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1.
Contrast Media Mol Imaging ; 2022: 4558702, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35510178

RESUMO

Magnetic resonance imaging (MRI) image segmentation based on a segmentation algorithm was performed to assess neurological function in patients with acute cerebral infarction, to investigate the efficacy evaluation of Ginkgo diterpene lactones meglumine injection (GDLI) in the treatment of cerebral infarction and the efficiency of MRI image segmentation algorithm. First, the results of the fast semisupervised segmentation algorithm (algorithm group) and traditional processing (control group) were compared and analyzed. The recall rate, accuracy, recognition accuracy, and segmentation time of the two groups were compared. The control group was given conventional treatment, while the algorithm group was given GDLI based on conventional treatment. Finally, the difference in serum vascular endothelial growth factor (VEGF), hypoxia-inducible factor-la (HIF-la), angiotensin (Ang)-1, Ang-2, and interleukin (IL)-6 protein concentration was analyzed after treatment. The algorithm evaluation results showed that the accuracy and recall rate of MRI images recognized by the algorithm group fluctuate at 90%. In the control group, the accuracy and recall rate of MRI image results fluctuated at 80%, and the data were statistically different (p < 0.05). The clinical index test results showed that the serum VEGF content of the test group was higher than that of the control group, and the data was statistically different (p < 0.05). In addition, the cerebral blood flow (CBF) and cerebral blood volume (CBV) of the lesion side of the algorithm group were greatly higher than those of the control group on the 30th day, and the differences were significant (p < 0.05). There was little difference between the method presented in this study and the manual delineation by a physician. Compared with traditional manual segmentation, this method greatly reduced the time required for the segmentation of lesions. The diagnostic specificity, sensitivity, and accuracy of the images segmented by the fast semisupervised algorithm were higher than those of the conventional method, and the diagnostic accuracy of acute cerebral infarction was high. In addition, it was sensitive and accurate to detect acute cerebral infarction, which provided a reliable reference for early diagnosis and condition judgment of patients.


Assuntos
Isquemia Encefálica , Diterpenos , Algoritmos , Infarto Cerebral/diagnóstico por imagem , Infarto Cerebral/tratamento farmacológico , Ginkgo biloba , Humanos , Processamento de Imagem Assistida por Computador , Lactonas , Imageamento por Ressonância Magnética/métodos , Meglumina , Fator A de Crescimento do Endotélio Vascular
2.
Comput Math Methods Med ; 2022: 2172412, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35479188

RESUMO

Ulinastatin, a common adjuvant drug in the clinical treatment of acute circulatory failure, has a good effect on various inflammatory diseases. In this study, we aim to explore the clinical efficacy of ulinastatin combined with meglumine adenosine cyclophosphate in patients with acute myocardial infarction (AMI) and its effect on cardiac function and endothelial function of patients. 100 AMI patients treated in our hospital (February 2020-October 2020) were randomly chosen and divided into group J and group Q, with 50 cases in each group. Group Q was treated with meglumine adenosine cyclophosphate only, while group J was treated with ulinastatin combined with meglumine adenosine cyclophosphate to compare the treatment efficiency, cardiac structure indexes, cardiac systolic function, blood lipid levels, vascular endothelial function, QLI (quality of life) scores, BI indexes, and FMA (motor function) scores between the two groups. The treatment efficiency, QLI score, BI index, and FMA score in group J were notably higher compared with group Q (P < 0.05). The cardiac structure indexes, cardiac systolic function, blood lipid level, and vascular endothelial function in group J were notably better compared with group Q (P < 0.05). Ulinastatin combined with meglumine adenosine cyclophosphate can obviously enhance the therapeutic effect of AMI patients and improve the endothelial function and cardiac function of patients, which is very promising in this medical area.


Assuntos
Adenosina , Infarto do Miocárdio , Adenosina/uso terapêutico , Glicoproteínas , Humanos , Meglumina/uso terapêutico , Infarto do Miocárdio/tratamento farmacológico , Qualidade de Vida , Resultado do Tratamento
3.
Artigo em Russo | MEDLINE | ID: mdl-35485066

RESUMO

OBJECTIVE: To study the efficacy of Reamberin in cognitive impairment in patients associated with traumatic brain injury, taking into account its effect on the parameters of neuropsychological and antioxidant status. MATERIAL AND METHODS: We examined 45 patients aged 35 to 60 years with cognitive impairment in the late period of traumatic brain injury. The patients were divided into two groups depending on the prescribed treatment. The first main group included 25 patients with cognitive impairment who received complex therapy: Reamberin against the background of standard treatment. The second control group consisted of 20 patients with cognitive impairment who received only standard therapy. In accordance with the purpose of the study, the parameters of the neuropsychological and antioxidant status were determined. RESULTS: The analysis of cognitive disorders according to the Montreal Cognitive Assessment made it possible to establish cognitive impairments in 100% of the patients included in the study in the late period of traumatic brain injury. The introduction of Reamberin to patients contributed to an improvement in work efficiency and a decrease in the amount of time required to prepare for work in relation to control (p<0.05), an increase in the volume of auditory short-term memory in dynamics from the moment of admission to the 11th day by 1.9 times (p<0.05). The evaluation of the parameters of the antioxidant status in the late period of traumatic brain injury made it possible to establish that in patients of the main group who received Reamberin as part of standard therapy, by the end of the observation (day 11), the concentration of lipid peroxidation products was lower than in the control by 13-43%, the level of ceruloplasmin and catalase activity are higher by 14 and 15%, respectively (p<0.05), which confirms the antioxidant activity of Reamberin. CONCLUSION: It was concluded that the inclusion of Reamberin in the treatment regimen for patients with cognitive impairment in the late period of traumatic brain injury should be considered clinically justified and promising.


Assuntos
Lesões Encefálicas Traumáticas , Disfunção Cognitiva , Antioxidantes/uso terapêutico , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/tratamento farmacológico , Disfunção Cognitiva/complicações , Disfunção Cognitiva/etiologia , Humanos , Meglumina/análogos & derivados , Testes de Estado Mental e Demência , Succinatos
4.
Cells ; 11(5)2022 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-35269379

RESUMO

Magnetic resonance imaging (MRI) is widely used in diagnostic medicine. MRI uses the static magnetic field to polarize nuclei spins, fast-switching magnetic field gradients to generate temporal and spatial resolution, and radiofrequency (RF) electromagnetic waves to control the spin orientation. All these forms of magnetic static and electromagnetic RF fields interact with human tissue and cells. However, reports on the MRI technique's effects on the cells and human body are often inconsistent or contradictory. In both research and clinical MRI, recent progress in improving sensitivity and resolution is associated with the increased magnetic field strength of MRI magnets. Additionally, to improve the contrast of the images, the MRI technique often employs contrast agents, such as gadolinium-based Dotarem, with effects on cells and organs that are still disputable and not fully understood. Application of higher magnetic fields requires revisiting previously observed or potentially possible bio-effects. This article focuses on the influence of a static magnetic field gradient with and without a gadolinium-based MRI contrast agent (Dotarem) and the cellular and molecular effects of Dotarem on macrophages.


Assuntos
Meios de Contraste , Gadolínio , Animais , Gadolínio/farmacologia , Macrófagos , Campos Magnéticos , Imageamento por Ressonância Magnética/métodos , Meglumina , Camundongos , Compostos Organometálicos
5.
Comp Immunol Microbiol Infect Dis ; 84: 101797, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35325685

RESUMO

Treatment of leishmaniasis by conventional synthetic compounds has faced a serious challenge worldwide. This study was performed to evaluate the effect and modes of action of aromatic Turmerone on the Leishmania major intra-macrophage amastigotes, the causative agent of zoonotic cutaneous leishmaniasis in the Old World. In the findings, the mean numbers of L. major amastigotes in macrophages were significantly decreased in exposure to Turmerone plus meglumine antimoniate (Glucantime®; MA) than MA alone, especially at 50 µg/mL. In addition, Turmerone demonstrated no cytotoxicity as the selectivity index (SI) was 21.1; while it induced significant apoptosis in a dose-dependent manner on L. major promastigotes. In silico molecular docking analyses indicated an affinity of Turmerone to IL-12, with the MolDock score of - 96.8 kcal/mol; which may explain the increased levels of Th1 cytokines and decreased level of IL-10. The main mechanism of action is more likely associated with stimulating a powerful antioxidant and promoting the immunomodulatory roles in the killing of the target organism.


Assuntos
Antiprotozoários , Leishmania major , Leishmaniose Cutânea , Compostos Organometálicos , Animais , Antioxidantes/farmacologia , Antiprotozoários/farmacologia , Antiprotozoários/uso terapêutico , Leishmaniose Cutânea/tratamento farmacológico , Leishmaniose Cutânea/veterinária , Meglumina/farmacologia , Meglumina/uso terapêutico , Antimoniato de Meglumina/farmacologia , Simulação de Acoplamento Molecular , Compostos Organometálicos/farmacologia , Compostos Organometálicos/uso terapêutico
6.
Radiol Med ; 127(3): 259-271, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35129757

RESUMO

PURPOSE: Hepatocellular carcinoma (HCC) is the most common liver cancer worldwide, and early recurrence of HCC after curative hepatic resection is indicative of poor prognoses. We aim to develop a predictive model for postoperative early recurrence of HCC based on deep and radiomics features from multi-phasic magnetic resonance imaging (MRI). MATERIALS AND METHODS: A total of 472 HCC patients were included and divided into the training (n = 378) and validation (n = 94) cohorts in the retrospective study. We separately extracted radiomics features and deep features from eight phases of gadoxetic acid-enhanced MRI and utilized the least absolute shrinkage and selection operator logistic regression algorithm for feature selection and model construction. We integrated the selected two types of features into a combined model and established a radiomics model as well as a deep learning (DL) model for comparison. RESULTS: In the training and validation cohorts, the combined model demonstrated better performance for stratifying patients at high risk of early recurrence (AUC of 0.911 and 0.840, accuracy of 0.779 and 0.777, sensitivity of 0.927 and 0.769, specificity 0.720 and 0.779) than the radiomics model (AUC of 0.740 and 0.780) and the DL model (AUC of 0.887 and 0.813). CONCLUSION: The combined model integrating deep and radiomics features from multi-phasic MRI is efficient for noninvasively stratifying patients at high risk of early HCC recurrence after resection.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Imageamento por Ressonância Magnética/métodos , Meglumina/análogos & derivados , Compostos Organometálicos , Estudos Retrospectivos
7.
Int Immunopharmacol ; 106: 108602, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35131571

RESUMO

Gadopentetate meglumine (Gd-DTPA) is a commonly used magnetic resonance imaging (MRI) enhancer in the clinic for improving the clarity of MRI. Reports have shown that severe anaphylactoid reactions can occur after intravenous injections, whereas the underlying mechanisms remain undefined. In this study, the effects of Gd-DTPA in causing allergic like reactions and mast cells (MCs) activation were investigated both in vitro and in vivo. Gd-DTPA induced a severe hand paw swelling and body temperature decrease in murine topical cutaneous allergy model, and murine systemic allergy model. Meanwhile, serum IgE was not significantly changed. Histamine, tryptase, and cytokines release in mice serum and LAD2 cells supernatant were increased significantly both in mice serum and LAD2 supernatant after treated with Gd-DTPA. Subsequently, the changes in mRNA levels after Gd-DTPA activated MCs were analyzed by RNAseq and found to be related to inflammation signaling pathways. The study provides a demonstration for the adverse reaction mechanism of Gd-DTPA and its safe use in clinic.


Assuntos
Anafilaxia , Mastócitos , Anafilaxia/metabolismo , Animais , Meios de Contraste/efeitos adversos , Meios de Contraste/metabolismo , Imunoglobulina E/metabolismo , Meglumina/metabolismo , Meglumina/farmacologia , Camundongos
8.
Eur Radiol ; 32(5): 3006-3015, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34989839

RESUMO

OBJECTIVES: To determine the value of gadobenate dimeglumine (Gd-BOPTA)-enhanced magnetic resonance imaging (MRI) from the hepatobiliary phase for predicting poor outcome in acute-on-chronic liver failure (ACLF) patients. METHODS: In this single-center retrospective study, 74 patients diagnosed as ACLF who underwent Gd-BOPTA-enhanced hepatobiliary magnetic resonance imaging were collected. The quantitative liver-spleen contrast ratio (Q-LSC) and the relative enhancement ratio of the biliary system (REB) at the hepatobiliary phase were measured. Cox proportional hazards regression models were used to evaluate prognostic factors. The capacity of the Q-LSC and REB to predict the 90-day outcome was evaluated via receiver operating characteristic (ROC) curve. RESULTS: During the follow-up period, twenty-eight of 74 ACLF patients (38%) had a poor outcome. The Q-LSC and REB were significant predictive factors (hazard ratio [HR] = 0.03 [0.002-0.54], p < 0.05; HR = 0.07 [0.01-0.88], p < 0.05) for prognosis in patients with ACLF. Moreover, the areas under the ROC curves of Q-LSC and REB for predicting poor outcome in patients with ACLF were 0.81 and 0.80, respectively. The most appropriate cutoff values for the Q-LSC and REB were 1.09 and 0.57, respectively. The ACLF patients with the Q-LSC ≤ 1.09 or REB ≤ 0.57 had a low cumulative survival. CONCLUSIONS: Gd-BOPTA-enhanced hepatobiliary phase MR imaging can predict poor outcome in patients with acute-on-chronic liver failure. KEY POINTS: • The quantitative liver-spleen contrast ratio at the hepatobiliary phase was a significant predictive prognostic factor in patients with acute-on-chronic liver failure. • The relative enhancement ratio of the biliary system at the hepatobiliary phase was a significant prognostic factor in patients with acute-on-chronic liver failure. • Gadobenate dimeglumine contrast-enhanced MR imaging from the hepatobiliary phase can predict poor outcome in patients with acute-on-chronic liver failure.


Assuntos
Insuficiência Hepática Crônica Agudizada , Compostos Organometálicos , Insuficiência Hepática Crônica Agudizada/diagnóstico por imagem , Meios de Contraste/farmacologia , Gadolínio DTPA , Humanos , Fígado/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Meglumina/análogos & derivados , Prognóstico , Estudos Retrospectivos
9.
Invest Radiol ; 57(5): 283-292, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35066532

RESUMO

PURPOSE: Several preclinical studies have reported the presence of gadolinium (Gd) in different chemical forms in the brain, depending on the class (macrocyclic versus linear) of Gd-based contrast agent (GBCA) administered. The aim of this study was to identify, with a special focus on insoluble species, the speciation of Gd retained in the deep cerebellar nuclei (DCN) of rats administered repeatedly with gadoterate or gadodiamide 4 months after the last injection. METHODS: Three groups (N = 6/group) of healthy female Sprague-Dawley rats (SPF/OFA rats; Charles River, L'Arbresle, France) received a cumulated dose of 50 mmol/kg (4 daily intravenous administrations of 2.5 mmol/kg, for 5 weeks, corresponding to 80-fold the usual clinical dose if adjusted for man) of gadoterate meglumine (macrocyclic) or gadodiamide (linear) or isotonic saline for the control group (4 daily intravenous administrations of 5 mL/kg, for 5 weeks). The animals were sacrificed 4 months after the last injection. Deep cerebellar nuclei were dissected and stored at -80°C before sample preparation. To provide enough tissue for sample preparation and further analysis using multiple techniques, DCN from each group of 6 rats were pooled. Gadolinium species were extracted in 2 consecutive steps with water and urea solution. The total Gd concentrations were determined by inductively coupled plasma mass spectrometry (ICP-MS). Soluble Gd species were analyzed by size-exclusion chromatography coupled to ICP-MS. The insoluble Gd species were analyzed by single-particle (SP) ICP-MS, nanoscale secondary ion mass spectroscopy (NanoSIMS), and scanning transmission electron microscopy with energy-dispersive X-ray spectroscopy (STEM-EDX) for elemental detection. RESULTS: The Gd concentrations in pooled DCN from animals treated with gadoterate or gadodiamide were 0.25 and 24.3 nmol/g, respectively. For gadoterate, the highest amount of Gd was found in the water-soluble fractions. It was present exclusively as low-molecular-weight compounds, most likely as the intact GBCA form. In the case of gadodiamide, the water-soluble fraction of DCN was composed of high-molecular-weight Gd species of approximately 440 kDa and contained only a tiny amount (less than 1%) of intact gadodiamide. Furthermore, the column recovery calculated for this fraction was incomplete, which suggested presence of labile complexes of dissociated Gd3+ with endogenous molecules. The highest amount of Gd was detected in the insoluble residue, which was demonstrated, by SP-ICP-MS, to be a particulate form of Gd. Two imaging techniques (NanoSIMS and STEM-EDX) allowed further characterization of these insoluble Gd species. Amorphous, spheroid structures of approximately 100-200 nm of sea urchin-like shape were detected. Furthermore, Gd was consistently colocalized with calcium, oxygen, and phosphorous, strongly suggesting the presence of structures composed of mixed Gd/Ca phosphates. No or occasional colocalization with iron and sulfur was observed. CONCLUSION: A dedicated analytical workflow produced original data on the speciation of Gd in DCN of rats repeatedly injected with GBCAs. The addition, in comparison with previous studies of Gd speciation in brain, of SP element detection and imaging techniques allowed a comprehensive speciation analysis approach. Whereas for gadoterate the main fraction of retained Gd was present as intact GBCA form in the soluble fractions, for linear gadodiamide, less than 10% of Gd could be solubilized and characterized using size-exclusion chromatography coupled to ICP-MS. The main Gd species detected in the soluble fractions were macromolecules of 440 kDa. One of them was speculated to be a Gd complex with iron-binding protein (ferritin). However, the major fraction of residual Gd was present as insoluble particulate species, very likely composed of mixed Gd/Ca phosphates. This comprehensive Gd speciation study provided important evidence for the dechelation of linear GBCAs and offered a deeper insight into the mechanisms of Gd deposition in the brain.


Assuntos
Gadolínio , Compostos Organometálicos , Animais , Encéfalo/metabolismo , Núcleos Cerebelares/diagnóstico por imagem , Núcleos Cerebelares/metabolismo , Meios de Contraste , Feminino , Gadolínio DTPA , Meglumina , Fosfatos/metabolismo , Ratos , Ratos Sprague-Dawley , Água/metabolismo
10.
Parasitol Res ; 121(3): 991-998, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35076777

RESUMO

This study was conducted to explore the frequency of positivity of cutaneous leishmaniasis (CL) in the tribal district Bajaur located near the Pak-Afghan border. The present study was conducted at the Leishmaniasis Center of Headquarter Hospital Khar District Bajaur, Pakistan. In total, 646 patients were recruited and included in the study after ethical approval and consent from the patients. CL was confirmed by taking blood samples from the sides of the lesion and observing them under a microscope using Giemsa staining. Information about demographic factors was collected from the study participants with a questionnaire and analyzed by SPSS. It was found that 73.8% of suspected patients were positive and 26.2% were negative for CL. There were 51.9% male and 48.1% female patients. The most frequently affected site was the face (42.6%), and most of the patients (85.8%) had only one lesion. The positivity of CL was higher among those under age 15 years. The area of most positivity, with 45.2% of the cases, was Tehsil Mamund. Most of the patients (46.6%) lived in stone houses, with 98.6% of patients having domestic animals in their houses. Approximately 198 patients were treated with intramuscular and intralesional injections of meglumine antimoniate, and their weekly follow-up revealed that 48% of patients recovered, while the remaining patients left the course of treatment at different stages of therapy. The positivity of CL is high in this area and is confirmed by the detection of Leishmania amastigotes in the blood collected from their lesions. Socioeconomic factors are the main underlying causes of the rapid spread of this disease and meglumine antimoniate is an effective drug.


Assuntos
Antiprotozoários , Leishmaniose Cutânea , Compostos Organometálicos , Adolescente , Animais , Antiprotozoários/uso terapêutico , Feminino , Seguimentos , Humanos , Leishmaniose Cutânea/diagnóstico , Leishmaniose Cutânea/tratamento farmacológico , Leishmaniose Cutânea/epidemiologia , Masculino , Meglumina/uso terapêutico , Compostos Organometálicos/uso terapêutico , Paquistão/epidemiologia
11.
AJR Am J Roentgenol ; 218(4): 687-698, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34817191

RESUMO

BACKGROUND. Gadobenate and gadoxetate show different degrees of intracellular accumulation within hepatocytes, potentially impacting these agents' relative performance for hepatocellular carcinoma (HCC) diagnosis. OBJECTIVE. The purpose of this article was to perform an intraindividual comparison of gadobenate-enhanced MRI and gadoxetate-enhanced MRI for detection of HCC and to assess the impact of inclusion of hepatobiliary phase images on HCC detection for both agents. METHODS. This prospective study enrolled 126 patients (112 men, 14 women; mean age, 52.3 years) at high risk for HCC who consented to undergo two 3-T liver MRI examinations (one using gadobenate [0.05 mmol/kg], one using gadoxetate [0.025 mmol/kg]) separated by 7-14 days. The order of the two contrast agents was randomized. All examinations included postcontrast dynamic and hepatobiliary phase images (120 minutes for gadobenate, 20 minutes for gadoxetate). Three radiologists independently reviewed the gadobenate and gadoxetate examinations in separate sessions and recorded the location of detected observations. Observations were classified using LI-RADS version 2018 and using a LI-RADS modification whereby hepatobiliary phase hypointensity may upgrade observations from category LR-4 to LR-5. Observations classified as LR-5 were considered positive interpretations for HCC. Diagnostic performance for histologically confirmed HCC (n = 96) was assessed. RESULTS. Across readers, sensitivity for HCC for gadobenate versus gadoxetate was 74.0-80.2% versus 54.2-67.7% using dynamic images alone and 82.1-87.4% versus 66.3-81.1% using dynamic and hepatobiliary phase images. For HCCs measuring 1.0-2.0 cm, sensitivity for gadobenate versus gadoxetate was 61.9% (all readers) versus 38.1-57.1% using dynamic images alone and 76.2-85.7% versus 52.4-61.9% using dynamic and hepatobiliary phase images. PPV for HCC ranged from 88.6% to 97.4% across readers, agents, and image sets. CONCLUSION. Sensitivity for HCC was higher for gadobenate than for gadoxetate, whether using dynamic images alone or dynamic and hepatobiliary phase images; the improved sensitivity using gadobenate was more pronounced for small HCCs. Whereas hepatobiliary phase images improved sensitivity for both agents, sensitivity of gadobenate using dynamic images alone compared favorably with that of gadoxetate using dynamic and hepatobiliary phase images. CLINICAL IMPACT. The findings support gadobenate as a preferred agent over gadoxetate when performing liver MRI in patients at high risk for HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Compostos Organometálicos , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/patologia , Meios de Contraste , Feminino , Gadolínio DTPA , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Imageamento por Ressonância Magnética/métodos , Masculino , Meglumina , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Sensibilidade e Especificidade
12.
Invest Radiol ; 57(2): 130-139, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-34411032

RESUMO

OBJECTIVES: The aim of the set of studies was to compare gadopiclenol, a new high relaxivity gadolinium (Gd)-based contrast agent (GBCA) to gadobenate dimeglumine in terms of small brain lesion enhancement and Gd retention, including T1 enhancement in the cerebellum. MATERIALS AND METHODS: In a first study, T1 enhancement at 0.1 mmol/kg body weight (bw) of gadopiclenol or gadobenate dimeglumine was evaluated in a small brain lesions rat model at 2.35 T. The 2 GBCAs were injected in an alternated and cross-over manner separated by an interval of 4.4 ± 1.0 hours (minimum, 3.5 hours; maximum, 6.1 hours; n = 6). In a second study, the passage of the GBCAs into cerebrospinal fluid (CSF) was evaluated by measuring the fourth ventricle T1 enhancement in healthy rats at 4.7 T over 23 minutes after a single intravenous (IV) injection of 1.2 mmol/kg bw of gadopiclenol or gadobenate dimeglumine (n = 6/group). In a third study, Gd retention at 1 month was evaluated in healthy rats who had received 20 IV injections of 1 of the 2 GBCAs (0.6 mmol/kg bw) or a similar volume of saline (n = 10/group) over 5 weeks. T1 enhancement of the deep cerebellar nuclei (DCN) was assessed by T1-weighted magnetic resonance imaging at 2.35 T, performed before the injection and thereafter once a week up to 1 month after the last injection. Elemental Gd levels in central nervous system structures, in muscle and in plasma were determined by inductively coupled plasma mass spectrometry (ICP-MS) 1 month after the last injection. RESULTS: The first study in a small brain lesion rat model showed a ≈2-fold higher number of enhanced voxels in lesions with gadopiclenol compared with gadobenate dimeglumine. T1 enhancement of the fourth ventricle was observed in the first minutes after a single IV injection of gadopiclenol or gadobenate dimeglumine (study 2), resulting, in the case of gadopiclenol, in transient enhancement during the injection period of the repeated administrations study (study 3). In terms of Gd retention, T1 enhancement of the DCN was noted in the gadobenate dimeglumine group during the month after the injection period. No such enhancement of the DCN was observed in the gadopiclenol group. Gadolinium concentrations 1 month after the injection period in the gadopiclenol group were slightly increased in plasma and lower by a factor of 2 to 3 in the CNS structures and muscles, compared with gadobenate dimeglumine. CONCLUSIONS: In the small brain lesion rat model, gadopiclenol provides significantly higher enhancement of brain lesions compared with gadobentate dimeglumine at the same dose. After repeated IV injections, as expected for a macrocyclic GBCA, Gd retention is minimalized in the case of gadopiclenol compared with gadobenate dimeglumine, resulting in no T1 hypersignal in the DCN.


Assuntos
Gadolínio , Compostos Organometálicos , Animais , Compostos Azabicíclicos , Encéfalo/diagnóstico por imagem , Meios de Contraste , Gadolínio DTPA , Imageamento por Ressonância Magnética/métodos , Meglumina/análogos & derivados , Ratos
13.
Abdom Radiol (NY) ; 47(3): 957-968, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34964069

RESUMO

OBJECTIVE: To identify the reliable imaging features and added-value of ancillary imaging features for differentiating hepatocellular carcinoma (HCC) and intrahepatic mass-forming cholangiocarcinoma (IMCC) assigned to LI-RADS M on Gd-BOPTA-enhanced MRI. METHODS: This retrospective study included 116 liver observations assigned to LI-RADS M, including 82 HCC and 34 IMCC histologically confirmed. Before and after adding ancillary imaging features, all variables with a p-value of < 0.05 in univariable analysis were entered into a multivariable logistic regression analysis to build diagnostic model 1 and model 2 to find reliable predictors of HCC diagnosis. Receiver operating characteristic (ROC) analysis and the DeLong test were used to compare the two models. RESULTS: Forty-nine of 82(59.8%) HCCs had a considerably higher frequency of enhancing "capsule" compared with IMCCs (p < 0.001). Based on LI-RADS major and LR-M features and clinical-pathologic factors, an elevated AFP level (OR = 10.676, 95%CI = 2.125-4.470, p = 0.004) and enhancing "capsule" (OR = 20.558, 95%CI = 4.470-94.550, p < 0.001) were extracted as independent risk factors in Model 1. After adding ancillary imaging features, Male (OR = 23.452, 95%CI = 1.465-375.404, p = 0.026), enhancing "capsule" (OR = 13.161, 95%CI = 1.725-100.400, p = 0.013), septum (OR = 17.983, 95%CI = 1.049-308.181, p = 0.046), small-scale central HBP hyperintensity (OR = 44.386, 95%CI = 1.610-1223.484, p = 0.025) were confirmed as independent significant variables associated with HCC. Model 2 demonstrated significantly superior AUC (0.918 vs 0.845, p = 0.021) compared with Model 1. When any two or more predictors in model 2 were satisfied, sensitivity was 91.46%, and accuracy was at the top (87.93%). CONCLUSION: Enhancing "capsule" was a reliable imaging feature to help identify HCC. Adding ancillary imaging features improved sensitivity and accuracy for HCC diagnosis with differentiation from IMCC in LR-M.


Assuntos
Neoplasias dos Ductos Biliares , Carcinoma Hepatocelular , Colangiocarcinoma , Neoplasias Hepáticas , Neoplasias dos Ductos Biliares/diagnóstico por imagem , Ductos Biliares Intra-Hepáticos/patologia , Carcinoma Hepatocelular/diagnóstico por imagem , Colangiocarcinoma/diagnóstico por imagem , Meios de Contraste , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Imageamento por Ressonância Magnética/métodos , Masculino , Meglumina/análogos & derivados , Compostos Organometálicos , Estudos Retrospectivos , Sensibilidade e Especificidade
14.
Eur Radiol ; 32(1): 331-345, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34218287

RESUMO

OBJECTIVES: We examined the effects of aging and of gadolinium-based contrast agent (GBCA) exposure on MRI measurements in brain nuclei of healthy women. METHODS: This prospective, IRB-approved single-center case-control study enrolled 100 healthy participants of our high-risk screening center for hereditary breast cancer, who had received at least six doses of macrocyclic GBCA (exposed group) or were newly entering the program (GBCA-naïve group). The cutoff "at least six doses" was chosen to be able to include a sufficient number of highly exposed participants. All participants underwent unenhanced 3.0-T brain MRI including quantitative T1, T2, and R2* mapping and T1- and T2-weighted imaging. The relaxation times/signal intensities were derived from region of interest measurements in the brain nuclei performed by a radiologist and a neuroradiologist, both board certified. Statistical analysis was based on descriptive evaluations and uni-/multivariable analyses. RESULTS: The participants (exposed group: 49, control group: 51) were aged 42 ± 9 years. In a multivariable model, age had a clear impact on R2* (p < 0.001-0.012), T2 (p = 0.003-0.048), and T1 relaxation times/signal intensities (p < 0.004-0.046) for the majority of deep brain nuclei, mostly affecting the substantia nigra, globus pallidus (GP), nucleus ruber, thalamus, and dentate nucleus (DN). The effect of prior GBCA administration on T1 relaxation times was statistically significant for the DN, GP, and pons (p = 0.019-0.037). CONCLUSIONS: In a homogeneous group of young to middle-aged healthy females aging had an effect on T2 and R2* relaxation times and former GBCA applications influenced the measured T1 relaxation times. KEY POINTS: The quantitative T1, T2, and R2* relaxation times measured in women at high risk of developing breast cancer showed characteristic bandwidth for all brain nuclei examined at 3.0-T MRI. The effect of participant age had a comparatively strong impact on R2*, T2, and T1 relaxation times for the majority of brain nuclei examined. The effect of prior GBCA administrations on T1 relaxation times rates was comparatively less pronounced, yielding statistically significant results for the dentate nucleus, globus pallidus, and pons. Healthy women with and without previous GBCA-enhanced breast MRI exhibited age-related T2* and T2 relaxation alterations at 3.0 T-brain MRI. T1 relaxation alterations due to prior GBCA administration were comparatively less pronounced.


Assuntos
Neoplasias da Mama , Compostos Organometálicos , Envelhecimento , Encéfalo/diagnóstico por imagem , Neoplasias da Mama/diagnóstico por imagem , Estudos de Casos e Controles , Núcleos Cerebelares , Meios de Contraste , Feminino , Gadolínio , Gadolínio DTPA , Globo Pálido , Humanos , Imageamento por Ressonância Magnética , Meglumina , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos
15.
Eur Radiol ; 32(1): 346-354, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34324024

RESUMO

OBJECTIVES: The goal of this study was to investigate the precise timeline of respiratory events occurring after the administration of two gadolinium-based contrast agents, gadoxetate disodium and gadoterate meglumine. MATERIALS AND METHODS: This retrospective study examined 497 patients subject to hepatobiliary imaging using the GRASP MRI technique (TR/TE = 4/2 ms; ST = 2.5 mm; 384 × 384 mm). Imaging was performed after administration of gadoxetate (N = 338) and gadoterate (N = 159). All GRASP datasets were reconstructed using a temporal resolution of 1 s. Four regions-of-interest (ROIs) were placed in the liver dome, the right and left cardiac ventricle, and abdominal aorta detecting liver displacement and increasing vascular signal intensities over time. Changes in hepatic intensity reflected respiratory dynamics in temporal correlation to the vascular contrast bolus. RESULTS: In total, 216 (67%) and 41 (28%) patients presented with transient respiratory motion after administration of gadoxetate and gadoterate, respectively. The mean duration from start to acme of the respiratory episode was similar (p = 0.4) between gadoxetate (6.0 s) and gadoterate (5.6 s). Its mean onset in reference to contrast arrival in the right ventricle differed significantly (p < 0.001) between gadoxetate (15.3s) and gadoterate (1.8 s), analogously to peak inspiration timepoint in reference to the aortic enhancement arrival (gadoxetate: 0.9s after, gadoterate: 11.2 s before aortic enhancement, p < 0.001). CONCLUSIONS: The timepoint of occurrence of transient respiratory anomalies associated with gadoxetate disodium and gadoterate meglumine differs significantly between both contrast agents while the duration of the event remains similar. KEY POINTS: • Transient respiratory anomalies following the administration of gadoterate meglumine occurred during a time period usually not acquired in MR imaging. • Transient respiratory anomalies following the administration of gadoxetate disodium occurred around the initiation of arterial phase imaging. • The estimated duration of respiratory events was similar between both contrast agents.


Assuntos
Gadolínio DTPA , Compostos Organometálicos , Meios de Contraste , Humanos , Imageamento por Ressonância Magnética , Meglumina , Estudos Retrospectivos
16.
Sci Rep ; 11(1): 21731, 2021 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-34741037

RESUMO

Gadolinium-based contrast agents (GBCAs) have been used in clinical Magnetic Resonance Imaging (MRI) for more than 30 years. However, there is increasing evidence that their dissociation in vivo leads to long-term depositions of gadolinium ions in the human body. In vitro experiments provide critical insights into kinetics and thermodynamic equilibria of underlying processes, which give hints towards the in vivo situation. We developed a time-resolved MRI relaxometry-based approach that exploits distinct relaxivities of Gd3+ in different molecular environments. Its applicability to quantify the transmetallation of GBCAs, the binding of Gd3+ to competing chelators, and the combined transchelation process is demonstrated. Exemplarily, the approach is applied to investigate two representative GBCAs in the presence of Zn2+ and heparin, which is used as a model for a macromolecular and physiologically occurring chelator. Opposing indirect impacts of heparin on increasing the kinetic stability but reducing the thermodynamic stability of GBCAs are observed. The relaxivity of resulting Gd-heparin complexes is shown to be essentially increased compared to that of the parent GBCAs so that they might be one explanation for observed long-term MRI signal enhancement in vivo. In forthcoming studies, the presented method could help to identify the most potent Gd-complexing macromolecular species.


Assuntos
Gadolínio DTPA/farmacocinética , Gadolínio/metabolismo , Heparina/metabolismo , Imageamento por Ressonância Magnética/métodos , Meglumina/farmacocinética , Compostos Organometálicos/farmacocinética , Quelantes/metabolismo , Humanos , Zinco/metabolismo
17.
Cells ; 10(10)2021 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-34685713

RESUMO

Fat accumulation (steatosis) in ballooned hepatocytes alters the expression of membrane transporters in Zucker fatty (fa/fa) rats. The aim of the study was to quantify the functions of these transporters and their impact on hepatocyte concentrations using a clinical hepatobiliary contrast agent (Gadobenate dimeglumine, BOPTA) for liver imaging. In isolated and perfused rat livers, we quantified BOPTA accumulation and decay profiles in fa/+ (normal) and fa/fa hepatocytes by placing a gamma counter over livers. Profiles of BOPTA accumulation and decay in hepatocytes were analysed with nonlinear regressions to characterise BOPTA influx and efflux across hepatocyte transporters. At the end of the accumulation period, BOPTA hepatocyte concentrations and influx clearances were not significantly different in fa/+ and fa/fa livers. In contrast, bile clearance was significantly lower in fatty hepatocytes while efflux clearance back to sinusoids compensated the low efflux into canaliculi. The time when BOPTA cellular efflux impacts the accumulation profile of hepatocyte concentrations was slightly delayed (2 min) by steatosis, anticipating a delayed emptying of hepatocytes. The experimental model is useful for quantifying the functions of hepatocyte transporters in liver diseases.


Assuntos
Fígado Gorduroso/metabolismo , Fígado Gorduroso/patologia , Hepatócitos/metabolismo , Hepatócitos/patologia , Proteínas de Membrana Transportadoras/metabolismo , Obesidade/metabolismo , Obesidade/patologia , Animais , Ácidos e Sais Biliares/metabolismo , Canalículos Biliares/efeitos dos fármacos , Canalículos Biliares/metabolismo , Hepatócitos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Meglumina/análogos & derivados , Meglumina/farmacocinética , Meglumina/farmacologia , Compostos Organometálicos/farmacocinética , Compostos Organometálicos/farmacologia , Perfusão , Ratos , Ratos Zucker , Reologia/efeitos dos fármacos
18.
Cardiovasc Diabetol ; 20(1): 215, 2021 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-34696783

RESUMO

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a major risk factor for coronary artery disease and myocardial infarction (MI). The interaction of diabetic cardiomyopathy and MI scars on myocardial deformation in T2DM patients is unclear. Therefore, we aimed to evaluate myocardial deformation using cardiac magnetic resonance (CMR) in T2DM patients with previous MI and investigated the influence of myocardial scar on left ventricular (LV) deformation. METHODS: Overall, 202 T2DM patients, including 46 with MI (T2DM(MI+)) and 156 without MI (T2DM(MI-)), and 59 normal controls who underwent CMR scans were included. Myocardial scars were assessed by late gadolinium enhancement. LV function and deformation, including LV global function index, LV global peak strain (PS), peak systolic strain rate (PSSR), and peak diastolic strain rate (PDSR), were compared among these groups. Correlation and multivariate linear regression analyses were used to investigate the relationship between myocardial scars and LV deformation. RESULTS: Decreases were observed in LV function and LV global PS, PSSR, and PDSR in the T2DM(MI+) group compared with those of the other groups. Reduced LV deformation (p < 0.017) was observed in the T2DM(MI+) group with anterior wall infarction. The increased total LV infarct extent and infarct mass of LV were related to decreased LV global PS (radial, circumferential, and longitudinal directions; p < 0.01) and LV global PSSR (radial and circumferential directions, p < 0.02). Multivariate analysis demonstrated that NYHA functional class and total LV infarct extent were independently associated with LV global radial PS (ß = - 0.400 and ß = - 0.446, respectively, all p < 0.01; model R2 = 0.37) and circumferential PS (ß = 0.339 and ß = 0.530, respectively, all p < 0.01; model R2 = 0.41), LV anterior wall infarction was independently associated with LV global longitudinal PS (ß = 0.398, p = 0.006). CONCLUSIONS: The myocardial scarring size in T2DM patients after MI is negatively correlated with LV global PS and PSSR, particularly in the circumferential direction. Additionally, different MI regions have different effects on the reduction of LV deformation, and relevant clinical evaluations should be strengthened.


Assuntos
Meios de Contraste , Diabetes Mellitus Tipo 2/complicações , Cardiomiopatias Diabéticas/diagnóstico por imagem , Imagem Cinética por Ressonância Magnética , Meglumina/análogos & derivados , Infarto do Miocárdio/diagnóstico por imagem , Miocárdio/patologia , Compostos Organometálicos , Função Ventricular Esquerda , Adulto , Idoso , Diabetes Mellitus Tipo 2/diagnóstico , Cardiomiopatias Diabéticas/etiologia , Cardiomiopatias Diabéticas/patologia , Cardiomiopatias Diabéticas/fisiopatologia , Feminino , Fatores de Risco de Doenças Cardíacas , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Medição de Risco
19.
Cell ; 184(20): 5138-5150.e12, 2021 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-34496225

RESUMO

Many transient receptor potential (TRP) channels respond to diverse stimuli and conditionally conduct small and large cations. Such functional plasticity is presumably enabled by a uniquely dynamic ion selectivity filter that is regulated by physiological agents. What is currently missing is a "photo series" of intermediate structural states that directly address this hypothesis and reveal specific mechanisms behind such dynamic channel regulation. Here, we exploit cryoelectron microscopy (cryo-EM) to visualize conformational transitions of the capsaicin receptor, TRPV1, as a model to understand how dynamic transitions of the selectivity filter in response to algogenic agents, including protons, vanilloid agonists, and peptide toxins, permit permeation by small and large organic cations. These structures also reveal mechanisms governing ligand binding substates, as well as allosteric coupling between key sites that are proximal to the selectivity filter and cytoplasmic gate. These insights suggest a general framework for understanding how TRP channels function as polymodal signal integrators.


Assuntos
Canais de Cátion TRPV/química , Canais de Cátion TRPV/metabolismo , Regulação Alostérica , Permeabilidade da Membrana Celular/efeitos dos fármacos , Microscopia Crioeletrônica , Diterpenos/farmacologia , Células HEK293 , Humanos , Ativação do Canal Iônico , Lipídeos/química , Meglumina/farmacologia , Modelos Moleculares , Ligação Proteica , Conformação Proteica , Prótons , Canais de Cátion TRPV/agonistas
20.
Int J Mol Sci ; 22(16)2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34445497

RESUMO

Membrane proteins responsible for transporting magnetic resonance (MR) and fluorescent contrast agents are of particular importance because they are potential reporter proteins in noninvasive molecular imaging. Gadobenate dimeglumine (Gd-BOPTA), a liver-specific MR contrast agent, has been used globally for more than 10 years. However, the corresponding molecular transportation mechanism has not been validated. We previously reported that the organic anion transporting polypeptide (OATP) 1B3 has an uptake capability for both MR agents (Gd-EOB-DTPA) and indocyanine green (ICG), a clinically available near-infrared (NIR) fluorescent dye. This study further evaluated OATP1B1, another polypeptide of the OATP family, to determine its reporter capability. In the OATP1B1 transfected 293T transient expression model, both Gd-BOPTA and Gd-EOB-DTPA uptake were confirmed through 1.5 T MR imaging. In the constant OAPT1B1 and OATP1B3 expression model in the HT-1080 cell line, both HT-1080-OAPT1B1 and HT-1080-OATP1B3 were observed to ingest Gd-BOPTA and Gd-EOB-DTPA. Lastly, we validated the ICG uptake capability of both OATP1B1 and OATP1B3. OAPT1B3 exhibited a superior ICG uptake capability to that of OAPT1B1. We conclude that OATP1B1 is a potential reporter for dual MR and NIR fluorescent molecular imaging, especially in conjunction with Gd-BOPTA.


Assuntos
Gadolínio DTPA/química , Transportador 1 de Ânion Orgânico Específico do Fígado/metabolismo , Meglumina/análogos & derivados , Imagem Óptica/métodos , Compostos Organometálicos/química , Genes Reporter , Células HEK293 , Humanos , Transportador 1 de Ânion Orgânico Específico do Fígado/química , Transportador 1 de Ânion Orgânico Específico do Fígado/genética , Imageamento por Ressonância Magnética , Meglumina/química , Imagem Molecular , Membro 1B3 da Família de Transportadores de Ânion Orgânico Carreador de Soluto/química , Membro 1B3 da Família de Transportadores de Ânion Orgânico Carreador de Soluto/genética , Membro 1B3 da Família de Transportadores de Ânion Orgânico Carreador de Soluto/metabolismo
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