young Jin Kim
Diagnostics 2026, 16(15), 2308; https://doi.org/10.3390/diagnostics16152308 - 23 Jul 2026
Viewed by 419
Abstract
Background/Objectives: This study aimed to develop an artificial intelligence-based method for generating virtual post-contrast T1 maps and extracellular volume (ECV) maps from native T1 maps and to evaluate its performance. Methods: The proposed method was based on a modified self-consistent recursive [...] Read more.
Background/Objectives: This study aimed to develop an artificial intelligence-based method for generating virtual post-contrast T1 maps and extracellular volume (ECV) maps from native T1 maps and to evaluate its performance. Methods: The proposed method was based on a modified self-consistent recursive diffusion bridge framework to generate virtual post-contrast T1 maps from native T1 maps. Cardiac magnetic resonance (CMR) data were collected from consecutive patients with suspected myocardial disease. A total of 813 well-registered image slices were selected for model development and evaluation. On an unseen test set of native T1 maps, the trained model generated virtual post-contrast T1 maps, which were subsequently combined with the corresponding native T1 maps to compute ECV maps. Results: The myocardial T1 values derived from the reference and virtual post-contrast T1 maps revealed similar distributions, although a systematic offset between the distribution peaks was observed. Following ECV transformation, this offset was substantially reduced. In the held-out test cohort, the virtual myocardial ECV showed acceptable agreement with the reference ECV, achieving a mean root mean square error (RMSE) of 3.05%, despite noticeable slice-to-slice variability (R2 = 0.585; Bland–Altman 95% limits of agreement, −5.98% to +6.06%). Conclusions: The proposed method enabled the generation of post-contrast T1 and ECV maps directly from native T1 maps without the administration of gadolinium-based contrast agents during CMR. These findings suggest that the proposed approach represents a promising contrast-free, non-invasive alternative for myocardial tissue characterization, with the potential to reduce examination costs, eliminate contrast-agent-related risks, and improve patient safety. Full article
(This article belongs to the Special Issue AI‑Driven Innovations in Medical Imaging)
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21 pages, 11076 KB  
Article
Can AI Detect What Is Not Injected? Evaluation of Lesion Detection in Virtual Contrast-Enhanced Breast MRI Using a Large-Scale AI Model Trained on GBCA-Enhanced Data
by Shirin Heidarikahkesh, Hannes Schreiter, Aju George, Tri-Thien Nguyen, Dominika Skwierawska, Luise Brock, Dominique Hadler, Michael Uder, Frederik B. Laun, Chris Ehring, Johanna Graber, Lorenz Döppmann, Ihor Horishnyi, Lorenz A. Kapsner, Sabine Ohlmeyer, Andrzej Liebert and Sebastian Bickelhaupt
Tomography 2026, 12(7), 105; https://doi.org/10.3390/tomography12070105 - 16 Jul 2026
Viewed by 621
Abstract
Background/Objectives: Artificial intelligence (AI) can support lesion detection in gadolinium-based contrast agent-enhanced (GBCA-enhanced) breast MRI. However, its effectiveness on virtual contrast-enhanced (vCE) images remains unclear. This feasibility study evaluated the publicly available MAMA-MIA nnU-Net model trained on GBCA-enhanced data using an independent cohort [...] Read more.
Background/Objectives: Artificial intelligence (AI) can support lesion detection in gadolinium-based contrast agent-enhanced (GBCA-enhanced) breast MRI. However, its effectiveness on virtual contrast-enhanced (vCE) images remains unclear. This feasibility study evaluated the publicly available MAMA-MIA nnU-Net model trained on GBCA-enhanced data using an independent cohort of both GBCA-enhanced and vCE breast MRI. Methods: This IRB-approved retrospective study included the publicly available nnU-Net model trained on n = 1506 MAMA-MIA breast MRI scans and a cohort of n = 2126 in-house 3T breast MRI scans. A generative adversarial network (Pix2Pix-GAN) was developed on n = 1870 of the in-house scans and used to generate vCE data on the remaining independent n = 256 in-house cases. The MAMA-MIA nnU-net was applied to both GBCA-enhanced (GBCA) and corresponding vCE images. Ground-truth segmentations of malignant lesions served to calculate the Dice score, Hausdorff distance, and lesion dimension differences. Results: The final test set comprised n = 250 cases (n = 69 malignant, n = 181 benign). Lesion detection rates were 91% (n = 63/n = 69; 95% confidence interval (CI): 82.3–96.0%) for GBCA and 84% (n = 58/n = 69; 95% CI: 73.7–90.9%) for vCE. Two lesions missed in GBCA were identified by vCE. The Hausdorff distances were similar (GBCA: 6.4 (IQR: 3.2–9.3; 95% CI: 5.2–7.8) mm; vCE: 6.7 (IQR: 3.9–9.7; 95% CI: 5.3–8.0) mm, p = 0.564). The Dice scores showed minor differences (GBCA: 0.829 (IQR: 0.723–0.900; 95% CI: 0.786–0.865) vs. vCE: 0.826 (IQR: 0.720–0.857; 95% CI: 0.770–0.836); p < 0.001). vCE images had slightly higher non-target tissue segmentation (median 6072 mm3 vs. 5754 mm3). Conclusions: A GBCA-trained algorithm demonstrated some cross-domain transferability to vCE images, albeit with a reduced case-level sensitivity of 84% (95% CI: 73.7–90.9%) vs. 91% (95% CI: 82.3–96.0%). Based on these preliminary results, further research, including larger cohorts and more diverse datasets, is warranted. Full article
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18 pages, 1417 KB  
Article
Short- and Long-Term Effects of a Single Exposure to Gadoteric Acid in Healthy Rats—Gadolinium, Iron and Other Metal Accumulation in Kidney and Brain
by Susana Coimbra, Susana Rocha, Rui Azevedo, Sofia D. Viana, Petronila Rocha-Pereira, Maria João Valente, Cristina Catarino, Luís Belo, Elsa Bronze-da-Rocha, Agostinho Almeida, Flávio Reis and Alice Santos-Silva
Int. J. Mol. Sci. 2026, 27(14), 6208; https://doi.org/10.3390/ijms27146208 - 11 Jul 2026
Viewed by 349
Abstract
Gadolinium [Gd (III)] released from gadolinium-based contrast agents, commonly used in magnetic resonance imaging, may accumulate in organs, altering metal homeostasis. We aimed to clarify Gd (III), iron and other metal accumulation in the kidney and brain, in the short (2 days) and [...] Read more.
Gadolinium [Gd (III)] released from gadolinium-based contrast agents, commonly used in magnetic resonance imaging, may accumulate in organs, altering metal homeostasis. We aimed to clarify Gd (III), iron and other metal accumulation in the kidney and brain, in the short (2 days) and long term (20 weeks), following exposure to gadoteric acid (Gd-DOTA) or free Gd (III). Wistar rats received one dose of Gd (III), Gd-DOTA, or saline. Gd (III) and metal levels in the blood (whole blood, and serum in the case of iron), kidney, and brain, and iron metabolism biomarkers, were assessed. Gd (III) was detectable in the blood, kidney, and brain, at both time points, for both Gd (III) and Gd-DOTA-treated groups. Exposure to free Gd (III) showed a significant Gd (III) accumulation in the kidney, brain and blood in the short term and long term; Gd-DOTA presented significant accumulation only in the short term. Gd-DOTA appears to have faster elimination and minimal brain deposition. Exposure to free Gd (III), but not to Gd-DOTA, led to disturbances in metal homeostasis and in iron metabolism markers (serum ferritin and transferrin saturation), but did not alter tissue iron levels. In summary, the kidney appears as the primary site of accumulation and retention. Despite the safer profile shown by Gd-DOTA in the long term, our data highlight the importance of clarifying the pathophysiological implications of Gd (III) retention and/or accumulation, particularly in vulnerable conditions and repeated exposures. Full article
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19 pages, 6226 KB  
Article
Comparative Study of Acute Toxicity and the Quantification of Cellular Effects Following Experimental Exposure to Gadolinium-Based Contrast Agents on the Planktonic Species Artemia sp. (Crustacea, Branchiopoda) Larvae
by Florența Mihai, Verginica Schröder, Ileana Rãu, Ana-Maria Mihalcescu, Irina Mihaela Iancu and Gabriela Mitea
Water 2026, 18(13), 1614; https://doi.org/10.3390/w18131614 - 2 Jul 2026
Viewed by 547
Abstract
(1) Background: This study examines the toxicologic effects of gadolinium in the context of the growing number of industrial and medical applications that use gadolinium compounds. Furthermore, understanding the cellular effects on aquatic organisms is a growing concern regarding emerging pollutants, as gadolinium [...] Read more.
(1) Background: This study examines the toxicologic effects of gadolinium in the context of the growing number of industrial and medical applications that use gadolinium compounds. Furthermore, understanding the cellular effects on aquatic organisms is a growing concern regarding emerging pollutants, as gadolinium is found in aquatic environments and drinking water as a pollutant. (2) Methods: The microplate-based experiments were designed to assess lethal effects (LC50) and analyze the cytological mechanisms in the larval stages of Artemia. Two gadolinium-containing compounds were comparatively analyzed: gadoteric acid (GA), an ionic compound, and gadoteridol (GD), a nonionic compound. Fluorescence analysis enabled detailed imaging and observations of the dynamics of the processes. Three fluorochromes were used for labeling: acridine orange (nuclear configuration), neutral red (lysosomal inclusions), and fluorescein isothiocyanate-labeled (cytoskeleton). (3) Results show that the effects became evident after more than 48 h of exposure. Cytotoxicity was higher for the nonionic macrocyclic compound GD (LC50 = 60 µmol/mL ± 0.00462 compared with GA (LC50 = 170 µmol/mL ± 0.01. The altered phenotype demonstrates the interference of the tested compounds at both the nuclear level (chromatin fragmentation, pyknotic nuclei) and the cytoplasmic level (enlarged lysosomal vesicles), as well as disorganized or condensed cytoskeleton. (4) Conclusions: Both compounds have effects on larvae, affecting their overall morphology and viability in 24–72 h after exposure. Identifying effects at the nuclear and cytoplasmic levels, as well as disruptions in cytoskeletal polymerization, helps to determine the factors that influence larval survival in an environment contaminated with such rare metals and to understand the cellular mechanisms induced by gadolinium compound poisoning. Full article
(This article belongs to the Special Issue Emerging Contaminants in the Water Environment)
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23 pages, 5892 KB  
Article
Deep Learning-Based Synthetic Contrast-Enhanced Breast MRI for Monitoring Response to Neoadjuvant Therapy
by Suleeporn Sujichantararat, Debosmita Biswas, Anum S. Kazerouni, Edric D. Tsang, Aditi Sathe, Daniel S. Hippe, Vivian Y. Park, Maggie Chung, Jennifer M. Specht, Suzanne M. Dintzis, Habib Rahbar, James H. Holmes, Wei Huang and Savannah C. Partridge
Cancers 2026, 18(11), 1835; https://doi.org/10.3390/cancers18111835 - 4 Jun 2026
Viewed by 994
Abstract
Background/Objectives: Contrast-enhanced (CE) breast MRI is highly sensitive for evaluating breast cancer extent and response to neoadjuvant therapy (NAT) but requires intravenous administration of gadolinium-based contrast agents (GBCA), increasing cost, time, patient discomfort, and health concerns. This study explored the feasibility of [...] Read more.
Background/Objectives: Contrast-enhanced (CE) breast MRI is highly sensitive for evaluating breast cancer extent and response to neoadjuvant therapy (NAT) but requires intravenous administration of gadolinium-based contrast agents (GBCA), increasing cost, time, patient discomfort, and health concerns. This study explored the feasibility of reducing GBCA use in treatment monitoring using a deep learning (DL) model to synthesize CE-MRI from non-contrast MRI. Methods: This IRB-approved retrospective pilot study evaluated women with breast cancer enrolled in an ongoing trial using serial MRI to monitor NAT prior to surgery. A pre-trained DL model was used to synthesize CE-MRI from T1-, T2-, and diffusion-weighted MRI. Changes in tumor volume at early (post-1-cycle NAT) and mid-treatment were measured on synthetic and acquired CE-MRI. Performance for predicting residual cancer burden (RCB) class 0/1 was evaluated using AUC and compared with DeLong’s test. Results: 27 women were included in the study (median age, 47 years [range = 28–75]); 14 (52%) achieved RCB class 0 and six (22%) achieved class 1. Synthetic CE-MRI-derived tumor volumes showed strong correlation with those from acquired CE-MRI at pre-treatment (ρ = 0.92, p < 0.001) and early treatment (ρ = 0.83, p < 0.001), but lower agreement at mid-treatment (ρ = 0.57, p = 0.002). Change in tumor volume on synthetic CE-MRI was numerically similar to acquired CE-MRI for predicting RCB class 0/1 vs. 2/3 at both early (AUC = 0.84 vs. 0.86, p = 0.83) and mid-treatment (AUC = 0.73 vs. 0.75, p = 0.80). Conclusions: Synthetic CE-MRI demonstrates preliminary feasibility as a non-contrast surrogate for predicting favorable outcomes (RCB class 0/1) in this pilot study, but inconsistencies in tumor volume measurement vs. acquired CE-MRI warrant further model refinement and validation. Full article
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29 pages, 1669 KB  
Review
Breast Cancer: Characteristics, Diagnostic and Therapeutic Options and the Potential of Nanoparticle Applications
by Ahmed El-Mallul, Małgorzata Katarzyna Kowalska, Karolina Sawicka, Sara Małgorzata Orłowska, Łukasz Bednarczyk and Łucja Radziszewska
Appl. Sci. 2026, 16(11), 5416; https://doi.org/10.3390/app16115416 - 29 May 2026
Viewed by 779
Abstract
Breast cancer is one of the most commonly diagnosed malignant tumors worldwide and represents a significant public health problem. This paper presents the characteristics of the disease, with particular emphasis on risk factors, mechanisms of development, and molecular classification. Current diagnostic methods and [...] Read more.
Breast cancer is one of the most commonly diagnosed malignant tumors worldwide and represents a significant public health problem. This paper presents the characteristics of the disease, with particular emphasis on risk factors, mechanisms of development, and molecular classification. Current diagnostic methods and available therapeutic strategies, such as surgery, chemotherapy (CT), radiotherapy (RT), and targeted therapies, are discussed. Particular attention is given to nanotechnology as a promising direction for the development of modern medicine. The potential applications of nanoparticles (NPs) in the diagnosis and treatment of breast cancer are presented, taking into account their mechanisms of action, potential clinical benefits, and limitations related to safety and efficacy. NPs may contribute to increased diagnostic precision and therapeutic efficacy, indicating their significant potential in the future of oncology. Full article
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28 pages, 5701 KB  
Article
Multi-Sequence Guided Generation of Contrast-Enhanced Magnetic Resonance Imaging Using Diffusion Models
by Yue Xu, Xiaokun Zhou, Wei Jiang, Chuanbing Wang, Xiangnan Geng, Da Cao, Wujin Xiao, Bin Liu and Wei Wang
Bioengineering 2026, 13(6), 634; https://doi.org/10.3390/bioengineering13060634 - 28 May 2026
Viewed by 505
Abstract
Objectives: Contrast-enhanced magnetic resonance imaging (CE-MRI) plays an important role in the diagnosis, treatment monitoring, and follow-up of brain tumors. However, the use of gadolinium-based contrast agents (GBCAs) is limited in patients with contraindications, such as severe renal impairment or situations requiring [...] Read more.
Objectives: Contrast-enhanced magnetic resonance imaging (CE-MRI) plays an important role in the diagnosis, treatment monitoring, and follow-up of brain tumors. However, the use of gadolinium-based contrast agents (GBCAs) is limited in patients with contraindications, such as severe renal impairment or situations requiring repeated examinations. This study aimed to develop a diffusion model-based Difference-Aware Guided Control Network (DAGCN) for synthesizing high-quality contrast-enhanced T1-weighted MRI (T1-CE) from non-contrast T1-weighted images in combination with an auxiliary sequence. Methods: Using the BraTS 2021 dataset, we proposed a two-stage generative framework that first localizes lesion-related enhancement cues and then guides image synthesis. In the first stage, a Difference-Aware Fusion and Prediction (DAFP) module was designed to extract complementary information from non-contrast T1-weighted images and an auxiliary sequence (T2-weighted or FLAIR) through dual-branch feature extraction and cross-modal channel attention fusion, followed by prediction of a lesion-related discrepancy map. In the second stage, the predicted discrepancy map was concatenated with the original T1-weighted images and introduced into a ControlNet-guided diffusion model to constrain the reverse denoising process and generate the target T1-CE image. Model performance was evaluated by visual comparison, quantitative metrics including peak signal-to-noise ratio (PSNR), structural similarity index measure (SSIM), visual information fidelity (VIF), and normalized cross-correlation (NCC), as well as blinded radiologist scoring of image quality (IQ), clinical replaceability (IC), contrast enhancement (CE), and lesion conformity (CF). Results: DAGCN generated synthetic T1-CE images with preserved global anatomical structure and faithful local lesion enhancement without the need for contrast agent administration. Compared with baseline methods, DAGCN achieved the highest PSNR and NCC under both T1 + T2 and T1 + FLAIR settings, while showing competitive SSIM and VIF performance. Visual comparison and radiologist-based subjective evaluation further indicated improved lesion-focused enhancement fidelity and reduced false-positive enhancement. Among the two auxiliary sequence settings, the T1 + FLAIR configuration provided more specific lesion localization and cleaner background suppression than the T1 + T2 configuration, particularly by reducing interference from cerebrospinal fluid signals. Conclusions: The proposed DAGCN framework enables the synthesis of clinically informative contrast-enhanced-like MRI from non-contrast multi-sequence inputs and may provide a promising alternative for patients in whom gadolinium administration is contraindicated or should be avoided. In particular, the FLAIR-guided setting showed advantages in lesion specificity, background cleanliness, and overall diagnostic quality. Full article
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49 pages, 2006 KB  
Review
Multinuclear NMR and MRI Beyond Proton Imaging: Principles, Contrast Mechanisms, and Applications in Materials and Biomedicine
by Dorota Bartusik-Aebisher, Klaudia Dynarowicz, Barbara Smolak, Rostyslav Marunych, Wiesław Guz and David Aebisher
Int. J. Mol. Sci. 2026, 27(10), 4384; https://doi.org/10.3390/ijms27104384 - 14 May 2026
Viewed by 868
Abstract
Magnetic resonance techniques have evolved beyond conventional proton-based imaging, enabling access to a broader range of nuclei that provide complementary structural, functional, and molecular information. This review presents a comprehensive overview of multinuclear NMR and MRI in solid and soft materials as well [...] Read more.
Magnetic resonance techniques have evolved beyond conventional proton-based imaging, enabling access to a broader range of nuclei that provide complementary structural, functional, and molecular information. This review presents a comprehensive overview of multinuclear NMR and MRI in solid and soft materials as well as in biomedical applications, with particular emphasis on 1H, 13C, 31P, 23Na, and 19F nuclei. Proton-based methods remain the foundation of magnetic resonance due to their high sensitivity and widespread applicability, offering insights into molecular mobility, hydration, and microstructural heterogeneity. In contrast, heteronuclear approaches enable more specific characterization of chemical structure (13C), phosphorus-containing functional groups and membranes (31P), ionic homeostasis and transport (23Na), and exogenous tracers with negligible biological background (19F). Together, these techniques extend magnetic resonance from primarily anatomical imaging toward functional, metabolic, and molecular-level analysis. The review further discusses key hardware aspects, including magnetic field strength and radiofrequency coil design, highlighting the trade-offs between low- and high-field systems and the growing importance of multinuclear coil architectures. For example, because 1H, 23Na, 31P, and 19F resonate at different Larmor frequencies, multinuclear experiments require dedicated or multi-tuned RF coils that balance sensitivity, field homogeneity, and decoupling between channels. Mechanisms of contrast generation are examined in detail, distinguishing between endogenous sources—such as water, ions, and metabolites—and exogenous contrast agents, including gadolinium-, manganese-, and fluorine-based compounds, as well as targeted and theranostic platforms. A comparative framework of endogenous and exogenous signals is presented, emphasizing their complementary roles in balancing safety, specificity, and sensitivity. Finally, the opportunities and challenges of multinuclear magnetic resonance are critically evaluated, including limitations in sensitivity, signal-to-noise ratio, data interpretation in heterogeneous systems, and technical complexity. Emerging directions such as ultrahigh-field imaging, advanced RF technologies, hyperpolarization, and artificial intelligence-assisted reconstruction are discussed as key drivers for future development. Overall, multinuclear NMR and MRI represent a powerful and expanding toolbox for probing complex material and biological systems, with the potential to significantly enhance diagnostic capabilities and deepen our understanding of structure–function relationships across multiple scales. Full article
(This article belongs to the Special Issue Application of NMR Spectroscopy in Biomolecules: 2nd Edition)
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24 pages, 5396 KB  
Article
Mn(II)-Tagged DOTA-Modified Sugar-Based Biopolymers as Gadolinium-Free Contrast Agents for Magnetic Resonance Imaging
by Irena Pashkunova-Martic, Joachim Friske, Silvester J. Bartsch, Daniela Prinz, Theresa Balber, Verena Pichler, Dieter Baurecht, Bernhard K. Keppler and Thomas H. Helbich
Pharmaceutics 2026, 18(5), 530; https://doi.org/10.3390/pharmaceutics18050530 - 27 Apr 2026
Viewed by 969
Abstract
Background: Paramagnetic manganese (Mn(II)) has emerged as a promising alternative to gadolinium-based contrast agents (GBCAs) due to its favorable magnetic properties. Despite extensive research, no Mn-based agent has yet achieved clinical translation. Because free Mn(II) is toxic, macromolecular complexes incorporating stable macrocyclic [...] Read more.
Background: Paramagnetic manganese (Mn(II)) has emerged as a promising alternative to gadolinium-based contrast agents (GBCAs) due to its favorable magnetic properties. Despite extensive research, no Mn-based agent has yet achieved clinical translation. Because free Mn(II) is toxic, macromolecular complexes incorporating stable macrocyclic DOTA chelators conjugated to polysaccharides may enhance coordination stability and improve the safety profile of Mn(II)-based contrast agents. Methods: Two chemical routes, maleimide- and ester-mediated, were evaluated for covalent coupling of DOTA-based macrocyclic ligands to the backbone of selected poly- and oligosaccharides. Subsequently, DOTA-modified carboxymethyldextran, aminodextran, and chitosan oligosaccharide were labeled with paramagnetic Mn(II) under mild conditions. ATR-FTIR confirmed the successful conjugation of DOTA chelators to the sugar backbone. The conjugates were further characterized by DLS, ICP-MS, and FPLC. In vitro relaxivity was measured at high field strength to evaluate MRI performance. In vivo contrast efficacy was first assessed using in ovo MRI in chicken embryos and subsequently evaluated by biodistribution studies in nude mice. Results: In vitro relaxivity studies demonstrated higher signal enhancement of the poly-/oligosaccharide-DOTA-Mn(II) conjugates compared with MnCl2 and the clinical agent gadoteridol (ProHance®). In ovo MRI showed persistent vascular enhancement up to 120 min, while in nude mice, contrast enhancement was observed in the liver, kidneys, and gallbladder 40 min post-injection. Conclusions: Mn(II)-tagged sugar-based imaging probes may offer a promising non-gadolinium alternative to GBCAs, with tunable biodistribution profiles depending on carrier molecular weight. Full article
(This article belongs to the Section Biopharmaceutics)
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22 pages, 4668 KB  
Article
Synthesis and Characterization of a Novel Biphenol-Based Gadolinium Complex for Encapsulation in Human Red Blood Cells
by Antonella Antonelli, Riccardo Di Corato, Luca Mancini, Michela Cangiotti, Laura Valentini, Luca Giorgi, Gianluca Ambrosi, Pietro Gobbi, Erika Palazzetti, Luigia Rossi and Mauro Magnani
Int. J. Mol. Sci. 2026, 27(8), 3492; https://doi.org/10.3390/ijms27083492 - 14 Apr 2026
Viewed by 730
Abstract
Gadolinium-based contrast agents are widely used in clinical magnetic resonance imaging (MRI) due to their strong paramagnetic properties and ability to enhance image contrast. Despite their diagnostic value, concerns remain regarding gadolinium toxicity and long-term tissue retention, particularly for less stable linear chelates. [...] Read more.
Gadolinium-based contrast agents are widely used in clinical magnetic resonance imaging (MRI) due to their strong paramagnetic properties and ability to enhance image contrast. Despite their diagnostic value, concerns remain regarding gadolinium toxicity and long-term tissue retention, particularly for less stable linear chelates. In this study, we report preliminary results on a newly synthesized gadolinium-based compound (L-Gd), in which the Gd3+ ion is coordinated to a specific ligand designed to improve biocompatibility. To evaluate the feasibility of L-Gd encapsulation within human RBCs (hRBCs) for drug delivery, its biocompatibility and cellular interactions were thoroughly investigated. RBCs represent an attractive biomimetic carrier system capable of limiting the direct exposure of tissues to paramagnetic agents while potentially improving circulation time and safety. In vitro assays demonstrated that L-Gd maintains high compatibility with hRBCs within specific concentration ranges, showing no significant hemolysis or morphological alterations. Furthermore, preliminary encapsulation studies indicate that L-Gd can be successfully associated with RBCs, supporting the potential of this approach for contrast agent delivery. These findings suggest that RBC-mediated transport of gadolinium complexes may represent a promising strategy to reduce toxicity and mitigate gadolinium retention. Further investigations will focus on optimizing encapsulation efficiency, relaxometric properties, and in vivo behavior of the L-Gd system. Full article
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16 pages, 4767 KB  
Article
Synthesis of BSA-Coated Iron Oxide Nanoparticles with Size Control for High-Performance T1 Contrast Agents in Magnetic Resonance Imaging
by Bosede Kolawole, Jie Zheng, Dongmei Cao and Yongfeng Zhao
Biomolecules 2026, 16(3), 478; https://doi.org/10.3390/biom16030478 - 23 Mar 2026
Viewed by 1096
Abstract
The excellent biocompatibility and favorable physicochemical properties of iron oxide nanoparticles have made them attractive candidates for magnetic resonance imaging. However, it remains challenging to synthesize high-performance T1 contrast agents with controlled sizes and biocompatible coating materials. In this study, we demonstrate [...] Read more.
The excellent biocompatibility and favorable physicochemical properties of iron oxide nanoparticles have made them attractive candidates for magnetic resonance imaging. However, it remains challenging to synthesize high-performance T1 contrast agents with controlled sizes and biocompatible coating materials. In this study, we demonstrate a simple and environmentally friendly approach for synthesizing ultra-small iron oxide nanoparticles using bovine serum albumin (BSA) as a template. Following synthesis, the iron oxide nanoparticles (Fe3O4) were oxidized to Fe2O3 via the addition of hydrogen peroxide, which resulted in enhanced T1-weighted magnetic resonance contrast. The use of BSA not only stabilized the nanoparticles but also enabled precise control over nanoparticle size by adjusting the Fe-to-BSA molar ratio. This method yielded highly uniform and crystalline ultra-small nanoparticles ranging from approximately 3.7 to 7.9 nm in diameter. The T1 contrast performance of the Fe2O3@BSA nanoparticles was evaluated at 3 T magnetic field. Among the synthesized samples, nanoparticles with sizes of 4.6 nm exhibited the strongest T1 contrast enhancement along with low r2/r1 ratios. These features highlight their potential as promising alternatives to gadolinium-based contrast agents. In addition to their superior performance, this synthesis method is low-cost and non-toxic, making it suitable for scalable biomedical applications. Full article
(This article belongs to the Special Issue Advances in Nano-Based Drug Delivery: Unveiling the Next Frontier)
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30 pages, 760 KB  
Review
Gadolinium Nanoparticles: Emerging Platforms Beyond Imaging for Drug Delivery and Theranostics
by Amir Nasrolahi Shirazi, Rajesh Vadlapatla, Ajoy Koomer, Heyam Zayed, Paris Marabut and Keykavous Parang
Pharmaceutics 2026, 18(3), 358; https://doi.org/10.3390/pharmaceutics18030358 - 13 Mar 2026
Cited by 3 | Viewed by 1837
Abstract
Gadolinium nanoparticles (GdNPs) have gained increasing attention as multifunctional metal-based nanoplatforms that extend far beyond their traditional use as magnetic resonance imaging (MRI) contrast agents. Their specific magnetic properties, tunable physicochemical features, and tunable biocompatibilities with biocompatible coatings give them great potential as [...] Read more.
Gadolinium nanoparticles (GdNPs) have gained increasing attention as multifunctional metal-based nanoplatforms that extend far beyond their traditional use as magnetic resonance imaging (MRI) contrast agents. Their specific magnetic properties, tunable physicochemical features, and tunable biocompatibilities with biocompatible coatings give them great potential as drug delivery and theranostic applications. They offer greater stability, lower systemic toxicity, and more surface modification options compared to molecular gadolinium chelates. The functionalized GdNPs not only show excellent properties as drug carriers for their specific indications but also serve as agents in various imaging modalities with superior therapeutic efficacy by means of radio sensitization and magnetically assisted delivery. Note too that GdNP-based formulations have demonstrated synergistic activity when administered with chemotherapeutic agents such as doxorubicin. GdNPs have demonstrated promising preclinical outcomes, and their clinical translation remains restricted due to a number of scale-up constraints, long-term safety challenges, pharmacokinetics, and regulatory problems. This review provides information on the use of GdNPs, their key physicochemical and magnetic properties, ligand engineering for targeted delivery, and biological mechanisms of their theranostic performance. Full article
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