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Abstract: Wave intensity analysis (WIA) of the carotid artery was conducted to determine the changes that occur in left ventricular systolic function after administration of doxorubicin in rabbits. Each randomly selected rabbit was subject to routine ultrasound, WIA of the carotid artery, cardiac catheterization and pathologic examination every week and was followed for 16 wk. The first positive peak (WI1) of the carotid artery revealed that left ventricular systolic dysfunction occurred earlier than conventional indexes of heart function. WI1 was highly, positively correlated with the maximum rate of rise in left ventricular pressure in cardiac catheterization (r = 0.94, p < 0.01) and moderately negatively correlated with the apoptosis index of myocardial cells, an indicator of myocardial damage (r = −0.69, p < 0.01). Ultrasound WIA of the carotid artery sensitively reflects early myocardial damage and cardiac function, and the result is highly consistent with cardiac catheterization findings and the apoptosis index of myocardial cells. [Copyright &y& Elsevier]

Acute-on-chronic liver failure (ACLF) is associated with a considerably high mortality, and accurate prognosis prediction is critical to navigate intervention decisions and improve clinical outcomes. The objective of this study was to establish a better prognostic model for ACLF based on multiparameter ultrasound in combination with clinical features. A total of 149 patients with ACLF were prospectively enrolled and underwent conventional ultrasound, 2-D shear wave elastography (SWE), attenuation imaging, color Doppler sonography, superb microvascular imaging and contrast-enhanced ultrasound (CEUS). Univariate and multivariate analyses were performed to identify independent ultrasound signatures for the prognosis of ACLF, which, when integrated with clinical characteristics, were used to establish a prognostic model. Hepatic perfusion features of CEUS differed significantly between the poor and good prognosis groups, among which the time interval (TI) between peak portal vein (PV) velocity and liver parenchyma (LP) enhancement, TI(PV, LP), was independently associated with the prognosis of ACLF. A prediction model comprising TI(PV, LP) and the international normalized ratio was established, and the area under the curve (AUC) was 0.851, which is greater than those of the Model for End-stage Liver Disease (0.785), fall time of LP model (0.754), 2-D SWE nomogram (0.708) and TI(PV, LP) (0.352). Furthermore, the performance of the model was verified in an independent validation cohort (AUC = 0.920). The newly developed model performs better than existing tested models; thus, it has potential as a better non-invasive model for predicting the prognosis of patients with ACLF. A future multicenter, large-sample study is required to validate the performance of this model. [ABSTRACT FROM AUTHOR]

Objectives: Accurate detection of carotid plaque using ultrasound (US) is essential for preventing stroke. However, the diagnostic performance of junior radiologists (with approximately 1 year of experience in carotid US evaluation) is relatively poor. We thus aim to develop a deep learning (DL) model based on US videos to improve junior radiologists' performance in plaque detection. Methods: This multicenter prospective study was conducted at five hospitals. CaroNet-Dynamic automatically detected carotid plaque from carotid transverse US videos allowing clinical detection. Model performance was evaluated using expert annotations (with more than 10 years of experience in carotid US evaluation) as the ground truth. Model robustness was investigated on different plaque characteristics and US scanning systems. Furthermore, its clinical applicability was evaluated by comparing the junior radiologists' diagnoses with and without DL-model assistance. Results: A total of 1647 videos from 825 patients were evaluated. The DL model yielded high performance with sensitivities of 87.03% and 94.17%, specificities of 82.07% and 74.04%, and areas under the receiver operating characteristic curve of 0.845 and 0.841 on the internal and multicenter external test sets, respectively. Moreover, no significant difference in performance was noted among different plaque characteristics and scanning systems. Using the DL model, the performance of the junior radiologists improved significantly, especially in terms of sensitivity (largest increase from 46.3 to 94.44%). Conclusions: The DL model based on US videos corresponding to real examinations showed robust performance for plaque detection and significantly improved the diagnostic performance of junior radiologists. Key Points: • The deep learning model based on US videos conforming to real examinations showed robust performance for plaque detection. • Computer-aided diagnosis can significantly improve the diagnostic performance of junior radiologists in clinical practice. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma, representing the most frequent primary liver cancer, is a common cancer disease that is the fourth leading cause of cancer-related mortality worldwide. In comparison, non-hepatocellular carcinoma liver cancers often present different prognoses and require distinct management which makes the accurate discrimination between hepatocellular carcinoma and non-hepatocellular carcinoma malignant lesions in contrast-enhanced ultrasound data critical for precise intervention. However, different types of liver cancers have similar enhanced patterns against the perfusion stages that raise the difficulty in the classification of hepatocellular carcinoma with the other liver cancers, especially when the contrast-enhanced ultrasound data is collected from different imaging machines. To this end, this paper innovatively proposes to extract perfusion features from a multi-view learning procedure for obtaining the inherent distinguishing features among liver cancers, leading to a more precise deep model in differentiating the hepatocellular carcinoma from other malignant cases. In particular, the proposed network consists of two novel structures for learning the correlation information among the different views to enhance the robustness of the features and fuse them by reducing redundant information. The proposed method is verified on a multi-source dataset collected from 1241 participants and achieves an AUC value of 89% for classification performance. The experimental results demonstrate the effectiveness of the proposed method for the diagnosis of hepatocellular carcinoma with a multi-source contrast-enhanced ultrasound dataset and might provide an effective assistant for clinical radiologists in liver cancer differentiation. • A novel deep neural network propose to extract perfusion features from a multi-view learning procedure in order for obtaining the inherent distinguishing features among liver cancers. • A VRL module is proposed to enhance the representations of views by adaptive learning of relevant information among different views. • A STOP module is proposed to effectively fuse the multi-view features by removing the redundant information among the three views. • The experimental results demonstrate the effectiveness of the proposed method. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to evaluate the safety of the ultrasound contrast agent sulfur hexafluoride microbubbles in a large group of patients referred for routine contrast-enhanced ultrasound (CEUS). Methods: A retrospective assessment was made of all patients that received sulfur hexafluoride microbubbles intravenously for CEUS at 24 centers between January 2006 and April 2019. Patient demographic details, examination type, and the dose of sulfur hexafluoride microbubbles administered were recorded with specific adverse events (AEs) documentation tools at each center. All AEs were recorded as serious or non-serious. Non-serious AEs were classified by intensity as mild, moderate, or severe according to ACR criteria. The frequencies of AEs across patient subgroups were compared using the chi-square test. Results: A total of 463,434 examinations were evaluated. Overall, 157 AEs (153 [0.033%] non-serious; 4 [0.001%] serious) were reported after sulfur hexafluoride microbubbles administration, giving an AE frequency of 0.034% (157/463,434). Among the non-serious AEs, 66 (0.014%) were mild, 70 (0.015%) moderate, and 17 (0.004%) severe in intensity. The liver was the most common examination site, presenting an AE frequency of 0.026%. The highest AE frequency (0.092%) was for patients undergoing CEUS for vascular disease. There were no significant gender differences in either the total number or the severity of non-serious AEs (chi-square = 2.497, p = 0.287). The onset of AEs occurred within 30 min of sulfur hexafluoride microbubbles administration in 91% of cases. Conclusion: The frequency of AEs to sulfur hexafluoride microbubbles is very low and severe reactions are rare, confirming that sulfur hexafluoride microbubbles are appropriate for routine CEUS applications. Key Point: • The frequency of AEs to sulfur hexafluoride microbubbles is very low and severe reactions are rare. [ABSTRACT FROM AUTHOR]

To compare the long-term efficacy and safety of microwave ablation (MWA) as first-line therapy for hepatocellular carcinoma (HCC) adjacent versus nonadjacent to the gallbladder. From 2006 to 2018, 657 patients with ≤5 cm HCC who underwent percutaneous ultrasound-guided MWA as first-line therapy from 5 hospitals were enrolled in this retrospective study. Patients were grouped into the adjacent group (n = 49) and the nonadjacent group (n = 608) according to whether the tumor was adjacent to the gallbladder. Propensity score matching (PSM) was used to balance baseline variables between the two groups. Forty-eight patient pairs were matched after PSM. For the PSM cohort, during a median follow-up time of 60 months, there were no differences in PFS (hazard ratio [HR], 1.011; 95% confidence interval [CI], 0.647-1.578; p = 0.963) or OS (HR 0.925; 95% CI 0.522-1.639; p = 0.789) between the adjacent and nonadjacent groups. Univariate and multivariate analyses revealed that the tumor adjacent to the gallbladder was not an independent risk factor for PFS or OS (all p > 0.05). Subgroup analysis showed comparable PFS and OS between the two groups in the <3 cm subgroup and the 3-5 cm subgroups (all p > 0.05). In addition to more use of assistive technology (p < 0.05), the adjacent group shared comparable local tumor progression, complications, technical success rate, and hospital stay (all p > 0.05) to the nonadjacent group. There were comparable long-term efficacy and complications between patients with HCC adjacent and nonadjacent to the gallbladder treated with MWA. The application of MWA to HCC adjacent and nonadjacent to the gallbladder resulted in comparable PFS and OS and complications. For both cohorts, MWA shared comparable complications (immediate and delayed), LTP, hospitalization, and operative time. MWA might be a first-line alternative for ≤5 cm HCC adjacent to the gallbladder with the use of assistive technologies and advances in technology. [ABSTRACT FROM AUTHOR]

Purpose: Ultrasound (US)-guided thermal ablation (TA) may cause major biliary complications, particularly in patients with malignant liver tumors (MLTs) adjacent to the bile ducts. Fusion imaging (FI), is postulated to reduce complication rate; however, there is a lack of clinical data to support this theory. Thus, the aim of our study was to evaluate the safety and efficacy of FI for TA of MLTs proximal to the bile ducts. Methods: A retrospective single-center review was conducted on a total of 289 patients with 316 MLTs adjacent to the bile ducts. The patients were divided into two groups based on whether FI was used in the ablation procedures. The choice of the FI-assisted procedure always depends on different operation periods and whether registrations will succeed. The baseline demographics and outcomes of these patients were compared. The efficacy was determined at the 1-month follow-up using contrast-enhanced computed tomography/magnetic resonance. Biliary complications and local tumor progression were subsequently followed-up every 3–6 months. The last follow-up visit was before August 30, 2019. Results: Among the included tumors, the incidence rate of major biliary complications after ablation in the FI group was 1.6%, which was significantly lower than that in the non-FI group (7.9%, p = 0.005). There was no significant difference in the efficacy rates of the techniques [99.5% (185/186) versus 98.4% (123/125), p = 0.56] or local progression rates [3.8% (7/185) versus 5.7% (7/123), p = 0.61] between the FI and non-FI groups. Conclusion: FI for US-guided TA could be a noninvasive means to decrease major biliary complications. Trial registration number and date of registration: retrospectively registered. [ABSTRACT FROM AUTHOR]

Aim: The present study was to evaluated the clinical value of anatomical thermal ablation to treat hepatocellular carcinoma compared with routine thermal ablation. Methods: Hepatocellular carcinoma patients with tumor diameter ≤50 mm treated by thermal ablation at our center were retrospectively enrolled from October 2015 to December 2018. Enrolled patients were grouped into the anatomical ablation group and routine ablation group, respectively. To minimize the effects of potential confounders from selection bias, a propensity score matching was carried out. Technical efficacy, recurrence and survivals rates were compared. Results: Altogether 101 patients (119 lesions) were grouped into the anatomical ablation group and 101 patients (131 lesions) into the routine ablation group. The ablation zone volume of the anatomical ablation group was 36.8 (2.5–176.9) ml, significantly larger than that of the routine ablation group (28.5 [28.5 (2.8–184.3) ml] (p = 0.005)). Adjusted with propensity score matching, The 1‐, 2‐, and 3‐year local recurrence rates were 0.0%, 0.0%, and 0.0% for the anatomical ablation group and 6.9%, 10.1%, and 10.1% for the routine ablation group, respectively (p = 0.013). The cumulative 1‐, 2‐, and 3‐year progression‐free survival rates were 93.4%, 82.7%, and 79.0% for the anatomical ablation group, 74.2%, 56.9%, and 51.6% for the routine ablation group (p = 0.001). Conclusions: Anatomical ablation could be a favorable ablation strategy to improve therapeutic effect of thermal ablation for HCC with visible feeding vessels and reserved liver function. [ABSTRACT FROM AUTHOR]

The aim of this study is to evaluate the efficacy of qualitative analysis of contrast-enhanced ultrasound (CEUS) in discrimination of adnexal masses which were undetermined by conventional ultrasound (US). A total of 120 patients underwent transabdominal CEUS. The initial enhancement time and intensity compared with the uterine myometrium, contrast agent distribution patterns and dynamic changes of enhancement were assessed. The sensitivity (Sen), specificity (Spe), positive predictive value (PPV), negative predictive value (NPV), accuracy (ACC) and Youden’s index were calculated for contrast variables. The gold standard was the histological diagnosis. There were 48 malignant tumors and 72 benign tumors. The enhancement features of malignant masses were different from benign ones. Earlier or simultaneous enhancement with inhomogeneous enhancement yielded the highest capability in differential diagnosis, and Sen, Spe, PPV, NPV, ACC, Youden’s index was 89.6%, 97.2%, 93.2%, 95.6%, 93.3%, and 0.88, respectively. The qualitative evaluation of CEUS is useful in the differential diagnosis of adnexal masses where conventional US is indeterminate. [ABSTRACT FROM AUTHOR]

A novel photoacoustic imaging system based on a semi-ring transducer array is proposed to image peripheral blood vessels. The system's penetration depth is deep (∼15 mm) with high spatial (∼200 μm) and temporal resolution. In a clinical study, volumetric photoacoustic data of limbs were obtained within the 50s (for a FOV of 15 cm × 4 cm) with the volunteers in the standing and sitting posture. Compared to the previous studies, our system has many advantages, including (1) Larger field of view; (2) Finer elevational and in-plane resolutions; (3) Enhanced 3D visualization of peripheral vascular networks; (4) Compact size and better portability. The 3D visualization and cross-sectional images of five healthy volunteers clearly show the vascular network and the system's ability to image submillimeter blood vessels. This high-resolution PA system has great potential for imaging human periphery vasculatures noninvasively in clinical research. [ABSTRACT FROM AUTHOR]

Background: To explore the feasibility of corrected slack angle acquired from two-dimensional shear wave elastography (2D-SWE) for quantitating the spasticity of medial gastrocnemius (MG) in stroke patients.Methods: Consecutive stroke patients with spastic MG and matched healthy controls were recruited. Intra- and interobserver reliability of 2D-SWE measurement were evaluated, and the correlation between corrected slack angle and modified Ashworth scale (MAS) score was examined. The corrected slack angle before and after botulinum toxin A (BoNT-A) injection was compared and its diagnostic performance in classifying the severity of spasticity were assessed with receiver operating characteristic (ROC) curve analysis.Results: The intra- (0.791 95% CI 0.432-0.932) and interobserver (0.751 95% CI 0.382-0.916) reliability of slack angle acquired with 2D-SWE were good. Significant correlation was found between corrected slack angle and MAS score (R = - 0.849, p < 0.001). The corrected slack angle increased after BoNT-A injection. The cutoff value of MAS ≥ 3 had the highest sensitivity (100%) and specificity (93.33%). The positive predictive value (PPV) for classification of MAS ≥ 1+ and the negative predictive value (NPV) for classification of MAS ≥ 3 were greater than 90%.Conclusion: 2D-SWE was a reliable method to quantitate the post-stroke spasticity. The corrected slack angle had advantage in classifying the severity of spasticity, especially in early identification of mild spasticity and confirmation of severe spasticity. [ABSTRACT FROM AUTHOR]

Background: To explore the feasibility of corrected slack angle acquired from two-dimensional shear wave elastography (2D-SWE) for quantitating the spasticity of medial gastrocnemius (MG) in stroke patients. Methods: Consecutive stroke patients with spastic MG and matched healthy controls were recruited. Intra- and interobserver reliability of 2D-SWE measurement were evaluated, and the correlation between corrected slack angle and modified Ashworth scale (MAS) score was examined. The corrected slack angle before and after botulinum toxin A (BoNT-A) injection was compared and its diagnostic performance in classifying the severity of spasticity were assessed with receiver operating characteristic (ROC) curve analysis. Results: The intra- (0.791 95% CI 0.432–0.932) and interobserver (0.751 95% CI 0.382–0.916) reliability of slack angle acquired with 2D-SWE were good. Significant correlation was found between corrected slack angle and MAS score (R = − 0.849, p < 0.001). The corrected slack angle increased after BoNT-A injection. The cutoff value of MAS ≥ 3 had the highest sensitivity (100%) and specificity (93.33%). The positive predictive value (PPV) for classification of MAS ≥ 1+ and the negative predictive value (NPV) for classification of MAS ≥ 3 were greater than 90%. Conclusion: 2D-SWE was a reliable method to quantitate the post-stroke spasticity. The corrected slack angle had advantage in classifying the severity of spasticity, especially in early identification of mild spasticity and confirmation of severe spasticity. [ABSTRACT FROM AUTHOR]

This study sought to investigate the feasibility of using magnetic resonance-magnetic resonance-ultrasound (MR-MR-US) fusion imaging navigation (FIN) with needle tail intelligent positioning (NTIP) to guide puncture in percutaneous transforaminal endoscopic discectomy (PTED). First, in a pig experiment, we found that puncture errors in lumbar intervertebral foramen (LIF) puncture using magnetic resonance-magnetic resonance-ultrasound (MR-MR-US) FIN with NTIP for experienced and novice operators were 2.00 ± 1.00 and 2.57 ± 0.98 mm, respectively (p = 0.231), suggesting this technique was minimally dependent on experience. Then, two experienced surgeons agreed (inter-observer agreement к=0.801) that the quality of MR-MR fusion images was good or sufficient. Finally, we performed PTED in eight patients using MR-MR-US FIN with NTIP, and no significant complications were reported during LIF puncture. Overall, MR-MR-US FIN with NTIP may be a potential application for guiding puncture in PTED, but more clinical studies with a larger sample size are required to further evaluate the advantages of MR-MR-US FIN with NTIP. [ABSTRACT FROM AUTHOR]

Objective: The non-invasive discrimination of significant fibrosis (≥ F2) in patients with chronic liver disease (CLD) is clinically critical but technically challenging. We aimed to develop an updated deep learning radiomics model of elastography (DLRE2.0) based on our previous DLRE model to achieve significantly improved performance in ≥ F2 evaluation. Methods: This was a retrospective multicenter study with 807 CLD patients and 4842 images from three hospitals. All of these patients have liver biopsy results as referenced standard. Multichannel deep learning radiomics models were developed. Elastography images, gray-scale images of the liver capsule, gray-scale images of the liver parenchyma, and serological results were gradually integrated to establish different diagnosis models, and the optimal model was selected for assessing ≥ F2. Its accuracy was thoroughly investigated by applying different F0–1 prevalence cohorts and independent external test cohorts. Analysis of receiver operating characteristic (ROC) curves was performed to calculate the area under the ROC curve (AUC) for significance of fibrosis (≥ F2) and cirrhosis (F4). Results: The AUC of the DLRE2.0 model significantly increased to 0.91 compared with the DLRE model (AUC 0.83) when evaluating ≥ F2 (p = 0.0167). However, it did not show statistically significant differences as integrating gray-scale images and serological data into the DLRE2.0 model. AUCs of DLRE and DLRE2.0 increased, when there was higher F0–1 prevalence. All radiomics models had good robustness in the independent external test cohort. Conclusions: DLRE2.0 was the most suitable model for staging significant fibrosis while considering the balance of diagnostic accuracy and clinical practicability. Key Points: • The non-invasive discrimination of significant fibrosis (≥ F2) in patients with chronic liver disease (CLD) is clinically critical but technically challenging. • We aimed to develop an updated deep learning radiomics model of elastography (DLRE2.0) based on our previous DLRE model to achieve significantly improved performance in ≥ F2 evaluation. • Our study based on 807 CLD patients and 4842 images with liver biopsy found that DLRE2.0 was the most suitable model for staging significant fibrosis while considering the balance of diagnostic accuracy and clinical practicability. [ABSTRACT FROM AUTHOR]

Background: While anti-tumor necrosis factor alpha (TNF-α) therapy has been proven effective in inflammatory bowel disease (IBD), approximately 40% of patients lose the response. Transmembrane TNF-α (mTNF-α) expression in the intestinal mucosa is correlated with therapeutic efficacy, and quantification of mTNF-α expression is significant for predicting response. However, conventional intravenous application of microbubbles is unable to assess mTNF-α expression in intestinal mucosa. Herein, we proposed intracolic ultrasound molecular imaging with TNF-α-targeted microbubbles (MBTNF-α) to quantitatively detect mTNF-α expression in the intestinal mucosa. Methods: MBTNF-α was synthesized via a biotin–streptavidin bridging method. TNF-α-targeted ultrasound imaging was performed by intracolic application of MBTNF-α to detect mTNF-α expression in surgical specimens from a murine model and patients with IBD. Linear regression analyses were performed to confirm the accuracy of quantitative targeted ultrasound imaging. Results: On quantitative TNF-α-targeted ultrasound images, a greater signal intensity was observed in the mouse colons with colitis ([1.96 ± 0.45] × 106 a.u.) compared to that of the controls ([0.56 ± 0.21] × 106 a.u., P < 0.001). Targeted US signal intensities and inflammatory lesions were topographically coupled in mouse colons. Linear regression analyses in specimens of mice and patients demonstrated significant correlations between the targeted ultrasound signal intensity and mTNF-α expression (both P < 0.001). Furthermore, TNF-α-targeted ultrasound imaging qualitatively distinguished the varying inflammatory severity in intestinal specimens from IBD patients. Conclusion: Intracolic ultrasound molecular imaging with MBTNF-α enables quantitative assessment of mTNF-α expression. It may be a potential tool for facilitating the implementation of personalized medicine in IBD. [ABSTRACT FROM AUTHOR]

Purpose: To assess the feasibility of ablation planning based on fusion imaging of three-dimensional ultrasound/contrast-enhanced ultrasound (3D US/CEUS) with real-time US/CEUS for liver tumor thermal ablation. Materials and methods: Between January 2017 and December 2018, 85 hepatic tumors from 82 patients who underwent percutaneous ablation were included. First, intraprocedural 3D US/CEUS imaging was performed for ablation planning. Then, fusion imaging of 3D US/CEUS with real-time US/CEUS was used to guide the implementation of the plan, immediately evaluate the technical success and indicate the need for supplemental ablation. In addition, contrast-enhanced CT/MR imaging was performed 1 month after the procedure to evaluate the presence of residual tumors, and follow-up scans were repeated every 3 months. Results: The average liver tumor diameter was 28 ± 9 mm (range, 10–55 mm). 3D US/CEUS-based planning was successfully conducted in all 85 tumors with a 100% technical success rate of planning. The immediate evaluation by 3D CEUS/US-CEUS fusion imaging showed a 100% technical success rate of ablation. The 1-month CT/MR scans found a residual tumor in one intrahepatic cholangiocarcinoma patient; the technique efficacy rate was 98.8%. The median follow-up period was 21.5 months (IQR: 4–36 months). During the follow-up period, the local tumor progression rate was 5.9% (5/84), and no major procedure-related complications occurred. Conclusions: Ablation planning based on 3D US/CEUS-US/CEUS fusion imaging is feasible for liver tumors. [ABSTRACT FROM AUTHOR]

Objective: Two-dimensional shear wave elastography performed by SurperSonics (2D-SWE.SSI) performs well in evaluating liver fibrosis. Steatosis is one of confounding factors which might decrease accuracy, and its effect on 2D-SWE.SSI is still controversial. Our purpose is to evaluate the diagnostic performance of 2D-SWE.SSI affected by different steatosis stages and pathological types in chronic hepatitis B (CHB) patients.Methods: 2D-SWE.SSI was performed on 1306 CHB patients. All patients were divided into mild steatosis, moderate to severe steatosis, and non-steatosis groups. Subgroup analysis was performed according to pathological type. Liver biopsy was reference standard. Propensity score matching was performed to adjust for differences in patient characteristics. The median values of different steatosis group were compared by non-parametric tests before and after propensity score matching. The area under the receiver operating characteristic curve (AUC) was analyzed to assess the diagnostic performance in different steatosis groups.Results: The median values were not significantly different in different steatosis degrees expected in F0-1 patients. The AUC of 2D-SWE.SSI was not affected by different stages of liver steatosis for cirrhosis (= F4) (0.896, 0.853, 0.929, p = 0.34). The high AUCs (0.847, 0.856) were achieved in the non-steatosis and mild steatosis groups, and all were significantly higher than those of the moderate to severe steatosis group for ≥ F2. Moreover, the panacinar type had the best AUC (0.980 for F4 and 0.930 for ≥ F2).Conclusion: In conclusion, moderate to severe steatosis affects 2D-SWE.SSI in CHB patients. These patients had high LSM values in patients with F0-1 and lower accuracy in ≥ F2. Patients with panacinar steatosis have the highest overall diagnostic performance.Key Points: • 2D-SWE.SSI was widely used in evaluating liver fibrosis and it has many confounding factors. Steatosis is one of the confounding factors and its effect on 2D-SWE.SSI was controversial. • Our study based on 1306 CHB patients with liver biopsy found that 2D-SWE.SSI might be affected by moderate to severe liver steatosis in diagnostically significant fibrosis (≥ F2) of CHB patients. • Patients with steatosis of the panacinar type have the highest overall diagnostic performance. [ABSTRACT FROM AUTHOR]

Non-invasive detection of microvascular alterations in deep tissues in vivo provides critical information for clinical diagnosis and evaluation of a broad-spectrum of pathologies. Recently, the emergence of super-resolution ultrasound localization microscopy (ULM) offers new possibilities for clinical imaging of microvasculature at capillary level. Currently, the clinical utility of ULM on clinical ultrasound scanners is hindered by the technical limitations, such as long data acquisition time, high microbubble (MB) concentration, and compromised tracking performance associated with low imaging frame-rate. Here we present a robust in-human ULM on a high frame-rate (HFR) clinical ultrasound scanner to achieve super-resolution microvessel imaging using a short acquisition time (<10 s). Ultrasound MB data were acquired from different human tissues, including a healthy liver and a diseased liver with acute-on-chronic liver failure, a kidney, a pancreatic tumor, and a breast mass using an HFR clinical scanner. By leveraging the HFR and advanced processing techniques including sub-pixel motion registration, MB signal separation, and Kalman filter-based tracking, MBs can be robustly localized and tracked for ULM under the circumstances of relatively high MB concentration associated with standard clinical MB administration and limited data acquisition time in humans. Subtle morphological and hemodynamic information in microvasculature were shown based on data acquired with single breath-hold and free-hand scanning. Compared with contrast-enhanced power Doppler generated based on the same MB dataset, ULM showed a 5.7-fold resolution improvement in a vessel based on a linear transducer, and provided a wide-range blood flow speed measurement that is Doppler angle-independent. Microvasculatures with complex hemodynamics can be well-differentiated at super-resolution in both normal and pathological tissues. This preliminary study implemented the ultrafast in-human ULM in various human tissues based on a clinical scanner that supports HFR imaging, indicating the potentials of the technique for various clinical applications. However, rigorous validation of the technique in imaging human microvasculature (especially for those tiny vessel structure), preferably with a gold standard, is still required. [ABSTRACT FROM AUTHOR]

Ultrasound localization microscopy (ULM) has been proposed to image microvasculature beyond the ultrasound diffraction limit. Although ULM can attain microvascular images with a sub-diffraction resolution, long data acquisition time and processing time are the critical limitations. Deep learning-based ULM (deep-ULM) has been proposed to mitigate these limitations. However, microbubble (MB) localization used in deep-ULMs is currently based on spatial information without the use of temporal information. The highly spatiotemporally coherent MB signals provide a strong feature that can be used to differentiate MB signals from background artifacts. In this study, a deep neural network was employed and trained with spatiotemporal ultrasound datasets to better identify the MB signals by leveraging both the spatial and temporal information of the MB signals. Training, validation and testing datasets were acquired from MB suspension to mimic the realistic intensity-varying and moving MB signals. The performance of the proposed network was first demonstrated in the chicken embryo chorioallantoic membrane dataset with an optical microscopic image as the reference standard. Substantial improvement in spatial resolution was shown for the reconstructed super-resolved images compared with power Doppler images. The full-width-half-maximum (FWHM) of a microvessel was improved from 133 μm to 35 μm, which is smaller than the ultrasound wavelength (73 μm). The proposed method was further tested in an in vivo human liver data. Results showed the reconstructed super-resolved images could resolve a microvessel of nearly 170 μm (FWHM). Adjacent microvessels with a distance of 670 μm, which cannot be resolved with power Doppler imaging, can be well-separated with the proposed method. Improved contrast ratios using the proposed method were shown compared with that of the conventional deep-ULM method. Additionally, the processing time to reconstruct a high-resolution ultrasound frame with an image size of 1024 × 512 pixels was around 16 ms, comparable to state-of-the-art deep-ULMs. [ABSTRACT FROM AUTHOR]

Contrast-enhanced ultrasound (CEUS) has become an established modality in various clinical indications for liver diseases. SonoVue®, a pure blood pure agent, and Sonazoid®, which exhibits an additional Kupffer phase, are contrast agents approved for liver imaging. This review discusses and compares the current clinical evidence for these two ultrasound contrast agents in the characterization and detection of focal liver lesions in the non-cirrhotic and cirrhotic liver, as well as for the use in interventional procedures such as liver biopsy guidance, and local ablation treatment monitoring. Reference is made to clinical studies which evaluated the accuracy of CEUS using a standard of reference, its safety, or to comparative studies of these two agents. [ABSTRACT FROM AUTHOR]

Background: To evaluate the feasibility and effectiveness of artificial ascites to assist thermal ablation of liver cancer adjacent to the gastrointestinal tract in patients with previous abdominal surgery.Methods: Thirty-nine patients with a total of 40 liver malignant tumors were enrolled between January 2016 and June 2019. All had histories of hepatectomy, splenectomy, cholecystectomy, and intestinal surgery. The distance between the tumor and the gastrointestinal tract was < 5 mm. Normal saline was used as artificial ascites to protect the gastrointestinal tract during thermal ablation. The success rate of the procedure, incidence of major complications, and the technical efficacy of ablation were recorded. Patients were followed for local tumor progression (LTP), and overall survival (OS).Results: The use of artificial ascites was successful in 38 of the 40 procedures (95%). Major complications occurred in two of the 39 patients (5.1%) following the procedure. One was an intestinal fistula that occurred in a failed case and was associated with an infection. The other was a liver abscess that occurred in a successful case. The technical efficacy of ablation was 100% (40/40 procedures). The median follow-up was 16 months. The 1-, 2-, and 3-year LTP rates were 2.9, 5.7 and 5.7%. The 1-, 2-, and 3-year OS rates were 97.1, 86.8 and 69.5%.Conclusion: In patients with previous abdominal surgery, artificial ascites is feasible and effective for assisting thermal ablation of liver cancer adjacent to the gastrointestinal tract. [ABSTRACT FROM AUTHOR]

Background: To obtain high-yield histological samples by targeted prostate cancer (PCa) biopsy is the current trend compared with transrectal ultrasound (TRUS)-guided systematic histological biopsy, which is regarded as the gold standard for prostate cancer (PCa) diagnosis. In this paper, we present a targeted PCa imaging strategy using a real-time molecular photoacoustic imaging system integrated with a handheld US probe (PAI/US) and synthesized an integrin αvβ3 targeted probe based on ICG (cRGD-ICG).Methods: To prepare cRGD-ICG, ICG-NHS was linked to cRGD through carboxyl-co-reaction. In vitro PA imaging ability of cRGD-ICG was tested. Orthotopic PCa-bearing rats were used as animal models. After injected with either cRGD-ICG or non-targeted probe, rats were implemented with PA imaging to confirm the specific accumulation of cRGD-ICG at tumor region. Moreover, pathological frozen slices were made to observe distribution of the probe in prostate tissue ex vivo.Results: A small molecular PAI probe was synthesized and exhibited excellent targeted imaging ability in vitro. In vivo photoacoustic imaging was carried out after intravenous injection of cRGD-ICG in orthotopic PCa-bearing rats under the facilitation of the PAI/US system. Maximum molecular photoacoustic signals were observed in the tumor area in vivo after the probe injection, which showed 3.8-fold higher signal enhancement than that in the control group (P < 0.05). Significantly higher cRGD-ICG accumulation was observed under confocal microscopy in the tumor region than in normal prostate tissue.Conclusions: All our results showed that the comprehensive strategy provided a high-yield and reliable method for PCa diagnosis and targeted prostate biopsy, with great clinical translation potential. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19) has become a global pandemic since its outbreak in December 2019, which posed a threat to the safety and well-being of people on a global scale. Cancer patients are at high risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and their critical morbidity and case fatality rates are high. The ablation expert committee of the Chinese Society of Clinical Oncology compiled corresponding expert recommendations. These recommendations summarize the preventive measures and management of tumor ablation treatment in medical institutions, including outpatient clinics, oncology wards, ablation operation room, and postablation follow-ups in accordance with the guidelines and protocols imposed by the National Health Commission of the People's Republic of China and the experience in management and prevention according to various hospitals. This consensus aims to reduce and prevent the spread of SARS-CoV-2 and its cross-infection between cancer patients in hospitals and provide regulatory advice and guidelines for medical personnel. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the impact of intrahepatic cholestasis on liver fibrosis staging using liver stiffness measurements (LSM).Methods: Between July 2011 and September 2016, a total of 1197 patients with chronic hepatitis B (CHB) infection were enrolled to collect clinical, biological, 2D shear wave elastography (SWE), and histological (METAVIR scoring system) data. LSM was compared in patients with normal total bilirubin (TB) versus abnormal TB for each group of fibrosis stage, alanine aminotransferase (ALT) levels, and inflammation grade. Logistic regression and ROC analyses were performed to assess the benefit of adding TB and to LSM for fibrosis staging.Results: Nine hundred and seventy-three patients were analyzed. Within the same fibrosis stage, LSMs showed significantly higher value in patients with abnormal TB than those with normal TB. Increased LSM for abnormal TB was generally found within different sub-groups of patients (≤ F2 or ≥ F3; ALT < 2 × upper limit of normal (ULN) or ALT ≥ 2 × ULN; METAVIR activity grade ≤ 1 or ≥ 2). Patients with abnormal TB level showed higher optimal cutoff values: 10.46 kPa for ≥ F2, 10.94 kPa for ≥ F3, and 15.88 kPa for F4, than those with normal TB (7.62 kPa, 8.26 kPa, and 11.01 kPa, respectively). LSM assessed fibrosis stage (≥ F2, ≥ F3, F4) showed higher false positive rate in patients with abnormal TB level (44.6%, 45.1%, 39.6%) than those with normal TB (20.7%, 17.1%, 14.4%). However, the area under the ROC curve did not change appreciably when adding TB to LSM for fibrosis stage.Conclusion: Intrahepatic cholestasis showed slight effect on LSM in patients with CHB, also leading to overestimation of liver fibrosis stages. But adding TB level to LSM did not improve the overall diagnostic performance of liver fibrosis stage.Key Points: • Intrahepatic cholestasis showed slight effect on liver stiffness measurements (LSMs) in chronic HBV patients. • Patients with abnormal total bilirubin (TB) level showed higher optimal cutoff values and false positive rate. • When taking into account intrahepatic cholestasis, the diagnostic performance of LSM for liver fibrosis staging in patients with chronic HBV infection will not improve. [ABSTRACT FROM AUTHOR]

To investigate the feasibility, efficacy and safety of one-lung ventilation for percutaneous thermal ablation of liver tumors in the hepatic dome. From 5 January 2017 to 16 April 2019, 64 patients who underwent ultrasound-guided thermal ablation with a total of 75 liver malignant tumors located in the hepatic dome were enrolled in the present study. One-lung ventilation was employed to improve the acoustic window and protect the lung and diaphragm. If the one-lung ventilation was unsuccessful, artificial pleural effusion was added. The technical efficacy was confirmed by contrast-enhanced computed tomography/magnetic resonance imaging (CT/MRI) 1 month later. After that, CT/MRI was performed every 3–6 months. Among the enrolled patients, the technical success rate of one lung ventilation was 92.2% (59/64). The visibility scores of tumors were improved significantly after one-lung ventilation compared to those before one-lung ventilation (p <.001). Finally, 78.6% (55/70) of the tumors achieved clinical success of one-lung ventilation to become clearly visible and underwent thermal ablation. Fourteen of the remaining 15 tumors achieved a satisfactory acoustic window after combination of artificial pleural effusion. One lesion remained inconspicuous and partly affected by pulmonary gas. The follow-up period was 8 months (3–30 months). The technical efficacy rate was confirmed to be 100% (75/75). During the follow-up period, local tumor progression occurred in 2 patients (2/75, 2.7%). Major complications occurred in two patients (2/64, 3.1%) receiving one-lung ventilation. One-lung ventilation is a promising noninvasive method for the thermal ablation of hepatic dome tumors due to its efficacy and safety. [ABSTRACT FROM AUTHOR]

The goal of this study was to investigate the accuracy of ultrasound-ultrasound (US-US) fusion imaging for evaluating the ablation effect via phantom-simulated liver tumors. Twenty special phantom models were established, ablated and divided into a complete ablation group (n = 10) and an incomplete ablation group (n = 10). US-US fusion imaging was performed to evaluate the ablation effect. Gross specimens were observed as a standard reference. In this US-US fusion imaging study, the registration success rate was 100% (20/20), and the assessment time was 3.8 ± 0.9 min. The accuracy rate of the evaluation was 100% (20/20). There was no significant difference in the residual pseudo-tumoral area between the evaluation with US-US fusion imaging and gross specimen observation (p = 0.811), and the measurement error was 1.1 ± 0.6 mm. In conclusion, the feasibility and accuracy of US-US fusion imaging when evaluating the ablation effect can be investigated with this phantom-simulated liver tumor ablation model in an ideal state. [ABSTRACT FROM AUTHOR]

Purpose: To compare the applicability of fusion imaging between contrast-enhanced ultrasound (CEUS) and computed tomography (CT) or magnetic resonance imaging (MRI) (CT/MRI-CEUS fusion imaging) and fusion imaging between CEUS and ultrasound (US-CEUS fusion imaging) in the assessment of treatment response during liver cancer ablation. Methods: From August to December 2015, patients who underwent US-guided thermal ablation of liver tumors at our hospital with available CT/MRI images were enrolled consecutively. Both CT/MRI-CEUS and US-CEUS fusion imaging were performed in all patients to evaluate treatment responses. The applicable rate, success rate of registration and duration time were recorded. Complications were monitored in the follow-up period, and CECT/MRI within three months were taken as the standard reference of technical efficacy. Results: A total of 157 liver tumors (19 ± 8 mm, range 8-55 mm) in 115 patients (54 ± 11 years old, range 2 7∼ 84 years old) were enrolled. The applicable rate of US-CEUS fusion imaging was 61.1% (96/157) because of inconspicuous lesions in US, lower than that of CT/MRI-CEUS fusion imaging (99.7% (155/157)) (p < .05). However, the success rate of registration in US-CEUS fusion imaging (93.8% (90/96)) was superior to that of CT/MRI-US fusion imaging (81.3% (126/155)) (p < .05), especially for cases combined with alternative preablation surgeries or procedures (p < .05). The technical efficacy rate was 99.3% (150/151) according to the CECT/CEMRI. Conclusions: Both CT/MRI-CEUS and US-CEUS fusion imaging are feasible means for intraprocedural immediate evaluation of treatment response for liver thermal ablation. US-CEUS fusion imaging is preferred because of its convenience and higher success rate of registration. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the safety of thermal ablation for hepatocellular carcinoma (HCC) in patients with abnormal coagulation function. Methods: Fifty-seven HCC tumours in 50 patients were treated with thermal ablation. All patients had a meted platelet count <50 × 109/L or international normalised ratio (INR) ≥ 1.7. Gastroscopy before ablation, platelet concentrate or fresh frozen plasma transfusion during ablation and contrast enhanced ultrasoundgraphy (CEUS)-guided ablation to cease needle tract bleeding were performed to reduce haemorrhage. The incidences of haemorrhage and other major complications were recorded and patients were followed up to observe the local tumour progression (LTP), intrahepatic distant recurrence (IDR), overall survival (OS) and recurrence-free survival (RFS) rates. Results: Two incidences of needle tract bleeding and one needle tract bleeding together with bleeding at the suture of the spleen fossa were found. Three needle tract bleeding events were detected by CEUS and ceased after CEUS-guided complementary ablation. CEUS failed to detect bleeding at the suture of the spleen fossa. Therefore, a laparotomy was conducted for haemostasis. No other major complications were found after ablation. The median follow-up periods were 18.7 ± 12.0 months (range 1 ∼ 42 months) and 1 LTP and 15 IDRs occurred. The 1-, 2- and 3-year OS rates were 84.8%, 82.7% and 82.7%, and RFS rates were 67.9%, 64.0% and 64.0%, respectively. Conclusion: With gastroscopy before ablation, platelet concentrate or fresh frozen plasma transfusion during ablation and CEUS-guided ablation to cease needle tract bleeding, thermal ablation is a safe treatment for HCC in patients with abnormal coagulation function. [ABSTRACT FROM AUTHOR]

This study assessed the diagnostic accuracy of 2-D shear wave elastography (2-D-SWE) for the non-invasive staging of liver fibrosis and compared the findings with those for biochemical markers (the aspartate aminotransferase-to-platelet index and fibrosis-4 index) of liver fibrosis in patients with elevated alanine aminotransferase (ALT) levels (>5 × the upper limit of normal). Patients with chronic liver diseases and elevated ALT levels who underwent liver biopsy were consecutively included. Receiver operating characteristic (ROC) curves were constructed to assess overall accuracy and to identify optimal cutoff values. After exclusions, data from 105 patients were analyzed. The areas under the ROC curves (AUROCs) for significant fibrosis, severe fibrosis and cirrhosis were 0.83, 0.86 and 0.91, respectively. The optimal cutoff values for predicting significant fibrosis, severe fibrosis and cirrhosis were 10.6, 13.2 and 17.6 kPa, respectively. The AUROCs of 2-D-SWE were significantly higher than those of biochemical markers for predicting significant fibrosis, severe fibrosis and cirrhosis (all p values < 0.05). Therefore, the diagnostic performance of 2-D-SWE in assessing liver fibrosis stages in patients with elevated ALT levels was promising. The optimal cutoff values were increased but appropriate for this cohort because the baseline levels of liver stiffness measurements were increased in these patients, even in the absence of fibrosis. [ABSTRACT FROM AUTHOR]

Introduction The stiffness of large arteries and the presence or absence of plaque are associated with coronary heart disease ( CHD). Because arterial walls are biologically heterogeneous, the standard deviation of Young's modulus ( YM-std) of the large arteries may better predict coronary atherosclerosis. However, the role of YM-std in the occurrence of coronary events has not been addressed so far. Therefore, this study investigated whether the carotid YM-std and the presence or absence of plaque improved CHD risk prediction. Methods One hundred and three patients with CHD (age 66 ± 11 years) and 107 patients at high risk of atherosclerosis (age 61 ± 7 years) were recruited. Carotid YM was measured by the vessel texture matching method, and YM-std was calculated. Carotid intima-media thickness was measured by the MyLab 90 ultrasound Platform employed dedicated software RF-tracking technology. Results In logistic regression analysis, YM-std ( OR = 1·010; 95% CI = 1·003-1·016), carotid plaque ( OR = 16·759; 95% CI = 3·719-75·533) and YM-std plus plaque ( OR = 0·989; 95% CI = 0·981-0·997) were independent predictors of CHD. The traditional risk factors ( TRF) plus YM-std plus plaque model showed a significant improvement in area under the receiver-operating characteristic curve ( AUC), which increased from 0·717 ( TRF only) to 0·777 (95% CI for the difference in adjusted AUC: 0·010-0·110). Conclusions Carotid YM-std is a powerful independent predictor of CHD. Adding plaque and YM-std to TRF improves CHD risk prediction. [ABSTRACT FROM AUTHOR]

This study compared 2-D shear wave elastography (SWE) and transient elastography (TE) for liver fibrosis staging in patients with chronic hepatitis B (CHB) infection using liver biopsy as the reference standard. Patients with CHB infection who underwent liver biopsy were consecutively included. After exclusions, 257 patients were analyzed. Two-dimensional SWE resulted in a significantly higher rate of reliable measurements (98.1%, 252/257) than TE (93.0%, 239/257) (p = 0.011). Liver stiffness measurements of the two examinations exhibited a strong correlation (r = 0.835, p < 0.001). In patients given a confirmed histologic diagnosis, Spearman's rank coefficients were 0.520 in stage F0 (p < 0.001), 0.684 in stage F1 (p < 0.001), 0.777 in stage F2 (p < 0.001), 0.672 in stage F3 (p < 0.001) and 0.755 in stage F4 (p < 0.001). There were no significant differences between the areas under the receiver operating characteristic (ROC) curves of 2-D SWE and TE for liver fibrosis staging (all p values > 0.05). Two-dimensional SWE had diagnostic accuracy comparable to that of TE for liver fibrosis staging. The measurements that the two techniques provide are not interchangeable. [ABSTRACT FROM AUTHOR]

Background: To assess the accuracy of contrast-enhanced ultrasound (CEUS)-CT/MR image fusion in evaluating the radiofrequency ablative margin (AM) of hepatocellular carcinoma (HCC) based on a custom-made phantom model and in HCC patients.Methods: Twenty-four phantoms were randomly divided into a complete ablation group (n = 6) and an incomplete ablation group (n = 18). After radiofrequency ablation (RFA), the AM was evaluated using ultrasound (US)-CT image fusion, and the results were compared with the AM results that were directly measured in a gross specimen. CEUS-CT/MR image fusion and CT-CT / MR-MR image fusion were used to evaluate the AM in 37 tumors from 33 HCC patients who underwent RFA.Results: The sensitivity, specificity, and accuracy of US-CT image fusion for evaluating AM in the phantom model were 93.8, 85.7 and 91.3%, respectively. The maximal thicknesses of the residual AM were 3.5 ± 2.0 mm and 3.2 ± 2.0 mm in the US-CT image fusion and gross specimen, respectively. No significant difference was observed between the US-CT image fusion and direct measurements of the AM of HCC. In the clinical study, the success rate of the AM evaluation was 100% for both CEUS-CT/MR and CT-CT/MR-MR, and the duration was 8.5 ± 2.8 min (range: 4-12 min) and 13.5 ± 4.5 min (range: 8-16 min) for CEUS-CT/MR and CT-CT/MR-MR, respectively. The sensitivity, specificity, and accuracy of CEUS-CT/MR imaging for evaluating the AM were 100.0, 80.0, and 90.0%, respectively.Conclusions: A phantom model composed of carrageenan gel and additives was suitable for the evaluation of HCC AM. CEUS-CT/MR image fusion can be used to evaluate HCC AM with high accuracy. [ABSTRACT FROM AUTHOR]

To evaluate computer-assisted hepatocellular carcinoma (HCC) ablation planning based on 3-D ultrasound, 3-D ultrasound images of 60 HCC lesions from 58 patients were obtained and transferred to a research toolkit. Compared with virtual manual ablation planning (MAP), virtual computer-assisted ablation planning (CAP) consumed less time and needle insertion numbers and exhibited a higher rate of complete tumor coverage and lower rate of critical structure injury. In MAP, junior operators used less time, but had more critical structure injury than senior operators. For large lesions, CAP performed better than MAP. For lesions near critical structures, CAP resulted in better outcomes than MAP. Compared with MAP, CAP based on 3-D ultrasound imaging was more effective and achieved a higher rate of complete tumor coverage and a lower rate of critical structure injury; it is especially useful for junior operators and with large lesions, and lesions near critical structures. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of our study was to assess the feasibility and reliability of 3D ultrasound-ultrasound (US-US) automatic registration-based analysis of the hepatic vessel tree (VT) (3D VT-based automatic registration) in clinical applications.Materials and methods: A total of 70 pairs of 3D ultrasound data were acquired from the livers of 10 healthy volunteers enrolled in the study. An automatic registration method was applied to the acquired volumetric data pairs, and anatomic landmarks were picked by an experienced sonographer as ‘ground truth’. The influences of respiration phase, subject posture, and liver lobe on data acquisition and scan volumetric angle on the registration accuracy and robustness were investigated. The registration time, success rate, median registration error distance, and sonographer’s subjective feedback were assessed.Results: The time required for the 3D VT-based automatic registration was approximately 15∼20 s. Overall, the success rate for the hepatic vessel-based registration was 71% (50/70), and the median registration error distance was 1.72 mm (0.57∼4.71 mm). When the influential factors were well controlled, the optimal registration accuracy (median registration error distance = 1.22 mm) could be obtained with an excellent success rate of 100% (10/10). According to the subjective assessment of the sonographer, over 90% (45/50) of the automatic registration results were not inferior to the ground truth. Among them, 42% (21/50) were superior to the fusion results from the ground truth.Conclusions: The results suggest that the 3D VT-based automatic registration is feasible and reliable and has potential for guidance and evaluation of intraoperative ablation of hepatocellular carcinoma. [ABSTRACT FROM PUBLISHER]

Real-time shear wave elastography (SWE) is a novel two-dimensional elastographic method that is used to estimate the severity of liver fibrosis. However, the normal range of liver stiffness (LS) and the possible factors that influence SWE are not well understood. The aims of the current study are to define the normal range of LS in healthy subjects and to explore the factors that may affect SWE. A total of 509 healthy subjects underwent SWE to determine the stiffness of their livers, and the effects of gender, age and body mass index (BMI) on LS were analyzed. The effects of different factors on SWE, including the testing position, measurement depth and size of the region of interest (ROI), were analyzed in 137 subjects. SWE imaging was successfully performed in 502 healthy subjects (98.6%, 502/509). The mean value of the SWE measurements in 502 individuals was 5.10 ± 1.02 kPa, and the 95% confidence interval was 5.02–5.19 kPa (range: 2.4–8.7 kPa). We found that the detective position within the liver had a significant impact on the liver stiffness measurement (LSM), and the lowest coefficient of variation (CV = 8%) was obtained for LSMs made at segment V. LS was greater at a depth >5 cm (5.78 ± 1.66 kPa) compared with depths ≤5 cm (4.66 ± 0.77 kPa, p < 0.001); LS was also greater in men than in women (5.45 ± 1.02 kPa vs. 4.89 ± 0.96 kPa, p < 0.001). However, there were no significant differences in the LS values regarding the size of the ROI, age or BMI (all p > 0.05). The mean LS value in all 502 healthy subjects was 5.10 ± 1.02 kPa. The mean LS value obtained by SWE was not influenced by the size of the ROI, age or BMI, but the mean value was significantly influenced by the different segments of the liver, the detection depth and gender. [ABSTRACT FROM AUTHOR]

Objective: Atherosclerosis is a chronic and systemic disease and its developmental process involves the synergism of multiple risk factors such as hypertension, dyslipidemia, diabetes, obesity and smoking. The diagnosis of subclinical atherosclerosis is essential for strategic guidance towards suitable treatments and efficient prevention against acute cardiovascular events. This study employed ultrasound radiofrequency (RF) tracking technology to characterize human carotid arteries in vivo in terms of intima-media thickness (IMT) and artery stiffness, and evaluated the statistical correlation between carotid IMT and stiffness, and the number of risk factors for atherosclerosis. Methods: A total of 160 asymptomatic subjects were enrolled. Ultrasound RF-tracking technology was employed to acquire carotid IMT and stiffness parameters: maximum IMT (MAXIMT), RF Quality IMT (RFQIMT), distensibility coefficient (), compliance coefficient (), index, index and local pulse wave velocity (). The subjects were categorized in four groups in terms of the number of risk factors: ‘zero’, ‘single’, ‘double’, and ‘multiple’, and statistical analyses of carotid IMT and stiffness parameters were performed between these different groups. Results: The subjects (n = 145) with MAXIMT smaller than 1.0 mm matched the IMT criteria for non-atherosclerosis and were named as NA-subjects. Spearman’s rho correlation analysis of the whole group and the NA-subjects both showed that MAXIMT correlated positively with RFQIMT, , , and , and negatively with and (p<0.01). The analysis of covariance of NA-subjects showed significant differences between subjects with and without risk factors, and also showed significant differences between the ‘zero’, ‘single’, ‘double’, and ‘multiple’ groups. Conclusions: The carotid IMT and stiffness parameters obtained by the ultrasound RF-tracking technology were demonstrated to possess significant statistical correlation with the number of risk factors from 160 subjects, and these anatomical and mechanical parameters may potentially be used together with the IMT criteria to support subclinical atherosclerosis diagnosis. [ABSTRACT FROM AUTHOR]

Abstract: Drug resistance is a big problem in systemic chemotherapy of hepatocellular carcinoma (HCC), and nanomedicines loaded with both chemotherapeutic agents (e.g. paclitaxel, PTX) and siRNA's targeting antiapoptosis genes (e.g. BCL-2) possess the advantages to simultaneously overcome the efflux pump-mediated drug resistance and antiapoptosis-related drug resistance. However, tumor-penetrating drug delivery with this type of nanomedicines is extremely difficult due to their relatively big size compared to the single drug-loaded nanomedicines. Aiming at address this problem, US-responsive nanobubbles encapsulating both anti-cancer drug paclitaxel (PTX) and siRNA (PTX–NBs/siRNA) for HCC treatment were developed by hetero-assembly of polymeric micelles and liposomes in the present study. Utilizing an external low-frequency US force imposed to the tumor site, effective tumor-penetrating codelivery of siRNA and PTX was achieved via tail vein injection of PTX–NBs/siRNA into nude mice bearing human HepG2 xerografts. Consequently, the PTX treatment-inducible antiapoptosis in HepG2 cells was effectively suppressed by the codelivered siRNA targeting an antiapoptosis gene (BCL-2 siRNA) during chemotherapy. Owing to the synergistic anti-cancer effect of two therapeutic agents, tumor growth was completely inhibited using low-dose PTX in animal study. Our results highlight the great potential of this type of US-responsive hetero-assemblies carrying both anti-cancer drug and siRNA as an effective nanomedicinal system for HCC therapy. [Copyright &y& Elsevier]

Abstract: Supersonic shear wave imaging (SSI) has recently been explored as a technique to evaluate tissue elasticity modulus and has become a valuable tool for tumor characterization. The purpose of this study was to develop a novel computer-aided diagnosis (CAD) system that can acquire quantitative elastographic information from color SSI elastography images automatically and objectively for the purpose of classifying benign and malignant breast tumors. Conventional ultrasonography (US) and SSI elastography images of 125 breast tumors (81 benign, 44 malignant), in 93 consecutive patients (mean age: 40 y, age range: 16–75 y), were obtained. After reconstruction of tissue elasticity data and automatic segmentation of each breast tumor, 10 quantitative elastographic features of the tumor and peri-tumoral areas, respectively (elasticity modulus mean, maximum and standard deviation, hardness degree and elasticity ratio), were computed and evaluated. A support vector machine (SVM) classifier was used for optimum classification via combination of these features. The B-mode Breast Imaging Reporting and Data System (BI-RADS) was used to compare gray-scale US and SSI elastography with respect to diagnostic performance. Histopathologic examination was used as the reference standard. Student's t-test, the Mann-Whitney U-test, the point biserial correlation coefficient and receiver operating characteristic curve analysis were performed for statistical analysis. As a result, the accuracy, sensitivity, specificity, positive predictive value and negative predictive value of benign/malignant classification were 95.2% (119/125), 90.9% (40/44), 97.5% (79/81), 95.2% (40/42) and 95.2% (79/83) for the CAD scheme, respectively, and 79.2% (99/125), 90.9% (40/44), 72.8% (59/81), 64.5% (40/62) and 93.7% (59/63) for BI-RADS assessment, respectively. The area under the receiver operating characteristic curve (A z value) for the proposed CAD system using the combination of elastographic features was significantly higher than the A z value for visual assessment by the radiologists using BI-RADS (0.97 vs. 0.91). The results indicate that SSI elastography could be used for computer-aided feature extraction, and the proposed CAD method could improve the diagnostic accuracy of classification of breast tumors to avoid unnecessary biopsy. Furthermore, elastographic features of the peri-tumoral area have the potential to provide critical information in differential diagnosis. [Copyright &y& Elsevier]

Background: Carotid intima-media thickness (IMT) and elasticity have been shown to be independent predictors of cardiovascular disease (CVD). Cardiovascular risk factors (CVRFs) includes hypertension, dyslipidemia, diabetes, overweight and smoking. The objective was to investigate whether the clustering of three or more components of CVRFs has a greater impact on carotid IMT and elasticity than individual components of CVRFs. Methods: One hundred and seventy-three participants without clinical CVD were classified as the multiple CVRFs patients with three or more CVRFs (n  = 55) and control group with two or less CVRFs (n  = 118). Carotid IMT and elastic modulus were measured by B-mode ultrasound and vessel texture matching method (VTMM), respectively. Results: The multiple CVRFs conferred a disproportionate increase in carotid IMT (43%, p<0.0001) and elastic modulus (60%, p<0.0001), compared with control group. Multiple regression models, which included age, gender, as well as each individual component of CVRFs as continuous variables, showed that multiple CVRFs was an independent determinant of both IMT (p  = 0.042) and elasticity (p  = 0.008). In the analysis of variance adjusted with age, subjects with single, double, and multiple CVRFs, increased by 8.1%, 42.2%, and 66% for IMT, 54.6%, 94.3%, and 125.2% for elastic modulus, respectively, compared to subjects without CVRFs. Conclusions: The clustering of multiple CVRFs has a greater impact on carotid IMT and elasticity than individual components of CVRFs. This suggests that the components of CVRFs interact to synergistically impact carotid IMT and elasticity. [ABSTRACT FROM AUTHOR]

Abstract: Ultrasound (US)-sensitive nanobubble (NB) which may utilize the physical power of US exposure to improve delivery efficiency to target cells is emerging as one of the most promising nanocarriers for drug delivery. On the basis of successfully fabricating NBs with the ability of passively accumulating in tumor tissue, in this study we synthesized a US-sensitive NB bearing siRNA (siRNA-NB) for tumor therapy via a hetero-assembling strategy using the siRNA-complexed polymeric micelles and gas-cored liposomes. The US exposure-aided siRNA transfection effectively enhanced the gene silencing effect of siRNA-NBs both in vitro and in vivo, which resulted in much elevated level of cancer cell apoptosis. Consequently, significantly improved therapeutic effect was achieved in a nude mouse glioma model, using siRNA-NBs bearing siRNA to target the anti-apoptosis gene sirtuin 2 (SIRT2). These results show that, with the aid of US exposure, the US-sensitive siRNA-NB may be an ideal delivery vector to mediate highly effective RNA interference for tumor treatment. [Copyright &y& Elsevier]

Purpose: Evaluating degree of hepatic steatosis is of great value for prognosis of liver transplantation. There is an urgent need for a non-invasive method to assess hepatic steatosis grade of donor livers. Purpose of our study was to evaluate diagnostic accuracy of attenuation coefficient estimation (ACE) by reference frequency method (RFM) in detecting hepatic steatosis of donor livers.Method: We retrospectively enrolled 62 potential liver donors which underwent ACE by RFM ex-vivo, in-vivo or both. We acquired raw data of B-mode images of liver parenchyma and offline-processes for attenuation estimation. Finally, we calculated and compared diagnostic performance of ACEs for steatosis grade detection and used histological results as the gold standard.Results: ACEs with none, mild and moderate hepatic steatosis were 0.57, 0.73 and 0.80 dB/cm/MHz in potential donor livers. The cutoff value to diagnose mild hepatic steatosis was 0.63 dB/cm/MHz and 0.77 dB/cm/MHz for moderate hepatic steatosis, and values for the area under the receiver operating characteristic curve for diagnosis of mild and moderate hepatic steatosis were 0.92 and 0.90, respectively.Conclusions: According to our results, ACE by RFM is an accurate non-invasive method in detecting hepatic steatosis, which may be of great help for clinical evaluation of donor livers before liver transplantation. [ABSTRACT FROM AUTHOR]

Multidrug-resistant Staphylococcus aureus (MRSA) seriously endanger human health. The development of efficient methods to eliminate the infections and monitor the treatment process are of great significance. Near-infrared-II (NIR-II) photoacoustic (PA) imaging and photothermal therapy (PTT) are highly integrated theranostic platforms with superior performance including a low imaging background, increased tissue penetration depth, and high photothermal threshold. Herein, we report an activatable near-infrared II (NIR-II) phototheranostic strategy using miniature Au/Ag nanorods (NRs) for the photochemical synergistic therapy of MRSA infections and in situ monitoring of the treatment progress. Au/Ag NRs were efficiently activated by ferricyanide solution and allowed to continuously release free Ag+ to eliminate MRSA, triggering NIR-II photothermal and PA performance enhancement. The activated NIR-II photothermal effect in turn accelerated the release of free Ag+ from Au/Ag NRs for the synergistic elimination of gram-positive Staphylococcus aureus and promoted wound healing. No photothermal damages or free Ag+-induced side effects were observed in treated mice. After synergistic treatment, a 20-fold NIR-II PA signal increase with a maximum signal-to-noise measurement of 9.5 was observed between the implanted site and normal tissue, enabling sensitive monitoring of Ag+ release process. The prepared Au/Ag NRs were stable and biocompatible, showing great potential for activatable NIR-II phototheranostic application. [ABSTRACT FROM AUTHOR]