Quantitative Contrast-enhanced Ultrasound Parameters Research Articles

The diagnositic value of dynamic contrast-enhanced ultrasound for evaluation of tissue oxygen status in rat hepatoma model

BackgroundHypoxia is a characteristic of solid tumors, but whether significant hypoxia exists in the hepatocellular carcinoma remains unclear. This animal study aims to explore the value of dynamic contrast-enhanced ultrasound (CEUS) quantitative parameters to evaluate the oxygen status in two rat hepatoma models.Materials and methodsN1S1 and McA-RH7777 S-D rat orthotopic hepatoma models were established. Once the tumors reached a diameter of 10–15 mm, CEUS and oxygen partial pressure (pO2) polarography were performed. Immunohistochemical staining for HIF-1α and pimonidazole was conducted after euthanizing the rats. Correlation between quantitative CEUS parameters, pO2, and the immunohistochemical integrated optical density (IOD) was analyzed to assess the predictive ability of CEUS quantitative parameters for the tissue oxygen environment.ResultEleven N1S1 models and ten McA-RH7777 models were established successfully. There was no significant difference in pO2 (35.5 mmHg vs 32.2 mmHg, P = 0.917), IOD of HIF-1α (13.4 vs 20.0, P = 0.159) and pimonidazole (0.70 vs 1.30, P = 0.926) between the tumor and the peritumoral liver tissue. The pO2 values were correlated with CEUS quantitative parameters including mean time-intensity curves (mTIC) (P = 0.003), peak intensity (PKI) (P = 0.010), area under the curve (AUC) (P = 0.009), area under the wash-in curve (WiAUC) (P = 0.006), and arrival time (AT) (P = 0.033). The IOD of HIF-1α correlated with AUC (P = 0.022), WiAUC (P = 0.009), ascending slope (AS) (P = 0.044), and falling time (FT) (P = 0.009). Multiple linear regression indicated that the “short AT” was an independent protective factor for hypoxia (β = -2.347, 95% CI: -4.948, -0.394, P = 0.022), and CEUS had the ability to predict the tumor pO2 (P = 0.003).ConclusionNo evidence of significant hypoxia was identified in two rat orthotopic hepatoma models. Quantitative CEUS parameters correlated with the oxygen status of the tumor, which could be utilized to predict the tumor tissue pO2.

Machine learning model based on dynamic contrast-enhanced ultrasound assisting LI-RADS diagnosis of HCC: A multicenter diagnostic study

BackgroundTo enhance the accuracy of hepatocellular carcinoma (HCC) diagnosis using contrast-enhanced (CE) US, the American College of Radiology developed the CEUS Liver Imaging Reporting and Data System (LI-RADS). However, the system still exhibits limitations in distinguishing between HCC and non-HCC lesions. PurposeTo investigate the viability of employing machine learning methods based on quantitative parameters of contrast-enhanced ultrasound for distinguishing HCC within LR-M nodules. Materials and methodsThis retrospective analysis was conducted on pre-treatment CEUS data from liver nodule patients across multiple centers between January 2013 and June 2022. Quantitative analysis was performed using CEUS images, and the machine learning diagnostic models based on quantitative parameters were utilized for the classification diagnosis of LR-M nodules. The performance of the model was assessed using the area under the receiver operating characteristic curve (AUC) and compared with the performance of four radiologists. ResultsThe training and internal testing datasets comprised 168 patients (median age, 53 years [IQR, 18 years]), while the external testing datasets from two other centers included 110 patients (median age, 54 years [IQR, 16 years]). In the internal independent test set, the top-performing Random Forest model achieved an AUC of 0.796 (95%CI: 0.729–0.853) for diagnosing HCC. This model exhibited a sensitivity of 0.752 (95%CI: 0.750–0.755) and a specificity of 0.761 (95%CI: 0.758–0.764), outperforming junior radiologists who achieved an AUC of 0.619 (95%CI: 0.543–0.691, p < .01) with sensitivity and specificity of 0.716 (95%CI: 0.713–0.718) and 0.522 (95%CI: 0.519–0.526), respectively. ConclusionSignificant differences in contrast-enhanced ultrasound quantitative parameters are observed between HCC and non-HCC lesions. Machine learning models leveraging these parameters effectively distinguish HCC categorized as LR-M, offering a valuable adjunct for the accurate classification of liver nodules within the CEUS LI-RADS framework.

Contrast-enhanced ultrasound (CEUS) characteristics of atypical-enhanced papillary thyroid carcinoma (PTC).

To investigate the diagnostic value of CEUS in atypical-enhanced PTC. The clinical data, qualitative and quantitative parameters of CEUS in 177 Iso/hyper-enhanced thyroid nodules with definite pathological results were retrospectively analyzed in the Lanzhou University Second Hospital from June 2019 to January 2021. And the clinical value of CEUS in the diagnosis of atypical-enhanced PTC was assessed using univariate and multivariate analysis. Among the 177 thyroid nodules, 59 were benign and 118 were PTC. There were significant differences in age, enhancement border, ring enhancement, speed of wash in, speed of wash out, enhancement pattern, capsule interruption, time to peak, time to wash out, RT, TPH, and TTP (P < 0.05). Multivariate analysis showed unclear enhancement border and concentric enhancement were independent risk factors for the diagnosis of atypical-enhanced PTC by CEUS. The sensitivity, specificity, PPV, NPV, and accuracy of the model in diagnosing atypical-enhanced PTC were 88.1%, 71.2%, 86.0%, 75.0%, and 82.5%, respectively. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve was 0.910. The diagnosis of atypical-enhanced PTC can be better performed by enhancement characteristics and time intensity curve (TIC) of CEUS, which have a good clinical application value.

Quantitative and qualitative analysis of contrast-enhanced ultrasound for differentiating benign and malignant superficial enlarged lymph nodes.

In many clinical situations, it is critical to exclude or identify abnormally lymph nodes (LNs). The nature of superficial abnormally LNs is closely related to the stage, treatment, and prognosis of the disease. Ultrasound (US) is an important method for examining superficial LNs due to its cheap and safe characteristics. However, it is still difficult to determine the nature of some LNs with overlapping benign and malignant features in images. Contrast-enhanced ultrasound (CEUS) can be used to evaluate the microperfusion status of tissues in real time, and it can improve diagnostic accuracy to a certain extent. Therefore, in this study, we will analyze the correlation between CEUS quantitative parameters and benign and malignant superficial abnormally LNs, to evaluate the efficacy and value of CEUS in distinguishing benign and malignant superficial LNs. This study retrospectively analyzed 120 patients of abnormal LNs who underwent US and CEUS at the China-Japan Union Hospital of Jilin University from December 2020 to August 2023. All 120 cases of abnormal LNs underwent US-guided coarse needle biopsy, and accurate pathological results were obtained, along with complete US and CEUS images. According to the pathological results, LNs were divided into benign and malignant groups, and the qualitative and quantitative parameters of US and CEUS between the two groups were analyzed. The cutoff value is determined by the receiver operating characteristic (ROC) curve of the subjects, and sensitivity, specificity, and accuracy are applied to evaluate the ability of the cutoff value to distinguish between the two groups. There were a total of 120 LNs, including 36 in the benign group and 84 in the malignant group. The results showed that malignant LNs were usually characterized by the disappearance of lymphatic hilum, round ness index (L/T) <2, irregular morphology, and the manifestation of uneven perfusion (P<0.05). The differences in the quantitative parameters peak enhancement (PE), rise time (RT), time to peak (TTP), wash-in rate (WIR), and wash-out rate (WOR) were statistically significant (P<0.05). The result showed that RT and TTP in the malignant LNs were higher than those in the benign LNs, while the PE, WIR, and WOR were lower. A comparison of the ∆ values showed that the differences in ∆PE, ∆WIR, and ∆fall time (FT) were statistically significant (P<0.05), Among them, the ∆PE and ∆WIR of malignant LNs were higher than those of benign LNs, while the ∆FT was lower than that of benign LNs. Quantitative analysis of CEUS features is valuable in the diagnosis of benign and malignant LNs, and US combined with CEUS helps to improve the accuracy of identifying the nature of LNs.

Contrast-enhanced ultrasound features as a potential biomarker for the prediction of breast cancer recurrence.

To investigate the associations between contrast-enhanced ultrasound imaging features and disease recurrence among patients with locally advanced breast cancer treated with neoadjuvant chemotherapy. In the study, pre- and post-neoadjuvant chemotherapy contrast-enhanced ultrasound images of 43 patients with breast cancer were retrospectively analysed. Post-acquisition image processing involved the placement of freehand-drawn regions of interest, followed by the generation of blood flow kinetics representing blood volume and velocity for these regions of interest. Qualitative and quantitative contrast-enhanced ultrasound parameters were compared to predict recurrence, and receiver operating characteristic analysis was used to evaluate predictive ability. Among the 43 patients, 10 (23%) exhibited disease recurrence (median [range]: 27 [4-68] months). Post-neoadjuvant chemotherapy peak enhancement, wash-in area under the curve, wash-out area under the curve, and wash-in and wash-out area under the curve (p=0.003, p=0.004, p=0.026, and p=0.014, respectively) differed between the no-recurrence and recurrence groups. The area under the receiver operating characteristic curve (0.88; 95% confidence interval: 0.75-1.00) for post-neoadjuvant chemotherapy peak enhancement was the highest among the contrast-enhanced ultrasound parameters, with a cut-off of 13.33 arbitrary units. Higher peak enhancement on post-neoadjuvant chemotherapy contrast-enhanced ultrasound images was associated with recurrence in women with locally advanced breast cancer and is a potential biomarker of tumor recurrence.

Application of Dynamic Contrast-Enhanced Ultrasound in Evaluation the Activity of Crohn's Disease.

The dynamic assessment of disease activity during the follow-up of patients with Crohn's disease (CD) remains a significant challenge. In this study, we aimed to identify the role of dynamic contrast-enhanced ultrasound (DCE-US) in the evaluation of activity of CD. In the retrospective study, patients diagnosed with CD in our hospital were included. All the diagnoses were confirmed by clinical symptoms and ileocolonoscopical results. All patients underwent intestinal ultrasound and contrast-enhanced ultrasound (CEUS) examinations within 1 week of the ileocolonoscopy examinations. Acuson Sequoia (Siemens Healthineers, Mountain View, CA, USA) and Resona R9 Elite (Mindray Medical Systems, China) with curved array and Line array transducers were used. The CEUS examination was performed with SonoVue (Bracco SpA, Milan, Italy). DCE-US analysis was performed by UltraOffice (version: 0.3-2010, Mindray Medical Systems, China) software. Two regions of interest (ROIs) were set in the anterior section of the infected bowel wall and its surrounding normal bowel wall 2 cm distant from the inflamed area. Time-intensity curves (TICs) were generated and quantitative perfusion parameters were obtained after curve fittings. The Simple Endoscopic Score for Crohn's disease (SES-CD) was regarded as the reference standard to evaluate the activity of CD. The receiver operating characteristic curve (ROC) analyses were used to determine the diagnostic efficiency of DCE-US quantitative parameters. From March 2023 to November 2023, 52 CD patients were included. According to SES-CD score, all patients were divided into active group with the SES-CD score > 5 (n = 39) and inactive group SES-CD score < 5 (n = 13). Most of the active CD patients showed bowel wall thickness (BWT) > 4.2 mm (97.4%, 38/39) or mesenteric fat hypertrophy (MFH) on intestinal ultrasound (US) scan (69.2%, 27/39). Color Doppler signal of the bowel wall mostly showed spotty or short striped blood flow signal in active CD patients (56.4%, 22/39). According to CEUS enhancement patterns, most active CD patients showed a complete hyperenhancement of the entire intestinal wall (61.5%, 24/39). The TICs of active CD showed an earlier enhancement, higher peak intensity, and faster decline. Among all CEUS quantitative parameters, amplitude-derived parameters peak enhancement (PE), wash-in area under the curve (WiAUC), wash-in rate (WiR), wash-in perfusion index (WiPI), and wash-out rate (WoR) were significantly higher in active CD than in inactive CD (p < 0.05). The combined AUROC of intestinal ultrasound features and DCE-US quantitative perfusion parameters in the diagnosis of active CD was 0.987, with 97.4% sensitivity, 100% specificity, and 98.1% accuracy. DCE-US with quantitative perfusion parameters is a potential useful noninvasive imaging method to evaluate the activity of Crohn's disease.

Quantitative parameters of contrast-enhanced ultrasound effectively promote the prediction of cervical lymph node metastasis in papillary thyroid carcinoma.

Papillary thyroid carcinoma (PTC), the most common endocrine tumor, often spreads to cervical lymph nodes metastasis (CLNM). Preoperative diagnosis of CLNM is important when selecting surgical strategies. Therefore, we aimed to explore the effectiveness of quantitative parameters of contrast-enhanced ultrasound (CEUS) in predicting CLNM in PTC. We retrospectively analyzed 193 patients with PTC undergoing conventional ultrasound (CUS) and CEUS. The CUS features and quantitative parameters of CEUS were evaluated according to PTC size ≤ 10 or > 10 mm, using pathology as the gold standard. For the PTC ≤ 10 mm, microcalcification and multifocality were significantly different between the CLNM (+) and CLNM (-) groups (both P < 0.05). For the PTC > 10 mm, statistical significance was noted between the two groups with respect to the margin, capsule contact, and multifocality (all P < 0.05). For PTC ≤ 10 mm, there was no significant difference between the CLNM (+) and CLNM (-) groups in all quantitative parameters of CEUS (all P > 0.05). However, for PTC > 10 mm, the peak intensity (PI), mean transit time, and slope were significantly associated with CLNM (all P < 0.05). Multivariate analysis showed that PI > 5.8 dB was an independent risk factor for predicting CLNM in patients with PTC > 10 mm (P < 0.05). The area under the curve of PI combined with CUS (0.831) was significantly higher than that of CUS (0.707) or PI (0.703) alone in the receiver operator characteristic curve analysis (P < 0.05). In conclusion, PI has significance in predicting CLNM for PTC > 10 mm; however, it is not helpful for PTC ≤ 10 mm.

Effect of quantitative parameters of contrast-enhanced ultrasound on the long-term prognosis of patients with chronic coronary syndrome.

Ultrasound is one of the most commonly used examination methods in patients with coronary artery disease (CAD) and is valuable in evaluating patient prognosis. Although contrast-enhanced ultrasound (CEUS) can assess more in depth the vascular lesions of patients, there is still a lack of relevant research on the value of quantitative parameters of CEUS in predicting the long-term prognosis of patients with chronic coronary syndrome (CCS), thus, we designed this study. From January 2016 to December 2017, a total of 473 patients with CCS admitted to Yueyang People's Hospital were retrospectively enrolled. The patients were followed up for five years. According to whether the patients had major adverse cardiovascular events (MACE), patients were divided into the MACE group (n=113) and the control group (n=360). The CEUS was performed to detect the myocardial perfusion status. The value of quantitative parameters of CEUS in predicting the MACE in patients with CCS was analyzed using the receiver operating characteristic (ROC) curve. Peak intensity of contrast agent at platform stage, rising rate of microbubble reperfusion, and left ventricular ejection fraction (LVEF) were found to be valuable in predicting the risk of MACE in patients with CCS. Among them, the peak intensity of contrast agent at platform stage had the highest predictive value, and the area under the curve (AUC) was 0.860 [95% confidence interval (CI): 0.827-0.894, P<0.001]. Multivariate logistics regression analysis showed that the peak intensity of contrast agent at platform stage <4.54 dB and rising rate of microbubble reperfusion <0.275 s were independent risk factors of MACE in patients with CCS. The relative risks were 12.238 (95% CI: 6.632-22.585) and 5.724 (95% CI: 3.149-10.405), respectively. Quantitative parameters of CEUS can be used as predictors of MACE in patients with CCS, and strengthening the management of such high-risk patients may be beneficial to reduce the incidence of MACE.

Contrast-Enhanced Ultrasound and Conventional Ultrasound Characteristics of Breast Cancer With Different Molecular Subtypes

BackgroundIdentifying molecular subtypes of breast cancer (BC) is of great significance in selecting optimal treatment strategy. Different molecular subtypes of BC have various vascular distribution characteristics. Contrast-enhanced ultrasound (CEUS) can dynamically display the microcirculation of tumor. This study intends to explore the conventional ultrasound and CEUS characteristics of different molecular subtypes of BC. MethodsDuring this prospective study, 86 patients with BC who were divided into Luminal A (LA), Luminal B (LB), HER2 over-expression (H2), and triple-negative (TN). The CEUS qualitative and quantitative characteristics of BC with different molecular subtypes was explored, as well as the conventional ultrasound features. In addition, the diagnostic efficiency of CEUS quantitative parameters in differentiating molecular subtypes of BC was analyzed. ResultsOur study found that the Adler grade differed significantly among 4 molecular subtypes (P < .05). The enhancement speed, enhancement degree and size after enhancement of 4 molecular subtypes were statistically different (P < .05). The wash in slope (WIS), peak intensity (PI), and wash-in area under the curve (WiAUC) differed significantly among 4 subtypes (P < .05). The diagnostic efficiency of PI was better for detecting LA and H2 subtype with the areas under the receiver operating characteristic curve was 0.778 and 0.734, respectively. ConclusionDifferent molecular subtypes of BC have different CEUS and conventional ultrasound characteristics. CEUS can provide valuable imaging basis for precise clinical diagnosis and individualized therapy of BC with different molecular subtypes.

Application of Quantitative Parameters of Contrast-Enhanced Ultrasound in Common Benign and Malignant Lesions in Pediatric Livers: A Preliminary Study.

We aimed to investigate the diagnostic utility of quantitative parameters of contrast-enhanced ultrasound (CEUS) for benign and malignant liver lesions in pediatric patients. This was a single-center retrospective analysis of children with liver lesions who underwent CEUS at our hospital between July 2019 and February 2023. The CEUS perfusion patterns for all lesions were qualitatively analyzed using histopathology, contrast-enhanced magnetic resonance imaging, contrast-enhanced computed tomography, or long-term clinical follow-up as reference standards. The CEUS images were quantitatively analyzed using SonoLiver® software (TomTec Imaging Systems, Munich, Germany) to obtain data regarding quantitative parameters and dynamic vascular pattern (DVP) parametric images, including rise time (RT), time to peak (TTP), mean transit time (mTT), and maximum intensity (IMAX). Statistical analysis was carried out using Student's t-test and receiver operating characteristic (ROC) curve analysis to evaluate the diagnostic value of quantitative parameters. A total of 53 pediatric cases were included in this study, and 88.57% (31/35) of malignant lesions exhibited hyper-enhancement with rapid washout patterns; the same proportion of DVP parametric images exhibited washout patterns. Conversely, 94.44% (17/18) of benign lesions showed hyper-enhancement with slow washout patterns, and the same proportion of DVP parametric images showed no-washout patterns. RT, TTP, and mTT were significantly shorter in the malignant group than in the benign group (p < 0.05), while IMAX showed no significant difference (p > 0.05). ROC analysis indicated that mTT < 113.34 had the highest diagnostic value, with an area under the curve of 0.82. CEUS quantitative analysis had an accuracy of 98.11%, while qualitative analysis had an accuracy of 92.45%, with no statistically significant difference (p > 0.05). Quantitative analysis of CEUS provides valuable assistance in differentiating benign and malignant liver lesions in children. Among all quantitative parameters, mTT holds promise as a potentially valuable tool for identifying liver tumors.

Intraoperative contrast-enhanced ultrasound evaluates the hemodynamic change of cerebral revascularization in adult moyamoya disease: Preliminary results

PurposeThis study aimed to determine the feasibility of using intraoperative contrast-enhanced ultrasound (CEUS) to assess subcortical hemodynamic changes in moyamoya disease patients who had undergone combined revascularization. It also aimed to investigate the correlation between quantitative CEUS parameters and post-operative neural functional recovery. MethodsThis study included seventeen patients diagnosed with moyamoya disease, confirmed through cerebral angiography, who underwent combined revascularization. Intraoperative subcortical hemodynamics were assessed using CEUS before and immediately after cerebrovascular bypass. Hemodynamic parameters were calculated by analyzing the time-intensity curve generated from a defined region of interest in each CEUS video. Post-operative neurological symptoms, computed tomography records, and short-term modified Rankin Scale (mRS) scores were also recorded. ResultsDuring the post-operative follow-up, 29.4 % of the patients experienced new neurological symptoms, including epilepsy, dyskinesia, and language impairment. Overall, CEUS quantitative parameters suggested that blood supply improved after surgery. And certain hemodynamic parameters exhibited a stronger correlation with the mRS scores, with correlation coefficients ranging up to 0.73 (p < 0.01). However, no statistically significant differences were observed among the different functional groups. The advanced parameter of wash-out intensity (δ WOI), which signifies the rate of change at the point when blood flow is completely washed out, demonstrated a significant difference between two functional groups (p = 0.02) and exhibited a correlation with mRS scores (correlation coefficients: 0.55, p = 0.02). ConclusionsThis preliminary study suggests that quantitative intraoperative CEUS can measure subcortical hemodynamic changes. It provides a novel non-invasive method that may predict the short-term post-operative neural functional recovery of combined revascularization in moyamoya disease patients.

Quantitative evaluation of colorectal tumour vasculature using contrast-enhanced ultrasound: Correlation with angiogenesis and prognostic significance.

Ultrasound is a vital tool for the diagnosis and management of colorectal cancer (CRC). Contrast-enhanced ultrasound (CEUS) is a non-invasive, safe, and cost-effective method for evaluating tumour blood vessels, that play a crucial role in tumour growth and progression. To explore CEUS's role in the quantitative evaluation of CRC blood vessels and their correlation with angiogenesis markers and prognosis. This study prospectively enrolled 100 patients with CRC confirmed by histopathology. All patients received preoperative CEUS examinations. Quantitative parameters, such as peak intensity (PI), time to peak (TTP), and area under the curve (AUC), were derived from time-intensity curve (TIC) analysis. Tumour tissue samples were obtained during surgery and examined immunohistochemically to assess the expression of angiogenesis markers, including vascular endothelial growth factor (VEGF) and microvessel density (MVD). The correlation between CEUS parameters, angiogenesis markers, and clinicopathological features was evaluated using appropriate statistical tests. Quantitative CEUS parameters (PI, TTP, and AUC) showed significant correlations with VEGF expression (P < 0.001) and MVD (P < 0.001), indicating a strong link between tumour blood vessels and angiogenesis. Increased PI, reduced TTP, and expanded AUC values were significantly related to higher tumour stage (P < 0.001), lymph node metastasis (P < 0.001), and distant metastasis (P < 0.001). Furthermore, these parameters were recognized as independent predictors of overall survival and disease-free survival in multivariate analysis (P < 0.001). CEUS has a high potential in guiding treatment planning and predicting patient outcomes. However, more comprehensive, multicentre studies are required to validate the clinical utility of CEUS in CRC management.

A contrast-enhanced ultrasound-based nomogram for the prediction of therapeutic efficiency of anti-PD-1 plus anti-VEGF agents in advanced hepatocellular carcinoma patients.

There is no study focusing on noninvasive predictors for the efficacy of sintilimab (anti-PD-1) plus IBI305 (a bevacizumab biosimilar) treatment in advanced hepatocellular carcinoma (HCC). A total of 33 patients with advanced HCC were prospectively enrolled and received sintilimab plus IBI305 treatment from November 2018 to October 2019. Baseline characteristics including clinical data, laboratory data, and tumor features based on pretreatment CT/MR were collected. Meanwhile, pretreatment contrast-enhanced ultrasound (CEUS) for target tumor was performed and quantitative parameters were derived from time-intensity curves (TICs). A nomogram was developed based on the variables identified by the univariable and multivariable logistic regression analysis. The discrimination, calibration, and clinical utility of the nomogram were evaluated. Tumor embolus and grad ratio were significant variables related to the efficacy of sintilimab plus IBI305 strategy. The nomogram based on these two variables achieved an excellent predictive performance with an area under curve (AUC) of 0.909 (95% CI, 0.813-1). A bootstrapping for 500 repetitions was performed to validate this model and the AUC of the bootstrap model was 0.91 (95% CI, 0.8-0.98). The calibration curve and decision curve analysis (DCA) showed that the nomogram had a good consistency and clinical utility. This study has established and validated a nomogram by incorporating the quantitative parameters of pretreatment CEUS and baseline clinical characteristics to predict the anti-PD-1 plus anti-VEGF treatment efficacy in advanced HCC patients.

Early adjunctive diagnostic value of contrast-enhanced ultrasound-related quantitative parameter and its relationship with micro-perfusion of nontraumatic necrosis of femoral head.

The aim of this study is to explore the early diagnostic value of contrast-enhanced ultrasound (CEUS)-related quantitative parameter and its relationship with the micro-perfusion of nontraumatic necrosis of the femoral head. According to the random and double-blind method, the patients with non-traumatic femoral head necrosis diagnosed and treated in our hospital from July 2019 to January 2022 were selected as the subjects (the research group). According to the staging of the International Society of Bone Circulation for Femoral Head Necrosis, 89 patients with stage Ⅱ and Ⅲ A were included (39 patients with stage Ⅱ and 50 patients with stage Ⅲ A). 25 patients who conducted physical examination in our hospital during the same time were taken as the control group. Quantitative parameters of CEUS were analyzed. The content of serum vascular endothelial growth factor (VEGF) and bone morphogenetic protein-2 (BMP-2) were evaluated. The relationship among the quantitative parameters of CEUS, the expression of VEGF and BMP-2 in serum and the patient's condition, and the value for assisting the early diagnosis of nontraumatic femoral head necrosis were analyzed. The body mass, body mass index (BMI), blood lipid, and cholesterol levels were much higher in the research group than in the control group (p < 0.05). The research group had a markedly higher slope of ascending branch (AS), strength enhancement index (EI), and VEGF and obviously lower decay slope (DS), mean transit time (MTT), and time to peak (TTP) than the control group (p < 0.05). In the research group, compared to stage Ⅱ, the levels of AS, EI, and VEGF in stage Ⅲ A patients were memorably higher, and the levels of DS, MTT, TTP and BMP-2 were dramatically lower (p < 0.05). Pearson's correlation test showed that AS, EI, and VEGF were positively correlated with the patients' condition, while DS, MTT, TTP and BMP-2 were negatively correlated with the patients' condition (p < 0.05). The receiver operating characteristic (ROC) curve analysis showed that the diagnostic area under the curve (AUC) of quantitative parameters of CEUS was 0.961, with sensitivity and specificity of 88.0% and 97.4%, respectively. The AUC of the combined detection of VEGF and BMP-2 was 0.945 with sensitivity and specificity of 82.3% and 87.5%, respectively, and the combined detection had a high diagnostic value (p < 0.05). The quantitative parameters of CEUS were of great value in the early diagnosis of nontraumatic necrosis of the femoral head with microvascular perfusion and the patients' condition, and provided a reference for the clinical treatment of non-traumatic necrosis of the femoral head. These parameters were expected to be useful indicators for judging the efficacy before and after treatment.

Contrast-Enhanced Ultrasound Imaging: Novel Method for the Evaluation of Chronic Alcohol-Induced Testicular Damage

The goals of this study were to determine whether contrast-enhanced ultrasound (CEUS) imaging could be used for assessment of chronic alcohol-induced testicular damage (CAITD) and to explore the relationships between the laboratory and pathological findings of CAITD and the quantitative parameters of CEUS. Thirty-six rabbits were randomly divided into a chronic ethanol exposure (CEE) group and negative control (NC) group, which were further randomly divided into six groups with equal numbers of rabbits by period of exposure (30 d, 60 d, 90 d). All rabbits underwent conventional US and CEUS imaging at the end of the induction period. Blood and histological specimens were collected for laboratory and pathological examination. The peak intensity (PI) and area under the curve (AUC) for the CEUS parameters decreased as CAITD progressed (p < 0.05). Both PI and AUC were positively correlated with the Johnsen score (r= 0.945 and 0.898, respectively, all p values <0.001) and the mean epithelium thickness of the seminiferous tubule (METST) (r= 0.927 and 0.881, respectively, all p values <0.001) of the testis, and negatively correlated with the serum levels of endothelin-1 (ET-1) (r = -0.940 and -0.899, respectively, all p values <0.001) and nitric oxide (NO) (r = -0.894 and -0.954, respectively, all p values <0.001), as well as the testicular tissue content of malondialdehyde (MDA) (r = -0.894 and -0.945, respectively, all p values <0.001). CEUS imaging can be used for monitoring organ perfusion of the testis to quantify the development of CAITD.

VueBox® perfusion analysis of dynamic contrast enhanced ultrasound provides added value in the diagnosis of small thyroid nodules.

To explore the potential added value of dynamic contrast enhanced ultrasound (DCE-US) using VueBox® software for the diagnosis of small solid thyroid nodules (≤1.0 cm). This prospective study was approved by the institutional review board and it was performed at two hospitals from January 2020 to October 2020. B mode ultrasound and contrast enhanced ultrasound (CEUS) images were obtained for 79 small solid thyroid nodules (≤1.0 cm) confirmed by ultrasound-guided fine needle aspiration cytology results in 79 consecutive patients (55 women and 24 men, median age: 41 years). The CEUS time-intensity curves (TICs) of thyroid nodules and surrounding parenchyma were created by VueBox® software (Bracco, Italy). The CEUS quantitative parameters were obtained after curve fitting. The diagnostic performance of CEUS and DCE-US was evaluated and compared. The weighted kappa statistic (κ) was performed to assess the interobserver agreement and consistency between the diagnosis of CEUS and DCE-US. Among the 79 thyroid nodules, 56 (70.9 %) were malignant and 23 (29.1 %) were benign lesions. Hypoenhancement during the arterial phase of CEUS was associated with malignancy (P < 0.001), with an AUC of 0.705 (sensitivity 71.4 %, specificity 69.6 %). Among all CEUS quantitative parameters, the peak enhancement (PE), wash-in rate (WiR), and wash-out rate (WoR) of DCE-US in malignancies were significantly lower than those in benign nodules (P = 0.049, P = 0.046, and P = 0.020, respectively). The area under the receiver operating characteristic curves (AUCs) of PE, WiR, and WoR were 0.642 (sensitivity 65.2 %, specificity 67.9 %), 0.643 (sensitivity 43.5 %, specificity 91.1 %), and 0.667 (sensitivity 69.6 %, specificity 69.6 %) in differentiation between benign and malignant small solid thyroid nodules (≤1.0 cm), respectively. Comparing the quantitative parameters of DCE-US between small solid thyroid nodules and surrounding normal thyroid parenchyma, the PE, WiAUC, WiR, wash-in perfusion index (WiPI), WoAUC, WiWoAUC, and WoR of the nodules were significantly lower than those of normal thyroid tissue (P = 0.008, P < 0.001, P = 0.037, P = 0.009, P = 0.003, P = 0.002, P = 0.049, respectively). A total of 16 (20.3 %) nodules showed isoenhancement during the arterial phase of CEUS, while the median PE ratio of surrounding tissue and thyroid nodules was 1.70 (IQR: 1.33-1.89). VueBox® is a helpful tool for the evaluation of dynamic microvascularization of thyroid nodules, and DCE-US using VueBox® perfusion analysis could provide added values for differential diagnosis of small solid thyroid nodules (≤1.0 cm).

The diagnostic value of contrast-enhanced ultrasonography in breast ductal abnormalities

BackgroundDuctal lesions are an important, often overlooked, and poorly understood issue in breast imaging, which have a risk of underlying malignancy ranging from 5 to 23%. Ultrasonography (US), which has largely replaced galactography or ductography, has become an important imaging method to assess patients with ductal lesions. However, it is difficult to distinguish benign from malignant ductal abnormalities only by ultrasonography, most of which are recommended to be at least in subcategory 4A; these require biopsy according to the ACR BI-RADS®atlas 5th Edition-breast ultrasound. Contrast-enhanced ultrasound (CEUS) has been shown to be valuable for differentiating benign from malignant tumors, but its value is unclear in breast ductal lesions. Therefore, the purposes of this study were to explore the characteristics of malignant ductal abnormalities on US and CEUS imaging and the diagnostic value of CEUS in breast ductal abnormalities.MethodsOverall, 82 patients with 82 suspicious ductal lesions were recruited for this prospective study. They were divided into benign and malignant groups according to the pathological results. Morphologic features and quantitative parameters of US and CEUS were analyzed by comparison and multivariate logistic regression to determine the independent risk factors. The diagnostic performance was assessed by receiver operating characteristic (ROC) curve analysis.ResultsShape, margin, inner echo, size, microcalcification and blood flow classification on US, wash-in time, enhancement intensity, enhancement mode, enhancement scope, blood perfusion defects, peripheral high enhancement and boundary on CEUS were identified as features correlated with malignant ductal lesions. However, multivariate logistic regression showed that only microcalcification (OR = 8.96, P = 0.047) and enhancement scope (enlarged, OR = 27.42, P = 0.018) were independent risk factors for predicting malignant ductal lesions. The sensitivity, specificity, positive predictive value, negative predictive value, accuracy and area under the ROC curve of microcalcifications combined with an enlarged enhancement scope were 0.895, 0.886, 0.872, 0.907, 0.890, and 0.92, respectively.ConclusionsMicrocalcification and enlarged enhancement scope are independent factors for predicting malignant ductal lesions. The combined diagnosis can greatly improve the diagnostic performance, indicating that CEUS can be useful in the differentiation of benign and malignant lesions to formulate more appropriate management for ductal lesions.

Correlations between contrast-enhanced ultrasound and microvessel density in non-small cell lung cancer: A prospective study.

Immunohistochemical microvessel density (MVD) is an early indicator of angiogenesis and it could be used to evaluate the therapeutic efficacy of non-small cell lung cancer (NSCLC). We sought to identify the ability of contrast-enhanced ultrasound (CEUS) in evaluating MVD of subpleural NSCLC. We prospectively collected CEUS data of NSCLC confirmed by ultrasound-guided transthoracic needle biopsy from October 2019 to February 2021, The MVD of NSCLC counted by CD34-positive vessels of immunohistochemical staining. Microflow enhancement (MFE) of CEUS was divided into "dead wood", "cotton", and "vascular" patterns. Pathology subgroup and MVD between different MFE patterns were analyzed, respectively. The arrival time, time to peak, peak intensity (PI), and area under curve (AUC) derivefrom time-intensity curve of CEUS with MVD in NSCLC and its pathological subgroups (adenocarcinoma and squamous cell carcinoma) were subjected to correlation analysis. A total of 87 patients were included in this study, consisting of 53 cases of adenocarcinoma and 34 cases of squamous cell carcinoma with a mean MVD of 27.8 ± 12.2 mm-1. There was a significant statistical difference in MFE patterns between two pathological subgroups (p < 0.05). Besides, the MVD of "cotton" and "vascular" patterns were significantly higher than that of "dead wood" pattern (both of p < 0.05), whereas there was no significant difference in MVD between "cotton" pattern and "vascular" pattern. PI and AUC of CEUS were positively correlated with the MVD of NSCLC (r = 0.497, p < 0.001, and r = 0.367, p < 0.001, respectively). Besides, PI and AUC of CEUS were positively correlated with the MVD of squamous cell carcinoma (r = 0.802, and r = 0.663, respectively; both of p < 0.001). Only the PI was positively correlated with the MVD of lung adenocarcinoma (r = 0.288, p = 0.037). MFE patterns and quantitative parameters of CEUS had good correlation with MVD of NSCLC, especially in squamous cell carcinoma.

Correlation of lymph node metastasis with contrast-enhanced ultrasound features, microvessel density and microvessel area in patients with papillary thyroid carcinoma.

This study aims to investigate the relationship of cervical lymph node metastasis (LNM) with contrast-enhanced ultrasound (CEUS) features, microvessel density (MVD) and microvessel area (MVA) in patients with papillary thyroid carcinoma (PTC), and to evaluate the diagnostic value of CEUS for PTC. A total of 108 patients diagnosed with PTC at the First Affiliated Hospital of Jinzhou Medical University from January 2016 to December 2018 were selected and underwent preoperative CEUS of the thyroid, surgical resection and postoperative histopathological examination of their resected lesion. They were divided into a lymphatic metastasis-positive group (LNM+, n = 61) and a lymphatic metastasis-negative group (LNM-, n = 47) based on their lymph node status. The CEUS quantitative parameters, MVD and MVA, were compared between the two groups, and risk factors for LNM were analyzed by univariate and multivariate logistic regression. Compared with patients with in the LNM-group, the tumor diameter and the proportion of capsule contact of patients in the LNM+group were significantly greater and the patients in this group were younger. The rise time (RT), peak intensity (PI), area under the curve (AUC), MVD, and MVA were also significantly higher in the LNM+group than in the LMN-group, while there was no significant difference in time to peak (TP), mean transit time (mTT), velocity of intensity increase (IIV), and velocity of intensity decrease (IDV) between the two groups. Univariate and multivariate correlation analysis indicated that tumor size, RT, PI, AUC, MVD, and MVA were risk factors for LNM, and ROC curves further suggested that RT had the best overall predictive performance. Tumor size, RT, PI, AUC, MVD and MVA are risk factors for LNM in PTC. In other words, CEUS is an important non-invasive and preoperative tool for evaluating PTC, with MVD and MVA identified as vital postoperative diagnostic indicators.

Assessment of Parotid Gland Tumors by Means of Quantitative Multiparametric Ultrasound (mpUS)

The preoperative diagnostical differentiation of parotid gland tumor (PGT) is not always simple due to several different entities. B-mode-ultrasound (US) remains the imaging modality of choice, while histopathology serves as the gold standard for finalizing the diagnosis. We aimed to evaluate the use of multiparametric US (mpUS) in the assessment of PGT. We included 97 PGTs from 96 patients. A standardized mpUS protocol using B-mode-US, shear-wave elastography (SWE), and standardized contrast-enhanced ultrasound (CEUS) was performed prior to surgical intervention. SWE was assessed by real-time measurement conducting a minimum of five measurements, while quantitative CEUS parameters were assessed with a post-processing perfusion software. SWE allowed differentiation between benign PGT (Warthin's Tumor (WT) paired with lymph nodes (LN) and pleomorphic adenoma (PA)), and WT and LN were softer compared to PA. WT showed lower velocities than squamous cell carcinoma (SCC): the most common malignant PGT. CEUS parameters showed significant group differences between WT and PA, WT and malignant lesions, WT and SCC, WT paired with LN versus PA, and WT paired with LN versus SCC. MpUS seems to be beneficial in the assessment of PGT characterization, with benign PGT appearing to be softer in SWE than tumors with malignant tendencies. The quantitative CEUS parameter shows higher perfusion in WT than in PA, and malignant PGTs are less vascularized than WTs.