The Value of CEUS LI-RADS combined with AFP in early diagnosis of hepatocellular carcinoma in low- and high-risk patients.

BACKGROUND: We found that the occurrence of hepatocellular carcinoma (HCC) has increased significantly in non-cirrhotic individuals, with HCC being frequently overlooked or misdiagnosed. Contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS) is known to have a high diagnostic quality in high-risk HCC patients. Therefore, we aimed to compare the detection accuracy of CEUS LI-RADS for HCC between low- and high-risk individuals, to confirm its value in low-risk patients at increased risk of HCC, but not yet included in the high-risk groups of LI-RADS. In addition, since CEUS LR-4 and LR-M categories contain a relatively high proportion of HCC, and serum alpha-fetoprotein (AFP) is the most commonly used biomarker for HCC, and the clinically valid, we attempted to further improve the early diagnostic capability of CEUS LI-RADS for HCC in the low-risk and high-risk patients by combining CEUS LR-4 and LR-M categories with AFP. METHODS: We defined high-risk groups (HR)-included in the high-risk patients of LI-RADS, low-risk groups (LR)-not included in the high-risk patients of LI-RADS and enrolled 189 HCC patients with LR and HR settings in a retrospective study. All lesions were confirmed histopathologically. The CEUS LI-RADS accuracy for detecting HCC in these two patients was compared. In addition, the diagnostic algorithm in our study was proposed (for CEUS LR-4 and LR-M patients with AFP>20 ng/ml). we analyzed the ability of CEUS LI-RADS as a valid method of establishing the early diagnosis of HCC in LR and HR patients by combining LR-4 and LR-M categories with AFP. RESULTS: Through comparative analysis, the specificity of the CEUS LR-5 category for HCC in the HR group was 78.4%, whereas in the LR group, it was 94.2%. Meanwhile, the sensitivity (63.2% vs. 63.0%) and positive predictive value (PPV) (75.0% vs. 88.7%) did not differ between the LR and HR groups (P = 0.990, P = 0.299). It is noteworthy that there were the high proportion of HCC in CEUS LR-4 and LR-M categories in our cases and when we combined CEUS LR-4 and LR-M categories with AFP significantly improved the sensitivity by 21.0% (84.2%) in the LR group, and by 16.0% (79.0%) in the HR group, with statistically difference in sensitivity after combination in the HR group (P = 0.014). CONCLUSIONS: The CEUS LR-5 category has real meaningful utility in the diagnosis of HCC in both LR and HR patients. The early detection power of the CEUS LI-RADS category for HCC patients was further increased when the CEUS LR-4 and LR-M categories were combined with elevated AFP.

The correlation between time-intensity curve parameters of transrectal contrast-enhanced ultrasound and pathological prognostic factors in rectal adenocarcinoma.

AIMS: To investigate the correlation between time-intensity curve (TIC) parameters obtained from transrectal contrast-enhanced ultrasound (TR-CEUS) and important pathological prognostic factors in rectal adenocarcinoma. MATERIAL AND METHODS:  We retrospectively included 477 patients with pathologically confirmed rectal adenocarcinoma. TIC parameters were derived from preoperative dynamic TR-CEUS images. These parameters included peak intensity (PI), time to peak (TTP),mean transit time (MTT), slope (S), and area under the curve (AREA). Pathological prognostic factors included TN stage, tumor diameter, lymphovascular invasion (LVI), perineural invasion, and tumor differentiation. Spearman's correlation analysis and binary logistic regression were used to analyze the association between TIC parameters and pathological prognostic factors. RESULTS: pT1-2 stages rectal carcinomas exhibited higher PI-max, PI-min, S-max, S-min, AREA-max, and AREA-min than pT3-4 stages (all p<0.05). pN0 stage rectal adenocarcinomas displayed higher PI-max, S-max, AREA-max, PI-ratio, Sratio, and AREA-ratio than pN1-2 stage (all p<0.05). PI-ratio and S-ratio were higher in the LVI-negative and tumor diameter ≥4cm group compared to the LVI-positive and tumor diameter <4cm group, respectively (p<0.05). Well-differentiated rectal adenocarcinomas displayed higher PI-max, AREA-max, PI-ratio, S-ratio, and AREA-ratio than the moderate-poor differentiated group (all p<0.05). PI-max, S-max, AREA-max, PI-ratio, S-ratio, and AREA-ratio were negatively correlated with pN stage (all p<0.05). PI-ratio and S-ratio were independent predictive factors for the pN stage (OR=0.774, OR=1.048). S-ratio and AREA-ratio were independent predictive factors for tumor differentiation (OR=1.071, OR=0.911). CONCLUSIONS: TIC parameters derived from TR-CEUS exhibit correlations with specific pathological prognostic factors in rectal adenocarcinomas. This non-invasive method may hold promise for preoperatively assessing the prognosis of rectal adenocarcinoma patients.

Assessment of the Effects of Sphingosine Kinase 1/Sphingosine-1-Phosphate on Microangiogenesis at Rat Myofascial Trigger Points Using Contrast-Enhanced Ultrasonography.

Purpose: Few studies have assessed the effects of sphingosine kinase 1/sphingosine-1-phosphate (SPHK1/S1P) on microangiogenesis at rat myofascial trigger points (MTrPs) using contrast-enhanced ultrasonography (CEUS). This study aimed to address these deficiencies. Here, we investigated the effects of SPHK1/S1P on MTrP microangiogenesis and the value of CEUS in evaluating these effects. Methods: Forty Sprague‒Dawley rats were subdivided into two groups: control and MTrP groups. MTrPs were established by 8 weeks of the strike procedure combined with eccentric motion and 4 weeks of recovery. All rats were euthanized after having undergone CEUS with an overdose of pentobarbital sodium. MTrP and control tissue samples were removed for haematoxylin and eosin (H&E) staining and transmission electron microscopy (TEM) imaging. The tissue was dehydrated, cleared, and embedded before sectioning. The sections were then incubated overnight at 4°C, and immunohistochemistry was carried out with primary antibodies including rabbit anti-CD31, rabbit anti-SPHK1and rabbit anti-S1PR1. Results: MTrP rats exhibited spontaneous electrical activity (SEA) and a local twitch response (LTR) during electromyography (EMG) examination. The CEUS time-intensity curves (TICs) showed that the perfusion intensity in the MTrPs and surrounding tissue area was increased, with faster perfusion than in normal sites, while the TICs in the control group slowly increased and then slowly decreased. The correlation coefficient between the microvessel density (MVD) and sphingosine 1-phosphate receptor 1 (S1PR1) was 0.716 (p <0.01). Spearman correlation analysis revealed that Spearman's rho (ρ) values between the MVD and peak intensity (PI), between the MVD and area under the curve (AUC), and between the MVD and SPHK1 were > 0.5 (p <0.05), > 0.7 (p <0.01), and > 0.7 (p <0.01), respectively. Conclusion: CEUS is valuable for detecting microangiogenesis within MTrPs, and SPHK1/S1P plays an important role in promoting MTrP tissue microangiogenesis.

Assessment of the effects of transforming growth factor beta1 (TGF-ß1)-Smad2/3 on fibrosis in rat myofascial trigger points using point shear wave elastography.

Background & Aims: Myofascial trigger points (MTrPs) are highly sensitive irritated points within a tense belt of skeletal muscle, and are the main cause of muscle pain and dysfunction. MTrPs can also cause paraesthesia and autonomic nervous dysfunction. Furthermore, long-term and chronic MTrPs can cause muscle atrophy and even disability, seriously affecting the quality of life and mental health of patients, and increasing the social and economic burden. However, to date, there have been few studies on fibrogenesis and changes in MTrPs. Therefore, this study investigated whether transforming growth factor beta1 (TGF-ß1)-Smad2/3 participates in the formation of MTrPs and how it affects fibrosis using point shear wave elastography. Methods: Forty Sprague‒Dawley rats were randomly divided into the MTrPs group and the control group. Blunt injury combined with eccentric exercise was used to establish an MTrPs model. Electromyography (EMG), haematoxylin and eosin (H&E) staining and transmission electron microscopy (TEM) were used to verify the model. The collagen volume fraction was measured by Masson staining, the protein expression of TGF-ß1 and p-Smad2/3 was measured by Western blotting (WB) and immunohistochemistry (IHC), and the shear wave velocity (SWV) was measured by point shear wave elastography. Results: EMG, H&E and TEM examination indicated that the modelling was successful. The collagen volume fraction and the protein expression of TGF-ß1 and p-Smad2/3 were higher in the MTrPs group than in the control group. The SWV of the MTrPs group was also higher than that of the control group. These differences suggest that MTrPs may exhibit fibrosis. The correlations between the collagen volume fraction and SWV and between the collagen volume fraction and TGF-ß1 were positive. Conclusion: Fibrotic conditions may be involved in the formation of MTrPs. Ultrasound point shear wave elastography and assessment of TGF-ß1 and p-Smad2/3 expression can reflect the degree of MTrPs fibrosis to some extent. Further exploration of the important role of TGF-ß1 and Smad2/3 in the pathogenesis of MTrPs will be of great significance for clinical treatment.

Risk Factors of Contrast Agent Intravasation With Sulfur Hexafluoride Microbubble During Hysterosalpingo-Contrast Sonography.

OBJECTIVES: To analyze the risk factors of sulfur hexafluoride microbubble contrast agent intravasation during hysterosalpingo-contrast sonography (HyCoSy), and to explore a simple prediction model by the obvious clinical history. METHODS: This was a retrospective study included 299 infertility women who had undergone HyCoSy examination from July 1, 2018 to June 31, 2019. The factors were recorded, including age, endometrial thickness, balloon length, infertility type, history of intrauterine surgery, history of pelvic surgery, and tubal patency. The method of multivariate logistic regression analysis was adopted to analyze the risk factors affecting the contrast agent intravasation, and the receiver operating characteristic curves were plotted to test their efficacy. RESULTS: Secondary infertility, a history of intrauterine surgery, thin endometrial thickness, and tubal obstruction were all risk factors of the occurrence of intravasation (P < .05). And the area under the receiver operating characteristic curves of the multifactor-combined prediction model of the intravasation was significantly larger than that of single-factor. CONCLUSIONS: Sonographers and gynecologists should be familiar with the risk factors of intravasation and select the appropriate timing of HyCoSy toward reducing the occurrence of intravasation and other complications after thoroughly explaining and communicating with the patients.

Contrast Enhanced Ultrasonography of Kidney in Chronic Intermittent Hypoxia Rat Model.

OBJECTIVES: The objective of our study was to assess the ability of contrast-enhanced ultrasound (CEUS) in evaluating renal microperfusion in an animal model. METHODS: Twenty Sprague-Dawley rats were subdivided into two groups: the normal and chronic intermittent hypoxia (CIH) groups. In the CIH model, 10 Sprague-Dawley rats were exposed to CIH for 8 weeks to mimic obstructive sleep apnea (OSA). The CEUS parameters of the renal cortex and medulla were obtained and compared between groups. The pathological changes of the kidney tissues were examined by histological staining such as hematoxylin and eosin (H&E) and Masson's trichrome. RESULTS: CIH caused morphological damage to kidneys. In the cortex, the peak intensity (PI) (P = .009) was significantly lower and time to peak (Ttop) (P = .019) was significantly prolonged in the CIH group compared with the controls. The area under ascending curve (WiAUC) in the medulla and cortex were both significantly lower in the CIH group than those in the control group (P both <.05). CEUS parameters (including PI and WiAUC of the cortex and WiAUC of the medulla) were negatively correlated with serum creatinine (P all <.05). In the medulla, the area under descending curve (WoAUC) was positively correlated with serum creatinine (P = .027), PI was negatively correlated with uric acid (P = .034). CONCLUSION: CEUS parameters (including Ttop, PI, WoAUC, and WiAUC) reflect renal microvascular changes in CIH. CEUS could be a safe and accurate imaging method to assess renal microvascular damage in CIH rats.

Operator's Influence on Contrast Agent Intravasation During Hysterosalpingo-Contrast Sonography: Explanation Based on a Physics Model.

Objective: To analyze the risk factors of the operators on contrast agent intravasation during hysterosalpingo-contrast sonography (HyCoSy). Methods: We retrospectively collected 399 infertile women who underwent HyCoSy by the same sonographer. These patients were divided into two groups according to the way how the assistants connected the syringe to the uterus radiography catheter to inject the contrast agent. We analyzed whether the use of different contrast bolus injection methods had any influence on the incidence of intravasation during HyCoSy. Results: There was no significant difference between the two groups with different cross-sectional areas of the syringe outflow tract in the risk variables for intravasation, but the intravasation rates of the two groups were different, 26.4% in group A and 17.1% in group B, P <0.05. The primary manifestation was that when both fallopian tubes were unobstructed, the intravasation rate of group B with smaller cross-sectional area of the outflow tract of the syringe was lower, and the difference was statistically significant. The inferences drawn from our physics model were also in line with the clinical results. Conclusion: The influence of different operators on the contrast agent intravasation rate of HyCoSy cannot be ignored. The assistants of HyCoSy examination should inject the contrast agent slowly and steady, and a needle can be used as a flow restrictor to control the flow into the uterine cavity per unit time, slow down the rising speed of intrauterine pressure, and avoid the accumulation of contrast agent in the uterine cavity, so as to reduce the intravasation caused by operator factors.

A New Stemness-Related Prognostic Model for Predicting the Prognosis in Pancreatic Ductal Adenocarcinoma.

OBJECTIVE: This study is aimed at identifying stemness-related genes in pancreatic ductal adenocarcinoma (PDAC). METHODS: The RNA-seq data of PADC patients were downloaded from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. The mRNA expression-based stemness index (mRNAsi) and epigenetically regulated mRNAsi (EREG-mRNAsi) of PADC patients were evaluated. The mRNAsi-related gene sets in PADC were identified by weighted gene coexpression network analysis (WGCNA). The key genes were further analyzed using functional enrichment analysis. The Kaplan-Meier survival analysis and the Cox proportional hazards model were used to evaluate the prognostic value of the key genes. Prognostic hub genes were used to establish nomograms. The receiver operating characteristic (ROC) curves, concordance index (C-index), and calibration curves were used to assess the discrimination and accuracy of the nomogram. Finally, these results were validated in the Gene Expression Omnibus (GEO) database. RESULTS: A total of 36 key genes related to mRNAsi were identified by WGCNA. A prognostic gene signature compromising seven genes (TPX2, ZWINT, UBE2C, CCNB2, CDK1, BUB1, and BIRC5) was established to predict the overall survival (OS) of PADC patients. The Cox regression analysis revealed that the risk score was an independent prognostic factor for PADC. Patients were then divided into the high-risk and low-risk groups. The ROC curves, C-index, and calibration curves indicated good performance of the prognostic signature in the TCGA and GEO datasets. Moreover, the nomogram incorporating clinical parameters showed better sensitivity and specificity for predicting the OS of PADC patients. CONCLUSION: The stemness-related prognostic model successfully predicted the OS of PADC patients and could be used for the treatment of PADC.

An Epithelial-Mesenchymal Transition Hallmark Gene-Based Risk Score System in Head and Neck Squamous-Cell Carcinoma.

BACKGROUND: Epithelial-to-mesenchymal transition (EMT) program plays a critical role in cancer. Thus, we attempted to generate a risk score system according to the expression pattern of different EMT hallmark genes in head and neck squamous-cell carcinoma (HNSC). METHODS: Differentially expressed EMT hallmark genes were screened to generate a risk score (RS) on TCGA HNSC dataset. The relative prognostic value of the RS compared to clinicopathological characteristics was explored using multivariable Cox analysis. Functional enrichment analysis was performed to reveal the biological characteristics. An external dataset was applied to validate the prognostic value of the RS. RESULTS: Nine genes constituted the EMT hallmark gene-based RS, which is significantly associated with poor prognosis and could successfully divide patients with HNSC into high- and low-risk groups. The RS was also an independent prognostic indicator compared to routine clinical factors. CONCLUSION: We proposed and validated a nine-EMT hallmark gene-based risk score system in HNSC.

Half-Brain Delineation for Prediction of Radiation-Induced Temporal Lobe Injury in Nasopharyngeal Carcinoma Receiving Intensity-Modulated Radiotherapy.

PURPOSE: To investigate the role of half-brain delineation in the prediction of radiation-induced temporal lobe injury (TLI) in nasopharyngeal carcinoma (NPC) receiving intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS: A total of 220 NPC cases treated with IMRT and concurrent platinum-based chemotherapy were retrospectively analyzed. Dosimetric parameters of temporal lobes, half-brains, and brains included maximum dose (Dmax), doses covering certain volume (DV) from 0.03 to 20 cc and absolute volumes receiving specific dose (VD) from 40 to 80 Gy. Inter-structure variability was assessed by coefficients of variation (CV) and paired samples t-tests. Receiver operating characteristic curve (ROC) and Youden index were used for screening dosimetric parameters to predict TLI. Dose/volume response curve was calculated using the logistic dose/volume response model. RESULTS: CVs of brains, left/right half-brains, and left/right temporal lobes were 9.72%, 9.96%, 9.77%, 27.85%, and 28.34%, respectively. Each DV in temporal lobe was significantly smaller than that in half-brain (P < 0.001), and the reduction ranged from 3.10% to 45.98%. The area under the curve (AUC) of DV and VD showed an "increase-maximum-decline" behavior with a peak as the volume or dose increased. The maximal AUCs of DVs in brain, half-brain and temporal lobe were 0.808 (D2cc), 0.828 (D1.2cc) and 0.806 (D0.6cc), respectively, and the maximal AUCs of VDs were 0.818 (D75Gy), 0.834 (V72Gy) and 0.814 (V70Gy), respectively. The cutoffs of V70Gy (0.86 cc), V71Gy (0.72 cc), V72Gy (0.60 cc), and V73Gy (0.45 cc) in half-brain had better Youden index. TD5/5 and TD50/5 of D1.2cc were 58.7 and 80.0 Gy, respectively. The probability of TLI was higher than >13% when V72Gy>0 cc, and equal to 50% when V72Gy = 7.66 cc. CONCLUSION: Half-brain delineation is a convenient and stable method which could reduce contouring variation and could be used in NPC patients. D1.2cc and V72Gy of half-brain are feasible for TLI prediction model. The dose below 70 Gy may be relatively safe for half-brain. The cutoff points of V70-73Gy could be considered when the high dose is inevitable.

Effectiveness of contrast-enhanced ultrasound for detecting the staging and grading of bladder cancer: a systematic review and meta-analysis.

AIM: The study retrospectively analysed the accuracy of preoperative contrast-enhanced ultrasound (CEUS) in differenti-ating stage Ta-T1 or low-grade bladder cancer (BC) from stage T2 or high-grade bladder cancer. MATERIAL AND METHODS: We systematically searched the literature indexed in PubMed, Embase, and the Cochrane Library for original diagnostic articles of bladder cancer. The diagnostic accuracy of CEUS was compared with cystoscopy and/or transurethral resection of bladder tumors (TURBT). The bivariate logistic regression model was used for data pooling, couple forest plot, diagnostic odds ratio (DOR) and summary receiver operating characteristic (SROC). RESULTS: Five studies met the selection criteria; the overall number of reported bladder cancers patients were 436. The pooled-sensitivity (P-SEN), pooled-specificity (P-SPE), pooled-positive likelihood ratio (PLR+), pooled-negative likelihood ratio (PLR-), DOR, and area under the SROC curve were 94.0% (95%CI: 85%-98%), 90% (95%CI: 83%-95%), 9.5 (95%CI: 5.1-17.6), 0.06 (95%CI: 0.02-0.17), 147 (95%CI: 35-612) and 97% (95% CI: 95%-98%) respectively. CONCLUSION: CEUS reaches a high efficiency in discriminating Ta-T1 or low-grade bladder cancer from stage T2 or high-grade bladder cancer. It can be a promising method in patients to distinguish T staging and grading of bladder cancer because of its high sensitivity, specificity and diagnostic accuracy.

Assessment of the effects of ischaemia/ hypoxia on angiogenesis in rat myofascial trigger points using colour Doppler flow imaging.

BACKGROUND & AIMS: Myofascial pain syndrome (MPS) is a common non-articular disorder of the musculoskeletal system that is characterized by the presence of myofascial trigger points (MTrPs). Despite the high prevalence of MPS, its pathogenesis, which induces the onset and maintenance of MTrPs, is still not completely understood. To date, no studies have investigated the changes in the biochemical milieu caused by ischaemia/hypoxia in the MTrP regions of muscle that are proposed in the integrated hypothesis. Therefore, this study investigated whether ischaemic/hypoxic conditions participate in the formation of active MTrPs and affect angiogenesis using colour Doppler flow imaging (CDFI). METHODS: Twenty-five Sprague-Dawley rats were randomly divided into a model group and a normal control group. A model of active MTrPs was established by a blunt strike combined with eccentric exercise. Enzyme-linked immunosorbent assays (ELISAs) were employed to detect the levels of HIF-1α and VEGF. Microvessel density (MVD) was evaluated using immunohistochemistry. CDFI was applied to observe the blood flow signals in the MTrPs, which were classified into four grades based on their strengths. RESULTS: Compared with the control group, the active MTrP group exhibited significantly higher HIF-1α and VEGF levels and MVD values. These differences were accompanied by increased blood flow signals. In the active MTrP group, the blood flow signal grade was positively correlated with the MVD (P < 0.05) and independently correlated with the VEGF level (P < 0.05) but was not correlated with the expression of HIF-1α (P > 0.05). CONCLUSION: Ischaemic/hypoxic conditions may be involved in the formation of MTrPs. CDFI is useful for detection of the features of angiogenesis in or surrounding MTrPs via assessment of blood flow signals.

Identification of Potential Biomarkers and Biological Pathways in Juvenile Dermatomyositis Based on miRNA-mRNA Network.

OBJECTIVE: The aim of this study is to explore the potential pathogenesis of juvenile dermatomyositis by bioinformatics analysis of gene chips, which would screen the hub genes, identify potential biomarkers, and reveal the development mechanism of juvenile dermatomyositis. MATERIAL AND METHODS: We retrieved juvenile dermatomyositis's original expression microarray data of message RNAs (mRNAs) and microRNAs (miRNAs) from NCBI's Gene Expression Omnibus database (GEO, http://www.ncbi.nlm.nih.gov/geo/); through the R package of limma in Bioconductor, we can screen the differentially expressed miRNAs and mRNAs, and then we further analyzed the predicted target genes by the methods such as Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and miRNA-mRNA regulatory network construction and protein-protein interaction (PPI) network using Cytoscape 3.6.1. RESULTS: Compared with normal juvenile skin tissues, 6 upregulated microRNAs and 5 downregulated microRNAs were identified from 166 downregulated microRNAs and 58 upregulated microRNAs in juvenile dermatomyositis tissues. The enrichment pathways of differentially expressed microRNAs include cell adhesion molecules (CAMs), autoimmune thyroid disease, Type I diabetes mellitus, antigen and presentation, viral myocardium, graft-versus-host disease, and Kaposi sarcoma-associated herpes virus infection. By screening of microRNA-messenger RNA regulatory network and construction of PPI network map, three target miRNAs were identified, namely, miR-193b, miR-199b-5p, and miR-665. CONCLUSION: We identified mir-193b, mir-199b-5p, and mir-6653 target miRNAs by exploring the miRNA-mRNA regulation network mechanism related to the pathogenesis of juvenile dermatomyositis, which will be of great significance for further study on the pathogenesis and targeted therapy of juvenile dermatomyositis.

Sonographic Assessment of Oropharynx Movement During Deep Breathing.

To investigate the feasibility of ultrasonography in detecting the oropharynx movement during deep breathing and to quantitatively analyze oropharynx airway lumen changes during deep breathing. The motions of oropharynx were monitored, and sonographic measurements of airway lumen were obtained during deep breathing in 448 healthy volunteers. Adequate visualization of oropharynx movement was obtained on all healthy volunteers. The anterior-posterior (AP) diameters and AP/transverse (T) diameter ratios were greater at the end of deep inspiration than that at the end of deep expiration for each sex (p < 0.01). The anterior-posterior dimensional changes were greater than lateral airway dimensional changes each sex (p < 0.05). Ultrasonography could provide realistic impression of the process on the oropharynx movement during deep breathing and perform the quantitative analysis of the oropharynx airway lumen changes during deep breathing. The results were encouraging and supported the utility of ultrasonography in future studies.

Contrast-enhanced Ultrasound in evaluating of angiogenesis and tumor staging of nasopharyngeal carcinoma in nude mice.

OBJECTIVE: To explore the use of Contrast-enhanced Ultrasound (CEUS) in evaluating angiogenesis in a xenograft nasopharyngeal carcinoma (NPC) model in nude mice and the evolution of CEUS parameters according to the growth of NPC. METHODS: Nude mice were divided into three groups according to experiments conducted at various times from tumor implantation (8 mice/group; group A: 4 weeks from implantation; group B:6 weeks from implantation; group C:8 weeks from implantation). CNE-2 cells were transplanted in 24 nude mice and CEUS evaluations of the tumors were performed at 4, 6 or 8 weeks from implantation. CEUS parametric perfusion images and pathological findings were recorded. R version 3.4.4 software was used to analyze the CEUS parameters and pathological findings. RESULTS: One-way anova analysis indicated statistically significant differences among the three groups with the parameters of peak intensity (PI) (p<0.001), area wash in (AWI) (p<0.001), area wash out (AWO) (p<0.001) and tumor volumes (p<0.001).Pearson correlation coefficient analysis indicated that microvessel density (MVD) was correlated with tumor volume (r = 0.644, p = 0.001), PI (r = 0.904, p<0.0001), AWI (r = 0.547, p = 0.008) and AWO (r = 0.744, P<0.0001). Tumor volume was correlated with MVD (r = 0.644, p = 0.001), PI (r = 0.625, p = 0.002), AWI (r = 0.528, p = 0.012) and AWO (r = 0.784, p<0.001). The percentage of necrosis in histological sections was correlated with the percentage of CEUS unperfused area (r = 0.446,p = 0.038). Spearman rank correlation coefficient analysis indicated that vascular endothelial growth factor (VEGF) was correlated with PI (r = 0.462, P = 0.032). Welch t test indicated PI, AWI and AWO parameters were significantly lower than that of kidneys (p<0.001, p = 0.009, p = 0.005). CONCLUSIONS: The CEUS parameters PI, AWI and AWO indirectly reflect the MVD and the tumor volume in our model of subcutaneous transplanted NPC in nude mice, providing precious information on angiogenesis and tumor growth. VEGF may play a role in promoting angiogenesis of NPC.

Contrast-enhanced ultrasonography of nasopharyngeal carcinoma: enhancement patterns and quantitative parameters.

OBJECTIVE: The aim of this study was to investigate the characteristics of nasopharyngeal carcinoma (NPC) using contrast-enhanced ultrasonography (CEUS), including the enhancement patterns and the quantitative parameters. METHODS: Having been scanned using conventional ultrasonography (US) and CEUS, every case was confirmed to be NPC under endoscopic biopsy, and no case received any anti-tumor treatment before CEUS examinations. Tumor/node/metastasis stages were determined in accordance with 2002 AJCC 6th edition. Contrast enhancement patterns and quantitative parameters were observed. RESULTS: CEUS imaging of NPC showed that the tumor signal intensity enhanced early, rapidly, and remarkably, and decreased slowly later. The patterns of enhancement included spot/linear enhancement, peripheral enhancement, and mass enhancement, and two types of time intensity curves of NPC included type I and type II. There was a significant difference between peak intensity (PI) and T stage (P<0.05), whereas time-to-peak (TP) and slope did not show significant differences with T stage (P>0.05). CONCLUSION: CEUS is feasible to be applied to the nasopharynx region. The use of CEUS makes it possible to observe vascular permeability of NPC. Our results suggest that the quantitative parameter PI of nasopharyngeal carcinoma is significantly different from T stages. Thus, PI may serve as a potential noninvasive radiological prognostic indicator for NPC.

Clinical evaluation of vascular normalization induced by recombinant human endostatin in nasopharyngeal carcinoma via dynamic contrast-enhanced ultrasonography.

BACKGROUND: The present study confirmed the presence and exact range of "vascular normalization window" induced by recombinant human endostatin (RHES) in patients with nasopharyngeal carcinoma (NPC) by analyzing the variation of dynamic contrast-enhanced ultrasonography (DCE-US) quantitative parameters. Also, the clinical application of DCE-US in the evaluation of vascular normalization was assessed. MATERIALS AND METHODS: A total of 30 previously untreated patients with stage III-IVA NPC were enrolled in the present study and were randomly but equally divided into RHES (endostar [ES]) and normal saline (NS) groups. The patients in the ES group were administered RHES intravenously, while the patients in the NS group were administered normal saline daily for 5 days prior to intensity modulated radiotherapy coupled with concurrent chemotherapy. All patients underwent DCE-US on the day before the administration and on days 3 and 5 subsequently. The Audio Video Interleave of each DCE-US examination was analyzed quantitatively using the CHI-Q software. Several parameters were investigated, such as peak intensity (PI), time to peak (TTP), and mean transit time (MTT). RESULTS: The PI, TTP, and MTT differed significantly at the three time points in the ES group (all P<0.001) but not in the NS group (all P>0.05). In the ES group, PI increased and subsequently decreased, whereas TTP, as well as MTT, lessened initially and then increased within the 5 days after administration of RHES. The maximum value of PI and the minimum value of TTP, as well as MTT, occurred on day 3 (all P<0.05). Furthermore, the values of PI, TTP, and MTT were similar prior to the administration of RHES in both groups (all P>0.05). However, the PI of the ES group was significantly higher (P<0.05), whereas the TTP and the MTT were significantly lower following administration of RHES (all P<0.05) compared with the corresponding parameters of the NS group. CONCLUSION: DCE-US is a suitable method for the clinical evaluation of vascular normalization induced by antiangiogenic agents. The "vascular normalization window" induced by RHES occurs in patients with NPC, and the exact range is within about 5 days post-administration, which contributes towards optimizing the modality of RHES combined with radiotherapy and chemotherapy for NPC patients.

T-Staging of maxillary sinus carcinoma: comparison of ultrasonography and computed tomography.

RATIONALE AND OBJECTIVES: Accurate staging forms the basis for the successful management of maxillary sinus carcinoma. The purpose of this study was to compare the efficacy of ultrasonography and computed tomography (CT) for detection and T-staging of maxillary sinus carcinoma. MATERIAL AND METHODS: T-staging of maxillary sinus carcinoma by ultrasonography and CT was studied in 37 patients: 25 with squamous cell carcinoma and 12 with tumors of other histologic types. The sites involved by the tumor were studied, and T-staging was performed using ultrasonography and CT, respectively, according to American Joint Committee classification system for maxillary sinus carcinoma. The accuracy of the two techniques was compared with the surgical and pathological findings. RESULTS: The diagnostic accuracy was evaluated considering histopathology as the gold standard. Of these 37 maxillary sinus tumors, 4 were staged T2, 24 were staged T3, 9 were staged T4, and none was staged T1. There was one T2 stage maxillary sinus carcinoma which was not detected by ultrasonography. Five T3 cancers were upstaged and one T3 was downstaged using ultrasonography. One T3 and one T4 were upstaged and one T3 was downstaged using CT. With regard to T staging, the overall accuracy was 81.1% for ultrasonography and 91.8% for CT. There was no statistically significant difference between the pretherapeutic T-staging accuracy of ultrasonography and CT (P=0.219). CONCLUSION: Ultrasonography is a sensitive technique for detecting soft tissue involvement and invasion of orbital contents. It can differentiate maxillary sinusitis from tumor with a reasonable accuracy. As of today, ultrasonography cannot replace CT scan, though it can be a valuable adjunct to CT for the initial evaluation and T-staging of maxillary sinus carcinoma.

Investigation of the Upper Airway Anatomy With Ultrasound.

OBJECTIVE: The aims of this study were to describe the relationship between the scanning planes and appearance of the upper airway on sonography and to demonstrate the reliability and reproducibility of sonographic measurements of the upper airway. METHODS: Airway sonoanatomy was recognized by comparing the airway images and the corresponding cadaver's anatomical specimens. Systemic sonographic examination of 267 healthy volunteers was conducted to obtain the sonographic measurement of airway lumen. The reliability and reproducibility studies were conducted in 40 healthy volunteers. RESULT: The air-filled upper airway appeared as a bright heterogeneous hyperechoic line. During deep inspiration, the upper airway lumen expanded to the highest anterior-posterior dimension, whereas during deep expiration, the lateral dimension tended to increase. The sonographic measurements had good reproducibility, with intraclass correlation coefficient ranging from 0.722 to 0.887 and 0.727 to 0.882 for interobserver and intraobserver reliability, respectively. CONCLUSIONS: Ultrasonography can determine the anatomy of the upper airway and perform the quantitative analysis of the upper airway lumen during respiration. The results were encouraging and support the utility of ultrasonography in future airway disorder studies.

Sonography for diagnosis of benign and malignant tumors of the nose and paranasal sinuses.

OBJECTIVES: The purpose of this study was to demonstrate the reliability of sonography for diagnosis of nose and paranasal sinus tumors. METHODS: Ninety-six consecutive patients with tumors underwent sonography and computed tomography (CT) before surgical treatment. Tumor detectability and imaging findings were evaluated independently and then compared with pathologic findings. RESULTS: Of 96 tumors, 75 were detected by sonography, for a detectability rate of 78.1%; 93 tumors were detected by CT, for a detectability rate of 96.9%. By comparison, sonography showed a trend toward higher detectability of nasal vestibular tumors than CT (87.5% for sonography versus 50.0% for CT) and small lumps on the wing of the nose (78.8% for sonography versus 33.3% for CT). Among the sonographic features, boundary, shape, internal echo, calcification, bone invasion, vascular pattern, and cervical lymph node metastasis all had significantly positive correlations with malignancy (P < .05), but size did not (P = .324). In addition, the vascular resistive index for malignant tumors was significantly higher (mean ± SD, 0.66 ± 0.20) than the index for benign lesions (0.24 ± 0.30; P < .001). Moreover, the detection rate for grade 1-3 (small-large) blood flow in benign lesions was only 43.8%, whereas the rate for malignant tumors was 97.7% (P < .001). CONCLUSIONS: The vascular pattern may be a promising predictive indicator for distinguishing benign and malignant tumors of the nose and paranasal sinuses. Consequently, sonography has high value for diagnosis of benign and malignant tumors of the nose and paranasal sinuses, especially for nasal vestibular tumors and small lumps on the wing of the nose.