Search Results (45)

PURPOSE: Contrast Enhancement Magnetic Resonance (CEMR) and Contrast-Enhanced Mammography (CEM) are important diagnostic tools to evaluate breast cancer patients, and both are objects of interest in the literature. The purpose of this systematic review was to select publications from the last ten years in order to evaluate the literature contributions related to the frequency of contrast agents used, administration techniques and the presence of adverse reactions. METHODS: We have selected, according to the PRISMA statement, publications reviewed on Pub Med in the period from 1 January 2012 to 31 December 2022. The search engine was activated using the following keywords: “CESM”, “CEM”, “CEDM”, “Contrast mammography” for CEM, “DCE-MRI”, “Contrast Enhancement MRI” for CEMR, excluding reviews, book chapters and meta-analyses. From the total number of publications, we made a preliminary selection based on titles and abstracts and excluded all articles published in languages other than English and all experimental studies performed on surgical specimen or animal population, as well as all articles for which the extended version was not available. Two readers evaluated all the articles and compiled a pre-compiled form accordingly. RESULTS: After a preliminary collection of 571 CEM publications, 118 articles were selected, relating to an overall population of 21,178 patients. From a total of 3063 CEMR publications, 356 articles relating to an overall population of 45,649 patients were selected. The most used contrast agents are Iohexol for CEM (39.83%) and Gadopentetic acid (Gd-DTPA) for CEMR (32.5%). Regarding the CEM contrast administration protocol, in 84.7% of cases a dose of 1.5 mL/kg was used with an infusion rate of 2–3 mL/s. Regarding the CEMR infusion protocol, in 71% of cases a dose of 1 mmol/kg was used at an infusion rate of 2–4 mL/s. Twelve out of 118 CEM articles reported allergic reactions, involving 29 patients (0.13%). In DCE-MRI, only one out of 356 articles reported allergic reactions, involving two patients (0.004%). No severe reactions were observed in either cohort of exams. CONCLUSIONS: CEM and CEMR are essential contrast methods to evaluate breast diseases. However, from the literature analysis, although there are preferences on the uses of the contrast agent (Iohexol for CESM, G-DTPA for CEMR), a wide range of molecules are still used in contrast methods, with different administration protocols. Based on the collected data, it is possible to state that both methods are safe, and no severe reactions were observed in our evaluation. Full article

This study uses magnetic resonance imaging (MRI) to investigate the potential of the hepatospecific contrast agent gadolinium ethoxybenzyl-diethylenetriaminepentaacetic acid (Gd-EOB-DTPA) in distinguishing G1- from G2/G3-differentiated hepatocellular carcinoma (HCC). Our approach involved analyzing the dynamic behavior of the contrast agent in different phases of imaging by signal intensity (SI) and lesion contrast (C), to surrounding liver parenchyma, and comparing it across distinct groups of patients differentiated based on the histopathological grading of their HCC lesions and the presence of liver cirrhosis. Our results highlighted a significant contrast between well- and poorly-differentiated lesions regarding the lesion contrast in the arterial and late arterial phases. Furthermore, the hepatobiliary phase showed limited diagnostic value in cirrhotic liver parenchyma due to altered pharmacokinetics. Ultimately, our findings underscore the potential of Gd-EOB-DTPA-enhanced MRI as a tool for improving preoperative diagnosis and treatment selection for HCC while emphasizing the need for continued research to overcome the diagnostic complexities posed by the disease. Full article

Advanced breast cancer remains a significant oncological challenge, requiring new approaches to improve clinical outcomes. This study investigated an innovative theranostic agent using the MCM-41-NH₂-DTPA-Gd³⁺-MIH nanomaterial, which combined MRI imaging for detection and a novel chemotherapy agent (MIH 2.4Bl) for treatment. The nanomaterial was based on the mesoporous silica type, MCM-41, and was optimized for drug delivery via functionalization with amine groups and conjugation with DTPA and complexation with Gd³⁺. MRI sensitivity was enhanced by using gadolinium-based contrast agents, which are crucial in identifying early neoplastic lesions. MIH 2.4Bl, with its unique mesoionic structure, allows effective interactions with biomolecules that facilitate its intracellular antitumoral activity. Physicochemical characterization confirmed the nanomaterial synthesis and effective drug incorporation, with 15% of MIH 2.4Bl being adsorbed. Drug release assays indicated that approximately 50% was released within 8 h. MRI phantom studies demonstrated the superior imaging capability of the nanomaterial, with a relaxivity significantly higher than that of the commercial agent Magnevist. In vitro cellular cytotoxicity assays, the effectiveness of the nanomaterial in killing MDA-MB-231 breast cancer cells was demonstrated at an EC₅₀ concentration of 12.6 mg/mL compared to an EC₅₀ concentration of 68.9 mg/mL in normal human mammary epithelial cells (HMECs). In vivo, MRI evaluation in a 4T1 syngeneic mouse model confirmed its efficacy as a contrast agent. This study highlighted the theranostic capabilities of MCM-41-NH₂-DTPA-Gd³⁺-MIH and its potential to enhance breast cancer management. Full article

Background: This study aimed to examine whether the coefficient of variation (CV) in the hepatobiliary-phase (HBP) of Gd-EOB-DTPA-MRI could be an independent predictive factor for tumor progression. Methods: Patients who underwent Gd-EOB-DTPA-MRI before Atezolizumab/bevacizumab therapy at six affiliated institutions between 2018 and 2022 were included. CV for each patient was calculated as the mean value for up to five tumors larger than 10 mm, and CV of the whole tumor was calculated using LIFEx software. The tumor response was evaluated within 6–10 weeks. The primary endpoint was to investigate the predictive factors, including CV, related to tumor progression using logistic regression analysis. The secondary endpoints were tumor response rate and progression-free survival (PFS) based on CV. Results: Of the 46 enrolled patients, 13 (28.3%) underwent early progressive disease. Multivariate analysis revealed that a high CV (≥0.22) was an independent predictive factor for tumor progression (p = 0.043). Patients with a high CV had significantly frequent PD than those with a low CV (43.5 vs. 13.0%, p = 0.047). Patients with a high CV tended to have shorter PFS than those with a low CV (3.5 vs. 6.7 months, p = 0.071). Conclusion: Quantitative analysis using CV in the HBP of Gd-EOB-DTPA-MRI may be useful for predicting tumor progression for atezolizumab/bevacizumab therapy. Full article

Cancer is one of the leading causes of global mortality, and its incidence is increasing annually. Neutron capture therapy (NCT) is a unique anticancer modality capable of selectively eliminating tumor cells within normal tissues. The development of accelerator-based, clinically mountable neutron sources has stimulated a worldwide search for new, more effective compounds for NCT. We synthesized magnetic iron oxide nanoparticles (NPs) that concurrently incorporate boron and gadolinium, potentially enhancing the effectiveness of NCT. These magnetic nanoparticles underwent sequential modifications through silane polycondensation and allylamine graft polymerization, enabling the creation of functional amino groups on their surface. Characterization was performed using Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), energy dispersive X-ray (EDX), dynamic light scattering (DLS), thermal gravimetric analysis (TGA), and transmission electron microscopy (TEM). ICP-AES measurements indicated that boron (B) content in the NPs reached 3.56 ppm/mg, while gadolinium (Gd) averaged 0.26 ppm/mg. Gadolinium desorption was observed within 4 h, with a peak rate of 61.74%. The biocompatibility of the NPs was confirmed through their relatively low cytotoxicity and sufficient cellular tolerability. Using NPs at non-toxic concentrations, we obtained B accumulation of up to 5.724 × 10¹⁰ atoms per cell, sufficient for successful NCT. Although limited by its content in the NP composition, the Gd amount may also contribute to NCT along with its diagnostic properties. Further development of the NPs is ongoing, focusing on increasing the boron and gadolinium content and creating active tumor targeting. Full article

The purpose of this study was to investigate the most appropriate methodological approach for the automatic measurement of rodent myocardial infarct polar map using histogram-based thresholding and unsupervised deep learning (DL)-based segmentation. A rat myocardial infarction model was induced by ligation of the left coronary artery. Positron emission tomography (PET) was performed 60 min after the administration of ¹⁸F-fluoro-deoxy-glucose (¹⁸F-FDG), and PET was performed after injecting ⁶⁴Cu-pyruvaldehyde-bis(N4-methylthiosemicarbazone). Single photon emission computed tomography was performed 60 min after injection of ^99mTc-hexakis-2-methoxyisobutylisonitrile and ²⁰¹Tl. Delayed contrast-enhanced magnetic resonance imaging was performed after injecting Gd-DTPA-BMA. Three types of thresholding methods (naive thresholding, Otsu’s algorithm, and multi-Gaussian mixture model (MGMM)) were used. DL segmentation methods were based on a convolution neural network and trained with constraints on feature similarity and spatial continuity of the response map extracted from images by the network. The relative infarct sizes measured by histology and estimated R² for ¹⁸F-FDG were 0.8477, 0.7084, 0.8353, and 0.9024 for naïve thresholding, Otsu’s algorithm, MGMM, and DL segmentation, respectively. DL-based method improved the accuracy of MI size assessment. Full article

In the context of liver surgery, predicting postoperative liver dysfunction is essential. This study explored the potential of preoperative liver function assessment by MRI for predicting postoperative liver dysfunction and compared these results with the established indocyanine green (ICG) clearance test. This prospective study included patients undergoing liver resection with preoperative MRI planning. Liver function was quantified using T1 relaxometry and correlated with established liver function scores. The analysis revealed an improved model for predicting postoperative liver dysfunction, exhibiting an accuracy (ACC) of 0.79, surpassing the 0.70 of the preoperative ICG test, alongside a higher area under the curve (0.75). Notably, the proposed model also successfully predicted all cases of liver failure and showed potential in predicting liver synthesis dysfunction (ACC 0.78). This model showed promise in patient survival rates with a Hazard ratio of 0.87, underscoring its potential as a valuable tool for preoperative evaluation. The findings imply that MRI-based assessment of liver function can provide significant benefits in the early identification and management of patients at risk for postoperative liver dysfunction. Full article

It has been reported that high intensity in the hepatobiliary (HB) phase of Gd-EOB-DTPA-enhanced MRI (EOB-MRI) is associated with an immune-cold microenvironment in HCC. The aim of this study is to reveal whether non-high-intensity HCCs are homogeneous with respect to the immune microenvironment and to investigate the predictive ability of EOB-MRI for the response to atezolizumab + bevacizumab therapy (Atezo/Bev). The association between differences in stepwise signal intensity of HB phase and molecular subtypes and somatic mutations associated with the immune microenvironment was investigated in 65 HCC patients (cohort 1). The association between EOB-MRI and the therapeutic effect of Atezo/Bev was evaluated in the Atezo/Bev cohort (60 patients in cohort 2). The proportion of HCCs having CTNNB1 mutations and classified as Chiang CTNNB1 and Hoshida S3 was high in the high-intensity HB-phase group. Infiltration of tumor-associated macrophages (TAM) and regulatory T-lymphocytes (Treg) was characteristic of the high-intensity and low-intensity groups, respectively. Although EOB-MRI could not predict the response to Atezo/Bev treatment, our results demonstrate that EOB-MRI could serve as a surrogate marker predicting the immune microenvironment. This suggests that Atezo/Bev treatment can be selected regardless of signal intensity in the EOB-MRI HB phase. Full article

The development of new neurotherapeutics depends on appropriate animal models being chosen in preclinical studies. The cuprizone model is an effective tool for studying demyelination and remyelination processes in the brain, but blood–brain barrier (BBB) integrity in the cuprizone model is still a topic for debate. Several publications claim that the BBB remains intact during cuprizone-induced demyelination; others demonstrate results that could explain the increased BBB permeability. In this study, we aim to analyze the permeability of the BBB for different macromolecules, particularly antibody conjugates, in a cuprizone-induced model of demyelination. We compared the traditional approach using Evans blue injection with subsequent dye extraction and detection of antibody conjugates using magnetic resonance imaging (MRI) and confocal microscopy to analyze BBB permeability in the cuprizone model. First, we validated our model of demyelination by performing T2-weighted MRI, diffusion tensor imaging, quantitative rt-PCR to detect changes in mRNA expression of myelin basic protein and proteolipid protein, and Luxol fast blue histological staining of myelin. Intraperitoneal injection of Evans blue did not result in any differences between the fluorescent signal in the brain of healthy and cuprizone-treated mice (IVIS analysis with subsequent dye extraction). In contrast, intravenous injection of antibody conjugates (anti-GFAP or non-specific IgG) after 4 weeks of a cuprizone diet demonstrated accumulation in the corpus callosum of cuprizone-treated mice both by contrast-enhanced MRI (for gadolinium-labeled antibodies) and by fluorescence microscopy (for Alexa488-labeled antibodies). Our results suggest that the methods with better sensitivity could detect the accumulation of macromolecules (such as fluorescent-labeled or gadolinium-labeled antibody conjugates) in the brain, suggesting a local BBB disruption in the demyelinating area. These findings support previous investigations that questioned BBB integrity in the cuprizone model and demonstrate the possibility of delivering antibody conjugates to the corpus callosum of cuprizone-treated mice. Full article

Gadopentetic acid and gadodiamide are paramagnetic gadolinium-based contrast agents (GBCAs) that are routinely used for dynamic contrast-enhanced magnetic resonance imaging (MRI) to monitor disease progression in cancer patients. However, growing evidence indicates that repeated administration of GBCAs may lead to gadolinium (III) cation accumulation in the cortical bone tissue, skin, basal ganglia, and cerebellum, potentially leading to a subsequent slow long-term discharge of Gd³⁺. Gd³⁺ is a known activator of the TRPC5 channel that is implicated in breast cancer’s resistance to chemotherapy. Herein, we found that gadopentetic acid (Gd-DTPA, 1 mM) potentiated the inward and outward currents through TRPC5 channels, which were exogenously expressed in HEK293 cells. Gd-DTPA (1 mM) also activated the Gd³⁺-sensitive R593A mutant of TRPC5, which exhibits a reduced sensitivity to GPCR-G_q/11-PLC dependent gating. Conversely, Gd-DTPA had no effect on TRPC5-E543Q, a Gd³⁺ insensitive TRPC5 mutant. Long-term treatment (28 days) of human breast cancer cells (MCF-7 and SK-BR-3) and adriamycin-resistant MCF-7 cells (MCF-7/ADM) with Gd-DTPA (1 mM) or gadodiamide (GDD, 1 mM) did not affect the IC₅₀ values of ADM. However, treatment with Gd-DTPA or GDD significantly increased TRPC5 expression and decreased the accumulation of ADM in the nuclei of MCF-7 and SK-BR-3 cells, promoting the survival of these two breast cancer cells in the presence of ADM. The antagonist of TRPC5, AC1903 (1 μM), increased ADM nuclear accumulation induced by Gd-DTPA-treatment. These data indicate that prolonged GBCA treatment may lead to increased breast cancer cell survival owing to the upregulation of TRPC5 expression and the increased ADM resistance. We propose that while focusing on providing medical care of the best personalized quality in the clinic, excessive administration of GBCAs should be avoided in patients with metastatic breast cancer to reduce the risk of promoting breast cancer cell drug resistance. Full article

Magnetic resonance imaging (MRI) is increasingly used to diagnose focal and diffuse liver disorders. Despite their enhanced efficacy, liver-targeted gadolinium-based contrast agents (GBCAs) raise safety concerns owing to the release of toxic Gd³⁺ ions. A π-conjugated macrocyclic chelate, Mn-NOTA-NP, was designed and synthesized as a non-gadolinium alternative for liver-specific MRI. Mn-NOTA-NP exhibits an r₁ relaxivity of 3.57 mM⁻¹ s⁻¹ in water and 9.01 mM⁻¹ s⁻¹ in saline containing human serum albumin at 3 T, which is significantly greater than the clinically utilized Mn²⁺-based hepatobiliary drug, Mn-DPDP (1.50 mM⁻¹ s⁻¹), and comparable with that of GBCAs. Furthermore, the in vivo biodistribution and MRI enhancement patterns of Mn-NOTA-NP were similar to those of the Gd³⁺-based hepatobiliary agent, Gd-DTPA-EOB. Additionally, a 0.05 mmol/kg dose of Mn-NOTA-NP facilitated high-sensitivity tumor detection with tumor signal enhancement in a liver tumor model. Ligand-docking simulations further indicated that Mn-NOTA-NP differed from other hepatobiliary agents in their interactions with several transporter systems. Collectively, we demonstrated that Mn-NOTA-NP could be a new liver-specific MRI contrast agent. Full article

We conducted a clinical veterinary study on neutron capture therapy (NCT) at a neutron-producing accelerator with seven incurable pets with spontaneous tumors and gadolinium as a neutron capture agent (gadolinium neutron capture therapy, or GdNCT). Gadolinium-containing dimeglumine gadopentetate, or Gd-DTPA (Magnevist^®, 0.6 mL/kg b.w.), was used. We observed mild and reversible toxicity related to the treatment. However, no significant tumor regression in response to the treatment was observed. In most cases, there was continued tumor growth. Overall clinical improvement after treatment was only temporary. The use of Gd-DTPA for NCT had no significant effects on the life expectancy and quality of life of animals with spontaneous tumors. Further experiments using more advanced gadolinium compounds are needed to improve the effect of GdNCT so that it can become an alternative to boron neutron capture therapy. Such studies are also necessary for further NCT implementation in clinical practice as well as in veterinary medicine. Full article

The application of magnetic resonance imaging (MRI) nano-contrast agents (nano-CAs) has increasingly attracted scholarly interest owing to their size, surface chemistry, and stability. Herein, a novel T1 nano-CA (Gd(DTPA)−GQDs) was successfully prepared through the functionalization of graphene quantum dots with poly(ethylene glycol) bis(amine) and their subsequent incorporation into Gd-DTPA. Remarkably, the resultant as-prepared nano-CA displayed an exceptionally high longitudinal proton relaxivity (r₁) of 10.90 mM⁻¹ s⁻¹ (R² = 0.998), which was significantly higher than that of commercial Gd-DTPA (4.18 mM⁻¹ s⁻¹, R² = 0.996). The cytotoxicity studies indicated that the Gd(DTPA)−GQDs were not cytotoxic by themselves. The results of the hemolysis assay and the in vivo safety evaluation demonstrate the outstanding biocompatibility of Gd(DTPA)−GQDs. The in vivo MRI study provides evidence that Gd(DTPA)−GQDs exhibit exceptional performance as T1-CAs. This research constitutes a viable approach for the development of multiple potential nano-CAs with high-performance MR imaging capabilities. Full article

Gadoxetic acid disodium (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) can detect early stages of hepatocellular carcinoma (HCC). However, the survival benefit of Gd-EOB-DTPA-enhanced MRI in the surveillance of patients with cirrhosis has not yet been determined. We explored whether the intermittent replacement of ultrasonography (USG) with Gd-EOB-DTPA-enhanced MRI during HCC surveillance improved the clinical outcomes of patients with cirrhosis. We performed a retrospective cohort study of 421 HCC patients who were newly diagnosed during surveillance. Of these patients, 126 (29.9%) underwent surveillance based on Gd-EOB-DTPA-enhanced MRI and USG (USG+MRI group). The patients (295, 70.1%) who did not undergo MRI during surveillance were referred to as the USG group. In the USG+MRI group, 120 (95.2%) of 126 patients were diagnosed with early-stage HCC, whereas 247 (83.7%) of 295 patients were diagnosed with early-stage HCC in the USG group (P = 0.009). The significantly longer overall survival and time to progression in patients in the USG+MRI group compared to the unmatched cohort USG group was consistently observed by inverse probability weighting and propensity score-matched analysis. Gd-EOB-DTPA-enhanced MRI combined surveillance improved the detection of early-stage HCC and clinical outcomes such as overall survival and the time to progression in patients with cirrhosis. Full article

Relative enhancement (RE) in gadoxetate disodium (Gd-EOB-DTPA)-enhanced MRI is a reliable, non-invasive method for the evaluation and differentiation between simple steatosis and non-alcoholic steatohepatitis in adults. This study evaluated the diagnostic accuracy of RE in Gd-EOB-DTPA-enhanced liver MRI and hepatic fat fraction (HFF) in unenhanced liver MRI and ultrasound (US) for non-alcoholic fatty liver disease (NAFLD) screening in pediatric obesity. Seventy-four liver US and MRIs from 68 pediatric patients (13.07 ± 2.95 years) with obesity (BMI > BMI-for-age + 2SD) were reviewed with regard to imaging biomarkers (liver size, volume, echogenicity, HFF, and RE in Gd-EOB-DTPA-enhanced MRIs, and spleen size), blood biomarkers, and BMI. The agreement between the steatosis grade, according to HFF in MRI and the echogenicity in US, was moderate. Alanine aminotransferase correlated better with the imaging biomarkers in MRI than with those in US. BMI correlated better with liver size and volume on MRI than in US. In patients with RE < 1, blood biomarkers correlated better with RE than those in the whole sample, with a significant association between gamma-glutamyltransferase and RE (p = 0.033). In conclusion, the relative enhancement and hepatic fat fraction can be considered as non-invasive tools for the screening and follow-up of NAFLD in pediatric obesity, superior to echogenicity on ultrasound. Full article