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1.
Sci Rep ; 12(1): 15099, 2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36064872

RESUMO

Current dynamic MRA techniques are limited by temporal resolution and signal-to-noise penalties. GRASP, a fast and flexible MRI technique combining compressed-sensing, parallel imaging, and golden-angle radial sampling, acquires volumetric data continuously and can be reconstructed post hoc for user-defined applications. We describe a custom pipeline to retrospectively reconstruct ultrahigh temporal resolution, dynamic MRA from GRASP imaging obtained in the course of routine practice. GRASP scans were reconstructed using a custom implementation of the GRASP algorithm and post-processed with MeVisLab (MeVis Medical Solutions AG, Germany). Twenty consecutive examinations were scored by three neuroradiologists for angiographic quality of specific vascular segments and imaging artifacts using a 4-point scale. Unsubtracted images, baseline-subtracted images, and a temporal gradient dataset were available in 2D and 3D reconstructions. Distinct arterial and capillary phases were identified in all reconstructions, with a median of 2 frames (IQR1-3 and 2-3, respectively). Median rating for vascular segments was 3 (excellent) in all reconstructions and for nearly all segments, with excellent intraclass correlation (range 0.91-1.00). No cases were degraded by artifacts. GRASP-MRI obtained in routine practice can be seamlessly repurposed to produce high quality 4D MRA with 1-2-s resolved isotropic cerebrovascular angiography. Further exploration into diagnostic accuracy in disease-specific applications is warranted.


Assuntos
Aumento da Imagem , Interpretação de Imagem Assistida por Computador , Angiografia , Meios de Contraste , Aumento da Imagem/métodos , Interpretação de Imagem Assistida por Computador/métodos , Imageamento Tridimensional/métodos , Imageamento por Ressonância Magnética/métodos , Estudos Retrospectivos
2.
J Int Adv Otol ; 18(5): 388-391, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36063094

RESUMO

BACKGROUND: A comparative study of 1.5T and 3.0T magnetic resonance imaging inner ear gadolinium enhancement was carried out to further explore the practicality and universality of 1.5T magnetic resonance imaging in the diagnosis of inner ear labyrinthine hydrops positive imaging. METHODS: This dual case-control study was conducted on 25 patients with Meniere's disease (experimental group), diagnosed by People's Hospital of Ordos Dongsheng District between April 2017 and April 2019 and 51 patients with Meniere's disease (control group), diagnosed by People's Hospital Affiliated to Fujian University of Traditional Chinese Medicine between March 2010 and February 2011 and published on Chinese Medical Journal in 2011. Both groups were injected with gadolinium diluent into bilateral tympanic chambers through the tympanic membrane, and 3 dimensional-Fluid Attenuated Inversion Recovery (FLAIR) magnetic resonance imaging scanning of the inner ear was performed 24 hours later. The results of the 2 groups were observed, calculated, and statistically processed. RESULTS: The positive rate of membranous labyrinthine hydrops was 96% (24/25) in the experimental group and 96.1% (49/51) in the control group. The results are very close. CONCLUSION: In clinical diagnoses of Meniere's disease, 1.5T magnetic resonance imaging and 3.0T magnetic resonance imaging have the same value and significance.


Assuntos
Orelha Interna , Hidropisia Endolinfática , Doença de Meniere , Estudos de Casos e Controles , Meios de Contraste , Orelha Interna/diagnóstico por imagem , Orelha Interna/patologia , Edema , Hidropisia Endolinfática/diagnóstico por imagem , Gadolínio , Gadolínio DTPA , Humanos , Imageamento por Ressonância Magnética/métodos , Doença de Meniere/diagnóstico por imagem , Doença de Meniere/patologia
3.
J Biomed Opt ; 27(9)2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36050818

RESUMO

SIGNIFICANCE: Methylene blue (MB) is an exogenous contrast agent that has the potential to assist with visualization and penetration challenges in photoacoustic imaging. However, monitoring the local concentration between MB and endogenous chromophores is critical for avoiding unnecessary MB accumulations that could lead to adverse effects such as hemolysis when exposed to increased dose and photodamage when exposed to high laser energies. AIM: We developed a modified version of a previously proposed acoustic-based atlas method to estimate concentration levels from a mixture of two photoacoustic-sensitive materials after two laser wavelength emissions. APPROACH: Photoacoustic data were acquired from mixtures of 100-µM MB and either human or porcine blood (Hb) injected in a plastisol phantom, using laser wavelengths of 710 and 870 nm. An algorithm to perform linear regression of the acoustic frequency response from an atlas composed of pure concentrations was designed to assess the concentration levels from photoacoustic samples obtained from 11 known MB/Hb volume mixtures. The mean absolute error (MAE), coefficient of determination (i.e., R2), and Spearman's correlation coefficient (i.e., ρ) between the estimated results and ground-truth labels were calculated to assess the algorithm performance, linearity, and monotonicity, respectively. RESULTS: The overall MAE, R2, and ρ were 12.68%, 0.80, and 0.89, respectively, for the human Hb dataset and 9.92%, 0.86, and 0.93, respectively, for the porcine Hb dataset. In addition, a similarly linear relationship was observed between the acoustic frequency response at 2.3 MHz and 870-nm laser wavelength and the ground-truth concentrations, with R2 and | ρ | values of 0.76 and 0.88, respectively. CONCLUSIONS: Contrast agent concentration monitoring is feasible with the proposed approach. The potential for minimal data acquisition times with only two wavelength emissions is advantageous toward real-time implementation in the operating room.


Assuntos
Técnicas Fotoacústicas , Animais , Meios de Contraste , Hemoglobinas , Humanos , Azul de Metileno , Imagens de Fantasmas , Técnicas Fotoacústicas/métodos , Suínos
4.
World J Gastroenterol ; 28(26): 3116-3131, 2022 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-36051340

RESUMO

Locoregional treatments, as alternatives to surgery, play a key role in the management of hepatocellular carcinoma (HCC). Liver magnetic resonance imaging (MRI) enables a multiparametric assessment, going beyond the traditional dynamic computed tomography approach. Moreover, the use of hepatobiliary agents can improve diagnostic accuracy and are becoming important in the diagnosis and follow-up of HCC. However, the main challenge is to quickly identify classical responses to loco-regional treatments in order to determine the most suitable management strategy for each patient. The aim of this review is to provide a summary of the most common and uncommon liver MRI findings in patients who underwent loco-regional treatments for HCC, with a special focus on ablative therapies (radiofrequency, microwaves and cryoablation), trans-arterial chemoembolization, trans-arterial radio-embolization and stereotactic ablative radiotherapy techniques, considering the usefulness of gadoxetate disodium (Gd-EOB-DTPA) contrast agent.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/terapia , Meios de Contraste , Gadolínio DTPA , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/terapia , Imageamento por Ressonância Magnética/métodos
5.
Biomed Res Int ; 2022: 6790665, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36082155

RESUMO

Since the early 1980s when MRI imaging technology was put into clinical use, the number of MRI clinical tests has steadily increased by more than 10% every year. At the same time, exogenous MRI contrast agents have also been developed with the development of MRI technology. However, there are still challenges in the preparation of contrast agents for magnetic resonance imaging, such as how to prepare high-efficiency contrast agents with high stability and low biological toxicity. In order to study the contrast agent with simple preparation method, low cost, and good imaging effect, a magnetic resonance contrast agent was prepared by magnetic nanoparticles. By acting on magnetic resonance imaging detection method, and using polymer ligands to synthesize magnetic nanoparticles, experiments and tests of P(MA-alt-VAc) polymer ligand-modified magnetic nanoparticles were carried out. The experimental results showed that when nanoparticles containing different iron ion concentrations were incubated with DC 2.4 normal cells for 48 hours, the cell viability was still higher than 80% at concentrations up to 200 µm. It shows that the nanoparticle has high cell activity and good biological adaptability. The transverse relaxation (r 2) value of the nanoparticles in aqueous solution at 37°C and 1.5 T magnetic field is 231.1 m-1 s-1, which is much higher than that of PTMP-PMAA (r 2 = 35.1 mM-1 s-1), which is also more than five times the relaxation of SHU-555C (r 2 = 44 mM-1 s-1). It shows that the nanoparticles prepared in this paper have good effect and can be used as a contrast agent in human brain for magnetic resonance imaging.


Assuntos
Meios de Contraste , Nanopartículas , Humanos , Imageamento por Ressonância Magnética/métodos , Espectroscopia de Ressonância Magnética , Neuroimagem , Polímeros
7.
Sensors (Basel) ; 22(17)2022 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-36081006

RESUMO

Photoacoustic (PA) imaging systems are spreading in the biomedical community, and the development of new PA contrast agents is an active area of research. However, PA contrast agents are usually characterized with spectrophotometry or uncalibrated PA imaging systems, leading to partial assessment of their PA efficiency. To enable quantitative PA spectroscopy of contrast agents in vitro with conventional PA imaging systems, we have developed an adapted calibration method. Contrast agents in solution are injected in a dedicated non-scattering tube phantom imaged at different optical wavelengths. The calibration method uses a reference solution of cupric sulfate to simultaneously correct for the spectral energy distribution of excitation light at the tube location and perform a conversion of the tube amplitude in the image from arbitrary to spectroscopic units. The method does not require any precise alignment and provides quantitative PA spectra, even with non-uniform illumination and ultrasound sensitivity. It was implemented on a conventional imaging setup based on a tunable laser operating between 680 nm and 980 nm and a 5 MHz clinical ultrasound array. We demonstrated robust calibrated PA spectroscopy with sample volumes as low as 15 µL of known chromophores and commonly used contrast agents. The validated method will be an essential and accessible tool for the development of new and efficient PA contrast agents by improving their quantitative characterization.


Assuntos
Técnicas Fotoacústicas , Meios de Contraste/química , Imagens de Fantasmas , Técnicas Fotoacústicas/métodos , Análise Espectral/métodos , Ultrassonografia/métodos
8.
Sensors (Basel) ; 22(17)2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36081110

RESUMO

In tumor surgery, the edges of the tumor can be visually observed using a fluorescent contrast agent and a fluorescent imaging device. By distinguishing it from normal tissues and blood vessels, it is possible to objectively judge the extent of resection while visually observing it during surgery, and it guarantees safe tumor resection based on more information. However, the main problem of such an imaging device is the specular reflection phenomenon. If specular reflection overlaps with important lesion locations, they are a major factor leading to diagnostic errors. Here, we propose a method to reduce specular reflection that occurs during tumor diagnosis using a linear polarization filter and fluorescent contrast agent. To confirm the effect of removing specular reflection, a self-made fluorescein sodium vial phantom was used, and the reliability of the results was increased using a large animal (pig) test. As a result of the experiment, it was possible to obtain an image in which specular reflection was removed by controlling the rotation angle of the filter by 90° and 270°, and the same results were confirmed in the phantom experiment and the animal experiment.


Assuntos
Meios de Contraste , Neoplasias , Animais , Fluoresceína , Neoplasias/diagnóstico por imagem , Reprodutibilidade dos Testes , Suínos
9.
Contrast Media Mol Imaging ; 2022: 7130533, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36101800

RESUMO

Objective: To explore the clinical value of contrast-enhanced ultrasound combined with enhanced CT in the early diagnosis of primary hepatic carcinoma (PHC). Methods: 84 patients with suspected PHC in the early stage treated in our hospital from January 2020 to January 2022 were selected as the study subjects. All patients underwent contrast-enhanced ultrasound and enhanced CT examinations, and the surgery was performed for resection of lesions within 1 month. According to the results of postoperative pathology diagnosis, the benign group and the malignant group were included. The case data were viewed for the retrospective study to analyze the clinical application value by evaluating the diagnostic efficiency of contrast-enhanced ultrasound, enhanced CT, and their combination for PHC. Results: Among 84 suspected patients, 70 patients had PHC (malignant group) and 14 patients had other hepatic lesions (benign group) after postoperative histopathological examination. There was no significant difference in age, gender, clinical symptoms, and educational level between the two groups (P > 0.05), with obvious differences in the history of chronic hepatic disease, smoking, drinking, and infection of hepatitis B virus (HBV) between the two groups (P < 0.05). The enhancement time and regression time of the two groups were significantly different (P < 0.05), with no statistical difference in the enhancement pattern of photography (P > 0.05). For patients with PHC, the imaging features of the two inspection methods at arterial phase and lag phase were statistically different (P < 0.05). Taking pathologic findings as the gold standard, the accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of joint diagnosis were significantly higher than those of contrast-enhanced ultrasound and enhanced CT (P < 0.05), and the area under the curve of joint diagnosis was obviously larger than that of contrast-enhanced ultrasound and enhanced CT by placing the ROC curve for examination (P < 0.05). Conclusion: The combination of contrast-enhanced ultrasound and enhanced CT has a higher accuracy in the early diagnosis of PHC, and the diagnostic efficiency of contrast-enhanced ultrasound is higher than that of enhanced CT. In clinical practice, the physical condition and state of illness in patients should be fully considered, and the most suitable examination method should be selected to reduce their medical burden by taking into account their economic situation.


Assuntos
Carcinoma , Neoplasias Hepáticas , Meios de Contraste , Diagnóstico Precoce , Humanos , Neoplasias Hepáticas/diagnóstico , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
10.
JAMA ; 328(9): 839-849, 2022 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-36066520

RESUMO

Importance: Contrast-associated acute kidney injury (AKI) is a common complication of coronary angiography and percutaneous coronary intervention (PCI) that has been associated with high costs and adverse long-term outcomes. Objective: To determine whether a multifaceted intervention is effective for the prevention of AKI after coronary angiography or PCI. Design, Setting, and Participants: A stepped-wedge, cluster randomized clinical trial was conducted in Alberta, Canada, that included all invasive cardiologists at 3 cardiac catheterization laboratories who were randomized to various start dates for the intervention between January 2018 and September 2019. Eligible patients were aged 18 years or older who underwent nonemergency coronary angiography, PCI, or both; who were not undergoing dialysis; and who had a predicted AKI risk of greater than 5%. Thirty-four physicians performed 7820 procedures among 7106 patients who met the inclusion criteria. Participant follow-up ended in November 2020. Interventions: During the intervention period, cardiologists received educational outreach, computerized clinical decision support on contrast volume and hemodynamic-guided intravenous fluid targets, and audit and feedback. During the control (preintervention) period, cardiologists provided usual care and did not receive the intervention. Main Outcomes and Measures: The primary outcome was AKI. There were 12 secondary outcomes, including contrast volume, intravenous fluid administration, and major adverse cardiovascular and kidney events. The analyses were conducted using time-adjusted models. Results: Of the 34 participating cardiologists who were divided into 8 clusters by practice group and center, the intervention group included 31 who performed 4327 procedures among 4032 patients (mean age, 70.3 [SD, 10.7] years; 1384 were women [32.0%]) and the control group included 34 who performed 3493 procedures among 3251 patients (mean age, 70.2 [SD, 10.8] years; 1151 were women [33.0%]). The incidence of AKI was 7.2% (310 events after 4327 procedures) during the intervention period and 8.6% (299 events after 3493 procedures) during the control period (between-group difference, -2.3% [95% CI, -0.6% to -4.1%]; odds ratio [OR], 0.72 [95% CI, 0.56 to 0.93]; P = .01). Of 12 prespecified secondary outcomes, 8 showed no significant difference. The proportion of procedures in which excessive contrast volumes were used was reduced to 38.1% during the intervention period from 51.7% during the control period (between-group difference, -12.0% [95% CI, -14.4% to -9.4%]; OR, 0.77 [95% CI, 0.65 to 0.90]; P = .002). The proportion of procedures in eligible patients in whom insufficient intravenous fluid was given was reduced to 60.8% during the intervention period from 75.1% during the control period (between-group difference, -15.8% [95% CI, -19.7% to -12.0%]; OR, 0.68 [95% CI, 0.53 to 0.87]; P = .002). There were no significant between-group differences in major adverse cardiovascular events or major adverse kidney events. Conclusions and Relevance: Among cardiologists randomized to an intervention including clinical decision support with audit and feedback, patients undergoing coronary procedures during the intervention period were less likely to develop AKI compared with those treated during the control period, with a time-adjusted absolute risk reduction of 2.3%. Whether this intervention would show efficacy outside this study setting requires further investigation. Trial Registration: ClinicalTrials.gov Identifier: NCT03453996.


Assuntos
Injúria Renal Aguda , Meios de Contraste , Angiografia Coronária , Sistemas de Apoio a Decisões Clínicas , Retroalimentação , Auditoria Médica , Intervenção Coronária Percutânea , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , Meios de Contraste/efeitos adversos , Angiografia Coronária/efeitos adversos , Angiografia Coronária/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/métodos , Medição de Risco
11.
BMC Med Imaging ; 22(1): 157, 2022 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-36057576

RESUMO

OBJECTIVES: We aimed to investigate the value of performing gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) enhanced magnetic resonance imaging (MRI) radiomics for preoperative prediction of microvascular invasion (MVI) of hepatocellular carcinoma (HCC) based on multiple sequences. METHODS: We randomly allocated 165 patients with HCC who underwent partial hepatectomy to training and validation sets. Stepwise regression and the least absolute shrinkage and selection operator algorithm were used to select significant variables. A clinicoradiological model, radiomics model, and combined model were constructed using multivariate logistic regression. The performance of the models was evaluated, and a nomogram risk-prediction model was built based on the combined model. A concordance index and calibration curve were used to evaluate the discrimination and calibration of the nomogram model. RESULTS: The tumour margin, peritumoural hypointensity, and seven radiomics features were selected to build the combined model. The combined model outperformed the radiomics model and the clinicoradiological model and had the highest sensitivity (90.89%) in the validation set. The areas under the receiver operating characteristic curve were 0.826, 0.755, and 0.708 for the combined, radiomics, and clinicoradiological models, respectively. The nomogram model based on the combined model exhibited good discrimination (concordance index = 0.79) and calibration. CONCLUSIONS: The combined model based on radiomics features of Gd-EOB-DTPA enhanced MRI, tumour margin, and peritumoural hypointensity was valuable for predicting HCC microvascular invasion. The nomogram based on the combined model can intuitively show the probabilities of MVI.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Meios de Contraste , Gadolínio DTPA , Humanos , Neoplasias Hepáticas/irrigação sanguínea , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Imageamento por Ressonância Magnética/métodos
12.
Int J Nanomedicine ; 17: 4105-4118, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36111314

RESUMO

Introduction: The realization of MRI contrast agents through chemical protocols of functionalization is a strong domain of research. In this work, we developed and formulated a novel hybrid gold nanoparticle system in which a gold salt (HAuCl4) is combined with dotarem, an MRI contrast agent (DOTA) by chelation (Method IN) and stabilized by a lactose-modified chitosan polymer (CTL; Chitlac) to form DOTA IN-CTL AuNPs. Result and Discussion: The authors demonstrate the biological efficiency of these nanoparticles in the case of three cell lines: Mia PaCa-2 (human pancreatic cancer cell line), TIB-75 (murine liver cell line) and KKU-M213 (cholangiocarcinoma cell line). DOTA IN-CTL AuNPs are stable under physiological conditions, are nontoxic, and are very efficient as PTT agents. The highlights, such as high stability and preliminary MRI in vitro and in vivo models, may be suitable for diagnosis and therapy. Conclusion: We proved that DOTA IN-CTL AuNPs have several advantages: i) Biological efficacy on three cell lines: MIA PaCa-2 (human pancreatic cancer cell line), TIB-75 (murine liver cell line) and KKU-M213 (cholangiocarcinoma cell line); ii) high stability, and no-toxicity; iii) high efficiency as a PPT agent. The study conducted on MRI in vitro and in vivo models will be suitable for diagnosis and therapy.


Assuntos
Quitosana , Colangiocarcinoma , Nanopartículas Metálicas , Neoplasias Pancreáticas , Animais , Quitosana/química , Meios de Contraste/química , Ouro/química , Compostos Heterocíclicos com 1 Anel , Humanos , Lactose , Meglumina , Nanopartículas Metálicas/química , Camundongos , Compostos Organometálicos , Neoplasias Pancreáticas/diagnóstico por imagem , Polímeros/química
13.
J Zhejiang Univ Sci B ; 23(9): 778-783, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36111574

RESUMO

To increase the efficiency and accuracy of clinical tumor detection, we explored multiple imaging by preparing carbon quantum dot (CQD)-loaded nanobubbles for ultrasonic fluorescence dual detection. In this experiment, we prepared 1,2-dioleoyl3-trimethylammonium-propane chloride (DOTAP) cationic liposomes using the film dispersion method and chose perfluoropentane as the core gas material of the nanobubbles. The nanobubbles were coupled with the negatively charged CQDs through the charge effect to prepare the testing agent for two-way diagnosis with ultrasound contrast and fluorescence detection. The formulation and preparation of the loaded CQD liposome nanobubbles were screened. In vivo experiments showed that nanobubbles can be enriched to the tumor site within 5 min, which enables clearer ultrasound imaging and is conducive to tumor detection. We expect CQD-loaded liposome (Lip-CQD) nanobubbles to become a new ultrasonic contrast agent for clinical applications that can provide a basis for early tumor diagnosis and thus earlier treatment.


Assuntos
Neoplasias , Pontos Quânticos , Carbono , Cloretos , Meios de Contraste , Fluorescência , Humanos , Lipossomos , Neoplasias/diagnóstico , Propano , Ultrassom
14.
BMC Plant Biol ; 22(1): 445, 2022 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-36114467

RESUMO

BACKGROUND: Drought is a significant condition that restricts vegetation growth on the Tibetan Plateau. Artemisia wellbyi is a unique semi-shrub-like herb in the family Compositae, which distributed in northern and northwest of Tibetan Plateau. It is a dominant species in the community that can well adapt to virous environment stress, such as drought and low temperature. Therefore, A. wellbyi. has a potential ecological value for soil and water conservation of drought areas. Understanding the molecular mechanisms of A. wellbyi. that defense drought stress can acquire the key genes for drought resistance breeding of A. wellbyi. and provide a theoretical basis for vegetation restoration of desertification area. However, they remain unclear. Thus, our study compared the transcriptomic characteristics of drought-tolerant "11" and drought-sensitive "6" material of A. wellbyi under drought stress. RESULTS: A total of 4875 upregulated and 4381 downregulated differentially expressed genes (DEGs) were induced by drought in the tolerant material; however, only 1931 upregulated and 4174 downregulated DEGs were induced by drought in the sensitive material. The photosynthesis and transcriptional regulation differed significantly with respect to the DEGs number and expression level. We found that CDPKs (calmodulin-like domain protein kinases), SOS3 (salt overly sensitive3), MAPKs (mitogen-activated protein kinase cascades), RLKs (receptor like kinase), and LRR-RLKs (repeat leucine-rich receptor kinase) were firstly involved in response to drought stress in drought tolerant A. wellbyi. Positive regulation of genes associated with the metabolism of ABA (abscisic acid), ET (ethylene), and IAA (indole acetic acid) could play a crucial role in the interaction with other transcriptional regulatory factors, such as MYBs (v-myb avian myeloblastosis viral oncogene homolog), AP2/EREBPs (APETALA2/ethylene-responsive element binding protein family), WRKYs, and bHLHs (basic helix-loop-helix family members) and receptor kinases, and regulate downstream genes for defense against drought stress. In addition, HSP70 (heat shock protein70) and MYB73 were considered as the hub genes because of their strong association with other DEGs. CONCLUSIONS: Positive transcriptional regulation and negative regulation of photosynthesis could be associated with better growth performance under drought stress in the drought-tolerant material. In addition, the degradation of sucrose and starch in the tolerant A. wellbyi to alleviate osmotic stress and balance excess ROS. These results highlight the candidate genes that are involved in enhancing the performance of drought-tolerant A. wellbyi and provide a theoretical basis for improving the performance of drought-resistant A. wellbyi.


Assuntos
Artemisia , Transcriptoma , Ácido Abscísico , Artemisia/genética , Calmodulina/genética , Meios de Contraste , Secas , Etilenos , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Leucina/genética , Proteínas Quinases Ativadas por Mitógeno/genética , Melhoramento Vegetal , Proteínas Quinases/genética , Espécies Reativas de Oxigênio , Solo , Amido , Sacarose
15.
J Biomed Opt ; 27(9)2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36114606

RESUMO

SignificanceDiffuse in vivo flow cytometry (DiFC) is an emerging technique for enumerating rare fluorescently labeled circulating cells noninvasively in the bloodstream. Thus far, we have reported red and blue-green versions of DiFC. Use of near-infrared (NIR) fluorescent light would in principle allow use of DiFC in deeper tissues and would be compatible with emerging NIR fluorescence molecular contrast agents.AimWe describe the design of a NIR-DiFC instrument and demonstrate its use in optical flow phantoms in vitro and in mice in vivo.ApproachWe developed an improved optical fiber probe design for efficient collection of fluorescence from individual circulating cells and efficient rejection of instrument autofluorescence. We built a NIR-DiFC instrument. We tested this with NIR fluorescent microspheres and cell lines labeled with OTL38 fluorescence contrast agent in a flow phantom model. We also tested NIR-DiFC in nude mice injected intravenously with OTL38-labeled L1210A cells.ResultsNIR-DiFC allowed detection of circulating tumor cells (CTCs) in flow phantoms with mean signal-to-noise ratios (SNRs) of 19 to 32 dB. In mice, fluorescently labeled CTCs were detectable with mean SNR of 26 dB. NIR-DiFC also exhibited orders significantly lower autofluorescence and false-alarm rates than blue-green DiFC.ConclusionsNIR-DiFC allows use of emerging NIR contrast agents. Our work could pave the way for future use of NIR-DiFC in humans.


Assuntos
Meios de Contraste , Células Neoplásicas Circulantes , Animais , Contagem de Células , Citometria de Fluxo/métodos , Corantes Fluorescentes , Humanos , Camundongos , Camundongos Nus , Células Neoplásicas Circulantes/patologia
16.
Acta Crystallogr D Struct Biol ; 78(Pt 9): 1120-1130, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36048152

RESUMO

Small-angle X-ray scattering (SAXS) has become an indispensable tool in structural biology, complementing atomic-resolution techniques. It is sensitive to the electron-density difference between solubilized biomacromolecules and the buffer, and provides information on molecular masses, particle dimensions and interactions, low-resolution conformations and pair distance-distribution functions. When SAXS data are recorded at multiple contrasts, i.e. at different solvent electron densities, it is possible to probe, in addition to their overall shape, the internal electron-density profile of biomacromolecular assemblies. Unfortunately, contrast-variation SAXS has been limited by the range of solvent electron densities attainable using conventional co-solutes (for example sugars, glycerol and salt) and by the fact that some biological systems are destabilized in their presence. Here, SAXS contrast data from an oligomeric protein and a protein-RNA complex are presented in the presence of iohexol and Gd-HPDO3A, two electron-rich molecules that are used in biomedical imaging and that belong to the families of iodinated and lanthanide-based complexes, respectively. Moderate concentrations of both molecules allowed solvent electron densities matching those of proteins to be attained. While iohexol yielded higher solvent electron densities (per mole), it interacted specifically with the oligomeric protein and precipitated the protein-RNA complex. Gd-HPDO3A, while less efficient (per mole), did not disrupt the structural integrity of either system, and atomic models could be compared with the SAXS data. Due to their elevated solubility and electron density, their chemical inertness, as well as the possibility of altering their physico-chemical properties, lanthanide-based complexes represent a class of molecules with promising potential for contrast-variation SAXS experiments on diverse biomacromolecular systems.


Assuntos
Meios de Contraste , Elementos da Série dos Lantanídeos , Iohexol , Proteínas/química , RNA/química , Espalhamento a Baixo Ângulo , Solventes , Difração de Raios X
17.
Oncotarget ; 13: 1004-1016, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36082359

RESUMO

Cystoscopic visualization of bladder cancer is an essential method for initial bladder cancer detection and diagnosis, transurethral resection, and monitoring for recurrence. We sought to develop a new intravesical imaging agent that is more specific and sensitive using a polypeptide based NIR (near-infrared) probe designed to detect cells bearing epidermal growth factor receptors (EGFR) that are overexpressed in 80% of urothelial carcinoma (UC) cases. The NIR imaging agent consisted of an elastin like polypeptide (ELP) fused with epidermal growth factor (EGF) and conjugated to Cy5.5 to give Cy5.5-N24-EGF as a NIR contrast agent. In addition to evaluation in human cells and tissues, the agent was tested in canine cell lines and tissue samples with naturally occurring invasive UC. Flow cytometry and confocal microscopy were used to test cell-associated fluorescence of the probe in T24 human UC cells, and in K9TCC-SH (high EGFR expression) and K9TCC-Original (low EGF expression) canine cell lines. The probe specifically engages these cells through EGFR within 15 min of incubation and reached saturation within a clinically relevant 1 h timeframe. Furthermore, ex vivo studies with resected canine and human bladder tissues showed minimal signal from normal adjacent tissue and significant NIR fluorescence labeling of tumor tissue, in good agreement with our in vitro findings. Differential expression of EGFR ex vivo was revealed by our probe and confirmed by anti-EGFR immunohistochemical staining. Taken together, our data suggests Cy5.5-ELP-EGF is a NIR probe with improved sensitivity and selectivity towards BC that shows excellent potential for clinical translation.


Assuntos
Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Animais , Carbocianinas , Carcinoma de Células de Transição/diagnóstico por imagem , Linhagem Celular Tumoral , Meios de Contraste , Cães , Elastina , Fator de Crescimento Epidérmico/metabolismo , Receptores ErbB/metabolismo , Humanos , Camundongos , Camundongos Nus , Neoplasias da Bexiga Urinária/diagnóstico por imagem
18.
Invest Radiol ; 57(10): 655-663, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-36069439

RESUMO

OBJECTIVES: In an effort to exploit the elevated need for phospholipids displayed by cancer cells relative to normal cells, we have developed tumor-targeted alkylphosphocholines (APCs) as broad-spectrum cancer imaging and therapy agents. Radioactive APC analogs have exhibited selective uptake and prolonged tumor retention in over 50 cancer types in preclinical models, as well as over 15 cancer types in over a dozen clinical trials. To push the structural limits of this platform, we recently added a chelating moiety capable of binding gadolinium and many other metals for cancer-targeted magnetic resonance imaging (MRI), positron emission tomography imaging, and targeted radionuclide therapy. The aim of this work was to synthesize, characterize, and validate the tumor selectivity of a new broad-spectrum, tumor-targeted, macrocyclic MRI chelate, Gd-NM600, in xenograft and orthotopic tumor models. A secondary aim was to identify and track the in vivo chemical speciation and spatial localization of this new chelate Gd-NM600 in order to assess its Gd deposition properties. MATERIALS AND METHODS: T1 relaxivities of Gd-NM600 were characterized in water and plasma at 1.5 T and 3.0 T. Tumor uptake and subcellular localization studies were performed using transmission electron microscopy. We imaged 8 different preclinical models of human cancer over time and compared the T1-weighted imaging results to that of a commercial macrocyclic Gd chelate, Gd-DOTA. Finally, matrix-assisted laser desorption and ionization-mass spectrometry imaging was used to characterize and map the tissue distribution of the chemical species of Gd-NM600. RESULTS: Gd-NM600 exhibits high T1 relaxivity (approximately 16.4 s-1/mM at 1.5 T), excellent tumor uptake (3.95 %ID/g at 48 hours), prolonged tumor retention (7 days), and MRI conspicuity. Moreover, minimal tumor uptake saturability of Gd-NM600 was observed. Broad-spectrum tumor-specific uptake was demonstrated in 8 different human cancer models. Cancer cell uptake of Gd-NM600 via endosomal internalization and processing was revealed with transmission electron microscopy. Importantly, tissue mass spectrometry imaging successfully interrogated the spatial localization and chemical speciation of Gd compounds and also identified breakdown products of Gd species. CONCLUSIONS: We have introduced a new macrocyclic cancer-targeted Gd chelate that achieves broad-spectrum tumor uptake and prolonged retention. Furthermore, we have demonstrated in vivo stability of Gd-NM600 by ultrahigh resolution MS tissue imaging. A tumor-targeted contrast agent coupled with the enhanced imaging resolution of MRI relative to positron emission tomography may transform oncologic imaging.


Assuntos
Meios de Contraste , Neoplasias , Quelantes , Meios de Contraste/química , Gadolínio , Humanos , Imageamento por Ressonância Magnética , Neoplasias/diagnóstico por imagem
19.
J Cardiovasc Magn Reson ; 24(1): 50, 2022 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-36089591

RESUMO

BACKGROUND: The underlying pathophysiology of post-coronavirus disease 2019 (long-COVID-19) syndrome remains unknown, but increased cardiometabolic demand and state of mitochondrial dysfunction have emerged as candidate mechanisms. Cardiovascular magnetic resonance (CMR) provides insight into pathophysiological mechanisms underlying cardiovascular disease and 31-phosphorus CMR spectroscopy (31P-CMRS) allows non-invasive assessment of the myocardial energetic state. The main aim of the study was to assess whether long COVID-19 syndrome is associated with abnormalities of myocardial structure, function, perfusion and energy metabolism. METHODS: Prospective case-control study. A total of 20 patients with a clinical diagnosis of long COVID-19 syndrome (seropositive) and no prior underlying cardiovascular disease (CVD) and 10 matching healthy controls underwent 31P-CMRS and CMR at 3T at a single time point. All patients had been symptomatic with acute COVID-19, but none required hospital admission. RESULTS: Between the long COVID-19 syndrome patients and matched contemporary healthy controls there were no differences in myocardial energetics (phosphocreatine to ATP ratio), in cardiac structure (biventricular volumes), function (biventricular ejection fractions, global longitudinal strain), tissue characterization (T1 mapping and late gadolinium enhancement) or perfusion (myocardial rest and stress blood flow, myocardial perfusion reserve). One patient with long COVID-19 syndrome showed subepicardial hyperenhancement on late gadolinium enhancement imaging compatible with prior myocarditis, but no accompanying abnormality in cardiac size, function, perfusion, extracellular volume fraction, native T1, T2 or cardiac energetics. CONCLUSIONS: In this prospective case-control study, the overwhelming majority of patients with a clinical long COVID-19 syndrome with no prior CVD did not exhibit any abnormalities in myocardial energetics, structure, function, blood flow or tissue characteristics.


Assuntos
COVID-19 , Miocardite , COVID-19/complicações , Estudos de Casos e Controles , Meios de Contraste , Gadolínio , Humanos , Imageamento por Ressonância Magnética , Valor Preditivo dos Testes , Análise Espectral
20.
Int J Mol Sci ; 23(17)2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36077324

RESUMO

For many cancer types, being undetectable from early symptoms or blood tests, or often detected at late stages, medical imaging emerges as the most efficient tool for cancer screening. MRI, ultrasound, X-rays (mammography), and X-ray CT (CT) are currently used in hospitals with variable costs. Diagnostic materials that can detect breast tumors through molecular recognition and amplify the signal at the targeting site in combination with state-of-the-art CT techniques, such as dual-energy CT, could lead to a more precise detection and assist significantly in image-guided intervention. Herein, we have developed a ligand-specific X-ray contrast agent that recognizes α5ß1 integrins overexpressed in MDA-MB-231 breast cancer cells for detection of triple (-) cancer, which proliferates very aggressively. In vitro studies show binding and internalization of our nanoprobes within those cells, towards uncoated nanoparticles (NPs) and saline. In vivo studies show high retention of ~3 nm ligand-PEG-S-AuNPs in breast tumors in mice (up to 21 days) and pronounced CT detection, with statistical significance from saline and iohexol, though only 0.5 mg of metal were utilized. In addition, accumulation of ligand-specific NPs is shown in tumors with minimal presence in other organs, relative to controls. The prolonged, low-metal, NP-enhanced spectral-CT detection of triple (-) breast cancer could lead to breakthrough advances in X-ray cancer diagnostics, nanotechnology, and medicine.


Assuntos
Nanopartículas Metálicas , Neoplasias , Animais , Meios de Contraste/química , Ouro/química , Ligantes , Mamografia/métodos , Nanopartículas Metálicas/química , Camundongos , Tomografia Computadorizada por Raios X/métodos
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