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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) are commonly used for enhancement in MR imaging and have long been considered safe when administered at recommended doses. However, since the report that nephrogenic systemic fibrosis is linked to the use of GBCAs in subjects with severe renal diseases, accumulating evidence has suggested that GBCAs are not cleared entirely from our bodies; some GBCAs are deposited in our tissues, including the brain. GBCA deposition in the brain is mostly linked to the specific chelate structure of the GBCA: linear GBCAs were responsible for brain deposition in almost all reported studies. This review aimed to summarize the current knowledge about GBCA brain deposition and discuss its clinical implications.

Gadolinium based contrast agents (GBCA) are used to image patients using magnetic resonance (MR) imaging. In recent years, there has been controversy around gadolinium retention after GBCA administration. We sought to evaluate the potential toxicity of gadolinium in the rat brain up to 1-year after repeated gadodiamide dosing and tissue retention kinetics after a single administration. Histopathological and ultrastructural transmission electron microscopy (TEM) analysis revealed no findings in rats administered a cumulative dose of 12 mmol/kg. TEM-energy dispersive X-ray spectroscopy (TEM-EDS) localization of gadolinium in the deep cerebellar nuclei showed ~ 100 nm electron-dense foci in the basal lamina of the vasculature. Laser ablation-ICP-MS (LA-ICP-MS) showed diffuse gadolinium throughout the brain but concentrated in perivascular foci of the DCN and globus pallidus with no observable tissue injury or ultrastructural changes. A single dose of gadodiamide (0.6 mmol/kg) resulted in rapid cerebrospinal fluid (CSF) and blood clearance. Twenty-weeks post administration gadolinium concentrations in brain regions was reduced by 16–72-fold and in the kidney (210-fold), testes (194-fold) skin (44-fold), liver (42-fold), femur (6-fold) and lung (64-fold). Our findings suggest that gadolinium does not lead to histopathological or ultrastructural changes in the brain and demonstrate in detail the kinetics of a human equivalent dose over time in a pre-clinical model.

Objectives The purpose of this study is to establish microvascular invasion (MVI) prediction models based on preoperative contrast-enhanced ultrasound (CEUS) and ethoxybenzyl-enhanced magnetic resonance imaging (EOB-MRI) in patients with a single hepatocellular carcinoma (HCC) ≤ 5 cm. Methods Patients with a single HCC ≤ 5 cm and accepting CEUS and EOB-MRI before surgery were enrolled in this study. Totally, 85 patients were randomly divided into the training and validation cohorts in a ratio of 7:3. Non-radiomics imaging features, the CEUS and EOB-MRI radiomics scores were extracted from the arterial phase, portal phase and delayed phase images of CEUS and the hepatobiliary phase images of EOB-MRI. Different MVI predicting models based on CEUS and EOB-MRI were constructed and their predictive values were evaluated. Results Since univariate analysis revealed that arterial peritumoral enhancement on the CEUS image, CEUS radiomics score, and EOB-MRI radiomics score were significantly associated with MVI, three prediction models, namely the CEUS model, the EOB-MRI model, and the CEUS-EOB model, were developed. In the validation cohort, the areas under the receiver operating characteristic curve of the CEUS model, the EOB-MRI model, and the CEUS-EOB model were 0.73, 0.79, and 0.86, respectively. Conclusions Radiomics scores based on CEUS and EOB-MRI, combined with arterial peritumoral enhancement on CEUS, show a satisfying performance of MVI predicting. There was no significant difference in the efficacy of MVI risk evaluation between radiomics models based on CEUS and EOB-MRI in patients with a single HCC ≤ 5 cm. Clinical relevance statement Radiomics models based on CEUS and EOB-MRI are effective for MVI predicting and conducive to pretreatment decision-making in patients with a single HCC within 5 cm. Key Points • Radiomics scores based on CEUS and EOB-MRI, combined with arterial peritumoral enhancement on CEUS, show a satisfying performance of MVI predicting. • There was no significant difference in the efficacy of MVI risk evaluation between radiomics models based on CEUS and EOB-MRI in patients with a single HCC ≤ 5 cm.

This study aimed to purify and prepare two isomers of Gadoxetate (Gd-A and Gd-B) from Pumexian and evaluate their stability, magnetic resonance (MR) imaging characteristics, and pharmacokinetics in rabbits. Reversed-phase liquid chromatography was employed to separate Gd-A and Gd-B, achieving purities exceeding 99% for both isomers. These purified isomers were then processed into vacuum-encapsulated solid powders via nitrogen blowing and freeze-drying. Stability assessments were conducted by storing the powders at various temperatures (25°C, −20°C, 50°C, and 80°C) for two months. The results indicated high stability at room temperature (25°C) and low temperature (−20°C), with both Gd-A and Gd-B maintaining 99% purity. At higher temperatures, purity slightly decreased: Gd-A was 98% at 50°C and 95% at 80°C, while Gd-B was 97% at 50°C and 94% at 80°C. For the in vivo evaluation, twelve rabbits were randomly assigned to two groups and received intravenous bolus injections of either pure Gd-A or Gd-B, followed by enhanced MR scanning and serial blood sampling. Pharmacokinetic and imaging analyses revealed statistically significant differences (p < 0.05) between the two isomers. Specifically, Gd-A exhibited a shorter time to peak enhancement in liver parenchyma (t peak A < t peak B), higher peak signal intensity in the liver parenchyma (SI peak A > SI peak B), greater plasma clearance (PCL-A > PCL-B), and a shorter half-life (t 1/2 A < t 1/2 B) compared to Gd-B. In conclusion, the vacuum-encapsulated solid powders of Gd-A and Gd-B demonstrate good long-term stability at room or low temperatures while maintaining high purity. Furthermore, the distinct pharmacokinetic profile and imaging characteristics of pure Gd-A suggest its potential value for clinical applications.

The glymphatic system is a recently defined brain-wide paravascular pathway for cerebrospinal fluid (CSF) and interstitial fluid (ISF) exchange that facilitates efficient clearance of solutes and waste from the brain. CSF enters the brain along para-arterial channels to exchange with ISF, which is in turn cleared from the brain along para-venous pathways. Because soluble amyloid β clearance depends on glymphatic pathway function, we proposed that failure of this clearance system contributes to amyloid plaque deposition and Alzheimer's disease progression. Here we provide proof of concept that glymphatic pathway function can be measured using a clinically relevant imaging technique. Dynamic contrast-enhanced MRI was used to visualize CSF-ISF exchange across the rat brain following intrathecal paramagnetic contrast agent administration. Key features of glymphatic pathway function were confirmed, including visualization of para-arterial CSF influx and molecular size-dependent CSF-ISF exchange. Whole-brain imaging allowed the identification of two key influx nodes at the pituitary and pineal gland recesses, while dynamic MRI permitted the definition of simple kinetic parameters to characterize glymphatic CSF-ISF exchange and solute clearance from the brain. We propose that this MRI approach may provide the basis for a wholly new strategy to evaluate Alzheimer's disease susceptibility and progression in the live human brain.

Background Imaging is an essential tool in the management of patients with Colorectal cancer (CRC) by helping evaluate number and sites of metastases, determine resectability, assess response to treatment, detect drug toxicities and recurrences. Although multidetector computed tomography (MDCT) is the first tool used for staging and patient’s surveillance, magnetic resonance imaging (MRI) is the most reliable imaging modality that allows to assess liver metastases. Our purpose is to compare the diagnostic performance of gadoxetic acid-(Gd-EOB) enhanced liver MRI and contrast-enhanced MDCT in the detection of liver metastasis from colorectal cancer (mCRC) . Methods One hundred and twenty-eight patients with pathologically proven mCRC (512 liver metastases) underwent Gd-EOB MRI and MDCT imaging. An additional 46 patients without mCRC were included as control subjects. Three radiologists independently graded the presence of liver nodules on a five-point confidence scale. Sensitivity and specificity for the detection of metastases were calculated. Weighted к values were used to evaluate inter-reader agreement of the confidence scale regarding the presence of the lesion. Results MRI detected 489 liver metastases and MDCT 384. In terms of per-lesion sensitivity in the detection of liver metastasis, all three readers had higher diagnostic sensitivity with Gd-EOB MRI than with MDCT (95.5% vs. 72% reader 1; 90% vs. 72% reader 2; 96% vs. 75% reader 3). Each reader showed a statistical significant difference ( p  < <.001 at Chi square test). MR imaging showed a higher performance than MDCT in per-patient detection sensitivity (100% vs. 74.2% [ p  < <.001] reader 1, 98% vs. 73% [ p  < <.001] reader 2, and 100% vs. 78% [ p  < <.001] reader 3). In the control group, MRI and MDCT showed similar per-patient specificity (100% vs. 98% [ p  = 0.31] reader 1, 100% vs. 100% [ p  = 0.92] reader 2, and 100% vs. 96% [ p  = 0.047] reader 3). Inter-reader agreement of lesion detection between the three radiologists was moderate to excellent (k range, 0.56–0.86) for Gd-EOB MRI and substantial to excellent for MDCT (k range, 0.75–0.8). Conclusion Gadoxetic acid-enhanced MRI performs significantly better in the detection of mCRC, than MDCT, particularly in patients treated with chemotherapy, in subcapsular lesions, and in peribiliary metastases .

Objectives To evaluate the impact of previous administration of gadodiamide and neural tissue gadolinium deposition in patients who received gadobenate dimeglumine. Methods Our population included 62 patients who underwent at least three administrations of gadobenate dimeglumine, plus an additional contrast-enhanced last MRI for reference, divided into two groups: group 1, patients who in addition to gadobenate dimeglumine administrations had prior exposure to multiple doses of gadodiamide; group 2, patients without previous exposure to other gadolinium-based contrast agent (GBCAs). Quantitative analysis was performed on the first and last gadobenate dimeglumine MRIs in both groups. Dentate nucleus-to-middle cerebellar peduncle signal intensity ratios (DN/MCP) and relative change (RC) in signal over time were calculated and compared between groups using generalized additive model. Results Group 1 showed significant increase in baseline and follow-up DN/MCP compared to group 2 ( p  < 0.0001). The RC DN/MCP showed a non-statistically significant trend towards an increase in patients who underwent previous gadodiamide ( p  = 0.0735). Conclusion There is increased T1 signal change over time in patients who underwent gadobenate dimeglumine and had received prior gadodiamide compared to those without known exposure to previous gadodiamide. A potentiating effect from prior gadodiamide on subsequent administered gadobenate dimeglumine may occur. Key Points • Neural gadolinium deposition is associated with multiple administrations of less stable GBCAs. • Less stable GBCA effect on subsequent more stable GBCA administrations is undetermined. • Significant increase of DN/MCP was seen in patients with previous gadodiamide exposure. • RC DN/MCP showed a non-significant increase in patients who received previous gadodiamide. • Potentiating effects from prior gadodiamide on subsequent administered gadobenate dimeglumine may occur.

Introduction Three-dimensional fluid-attenuated inversion recovery (3D-FLAIR) imaging 24 h after intratympanic gadolinium injection (IT method) or 4 h after intravenous injection (IV method) has been used to visualize endolymphatic hydrops in Ménière’s disease. The aims of this study were to evaluate the difference in gadolinium distribution in cochlear perilymph between the two methods by comparing the enhancement of the basal and apical turns and clarify the pharmacokinetics in cochlear perilymph. Methods A total of 24 ears of 22 patients who underwent the IT method (gadolinium-diethylene-triamine pentaacetic acid was diluted eightfold with saline) and 28 ears of 17 patients who underwent the IV method (double dose of gadoteridol (0.5 mmol/ml); 0.2 mmol/kg body weight in total amount) at 3 T was analyzed retrospectively. Regions of interest of the perilymph of the cochlear basal turn (B), of the apical turn (A), and the medulla oblongata (M) were determined on each patient. The signal intensity ratios between B and M (BMR), A and M (AMR), and A and B (ABR) were subsequently evaluated. Results The IT-BMR (2.63 ± 1.22) was higher than the IV-BMR (1.46 ± 0.45) ( p  < 0.001). There was no significant difference between the IT- (1.46 ± 0.76) and IV-AMRs (1.21 ± 0.48) ( p  = 0.15). The IT-ABR (0.58 ± 0.17) was lower than the IV-ABR (0.84 ± 0.22) ( p  < 0.001). Conclusion Gadolinium was predominantly distributed in the basal turn compared with the apical turn in the IT method, whereas it was more uniformly distributed in the IV method. These characteristics might reflect the distribution of therapeutic medications administered either intratympanically or systemically.

Gadolinium-based contrast agents (GBCAs), routinely used in magnetic resonance imaging (MRI), end up directly in coastal seawaters where gadolinium concentrations are now increasing. Because many aquatic species could be sensitive to this new pollution, we have evaluated the possibility of using shellfish to assess its importance. Gadolinium excesses recorded by scallop shells collected in Bay of Brest (Brittany, France) for more than 30 years do not reflect the overall consumption in GBCAs, but are largely controlled by one of them, the gadopentetate dimeglumine. Although its use has been greatly reduced in Europe over the last ten years, gadolinium excesses are still measured in shells. Thus, some gadolinium derived from other GBCAs is bioavailable and could have an impact on marine wildlife.