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1.
Medicine (Baltimore) ; 100(37): e27044, 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34664829

RESUMO

ABSTRACT: The purpose of this retrospective study was to explore the advantages of computed tomography (CT) nano-contrast agent in tumor diagnosis.A total of 100 patients with malignant tumor who were diagnosed in Shaanxi Province Public Hospital between January 2018 and January 2019 were included in this retrospective study. They were randomly divided into observation and control groups with 50 patients in each group. The patients in the observation group used new type of nano-contrast agent for examination, and the patients in the control group used traditional iohexol contrast agent for examination. The detection rate, misdiagnosis rate, and incidence of adverse reactions were observed. In addition, single photon emission computed tomography or CT scan was performed on patients to observe the radioactive concentration.The detection rate was 100% in the observation group and 84% in the control group, and the difference between the 2 groups was statistically significant (χ2 = 8.763, P = .001). The incidence of adverse reactions was 2% in the observation group and 30% in the control group, and the difference between the 2 groups was significantly different (χ2 = 12.683, P = .000). The radioactive concentration in the observation group was markedly higher than that in the control group (t = 19.692, P = .001).The use of CT nano-contrast agent in tumor diagnosis had higher detection rate of tumor and radioactive concentration, and it had lower misdiagnosis rate and adverse reaction rate than traditional iohexol contrast agent.


Assuntos
Neoplasias/diagnóstico por imagem , Neoplasias/diagnóstico , Tomografia Computadorizada por Raios X/normas , China , Meios de Contraste/farmacologia , Meios de Contraste/uso terapêutico , Humanos , Neoplasias/classificação , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Tomografia Computadorizada por Raios X/estatística & dados numéricos
2.
Molecules ; 26(15)2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34361743

RESUMO

While investigating the possible synergistic effect of the conventional anticancer therapies, which, taken individually, are often ineffective against critical tumors, such as central nervous system (CNS) ones, the design of a theranostic nanovector able to carry and deliver chemotherapy drugs and magnetic hyperthermic agents to the target radiosensitizers (oxygen) was pursued. Alongside the original formulation of polymeric biodegradable oxygen-loaded nanostructures, their properties were fine-tuned to optimize their ability to conjugate therapeutic doses of drugs (doxorubicin) or antitumoral natural substances (curcumin). Oxygen-loaded nanostructures (diameter = 251 ± 13 nm, ζ potential = -29 ± 5 mV) were finally decorated with superparamagnetic iron oxide nanoparticles (SPIONs, diameter = 18 ± 3 nm, ζ potential = 14 ± 4 mV), producing stable, effective and non-agglomerating magnetic nanovectors (diameter = 279 ± 17 nm, ζ potential = -18 ± 7 mV), which could potentially target the tumoral tissues under magnetic driving and are monitorable either by US or MRI imaging.


Assuntos
Antibióticos Antineoplásicos/farmacologia , Quitosana/química , Hipertermia Induzida/métodos , Nanopartículas de Magnetita/química , Radiossensibilizantes/farmacologia , Nanomedicina Teranóstica/métodos , Antibióticos Antineoplásicos/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Meios de Contraste/síntese química , Meios de Contraste/farmacologia , Curcumina/química , Curcumina/farmacologia , Sulfato de Dextrana/química , Doxorrubicina/química , Doxorrubicina/farmacologia , Composição de Medicamentos/métodos , Humanos , Cinética , Nanopartículas de Magnetita/ultraestrutura , Oxigênio/química , Oxigênio/farmacologia , Radiossensibilizantes/síntese química
3.
Radiology ; 301(2): 409-416, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34463554

RESUMO

Background Recent studies showing gadolinium deposition in multiple organs have raised concerns about the safety of gadolinium-based contrast agents (GBCAs). Purpose To explore whether gadolinium deposition in brain structures will cause any motor or behavioral alterations. Materials and Methods This study was performed from July 2019 to December 2020. Groups of 17 female BALB/c mice were each repeatedly injected with phosphate-buffered saline (control group, group A), a macrocyclic GBCA (group B), or a linear GBCA (group C) for 8 weeks (5 mmol per kilogram of bodyweight per week for GBCAs). Brain MRI studies were performed every other week to observe the signal intensity change caused by the gadolinium deposition. After the injection period, rotarod performance test, open field test, elevated plus-maze test, light-dark anxiety test, locomotor activity assessment test, passive avoidance memory test, Y-maze test, and forced swimming test were performed to assess the locomotor abilities, anxiety level, and memory. Among-group differences were compared by using one-way or two-way factorial analysis of variance with Tukey post hoc testing or Dunnett post hoc testing. Results Gadolinium deposition in the bilateral deep cerebellar nuclei was confirmed with MRI only in mice injected with a linear GBCA. At 8 weeks, contrast ratio of group C (0.11; 95% CI: 0.10, 0.12) was higher than that of group A (-2.1 × 10-3; 95% CI: -0.011, 7.5 × 10-3; P < .001) and group B (2.7 × 10-4; 95% CI: -8.2 × 10-3, 8.7 × 10-3; P < .001). Behavioral analyses showed that locomotor abilities, anxiety level, and long-term or short-term memory were not different in mice injected with linear or macrocyclic GBCAs. Conclusion No motor or behavioral alterations were observed in mice with brain gadolinium deposition. Also, the findings support the safety of macrocyclic gadolinium-based contrast agents. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Chen in this issue.


Assuntos
Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Meios de Contraste/farmacologia , Gadolínio/farmacologia , Atividade Motora/efeitos dos fármacos , Animais , Encéfalo/diagnóstico por imagem , Modelos Animais de Doenças , Feminino , Imageamento por Ressonância Magnética/métodos , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C
4.
Medicine (Baltimore) ; 100(27): e26489, 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34232180

RESUMO

ABSTRACT: To analyze the correlation between quantitative contrast-enhanced ultrasonography (CEUS) parameters and angiogenesis in primary small hepatocellular carcinoma (sHCC) with varying degrees of differentiation.According to varying degrees of differentiation, a total of 90 primary sHCC patients admitted to our hospital from July 2018 to January 2020 were selected and divided into poorly differentiated group (24 cases), moderately differentiated group (31 cases), and highly differentiated group (35 cases). All patients received real-time CEUS before surgery. The tumor diameter, microvascular morphology, grading of color blood flow, contrast-enhanced performance in different phases, quantitative CEUS parameters, expression of angiogenesis-related genes, and microvessel density (MVD) were compared among the 3 groups. The correlation between quantitative parameters of CEUS and angiogenesis indexes was analyzed by Spearman rank correlation analysis.Spearman rank correlation analysis showed that vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), epidermal growth factor receptor (EGFR), and angiopoietin-2 (Ang-2) expression and MVD were negatively correlated with the time to peak (TTP), wash-out time, and peak accelerating time (PAT) (r < 0, P < .05), and were positively correlated with enhancing slope rate (ESR) and peak intensity increasing rate (PIIR) (r > 0, P < .05).CEUS is able to identify varying degrees of differentiation in primary sHCC, and the quantitative CEUS parameters are closely related to angiogenesis.


Assuntos
Carcinoma Hepatocelular/diagnóstico , Meios de Contraste/farmacologia , Neoplasias Hepáticas/diagnóstico , Microvasos/diagnóstico por imagem , Gradação de Tumores , Ultrassonografia Doppler em Cores/métodos , Adulto , Idoso , Carcinoma Hepatocelular/irrigação sanguínea , Feminino , Humanos , Neoplasias Hepáticas/irrigação sanguínea , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
5.
Open Heart ; 8(1)2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34099530

RESUMO

OBJECTIVE: In a proof-of-concept study, to quantify myocardial viability in patients with acute myocardial infarction using manganese-enhanced MRI (MEMRI), a measure of intracellular calcium handling. METHODS: Healthy volunteers (n=20) and patients with ST-elevation myocardial infarction (n=20) underwent late gadolinium enhancement (LGE) using gadobutrol and MEMRI using manganese dipyridoxyl diphosphate. Patients were scanned ≤7 days after reperfusion and rescanned after 3 months. Differential manganese uptake was described using a two-compartment model. RESULTS: After manganese administration, healthy control and remote non-infarcted myocardium showed a sustained 25% reduction in T1 values (mean reductions, 288±34 and 281±12 ms). Infarcted myocardium demonstrated less T1 shortening than healthy control or remote myocardium (1157±74 vs 859±36 and 835±28 ms; both p<0.0001) with intermediate T1 values (1007±31 ms) in peri-infarct regions. Compared with LGE, MEMRI was more sensitive in detecting dysfunctional myocardium (dysfunctional fraction 40.5±11.9 vs 34.9%±13.9%; p=0.02) and tracked more closely with abnormal wall motion (r2=0.72 vs 0.55; p<0.0001). Kinetic modelling showed reduced myocardial manganese influx between remote, peri-infarct and infarct regions, enabling absolute discrimination of infarcted myocardium. After 3 months, manganese uptake increased in peri-infarct regions (16.5±3.5 vs 22.8±3.5 mL/100 g/min, p<0.0001), but not the remote (23.3±2.8 vs 23.0±3.2 mL/100 g/min, p=0.8) or infarcted (11.5±3.7 vs 14.0±1.2 mL/100 g/min, p>0.1) myocardium. CONCLUSIONS: Through visualisation of intracellular calcium handling, MEMRI accurately differentiates infarcted, stunned and viable myocardium, and correlates with myocardial dysfunction better than LGE. MEMRI holds major promise in directly assessing myocardial viability, function and calcium handling across a range of cardiac diseases. TRIAL REGISTRATION NUMBERS: NCT03607669; EudraCT number 2016-003782-25.


Assuntos
Ácido Edético/análogos & derivados , Imagem Cinética por Ressonância Magnética/métodos , Miocárdio Atordoado/diagnóstico , Miocárdio/patologia , Fosfato de Piridoxal/análogos & derivados , Adulto , Cálcio/metabolismo , Meios de Contraste/farmacologia , Ácido Edético/farmacologia , Feminino , Seguimentos , Humanos , Espaço Intracelular/metabolismo , Masculino , Manganês , Pessoa de Meia-Idade , Miocárdio Atordoado/metabolismo , Miocárdio/metabolismo , Fosfato de Piridoxal/farmacologia , Estudos Retrospectivos
6.
Sci Rep ; 11(1): 13446, 2021 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-34188103

RESUMO

Electrochemotherapy with bleomycin (ECT BLM) is an effective antitumor treatment already used in clinical oncology. However, ECT alone is still considered a local antitumor therapy because it cannot induce systemic immunity. When combined with adjuvant gene electrotransfer of plasmid DNA encoding IL-12 (GET pIL-12), the combined therapy leads to a systemic effect on untreated tumors and distant metastases. Although the antitumor efficacy of both therapies alone or in combination has been demonstrated at both preclinical and clinical levels, data on the predictors of efficacy of the treatments are still lacking. Herein, we evaluated the results of dynamic contrast-enhanced ultrasound (DCE-US) as a predictive factor for ECT BLM and GET pIL-12 in murine melanoma. Melanoma B16F10 tumors grown in female C57Bl/6NCrl mice were treated with GET pIL-12 and ECT BLM. Immediately after therapy, 6 h and 1, 3, 7 and 10 days later, tumors were examined by DCE-US. Statistical analysis was performed to inspect the correlation between tumor doubling time (DT) and DCE-US measurements using semilinear regression models and Bland-Altman plots. Therapeutic groups in which DCE-US showed reduced tumor perfusion had longer tumor DTs. It was confirmed that the DCE-US parameter peak enhancement (PE), reflecting relative blood volume, had predictive value for the outcome of therapy: larger PE correlated with shorter DT. In addition, perfusion heterogeneity was also associated with outcome: tumors that had more heterogeneous perfusion had faster growth, i.e., shorter DTs. This study demonstrates that DCE-US can be used as a method to predict the efficacy of electroporation-based treatment.


Assuntos
Meios de Contraste/farmacologia , Eletroquimioterapia , Técnicas de Transferência de Genes , Interleucina-12 , Melanoma Experimental , Plasmídeos , Animais , Feminino , Interleucina-12/genética , Interleucina-12/imunologia , Melanoma Experimental/diagnóstico por imagem , Melanoma Experimental/genética , Melanoma Experimental/imunologia , Melanoma Experimental/terapia , Camundongos , Perfusão , Plasmídeos/genética , Plasmídeos/imunologia , Ultrassonografia
7.
Int J Comput Assist Radiol Surg ; 16(6): 979-988, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33966155

RESUMO

PURPOSE: CESM (contrast-enhanced spectral mammography) is an efficient tool for detecting breast cancer because of its image characteristics. However, among most deep learning-based methods for breast cancer classification, few models can integrate both its multiview and multimodal features. To effectively utilize the image features of CESM and thus help physicians to improve the accuracy of diagnosis, we propose a multiview multimodal network (MVMM-Net). METHODS: The experiment is carried out to evaluate the in-house CESM images dataset taken from 95 patients aged 21-74 years with 760 images. The framework consists of three main stages: the input of the model, image feature extraction, and image classification. The first stage is to preprocess the CESM to utilize its multiview and multimodal features effectively. In the feature extraction stage, a deep learning-based network is used to extract CESM images features. The last stage is to integrate different features for classification using the MVMM-Net model. RESULTS: According to the experimental results, the proposed method based on the Res2Net50 framework achieves an accuracy of 96.591%, sensitivity of 96.396%, specificity of 96.350%, precision of 96.833%, F1_score of 0.966, and AUC of 0.966 on the test set. Comparative experiments illustrate that the classification performance of the model can be improved by using multiview multimodal features. CONCLUSION: We proposed a deep learning classification model that combines multiple features of CESM. The results of the experiment indicate that our method is more precise than the state-of-the-art methods and produces accurate results for the classification of CESM images.


Assuntos
Neoplasias da Mama/diagnóstico , Mama/diagnóstico por imagem , Meios de Contraste/farmacologia , Mamografia/métodos , Imagem Multimodal/métodos , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Adulto Jovem
8.
Khirurgiia (Mosk) ; (6. Vyp. 2): 89-94, 2021.
Artigo em Russo | MEDLINE | ID: mdl-34032794

RESUMO

Chronic liver disease is a serious worldwide problem because its progression is accompanied by liver fibrosis and cirrhosis at the terminal stages. Primary diagnosis and dynamic assessment of liver fibrosis are essential to determine the prognosis of disease and optimal treatment strategy. Long-term world experience in the use of gadoxetic acid (primovist, eovist) for diagnosis of liver diseases confirms its hepatotropic properties. Thus, magnetic resonance imaging (MRI) in hepatobiliary phase of contrast enhancement is valuable for differential diagnosis of focal liver lesions and assessment of liver structure and fibrotic changes. This review is devoted to the most common methods of contrast-enhanced MRI for assessment of liver function and correlation between severity of diffuse structural liver changes and gadoxetic acid accumulation in liver parenchyma. There is no a single method for MRI-based analysis of liver function that is confirmed by active researches in this direction. It was found that liver biopsy can by unnecessary in some cases if contrast-enhanced MRI with gadoxetic acid is available. The advantage of gadoxetic acid is also elimination properties. Indeed, biliary excretion ensures T1-weighted MR-cholangiography for additional assessment of patency, function and anatomy of the bile ducts. However, there are still several questions in this area that necessitates further research.


Assuntos
Meios de Contraste , Neoplasias Hepáticas , Meios de Contraste/farmacologia , Gadolínio DTPA , Humanos , Fígado/diagnóstico por imagem , Cirrose Hepática , Imageamento por Ressonância Magnética , Estudos Retrospectivos , Sensibilidade e Especificidade
9.
Int J Nanomedicine ; 16: 3105-3119, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33967577

RESUMO

Background: Photothermal therapy (PTT) has attracted considerable attention for cancer treatment as it is highly controllable and minimally invasive. Various multifunctional nanosystems have been fabricated in an "all-in-one" form to guide and enhance PTT by integrating imaging and therapeutic functions. However, the complex fabrication of nanosystems and their high cost limit its clinical translation. Materials and Methods: Herein, a high efficient "one-for-all" nanodroplet with a simple composition but owning multiple capabilities was developed to achieve ultrasound (US) imaging-guided and cavitation-enhanced PTT. Perfluoropentane (PFP) nanodroplet with a polypyrrole (PPy) shell (PFP@PPy nanodroplet) was synthesized via ultrasonic emulsification and in situ oxidative polymerization. After characterization of the morphology, its photothermal effect, phase transition performance, as well as its capabilities of enhancing US imaging and acoustic cavitation were examined. Moreover, the antitumor efficacy of the combined therapy with PTT and acoustic cavitation via the PFP@PPy nanodroplets was studied both in vitro and in vivo. Results: The nanodroplets exhibited good stability, high biocompatibility, broad optical absorption over the visible and near-infrared (NIR) range, excellent photothermal conversion with an efficiency of 60.1% and activatable liquid-gas phase transition performance. Upon NIR laser and US irradiation, the phase transition of PFP cores into microbubbles significantly enhanced US imaging and acoustic cavitation both in vitro and in vivo. More importantly, the acoustic cavitation enhanced significantly the antitumor efficacy of PTT as compared to PTT alone thanks to the cavitation-mediated cell destruction, which demonstrated a substantial increase in cell detachment, 81.1% cell death in vitro and 99.5% tumor inhibition in vivo. Conclusion: The PFP@PPy nanodroplet as a "one-for-all" theranostic agent achieved highly efficient US imaging-guided and cavitation-enhanced cancer therapy, and has considerable potential to provide cancer theranostics in the future.


Assuntos
Meios de Contraste/química , Nanoestruturas/química , Neoplasias Experimentais/diagnóstico por imagem , Terapia Fototérmica/métodos , Ultrassonografia/métodos , Animais , Meios de Contraste/farmacologia , Feminino , Fluorcarbonetos/química , Células HeLa , Humanos , Camundongos Endogâmicos BALB C , Microbolhas , Nanoestruturas/uso terapêutico , Neoplasias/terapia , Neoplasias Experimentais/terapia , Transição de Fase , Técnicas Fotoacústicas/métodos , Polímeros/química , Pirróis/química , Ensaios Antitumorais Modelo de Xenoenxerto
10.
Sci Rep ; 11(1): 9753, 2021 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-33963211

RESUMO

Radiolabeled magnetic nanoparticles are promising candidates as dual-modality-contrast-agents (DMCA) for diagnostic applications. The immunocompatibility of a new DMCA is a prerequisite for subsequent in vivo applications. Here, a new DMCA, namely Fe3O4 nanoparticles radiolabeled with 68Ga, is subjected to immunocompatibility tests both in vitro and in vivo. The in vitro immunocompatibility of the DMCA relied on incubation with donated human WBCs and PLTs (five healthy individuals). Optical microscopy (OM) and atomic force microscopy (AFM) were employed for the investigation of the morphological characteristics of WBCs and PLTs. A standard hematology analyzer (HA) provided information on complete blood count. The in vivo immunocompatibility of the DMCA was assessed through its biodistribution among the basic organs of the mononuclear phagocyte system in normal and immunodeficient mice (nine in each group). In addition, Magnetic Resonance Imaging (MRI) data were acquired in normal mice (three). The combined OM, AFM and HA in vitro data showed that although the DMCA promoted noticeable activation of WBCs and PLTs, neither degradation nor clustering were observed. The in vivo data showed no difference of the DMCA biodistribution between the normal and immunodeficient mice, while the MRI data prove the efficacy of the particular DMCA when compared to the non-radiolabeled, parent CA. The combined in vitro and in vivo data prove that the particular DMCA is a promising candidate for future in vivo applications.


Assuntos
Meios de Contraste , Radioisótopos de Gálio , Leucócitos/metabolismo , Imageamento por Ressonância Magnética , Nanopartículas de Magnetita , Teste de Materiais , Meios de Contraste/química , Meios de Contraste/farmacologia , Radioisótopos de Gálio/química , Radioisótopos de Gálio/farmacologia , Humanos , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/uso terapêutico
11.
J Alzheimers Dis ; 82(2): 541-560, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34057079

RESUMO

BACKGROUND: The roles of amyloid-ß and tau in the degenerative process of Alzheimer's disease (AD) remain uncertain. [18F]AV-45 and [18F]AV-1451 PET quantify amyloid-ß and tau pathology, respectively, while diffusion tractography enables detection of their microstructural consequences. OBJECTIVE: Examine the impact of amyloid-ß and tau pathology on the structural connectome and cognition, in mild cognitive impairment (MCI) and AD. METHODS: Combined [18F]AV-45 and [18F]AV-1451 PET, diffusion tractography, and cognitive assessment in 28 controls, 32 MCI, and 26 AD patients. RESULTS: Hippocampal connectivity was reduced to the thalami, right lateral orbitofrontal, and right amygdala in MCI; alongside the insula, posterior cingulate, right entorhinal, and numerous cortical regions in AD (all p < 0.05). Hippocampal strength inversely correlated with [18F]AV-1451 SUVr in MCI (r = -0.55, p = 0.049) and AD (r = -0.57, p = 0.046), while reductions in hippocampal connectivity to ipsilateral brain regions correlated with increased [18F]AV-45 SUVr in those same regions in MCI (r = -0.33, p = 0.003) and AD (r = -0.31, p = 0.006). Cognitive scores correlated with connectivity of the right temporal pole in MCI (r = -0.60, p = 0.035) and left hippocampus in AD (r = 0.69, p = 0.024). Clinical Dementia Rating Scale scores correlated with [18F]AV-1451 SUVr in multiple areas reflecting Braak stages I-IV, including the right (r = 0.65, p = 0.004) entorhinal cortex in MCI; and Braak stages III-VI, including the right (r = 0.062, p = 0.009) parahippocampal gyrus in AD. CONCLUSION: Reductions in hippocampal connectivity predominate in the AD connectome, correlating with hippocampal tau in MCI and AD, and with amyloid-ß in the target regions of those connections. Cognitive scores correlate with microstructural changes and reflect the accumulation of tau pathology.


Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides/metabolismo , Disfunção Cognitiva , Conectoma/métodos , Proteínas tau/metabolismo , Idoso , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/metabolismo , Doença de Alzheimer/psicologia , Carbolinas/farmacologia , Cognição/fisiologia , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/fisiopatologia , Meios de Contraste/farmacologia , Correlação de Dados , Imagem de Tensor de Difusão/métodos , Feminino , Hipocampo/diagnóstico por imagem , Hipocampo/patologia , Humanos , Masculino , Testes de Estado Mental e Demência , Tomografia por Emissão de Pósitrons
12.
Ophthalmology ; 128(11): 1592-1603, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-33989683

RESUMO

PURPOSE: To evaluate pneumatic vitreolysis (PVL) in eyes with vitreomacular traction (VMT) with and without full-thickness macular hole (FTMH). DESIGN: Two multicenter (28 sites) studies: a randomized clinical trial comparing PVL with observation (sham injection) for VMT without FTMH (Protocol AG) and a single-arm study assessing PVL for FTMH (Protocol AH). PARTICIPANTS: Participants were adults with central VMT (vitreomacular adhesion was ≤3000 µm). In Protocol AG, visual acuity (VA) was 20/32 to 20/400. In Protocol AH, eyes had a FTMH (≤250 µm at the narrowest point) and VA of 20/25 to 20/400. METHODS: Pneumatic vitreolysis using perfluoropropane (C3F8) gas. MAIN OUTCOME MEASURES: Central VMT release at 24 weeks (Protocol AG) and FTMH closure at 8 weeks (Protocol AH). RESULTS: From October 2018 through February 2020, 46 participants were enrolled in Protocol AG, and 35 were enrolled in Protocol AH. Higher than expected rates of retinal detachment and tear resulted in early termination of both protocols. Combining studies, 7 of 59 eyes (12% [95% CI, 6%-23%]; 2 eyes in Protocol AG, 5 eyes in Protocol AH) that received PVL developed rhegmatogenous retinal detachment (n = 6) or retinal tear (n = 1). At 24 weeks in Protocol AG, 18 of 23 eyes in the PVL group (78%) versus 2 of 22 eyes in the sham group (9%) achieved central VMT release without rescue vitrectomy (adjusted risk difference, 66% [95% CI, 44%-88%]; P< 0.001). The mean change in VA from baseline at 24 weeks was 6.7 letters in the PVL group and 6.1 letters in the sham group (adjusted difference, -0.8 [95% CI, -6.1 to 4.5]; P = 0.77). In Protocol AH, 10 of 35 eyes (29% [95% CI, 16%-45%]) achieved FTMH closure without rescue vitrectomy at 8 weeks. The mean change in VA from baseline at 8 weeks was -1.5 letters (95% CI, -10.3 to 7.3 letters). CONCLUSIONS: In most eyes with VMT, PVL induced hyaloid release. In eyes with FTMH, PVL resulted in hole closure in approximately one third of eyes. These studies were terminated early because of safety concerns related to retinal detachments and retinal tears.


Assuntos
Fluorcarbonetos/farmacologia , Acuidade Visual , Vitrectomia/métodos , Corpo Vítreo/cirurgia , Descolamento do Vítreo/cirurgia , Idoso , Meios de Contraste/farmacologia , Feminino , Seguimentos , Humanos , Injeções Intravítreas , Masculino , Perfurações Retinianas/diagnóstico , Perfurações Retinianas/cirurgia , Estudos Retrospectivos , Tomografia de Coerência Óptica , Corpo Vítreo/diagnóstico por imagem , Descolamento do Vítreo/diagnóstico
13.
J Med Chem ; 64(9): 5874-5885, 2021 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-33945286

RESUMO

Myeloperoxidase (MPO) is a key component of innate immunity but can damage tissues when secreted abnormally. We developed a new generation of a highly efficient MPO-activatable MRI probe (heMAMP) to report MPO activity. heMAMP has improved Gd stability compared to bis-5-HT-Gd-DTPA (MPO-Gd) and demonstrates no significant cytotoxicity. Importantly, heMAMP is more efficiently activated by MPO compared to MPO-Gd, 5HT-DOTA(Gd), and 5HT-DOTAGA-Gd. Molecular docking simulations revealed that heMAMP has increased rigidity via hydrogen bonding intramolecularly and improved binding affinity to the active site of MPO. In animals with subcutaneous inflammation, activated heMAMP showed a 2-3-fold increased contrast-to-noise ratio (CNR) compared to activated MPO-Gd and 4-10 times higher CNR compared to conventional DOTA-Gd. This increased efficacy was further confirmed in a model of unstable atherosclerotic plaque where heMAMP demonstrated a comparable signal increase and responsiveness to MPO inhibition at a 3-fold lower dosage compared to MPO-Gd, further underscoring heMAMP as a potential translational candidate.


Assuntos
Meios de Contraste/química , Imageamento por Ressonância Magnética , Peroxidase/metabolismo , Animais , Aterosclerose/diagnóstico por imagem , Sítios de Ligação , Cálcio/química , Cálcio/metabolismo , Domínio Catalítico , Sobrevivência Celular/efeitos dos fármacos , Meios de Contraste/metabolismo , Meios de Contraste/farmacologia , Modelos Animais de Doenças , Desenho de Fármacos , Feminino , Gadolínio DTPA/química , Gadolínio DTPA/metabolismo , Meia-Vida , Camundongos , Camundongos Endogâmicos BALB C , Peroxidase/química , Células RAW 264.7 , Razão Sinal-Ruído , Distribuição Tecidual , Zinco/química , Zinco/metabolismo
14.
Molecules ; 26(6)2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33808910

RESUMO

It is known that phenylboronic acid (PBA) can target tumor tissues by binding to sialic acid, a substrate overexpressed by cancer cells. This capability has previously been explored in the design of targeting diagnostic probes such as Gd- and 68Ga-DOTA-EN-PBA, two contrast agents for magnetic resonance imaging (MRI) and positron emission tomography (PET), respectively, whose potential has already been demonstrated through in vivo experiments. In addition to its high resolution, the intrinsic low sensitivity of MRI stimulates the search for more effective contrast agents, which, in the case of small-molecular probes, basically narrows down to either increased tumbling time of the entire molecule or elevated local concentration of the paramagnetic ions, both strategies resulting in enhanced relaxivity, and consequently, a higher MRI contrast. The latter strategy can be achieved by the design of multimeric GdIII complexes. Based on the monomeric PBA-containing probes described recently, herein, we report the synthesis and characterization of the dimeric analogues (GdIII-DOTA-EN)2-PBA and (GdIII-DOTA-EN)2F2PBA. The presence of two Gd ions in one molecule clearly contributes to the improved biological performance, as demonstrated by the relaxometric study and cell-binding investigations.


Assuntos
Ácidos Borônicos , Meios de Contraste , Imageamento por Ressonância Magnética , Melanoma Experimental , Animais , Ácidos Borônicos/síntese química , Ácidos Borônicos/química , Ácidos Borônicos/farmacologia , Linhagem Celular Tumoral , Meios de Contraste/síntese química , Meios de Contraste/química , Meios de Contraste/farmacologia , Melanoma Experimental/diagnóstico por imagem , Melanoma Experimental/metabolismo , Camundongos
15.
J Zoo Wildl Med ; 52(1): 320-326, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33827193

RESUMO

Hepatic veno-occlusive disease (VOD) is a significant cause of morbidity and mortality in captive cheetahs (Acinonyx jubatus), and the appearance of this disease in humans by computed tomography (CT) has been well described. Contrast-enhanced CT abdominal scans of cheetahs without evidence of hepatic disease (n = 5) were reviewed retrospectively to describe the normal appearance of cheetah livers as an aid to antemortem VOD diagnosis. Despite having no clinical signs, clinical pathology abnormalities, or hepatic biopsy histopathology supportive of VOD, all five cheetahs had at least one VOD consistent finding on CT. The results of this study suggest that given the progressive and potentially subclinical nature of VOD, CT could serve as a noninvasive screening tool and be used to monitor disease progression.


Assuntos
Acinonyx , Meios de Contraste/farmacologia , Fígado/diagnóstico por imagem , Tomografia Computadorizada por Raios X/veterinária , Animais , Animais de Zoológico , Feminino , Masculino , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos
16.
Indian Heart J ; 73(1): 49-55, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33714409

RESUMO

OBJECTIVE: This is a prospective study of patients with LVEF ≤40%, with the objective of correlating CV events to LGE detected and quantified by CMRI. METHODS: Heart Failure (HF) patients with LVEF <40% who underwent CMRI were included. LGE volume of ≥6% of the myocardial volume was considered significant. Data of appropriate ICD shocks, CV hospitalizations and mortality were recorded. RESULTS: There were 133 HF (72 ICM & 62 NIDCM) patients with a mean age of 54 ± 12 years, mean LVEF of 34 ± 6% and a follow up of 24 ± 3 months. Totally 46 CV events were recorded in 30 patients, 44 in LGE +ve & 2 in LGE -ve groups (HR 17.8, 95% CI-8.03-39.3, P = 0.000095). All the 7 deaths were in LGE +ve group. CV events were 22 (30.5%) in ICM group and 8 (13.1%) in NIDCM group (p = 0.03). All the 22 ICM patients and 6 of the 8 NIDCM with CV events were LGE +ve. The distribution of CV events amongst LGE +ve and LGE -ve were 35 vs 0 (ICM) and 9 vs 2 (NIDCM); p < 0.005.CV events in LVEF ≤ 30% group, were seen in 19 (47.5%) vs 1 (5.8%) in LGE +ve vs LGE -ve and no of events were 29 vs 1 (p = 0.003). In those with LVEF >30% the corresponding figures were 9 (22.5%) vs 1 (2.8%) and 15 vs 1 respectively (p = 0.02). CONCLUSION: Demonstration of significant LGE by CMRI indicates high risk occurrence of CV events (CV hospitalization, appropriate shocks and total mortality) in NIDCM & ICM patients with LVEF < 40%.


Assuntos
Insuficiência Cardíaca/diagnóstico , Imagem Cinética por Ressonância Magnética/métodos , Meglumina/farmacologia , Medição de Risco/métodos , Volume Sistólico/fisiologia , Disfunção Ventricular Esquerda/fisiopatologia , Função Ventricular Esquerda/fisiologia , Meios de Contraste/farmacologia , Feminino , Seguimentos , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/etiologia , Humanos , Incidência , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores de Tempo , Disfunção Ventricular Esquerda/complicações , Disfunção Ventricular Esquerda/diagnóstico
18.
J Neuroimaging ; 31(3): 602-608, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33783925

RESUMO

BACKGROUND AND PURPOSE: To determine whether cerebral adrenoleukodystrophy (cALD) or brain irradiation in patients with primary brain tumor affects T1-weighted imaging (T1WI) signal intensity (SI) of the dentate nucleus (DN) in a pediatric cohort who had received consecutive macrocyclic gadolinium-based contrast agent (mcGBCA) gadobutrol. METHODS: This study included 97 pediatric patients who underwent mcGBCA-enhanced MRI from 2010 to 2020 (29 children with primary brain tumors without brain radiation therapy [mcGBCA group-1], 33 children with primary brain tumors and radiation treatment [mcGBCA group-2], 35 children with cALD [mcGBCA group-3], and 97 sex-/age-matched control subjects [subgroups matched to each of the three subject groups] without GBCA administration). The DN-to-middle cerebellar peduncle (MCP) SI ratios on T1WI were then determined. A paired t-test was performed to compare SI ratios between children exposed to mcGBCA in each group and control subjects. The relationships between SI ratios and confounding variables were analyzed utilizing the Pearson correlation analysis. RESULTS: The DN-to-MCP SI ratio was significantly higher of mcGBCA group-2 (1.046±.071) or mcGBCA group-3 (.972±.038) than in the control group-2 (.983±.041, P<.001) and control group-3 (.937±.051, P = .002), respectively, but no significant difference of the SI ratio was noted between mcGBCA group-1 (.984±.032) and control-group-1 (.982±.035, P = .860). No significant correlation was noted between SI ratio values and the cumulative dose or number of mcGBCA administrations, age, or the elapsed time between the MRI examinations (all P>.05). CONCLUSIONS: Hyperintense T1WI signal in the DN may be seen in children with brain tumors undergoing brain irradiation, as well as in children with cALD.


Assuntos
Adrenoleucodistrofia/patologia , Neoplasias Encefálicas/radioterapia , Núcleos Cerebelares/diagnóstico por imagem , Meios de Contraste/farmacologia , Imageamento por Ressonância Magnética/métodos , Compostos Organometálicos/farmacologia , Adolescente , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Núcleos Cerebelares/fisiologia , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Estudos Retrospectivos
19.
Cardiovasc Intervent Radiol ; 44(7): 1089-1094, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33660064

RESUMO

PURPOSE: To evaluate the effect of cone-beam computed tomography (CBCT) on radiation exposure, procedure time, and contrast media (CM) use in prostatic artery embolization (PAE). MATERIALS AND METHODS: Seventy-eight patients were enrolled in this retrospective, single-center study. All patients received PAE without (group A; n = 39) or with (group B; n = 39) CBCT. Total dose-area product (DAPtotal; Gycm2), total entrance skin dose (ESDtotal; mGy), and total effective dose (EDtotal; mSv) were primary outcomes. Number of digital subtraction angiography (DSA) series, CM use, fluoroscopy time, and procedure time were secondary outcomes. PAE in group A was performed by a single radiologist with 15 years experience, PAE in group B was conducted by four radiologists with 4 to 6 years experience. RESULTS: For groups A vs. B, respectively, median (IQR): DAPtotal 236.94 (186.7) vs. 281.20 (214.47) Gycm2(p = 0.345); EDtotal 25.82 (20.35) vs. 39.84 (23.75) mSv (p = < 0.001); ESDtotal 2833 (2278) vs. 2563 (3040) mGy(p = 0.818); number of DSA series 25 (15) vs. 23 (10)(p = 0.164); CM use 65 (30) vs. 114 (40) mL(p = < 0.001); fluoroscopy time 23 (20) vs. 28 (25) min(p = 0.265), and procedure time 70 (40) vs.120 (40) min(p = < 0.001). Bilateral PAE was achieved in 33/39 (84.6%) group A and 32/39 (82.05%) group B(p = 0.761), all other patients received unilateral PAE. There were no significant differences between clinical parameters and origins of the prostatic arteries (PA) (p = 0.206-1.00). CONCLUSION: Operators with extensive expertise on PAE may not benefit from addition of CBCT to DSA runs, whereas for operators with less expertise, CBCT when used alongside with DSA runs increased the overall radiation exposure.


Assuntos
Angiografia Digital/métodos , Tomografia Computadorizada de Feixe Cônico/métodos , Meios de Contraste/farmacologia , Embolização Terapêutica/métodos , Hiperplasia Prostática/terapia , Idoso , Fluoroscopia , Humanos , Masculino , Hiperplasia Prostática/diagnóstico , Exposição à Radiação , Estudos Retrospectivos
20.
Cardiovasc Intervent Radiol ; 44(7): 1103-1108, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33709269

RESUMO

PURPOSE: To investigate if the detergent sclerosant sodium tetradecyl sulfate (STS) is deactivated by the lipid-based contrast agent ethiodised oil. METHOD: 3% STS was mixed with ethiodised oil and room air in a 2:1:4 ratio in two luer lock syringes and a three way connector and agitated to make foam (the Tessari technique) to replicate the clinical use of the products. The assay of STS in the mixture was assessed using the British Pharmacopoeia method. Briefly this is a manual titration method where the solution of STS is mixed with an indicator solution and titrated with hyamine solution of known concentration; the concentration of the STS can then be calculated with the titration results. To further mimic the clinical environment with the presence of blood, the effect of adding increasing amounts of albumin to the STS-ethiodised oil mixture was assessed. RESULTS: The assay of STS in the solution after mixing with ethiodised oil was 3% indicating that the ethiodised oil did not deactivate the STS. The addition of albumin to the STS-contrast mixture resulted in near linear neutralisation of the STS with increasing concentrations in the same quantities as with STS alone. CONCLUSIONS: The mixture of the lipid-based contrast agent ethiodised oil with the detergent sclerosant STS did not affect the availability of the sclerosant. The continued use of STS-ethiodised oil in the management of vascular malformations can be supported.


Assuntos
Óleo Etiodado/farmacologia , Escleroterapia/métodos , Tetradecilsulfato de Sódio/farmacologia , Malformações Vasculares/terapia , Meios de Contraste/farmacologia , Humanos , Soluções Esclerosantes/uso terapêutico , Seringas
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