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[This corrects the article DOI: 10.7150/thno.22469.].
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Hepatocellular carcinoma (HCC) is a highly aggressive malignant tumor with limited treatment options and poor prognosis. In this study, we reveal the pivotal role of Stratifin (SFN), also recognized as 14-3-3σ, in driving HCC progression. Our investigation underscores a substantial upregulation of SFN within HCC tissues, manifesting a significant association with worse prognostic outcomes among HCC patients. In vitro and in vivo experiments reveal that SFN overexpression significantly amplifies proliferation, mitigates sorafenib-induced effects on HCC cells, and enhances tumorigenesis. While SFN silencing exerts converse effects on HCC progression. Additionally, we unveil a critical interaction between SFN and AKT, where SFN boosts AKT kinase activity by disrupting the binding of PHLPP2 and AKT, thereby intensifying the malignant progression of HCC cells. In conclusion, this study identifies the oncogenic role of SFN and elucidates the regulatory mechanism of the SFN/AKT axis in HCC, which may provide valuable insights into the mechanisms of HCC progression and potential targets for therapeutic intervention.
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Proteínas 14-3-3 , Carcinoma Hepatocelular , Proliferación Celular , Progresión de la Enfermedad , Exorribonucleasas , Neoplasias Hepáticas , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Animales , Femenino , Humanos , Masculino , Ratones , Proteínas 14-3-3/metabolismo , Proteínas 14-3-3/genética , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/genética , Línea Celular Tumoral , Exorribonucleasas/metabolismo , Exorribonucleasas/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/genética , Pronóstico , Proteínas Proto-Oncogénicas c-akt/metabolismo , Persona de Mediana EdadRESUMEN
OBJECTIVES: To evaluate the additional advantages of integrating contrast-enhanced ultrasound (CEUS) into the Ovarian-Adnexal Reporting and Data System (O-RADS) ultrasound (US) for the characterization of adnexal lesions with solid components. MATERIALS AND METHODS: This prospective multicenter study recruited women suspected of having adnexal lesions with solid components between September 2021 and December 2022. All patients scheduled for surgery underwent preoperative CEUS and US examinations. The lesions were categorized according to the O-RADS US system, and quantitative CEUS indexes were recorded. Pathological results served as the reference standard. Univariable and multivariable analyses were performed to identify risk factors for malignancy in adnexal lesions with solid components. Receiver operating characteristic (ROC) curve analysis was employed to assess diagnostic performance. RESULTS: A total of 180 lesions in 175 women were included in the study. Among these masses, 80 were malignant and 100 were benign. Multivariable analysis revealed that serum CA-125, the presence of acoustic shadowing, and peak intensity (PI) ratio (PImass/PIuterus) of solid components on CEUS were independently associated with adnexal malignancy. The modified CEUS risk stratification model demonstrated superior diagnostic value in assessing adnexal lesions with solid components compared to O-RADS US (AUC: 0.91 vs 0.78, p < 0.001) and exhibited comparable performance to the Assessment of Different NEoplasias in the adnexa (ADNEX) model (AUC 0.91 vs 0.86, p = 0.07). CONCLUSION: Our findings underscore the potential value of CEUS as an adjunctive tool for enhancing the precision of diagnostic evaluations of O-RADS US. CLINICAL RELEVANCE STATEMENT: The promising performance of the modified CEUS risk stratification model suggests its potential to mitigate unnecessary surgeries in the characterization of adnexal lesions with solid components. KEY POINTS: ⢠The additional value of CEUS to O-RADS US in distinguishing between benign and malignant adnexal lesions with solid components requires further evaluation. ⢠The modified CEUS risk stratification model displayed superior diagnostic value and specificity in characterizing adnexal lesions with solid components when compared to O-RADS US. ⢠The inclusion of CEUS demonstrated potential in reducing the need for unnecessary surgeries in the characterization of adnexal lesions with solid components.
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INTRODUCTION AND HYPOTHESIS: Transperineal ultrasound (TPUS) is an effective tool for evaluating the integrity of the levator ani muscle (LAM). Several operating steps are required to obtain the standard multi-slice image of the LAM, which is experience dependent and time consuming. This study was aimed at evaluating the feasibility and reproducibility of the built-in software, Smart-pelvic™, in reconstructing standard tomographic images of LAM from 3D/4D TPUS volumes. METHODS: This study was conducted at a tertiary teaching hospital, enrolling women who underwent TPUS. Tomographic images of the LAM were automatically reconstructed by Smart-pelvicTM and rated by two experienced observers as standard or nonstandard. The anteroposterior diameter (APD) of the levator hiatus was also measured on the mid-sagittal plane of the automatically and manually reconstructed images. The APD measurements of each approach were compared using Bland-Altman plots, and interclass correlation coefficient (ICC) was used to evaluate intra- and inter-observer reproducibility. Meanwhile, the time taken for the reconstruction process of both methods was also recorded. RESULTS: The ultrasound volume of a total of 104 patients were included in this study. Using Smart-pelvicTM, the overall success rate of the tomographic image reconstruction was 98%. Regarding measurements of APD, the ICC between the automatic and manual reconstruction methods was 0.99 (0.98, 0.99). The average time taken for reconstruction per case was 2.65 ± 0.52 s and 22.08 ± 3.45 s, respectively. CONCLUSIONS: Using Smart-pelvicTM to reconstruct tomographic images of LAM is feasible, and it can promote TPUS by reducing operator dependence and improving examination efficiency in a clinical setting.
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Diafragma Pélvico , Programas Informáticos , Humanos , Femenino , Reproducibilidad de los Resultados , Diafragma Pélvico/diagnóstico por imagen , Ultrasonografía/métodos , Imagenología TridimensionalRESUMEN
Background: Transperineal ultrasound (TPUS) is a vital examination method for diagnosing pelvic floor diseases. However, the quality of TPUS largely relies on the operator's experience, and there is a lack of studies on the evaluation of TPUS quality. Therefore, the objective of this study was to assess the quality of TPUS examinations in Chinese tertiary medical centers. Methods: This multicenter study conducted in 44 Chinese tertiary medical centers recruited postpartum women between September 2020 and September 2021. All participants underwent a standardized inquiry and TPUS examination. The participating centers were required to submit 5 parts of ultrasound data to the National Ultrasound Quality Control Center: 2-dimensional images at rest, 2-dimensional images at strain; 4-dimensional images of the levator ani hiatus; 4-dimensional images of the levator ani muscle; and 4-dimensional images of the anal sphincter. Quality assessment was performed by 2 experts with more than 5 years of experience in TPUS, and the reasons for nonqualification were stated. Results: In this study, 31 hospitals that were distributed across 20 provinces in China were included, submitting 2,251 cases in total. The overall qualified rate ranged from 12.00% to 86.92%. In each part, the qualified rate of 2-dimensional images at rest, 2-dimensional images at straining, levator ani hiatus, levator ani muscle, and anal sphincter was 94.27% (2,122/2,251), 78.54% (1,768/2,251), 85.52% (1,925/2,251), 93.03% (2,094/2,251), and 88.09% (1,983/2,251), respectively. Most of the nonqualified images belonged to 2-dimensional images at strain, and the errors in image acquisition (221/483, 45.76%) and measurement (262/483, 54.24%) were the main reasons for nonqualification. For levator ani hiatus images, error in image acquisition (275/326, 84.36%) was the main reason for nonqualification. Reconstruction error was the most common reason for nonqualification for levator ani muscle (133/157, 84.71%) and anal sphincter images (133/268, 49.63%). Conclusions: This multicenter study assessed the quality of TPUS in tertiary medical centers in China and identified the common reasons for nonqualification in each part. These findings can aid in forming the basis for quality control management and training for TPUS.
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Efficient and stable near-infrared silicon-based light source is a challenge for future optoelectronic integration and interconnection. In this paper, alkaline earth metal Ca2+ doped SiO2-SnO2: Er3+ films were prepared by sol-gel method. The oxygen vacancies introduced by the doped Ca2+ significantly increase the near-infrared luminescence intensity of Er3+ ions. It was found that the doping concentration of Sn precursors not only modulate the crystallinity of SnO2 nanocrystals but also enhance the luminescence performance of Er3+ ions. The stable electroluminescent devices based on SiO2-SnO2: Er3+/Ca2+ films exhibit the power efficiency as high as 1.04×10-2 with the external quantum efficiency exceeding 10%.
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OBJECTIVES: To evaluate the concordance between an automatic software program and manual evaluation in reconstructing, delineating, and measuring the levator hiatus (LH) on maximal Valsalva maneuver. METHODS: This was a retrospective study analyzing archived raw ultrasound imaging data of 100 patients underwent transperineal ultrasound (TPUS) examination. Each data were assessed by the automatic Smart Pelvic System software program and manual evaluation. The Dice similarity index (DSI), mean absolute distance (MAD), and Hausdorff distance (HDD) were calculated to quantify delineation accuracy of LH. Agreement between automatic and manual measurement of levator hiatus area was assessed by intraclass correlation coefficient (ICC) and Bland-Altman method. RESULTS: The satisfaction rate of automatic reconstruction was 94%. Six images were recognized as unsatisfactory reconstructed images for some gas in the rectum and anal canal. Compared with satisfactory reconstructed images, DSI of unsatisfactory reconstructed images was lower, MAD and HDD were larger (p = 0.001, p = 0.001, p = 0.006, respectively). The ICC was up to 0.987 in 94 satisfactory reconstructed images. CONCLUSIONS: The Smart Pelvic System software program had good performance in reconstruction, delineation, and measurement of LH on maximal Valsalva maneuver in clinical practice, despite misidentification of the border of posterior aspect of LH due to the influence of gas in the rectum.
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Contracción Muscular , Diafragma Pélvico , Humanos , Diafragma Pélvico/diagnóstico por imagen , Estudios Retrospectivos , Imagenología Tridimensional/métodos , Ultrasonografía/métodos , Maniobra de ValsalvaRESUMEN
Alkaline earth metal ions (Mg2+, Ca2+, Sr2+) have been introduced into Er3+:SnO2 nanocrystal co-doped silica thin films fabricated by a sol-gel method combined with a spin-coating technique. It is found that the incorporation of alkaline earth metal ions can enhance the light emission from Er3+ at the wavelength around 1540 nm and the strongest enhancement is observed in samples doped with 5 mol% Sr2+ ions. Based on X-ray diffraction, X-ray photoelectron spectroscopy and other spectroscopic measurements, the improved light emission can be attributed to more oxygen vacancies, better crystallinity and a stronger cross-relaxation process with the introduction of alkaline earth metal ions.
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ABSTRACT: This study investigated the correlation between magnetic resonance elastography (MRE) and shear wave ultrasound elastography (SWE) in patients with clinically diagnosed or suspected nonalcoholic fatty liver disease (NAFLD). Subjects with or at risk of NAFLD identified by magnetic resonance imaging (MRI) proton density fat fraction (PDFF) were prospectively enrolled. For each patient, 6 valid 2-dimensional SWE measurements were acquired using a Logiq E10 scanner (GE HealthCare, Waukesha, WI). A reliability criterion of an interquartile range to median ratio of ≤15% was used for SWE to indicate quality dataset. Magnetic resonance elastography, and MR-fat quantification data were collected the same day as part of the patient's clinical standard of care. Magnetic resonance imaging PDFF was used as a reference to quantify fat with >6.4% indicating NAFLD. Pearson correlation and t-test were performed for statistical analyses. A total of 140 patients were enrolled, 112 of which met SWE reliability measurement criteria. Magnetic resonance elastography and 2-dimensional SWE showed a positive correlation across all study subjects ( r = 0.27; P = 0.004). When patients were grouped according to steatosis and fibrosis state, a positive correlation was observed between MRE and SWE in patients with fibrosis ( r = 0.30; P = 0.03), without fibrosis ( r = 0.27; P = 0.03), and with NAFLD ( r = 0.28; P = 0.02). No elastography technique correlated with liver fat quantification ( P > 0.52). Magnetic resonance elastography was significantly different between patients with and without fibrosis ( P < 0.0001). However, this difference was not apparent with SWE ( P = 0.09). In patients with suspected or known NAFLD, MRE, and SWE demonstrated a positive correlation. In addition, these noninvasive imaging modalities may be useful adjunct techniques for monitoring NAFLD.
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Diagnóstico por Imagen de Elasticidad , Enfermedad del Hígado Graso no Alcohólico , Humanos , Enfermedad del Hígado Graso no Alcohólico/diagnóstico por imagen , Enfermedad del Hígado Graso no Alcohólico/patología , Diagnóstico por Imagen de Elasticidad/métodos , Cirrosis Hepática/patología , Reproducibilidad de los Resultados , Hígado/diagnóstico por imagen , Hígado/patología , Imagen por Resonancia Magnética/métodos , Espectroscopía de Resonancia MagnéticaRESUMEN
This study aimed to evaluate the diagnostic value of HyCoSy using sulfur hexafluoride microbubbles for fallopian tubal patency assessment in infertile females. Twenty-four studies, including 1358 females with 2661 detected fallopian tubes published from January 2003 to May 2019, were identified. The pooled sensitivity was 93% (95% CI: 90-95%), while the specificity was 90% (95% CI: 87-92%). The area under the receiver-operating characteristic curve was 0.96 (95% CI: 94-98%). The specificity of the four-dimensional HyCoSy subgroup was higher than the 2D/3D subgroup; an increased dose of contrast agent did not affect the specificity, with only a slightly reduced sensitivity.
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Trompas Uterinas , Infertilidad Femenina , Femenino , Humanos , Trompas Uterinas/diagnóstico por imagen , Hexafluoruro de Azufre , Histerosalpingografía/métodos , Pruebas de Obstrucción de las Trompas Uterinas/métodos , Microburbujas , Medios de Contraste , Ultrasonografía/métodosRESUMEN
OBJECTIVES: This retrospective study aimed to compare the performance of contrast-enhanced ultrasound (CEUS) and magnetic resonance imaging (MRI) in staging surgically treated early-stage cervical cancer. METHODS: Patients with surgically treated cervical carcinoma confirmed by post-operative pathological findings were included between December 2016 and December 2018. All included patients underwent both CEUS and MRI examinations before the surgery. Post-operative pathology was used as the gold standard. The κ values were calculated to assess the agreements of CEUS and MRI in staging cervical carcinoma in comparison with post-operative pathology. RESULTS: Complete data were available for 39 patients. CEUS showed great inter-observer reproducibility in tumor measurement [Intra-class Correlation Coefficient (ICC) 0.831] and moderate inter-observer reproducibility in the evaluation of vaginal infiltration and parametrial invasion (Cohen's κ 0.692 and 0.624). Tumor size was comparable as measured by CEUS and MRI (ICC 0.769). Both CEUS and MRI presented good concordance with post-operative pathology in staging cervical cancer (weighted κ 0.732 and 0.761). CONCLUSION: CEUS was comparable to MRI in staging surgically treated cervical cancer and might be considered in the pre-treatment work-up for cervical cancer.
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Neoplasias Hepáticas , Neoplasias del Cuello Uterino , Medios de Contraste , Femenino , Humanos , Neoplasias Hepáticas/patología , Imagen por Resonancia Magnética/métodos , Reproducibilidad de los Resultados , Estudios Retrospectivos , Ultrasonografía/métodos , Neoplasias del Cuello Uterino/diagnóstico por imagen , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/cirugíaRESUMEN
Purpose: To automatically segment and measure the levator hiatus with a deep learning approach and evaluate the performance between algorithms, sonographers, and different devices. Methods: Three deep learning models (UNet-ResNet34, HR-Net, and SegNet) were trained with 360 images and validated with 42 images. The trained models were tested with two test sets. The first set included 138 images to evaluate the performance between the algorithms and sonographers. An independent dataset including 679 images assessed the performances of algorithms between different ultrasound devices. Four metrics were used for evaluation: DSC, HDD, the relative error of segmentation area, and the absolute error of segmentation area. Results: The UNet model outperformed HR-Net and SegNet. It could achieve a mean DSC of 0.964 for the first test set and 0.952 for the independent test set. UNet was creditable compared with three senior sonographers with a noninferiority test in the first test set and equivalent in the two test sets collected by different devices. On average, it took two seconds to process one case with a GPU and 2.4 s with a CPU. Conclusions: The deep learning approach has good performance for levator hiatus segmentation and good generalization ability on independent test sets. This automatic levator hiatus segmentation approach could help shorten the clinical examination time and improve consistency.
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The purpose of this study was to evaluate an artificial intelligence (AI) system for the classification of axillary lymph nodes on ultrasound compared to radiologists. Ultrasound images of 317 axillary lymph nodes from patients referred for ultrasound guided fine needle aspiration or core needle biopsy and corresponding pathology findings were collected. Lymph nodes were classified into benign and malignant groups with histopathological result serving as the reference. Google Cloud AutoML Vision (Mountain View, CA) was used for AI image classification. Three experienced radiologists also classified the images and gave a level of suspicion score (1-5). To test the accuracy of AI, an external testing dataset of 64 images from 64 independent patients was evaluated by three AI models and the three readers. The diagnostic performance of AI and the humans were then quantified using receiver operating characteristics curves. In the complete set of 317 images, AutoML achieved a sensitivity of 77.1%, positive predictive value (PPV) of 77.1%, and an area under the precision recall curve of 0.78, while the three radiologists showed a sensitivity of 87.8% ± 8.5%, specificity of 50.3% ± 16.4%, PPV of 61.1% ± 5.4%, negative predictive value (NPV) of 84.1% ± 6.6%, and accuracy of 67.7% ± 5.7%. In the three external independent test sets, AI and human readers achieved sensitivity of 74.0% ± 0.14% versus 89.9% ± 0.06% (p = .25), specificity of 64.4% ± 0.11% versus 50.1 ± 0.20% (p = .22), PPV of 68.3% ± 0.04% versus 65.4 ± 0.07% (p = .50), NPV of 72.6% ± 0.11% versus 82.1% ± 0.08% (p = .33), and accuracy of 69.5% ± 0.06% versus 70.1% ± 0.07% (p = .90), respectively. These preliminary results indicate AI has comparable performance to trained radiologists and could be used to predict the presence of metastasis in ultrasound images of axillary lymph nodes.
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Inteligencia Artificial , Neoplasias de la Mama , Axila , Neoplasias de la Mama/diagnóstico por imagen , Femenino , Humanos , Ganglios Linfáticos/diagnóstico por imagen , Metástasis Linfática , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: There has been a long-standing controversy about diastasis recti diagnostic criteria and its relation to pelvic floor dysfunction (PFD). This study aimed to establish ultrasound diagnostic criteria for diastasis recti and investigate the correlation between it and PFD in early postpartum females. METHODS: The inter-rectus distance (IRD) was measured at 3 locations in 116 healthy nulliparous females and 108 postpartum females. At the same time, they remained relaxed and then maintained a head-lift posture. The measurement for the 90th percentile was used to define the normal IRD in the nulliparous group. Afterward, the 108 postpartum females underwent an ultrasonographic examination of pelvic floor function. The correlations of these values with the IRD were then examined. RESULTS: We established the following ultrasonographic diagnostic criteria for diastasis recti: an IRD of >2 mm at 3 cm below the umbilicus, >20 mm at the umbilicus, and >14 mm at 3 cm above the umbilicus. The IRD was positively correlated with body mass index (BMI) in the nulliparous group (r=0.286, P<0.01) and with age in the postpartum group (r=0.230, P<0.05). The IRD was not relative to either the PFD ultrasound results or the clinical symptoms. CONCLUSIONS: We established a set of ultrasonographic diagnostic criteria for diastasis recti at 3 locations along the umbilicus. There is no clear correlation between diastasis recti and PFD in early postpartum females.
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BACKGROUND: Recent studies have revealed that combining of the platelet to lymphocyte ratio (PLR) and the neutrophil to lymphocyte ratio (NLR) [(combination of neutrophil-lymphocyte ratio and platelet-lymphocyte ratio (CNP)] links with dismal prognosis in diverse cancers. Here, we elucidated the prognostic significance of CNP, acting as a novel inflammation-based score, for predicting the survival of hepatocellular carcinoma (HCC) patients following liver transplantation. METHOD: We retrospectively recruited 100 patients with HCC who met the Hangzhou criteria for liver transplantation. The Kaplan-Meier approach, univariate, and multivariate assessments were employed to examine prognostic factors. We determined the optimal cutoff values for NLR, PLR, and haematological parameters using the receiver operating characteristic (ROC) curve evaluation. On the basis of the ROC curve, the optimal cutoff values for PLR and NLR were 3.4 and 114.6, discretely. Patients with increased NLR (>3.4) and high PLR (>114.6) scored 2, while one or none scored 1 or 0, respectively. RESULTS: Distinct differences were reported between CNP and Fibrinogen (P = 0.002), White blood cell (P = 0.048), NLR (P < 0.001), and PLR (P < 0.001). Based on the findings of Kaplan-Meier assessments, the CNP score linked to dismal overall survival (OS; P < 0.0001), as well as recurrence-free survival (RFS; P < 0.0001) in HCC patients after liver transplantation. Furthermore, multivariate assessments indicated that the CNP score was an independent prediction factor for OS (P = 0.002) and RFS (P < 0.001) in HCC patients after liver transplantation. CONCLUSION: The CNP score can be considered as an effective predictor of survival events in HCC patients after liver transplantation.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Trasplante de Hígado , Plaquetas/patología , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/cirugía , Humanos , Inflamación/diagnóstico , Inflamación/patología , Neoplasias Hepáticas/patología , Trasplante de Hígado/efectos adversos , Linfocitos , Neutrófilos/patología , Pronóstico , Estudios RetrospectivosRESUMEN
Purpose: While mammography has excellent sensitivity for the detection of breast lesions, its specificity is limited. Adjunct screening with ultrasound may partially alleviate this issue but also increases false positives, resulting in unnecessary biopsies. Our study investigated the use of Google AutoML Vision (Mountain View, California), a commercially available machine learning service, to both identify and characterize indeterminate breast lesions on ultrasound. Approach: B-mode images from 253 independent cases of indeterminate breast lesions scheduled for core biopsy were used for model creation and validation. The performances of two sub-models from AutoML Vision, the image classification model and object detection model, were evaluated, while also investigating training strategies to enhance model performances. Pathology from the patient's biopsy was used as a reference standard. Results: The image classification models trained under different conditions demonstrated areas under the precision-recall curve (AUC) ranging from 0.85 to 0.96 during internal validation. Once deployed, the model with highest internal performance demonstrated a sensitivity of 100% [95% confidence interval (CI) of 73.5% to 100%], specificity of 83.3% (CI=51.6% to 97.9%), positive predictive value (PPV) of 85.7% (CI=62.9% to 95.5%), and negative predictive value (NPV) of 100% (CI non-evaluable) in an independent dataset. The object detection model demonstrated lower performance internally during development (AUC=0.67) and during prediction in the independent dataset [sensitivity=75% (CI=42.8 to 94.5), specificity=80% (CI=51.9 to 95.7), PPV=75% (CI=50.8 to 90.0), and NPV=80% (CI=59.3% to 91.7%)], but was able to demonstrate the location of the lesion within the image. Conclusions: Two models appear to be useful tools for identifying and classifying suspicious areas on B-mode images of indeterminate breast lesions.
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OBJECTIVES: To investigate hemodynamic changes in the hepatic artery after hepatic ischemia-reperfusion injury (IRI) in rats via ultrasound (US) imaging and to discuss the protective effect of phentolamine (PHT) pretreatment on hepatic IRI. METHODS: Fifty rats were randomly divided into 3 groups: a sham operation group (n = 10), a control ischemia-reperfusion group (n = 20), and a PHT pretreatment group (n = 20). Color Doppler flow imaging and contrast-enhanced US examinations were performed in each group at 30 minutes (n = 10) and 90 minutes (n = 10) after reperfusion. Blood samples were obtained to analyze serum alanine aminotransferase and aspartate aminotransferase levels, and liver tissue specimens were collected for pathologic analysis. RESULTS: Using US, we found that hepatic artery resistance at 30 minutes after reperfusion in the control group was higher than that in the sham group (mean resistive index [RI] ± SD, 0.65 ± 0.09 versus 0.50 ± 0.09; P < .01), which was higher at 30 than 90 minutes (RI, 0.65 ± 0.09 versus 0.50 ± 0.08; P < .01) after reperfusion in the control group. However, the hepatic artery resistance and liver microcirculation in the PHT group were better than those in the control group at 30 minutes after reperfusion (RI, 0.54 ± 0.09 versus 0.65 ± 0.09; P < .05; time to peak, 31.94 ± 2.02 versus 48.34 ± 4.74 seconds; P < .01). Compared to the control group, the aspartate aminotransferase and alanine aminotransferase levels were significantly lower at 30 minutes after reperfusion in the PHT group (P < .05). A pathologic examination revealed a smaller hepatic artery diameter and a depressed vessel wall in the control group. CONCLUSIONS: The hepatic artery can undergo a transient spasm during the hepatic IRI process, which can exacerbate liver damage. Phentolamine treatment can alleviate hepatic artery spasms, improve liver perfusion, and reduce liver injury by ameliorating the hepatic microcirculation.
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Arteria Hepática/diagnóstico por imagen , Arteria Hepática/fisiopatología , Daño por Reperfusión/diagnóstico , Daño por Reperfusión/patología , Animales , Modelos Animales de Enfermedad , Hígado/diagnóstico por imagen , Hígado/fisiopatología , Masculino , Ratas , Ratas Sprague-Dawley , Ultrasonografía/métodosRESUMEN
Photodynamic therapy (PDT) holds promise for focal therapy of prostate cancer (PCa). However, the therapeutic efficacy needs improvement, and further development of PDT for PCa has challenges, including uncertainty of photosensitizers (PSs) accumulation at the tumor site and difficulty in visualizing lesions using conventional ultrasound (US) imaging. We have developed novel porphyrin-grafted lipid (PGL) microbubbles (MBs; PGL-MBs) and propose a strategy to integrate PGL-MBs with US imaging to address these limitations and enhance PDT efficacy. METHODS: PGL-MBs have two functions: imaging guidance by contrast-enhanced ultrasound (CEUS) and targeted delivery of PSs by ultrasound targeted microbubble destruction (UTMD). PGL-MBs were prepared and characterized before and after low-frequency US (LFUS) exposure. Then, in vitro studies validated the efficacy of PDT with PGL-MBs in human prostate cancer PC3 cells. PC3-xenografted nude mice were used to validate CEUS imaging, accumulation at the tumor site, and in vivo PDT efficacy. RESULTS: PGL-MBs showed good contrast enhancement for US imaging and were converted into nanoparticles upon LFUS exposure. The resulting uniquely structured nanoparticles avoided porphyrin fluorescence quenching and efficiently accumulated at the tumor site through the sonoporation effect created with the assistance of US to achieve excellent PDT efficacy. CONCLUSIONS: This is the first preclinical investigation of MBs applied in PDT for PCa. PGL-MBs possess favorable CEUS imaging effects to enhance the localization of tumors. PGL-MBs with LFUS control PS accumulation at the tumor site to achieve highly effective PDT of PCa. This strategy carries enormous clinical potential for PCa management.
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Terapia Combinada/métodos , Microburbujas/uso terapéutico , Porfirinas/química , Neoplasias de la Próstata/terapia , Ultrasonografía/métodos , Animales , Línea Celular Tumoral , Colesterol/química , Medios de Contraste/uso terapéutico , Humanos , Masculino , Ratones , Ratones Desnudos , Nanopartículas/química , Fosfatidilcolinas/química , Fosfatidiletanolaminas/química , Fotoquimioterapia , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Porfirinas/farmacología , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/cirugía , Cirugía Asistida por Computador/instrumentación , Cirugía Asistida por Computador/métodos , Nanomedicina Teranóstica/métodos , Ultrasonografía/instrumentación , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
This study was conducted with the aim of developing a microbubble agent for near-infrared (NIR) fluorescence and ultrasound dual-modality contrast microbubbles applicable to imaging of sentinel lymph nodes in the VX2 rabbit tumor model. Specific ligands of phosphatidylserine (PS) and Cy7 NIR fluorescent dyes with long emission wavelengths (750-900 nm) were conjugated to the surface of ultrasound contrast microbubbles (MBs), termed Cy7 PS MBs. Ultrasound lymphography and NIR fluorescence imaging were performed using subcutaneous injection of Cy7 PS MBs to visualize the sentinel lymph node. Sentinel lymph node detection rates using the patent blue method, ultrasound lymphography and NIR fluorescence imaging were 95%, 79% and 95%, respectively, and sensitivity was 87%, 74% and 92%, respectively. With 2-D ultrasound, the diagnostic sensitivity for detection of sentinel lymph node metastases was 60% and the specificity was 74%, whereas Cy7 PS MB-enhanced ultrasound had a sensitivity of 80% and a specificity of 87%. The results indicate that dual-modality Cy7 PS MBs combined with ultrasound lymphography and NIR fluorescence may be useful in the detection of normal and metastasized sentinel lymph nodes.