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Magnetic resonance imaging (MRI) has revolutionized medical imaging diagnostics with the advantages of non-invasive nature, absence of ionizing radiation, unrestricted penetration depth, high-resolution imaging of soft tissues, organs and blood vessels, and multi-parameter and multi-sequence imaging. Contrast agents (CAs) are crucial for enhancing image quality, detecting molecular-level changes, and providing comprehensive diagnostic information in contrast enhanced MRI. However, the performance of clinical Gd-based CAs represents a limitation to the improvement of MRI sensitivity, specificity, and versatility, thereby impeding the achievement of satisfactory imaging outcomes. In recent years, the development of magnetic nanoparticle-based CAs has emerged as a promising avenue to enhance the capabilities of MRI. Here, we review the advances in magnetic nanoparticle-based MRI CAs, including blood pool CAs, biochemically-targeted CAs, stimulus-responsive CAs, and ultra-high field MRI CAs, as well as the use of CAs for cell labeling and tracking. Additionally, we offer insights into the future prospects and challenges associated with the integration of these nanoparticles into clinical practice.

Magnetic Resonance Imaging (MRI) is a powerful, noninvasive and nondestructive technique, capable of providing three-dimensional (3D) images of living organisms. The use of magnetic contrast agents has allowed clinical researchers and analysts to significantly increase the sensitivity and specificity of MRI, since these agents change the intrinsic properties of the tissues within a living organism, increasing the information present in the images. Advances in nanotechnology and materials science, as well as the research of new magnetic effects, have been the driving forces that are propelling forward the use of magnetic nanostructures as promising alternatives to commercial contrast agents used in MRI. This review discusses the principles associated with the use of contrast agents in MRI, as well as the most recent reports focused on nanostructured contrast agents. The potential applications of gadolinium- (Gd) and manganese- (Mn) based nanomaterials and iron oxide nanoparticles in this imaging technique are discussed as well, from their magnetic behavior to the commonly used materials and nanoarchitectures. Additionally, recent efforts to develop new types of contrast agents based on synthetic antiferromagnetic and high aspect ratio nanostructures are also addressed. Furthermore, the application of these materials in theragnosis, either as contrast agents and controlled drug release systems, contrast agents and thermal therapy materials or contrast agents and radiosensitizers, is also presented.

Gadolinium-based contrast agents (GBCAs) have been used for more than 30 years to improve magnetic resonance imaging, a crucial tool for medical diagnosis and treatment monitoring across multiple clinical settings. Studies have shown that exposure to GBCAs is associated with gadolinium release and tissue deposition that may cause short- and long-term toxicity in several organs, including the kidney, the main excretion organ of most GBCAs. Considering the increasing prevalence of chronic kidney disease worldwide and that most of the complications following GBCA exposure are associated with renal dysfunction, the mechanisms underlying GBCA toxicity, especially renal toxicity, are particularly important. A better understanding of the gadolinium mechanisms of toxicity may contribute to clarify the safety and/or potential risks associated with the use of GBCAs. In this work, a review of the recent literature concerning gadolinium and GBCA mechanisms of toxicity was performed.

Contrast enhanced MRI of the liver provides valuable information in the evaluation of both chronic liver disease and focal liver lesions. Currently, two classes of MRI contrast agents are available for clinical use, namely the extracellular contrast agent (ECA) and the hepatobiliary agent (HBA). The use of appropriate contrast agents for liver MRI requires knowledge of the clinical situation and question to be answered. ECAs have been used for decades since their introduction into clinical practice and provide excellent dynamic phase information that is useful in characterizing focal liver lesions. In the last decade, HBAs, particularly Gadoxetate, have been found useful for characterizing lesions with functioning hepatocytes and more importantly in evaluating the biliary tree. Gadoxetate, however, provides less satisfactory dynamic phase images compared to ECAs, particularly during the arterial phase. In this perspective article, we will discuss the various intravenous contrast agents used for liver MRI and their ideal utilization.

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

Contrast-enhanced ultrasound (CEUS) has been increasingly used in pediatric radiology practice worldwide. For nearly two decades, CEUS applications have been performed with the off-label use of gas-containing second-generation ultrasound contrast agents (UCAs). Since 2016, the United States Food and Drug Administration (FDA) has approved the UCA Lumason for three pediatric indications: the evaluation of focal liver lesions and echocardiography via intravenous administration and the assessment of vesicoureteral reflux via intravesical application (contrast-enhanced voiding urosonography, ceVUS). Prior to the FDA approval of Lumason, numerous studies with the use of second-generation UCAs had been conducted in adults and children. Comprehensive protocols for clinical safety evaluations have demonstrated the highly favorable safety profile of UCA for intravenous, intravesical and other intracavitary uses. The safety data on CEUS continue to accumulate as this imaging modality is increasingly utilized in clinical settings worldwide. As of August 2021, 57 pediatric-only original research studies encompassing a total of 4,518 children with 4,906 intravenous CEUS examinations had been published. As in adults, there were a few adverse events; the majority of these were non-serious, although very rarely serious anaphylactic reactions were reported. In the published pediatric-only intravenous CEUS studies included in our analysis, the overall incidence rate of serious adverse events was 0.22% (10/4,518) of children and 0.20% (10/4,906) of all CEUS examinations. Non-serious adverse events from the intravenous CEUS were observed in 1.20% (54/4,518) of children and 1.10% (54/4,906) of CEUS examinations. During the same time period, 31 studies with the intravesical use of UCA were conducted in 12,362 children. A few non-serious adverse events were encountered (0.31%; 38/12,362), but these were most likely attributable to the bladder catheterization rather than the UCA. Other developing clinical applications of UCA in children, including intracavitary and intralymphatic, are ongoing. To date, no serious adverse events have been reported with these applications. This article reviews the existing pediatric CEUS literature and provides an overview of safety-related information reported from UCA uses in children.

Contrast media are widely diffused in biomedical imaging, due to their relevance in the diagnosis of numerous disorders. However, the risk of adverse reactions, the concern of potential damage to sensitive organs, and the recently described brain deposition of gadolinium salts, limit the use of contrast media in clinical practice. In recent years, the application of artificial intelligence (AI) techniques to biomedical imaging has led to the development of ‘virtual’ and ‘augmented’ contrasts. The idea behind these applications is to generate synthetic post-contrast images through AI computational modeling starting from the information available on other images acquired during the same scan. In these AI models, non-contrast images (virtual contrast) or low-dose post-contrast images (augmented contrast) are used as input data to generate synthetic post-contrast images, which are often undistinguishable from the native ones. In this review, we discuss the most recent advances of AI applications to biomedical imaging relative to synthetic contrast media.

To overcome the problems of Gd‐based contrast agents (GBCAs) (nephrotoxicity and brain deposition) and stimulator of interferon genes (STING) agonists (poor stability, low delivery efficiency, and potential toxicity), in this study, a Turbo‐charging system‐like GBCA is designed and constructed for magnetic resonance imaging (MRI) guided STING pathway‐activated cancer immunotherapy. Poly(acrylic acid) (PAA) is used to coordinate with Gd3+, forming a Gd/PAA macrochelate. Both Gd/PAA macrochelate and SR717 are conjugated to cystamine (CA) to obtain SR717‐CA@Gd/PAA self‐assembled nanoparticles (SAN), which are termed as Turbo S because of its similarity with the Turbo‐charging system of cars. After accumulation in tumors and internalization in tumor cells, the disulfide linkage in Turbo S undergoes a cleavage process catalyzed by glutathione (GSH), leading to the release of Gd/PAA and SR717. The released Gd/PAA gain a high r1 value (17.11 mM−1 s−1 at 7.0 T; 57.81 mM−1 s−1 at 3.0 T), indicating its strong T1 imaging capability. Turbo S with a low dosage of SR717 (8.9 mg kg−1) achieved a higher tumor immunotherapeutic efficacy than free SR717 with a high dosage (30 mg kg−1). The excellent delivery efficiency, high tumor treatment efficacy, and superior biosafety demonstrate that the Turbo S can be used as a promising candidate for tumor immunotherapy. To overcome the problems of Gd‐based contrast agents (GBCAs) and stimulator of interferon genes (STING) agonists, in this study, a Turbo‐charging system‐like GBCA termed as Turbo S are designed and constructed for MRI‐guided STING pathway‐activated cancer immunotherapy.

Medical imaging is routine in the diagnosis and staging of a wide range of medical conditions. In particular, magnetic resonance imaging (MRI) is critical for visualizing soft tissue and organs, with over 60 million MRI procedures performed each year worldwide. About one-third of these procedures are contrast-enhanced MRI, and gadolinium-based contrast agents (GBCAs) are the mainstream MRI contrast agents used in the clinic. GBCAs have shown efficacy and are safe to use with most patients; however, some GBCAs have a small risk of adverse effects, including nephrogenic systemic fibrosis (NSF), the untreatable condition recently linked to gadolinium (Gd) exposure during MRI with contrast. In addition, Gd deposition in the human brain has been reported following contrast, and this is now under investigation by the US Food and Drug Administration (FDA). To address a perceived need for a Gd-free contrast agent with pharmacokinetic and imaging properties comparable to GBCAs, we have designed and developed zwitterion-coated exceedingly small superparamagnetic iron oxide nanoparticles (ZES-SPIONs) consisting of ∼3-nm inorganic cores and ∼1-nm ultrathin hydrophilic shell. These ZES-SPIONs are free of Gd and show a high T₁ contrast power. We demonstrate the potential of ZES-SPIONs in preclinical MRI and magnetic resonance angiography.

Gadolinium-based contrast agents (GBCAs) have transformed magnetic resonance imaging (MRI) by facilitating the use of contrast-enhanced MRI to allow vital clinical diagnosis in a plethora of disease that would otherwise remain undetected. Although over 500 million doses have been administered worldwide, scientific research has documented the retention of gadolinium in tissues, long after exposure, and the discovery of a GBCA-associated disease termed nephrogenic systemic fibrosis, found in patients with impaired renal function. An understanding of the pharmacokinetics in humans and animals alike are pivotal to the understanding of the distribution and excretion of gadolinium and GBCAs, and ultimately their potential retention. This has been well studied in humans and more so in animals, and recently there has been a particular focus on potential toxicities associated with multiple GBCA administration. The purpose of this review is to highlight what is currently known in the literature regarding the pharmacokinetics of gadolinium in humans and animals, and any toxicity associated with GBCA use.