Computer-Aided Color Parameter Imaging of Contrast-Enhanced Ultrasound Evaluates Hepatocellular Carcinoma Hemodynamic Features and Predicts Radiofrequency Ablation Outcome

Computer-aided color parameter imaging (CPI) is a novel technique for contrast-enhanced ultrasound (CEUS) that can highlight hemodynamic features of focal lesions. The purpose of the study was to investigate the role of CPI in evaluation of hepatocellular carcinoma (HCC) hemodynamic features and prognosis after radiofrequency ablation (RFA). One hundred twenty-one patients with HCC underwent CEUS with CPI analysis before RFA. Eighty-nine patients had pathologically proven well- to moderately differentiated HCC (WM-HCC), and 32 patients had poorly differentiated or undifferentiated HCC (PU-HCC). Perfusion features of CEUS and contrast-enhanced computed tomography/magnetic resonance imaging were compared with CPI parameters for WM-HCC and PU-HCC. The results indicated that 67.4% of WM-HCC had a centrifugal perfusion CPI pattern, whereas 84.4% of PU-HCC tumors had a centripetal pattern (p < 0.001, odds ratio = 11.2). The specificity, sensitivity and accuracy of the CPI perfusion pattern regarding HCC pathological grade were higher than those with routine CEUS (84.4% vs. 9.4%, p < 0.001; 67.4% vs. 3.4%, p < 0.001; 71.9% vs. 5.0%, p < 0.001). Moreover, multivariable analysis revealed that the CPI perfusion pattern was an independent risk factor for progression-free survival post-RFA (centripetal group: 28.3 ± 4.1 mo vs. centrifugal group: 45.8 ± 4.4 mo, p = 0.002). A novel CPI technique for CEUS could non-invasively provide valuable hemodynamic information and predict prognosis for HCC patients treated by RFA.     

Vascularity of Intra-testicular Lesions: Inter-observer Variation in the Assessment of Non-neoplastic Versus Neoplastic Abnormalities After Vascular Enhancement With Contrast-Enhanced Ultrasound

The aim of this study is to assess the additional benefit of contrast-enhanced ultrasound (CEUS) over conventional ultrasonography (US) in identifying intra-testicular abnormalities among observers of different experiences. In this study, 91 focal testicular lesions (46 neoplastic, 45 non-neoplastic) imaged with gray-scale US/Doppler US and CEUS were classified using a 5-point scale. Three experienced and four inexperienced observers rated each lesion using gray-scale/color Doppler US alone and then with the addition of CEUS. Improved diagnostic specificity and accuracy with the addition of CEUS was observed for both experienced (specificity: 71.1% vs. 59.3%, p = 0.005; accuracy: 83.5% vs. 76.9%, p = 0.003) and inexperienced observers (specificity: 75.6% vs. 51.7%, p = 0.005; accuracy: 80.2% vs. 72.0%, p < 0.001). Significant inter-observer variability between the experienced and inexperienced observers when assessing conventional US alone was eliminated with the addition of CEUS. CEUS improves diagnostic accuracy of focal intra-testicular lesions for both experienced and inexperienced observers and reduces inter-observer variability in inexperienced operators.     

Establishment of a Diagnostic Method for Pelvic Sentinel Lymph Node Metastasis by Contrast-Enhanced Ultrasound in Uterine Cancer

This study investigated the usefulness of conventional ultrasound (US) and contrast-enhanced ultrasound (CEUS) in distinguishing metastasis of pelvic sentinel lymph nodes (SLNs) in patients with gynecological cancer. We examined 74 SLNs of patients with endometrial cancer (n = 26) and cervical cancer (n = 11). Patients underwent US and CEUS followed by SLN biopsy; US and CEUS results were evaluated visually and quantitatively and compared between pathological metastasis-negative and -positive groups. To support CEUS results, the microvessel density of SLNs was evaluated immunohistochemically. Seventeen positive and 40 negative SLNs were evaluable. Margin and enhancement patterns by visual assessment revealed significant differences (p = 0.046 and 0.022, respectively). In quantitative time–intensity curve analyses, the weakest peak intensities (PI_min), PI ratio and PI difference indicated significant differences (p = 0.045, p < 0.001 and p < 0.001, respectively). The areas under the receiver operating characteristic curves (AUCs) were 0.64, 0.82 and 0.83, respectively. The most effective PI ratio from the AUC was 1.3 (sensitivity = 82%, specificity = 70%), and the PI difference from the AUC was 20 (sensitivity = 88%, specificity = 70%). Microvessel density was significantly lower in metastatic lesions than in other areas. The quantitative analysis of CEUS seemed to be a reasonable method for distinguishing lymph node metastasis in patients with gynecological cancer.     

Non-enhanced Pattern on Contrast-Enhanced Ultrasound in the Local Efficacy Assessment of Irreversible Electroporation Ablation of Pancreatic Adenocarcinoma

The objective was to evaluate the diagnostic value of contrast-enhanced ultrasound in the assessment of the local efficacy after irreversible electroporation (IRE) ablation of pancreatic adenocarcinoma 1 mo after ablation. Fifteen patients with pancreatic adenocarcinoma were treated with IRE and then examined by contrast-enhanced ultrasound 1 mo after ablation. The contrast agent was SonoVue. Technical efficacy was assessed at 3 mo after IRE and classified as technical efficiency (TE) and technical inefficiency (TIE). Diagnostic performance was analyzed using a receiver operating characteristic curve. Ten patients were considered as having TE, and five, TIE. Complete non-enhancement was observed in seven ablation zones (70.0%) in the TE group, and peripheral heterogeneous enhancement, in all five ablation zones (100.0%) in the TIE group. The non-enhancement pattern differed significantly between the TE and TIE groups (p?=?0.026), with significant correlation with technical efficacy (p?=?0.007). The area under the receiver operating characteristic curve was 0.85 (p?=?0.008, 95% confidence interval: 0.65–1.05). A non-enhancement pattern using contrast-enhanced ultrasound was useful in the assessment of local efficacy after IRE ablation of pancreatic adenocarcinoma.     

Qualitative and Quantitative Contrast-Enhanced Ultrasound Combined with Conventional Ultrasound for Predicting the Malignancy of Soft Tissue Tumors

This study was aimed at evaluating the performance of perfusion patterns and the quantitative parameters of contrast-enhanced ultrasound (CEUS) in the detection of soft tissue tumors (STTs) and establishing a US workflow for STTs to improve patient management. Conventional ultrasound (US) and CEUS data were retrospectively collected from 156 soft tissue masses. Six perfusion patterns (P1–P6) were applied for CEUS qualitative analysis. Multivariate logistic regression was used to evaluate the performance of conventional US and qualitative and quantitative CEUS in distinguishing benign and malignant STTs. The malignancy rates of P1–P6 in STTs were 0%, 50.0%, 9.1%, 33.3%, 73.4% and 61.0%, respectively. For "non-P1" STTs, the predictive model combining quantitative CEUS parameters with conventional US features, including margin (odds ratio [OR] = 4.490, p = 0.000), vascular density (OR = 2.307, p = 0.013), 50% wash-out intensity (OR = 1.904, p = 0.032) and 50% wash-out time (OR = 1.031, p = 0.019), performed favorably in predicting malignancy, with an accuracy of 81.0% and an area under the receiver operating characteristic curve of 0.868. Furthermore, a US workflow for the detection of STTs based on conventional US and CEUS was established. CEUS with qualitative and quantitative analyses could be an effective tool for STT diagnosis. The US workflow in this study may improve the management of STT patients.     

Assessment of Tumor Response in Mice with Ovarian Peritoneal Carcinomatosis using Doppler Ultrasound of the Superior Mesenteric Artery and Celiac Trunk

The goal of the work described here was to assess the performance of Doppler ultrasound (US) of the superior mesenteric artery (SMA) and celiac trunk (CT) in the evaluation of tumor response in female mice with ovarian peritoneal carcinomatosis treated either with bevacizumab or with carboplatin. Compared with untreated mice, carboplatin-treated mice had a lower weight (23.3 ± 2.0 vs. 27.9 ± 2.9 g, p < 0.001), peritoneal carcinomatosis index (PCI, 11 ± 3 vs. 28 ± 6, p < 0.001), Ki67-positive staining surfaces (p < 0.001), vascular density (p < 0.001), mean blood flow velocity (mBFVel) in the SMA (7.0 ± 1.4 vs. 10.9 ± 1.8 cm/s, p < 0.001) and CT (8.0 ± 1.8 vs. 14.3 ± 4.6 cm/s, p < 0.001) and no ascites. Weight and mBFVel were similar in bevacizumab-treated and untreated mice. The mBFVels in the SMA and CT correlated with the PCI used as an estimation of the tumor burden, R = 0.70 (p < 0.0001) and R = 0.65 (p < 0.0001), respectively. Doppler US allows non-invasive assessment of the effects of anticancer therapy in ovarian peritoneal carcinomatosis-induced mice.     

超声造影在肝肿瘤热消融术中评估胆囊损伤的应用

目的探讨超声造影在胆囊旁肝肿瘤的热消融术中评估胆囊损伤的价值。 方法选取2016年1月至2017年3月在中山大学附属第三医院接受射频或微波消融治疗的患者40例,共42个胆囊旁肝肿瘤。采用常规超声检查评估患者术前术后胆囊壁厚度变化情况的同时,消融术中即时行超声造影检查评估胆囊壁血流灌注情况,判断胆囊壁损伤情况,并进行后续处理。通过随访评估胆囊旁肝肿瘤消融治疗的有效性、安全性。术前、术中及术后胆囊壁厚度的比较采用配对符号秩和检验。 结果与消融术前比较,40例接受消融治疗患者的胆囊壁术中评估有8例患者胆囊壁明显增厚。术中超声造影检查除2例评估为胆囊壁血流灌注缺损外,其他患者胆囊壁灌注较好,这2例患者行腹腔镜胆囊切除术并病理证实胆囊壁热损伤坏死（其中1例出现胆囊穿孔）,另有4例患者因多发胆囊结石行切除胆囊。34例保留胆囊患者中有6例在术后3 d内复查仍有胆囊壁增厚,后续随访中4例恢复,2例保持胆囊壁增厚状态,但均未出现胆囊消融热损伤相关症状。患者术中、术后的胆囊壁厚度与术前比较,差异均有统计学意义[5.00 mm（4.00~6.25 mm） vs 3.50 mm（3.00~5.00 mm）,Z=-3.741,P<0.001;5.0 mm（3.0~8.0 mm） vs 3.5 mm（3.0~5.0 mm）,Z=-3.735,P<0.001]。术后1个月增强CT/MRI检查证实41个病灶消融完全,完全消融率为97.6%（41/42）,所有消融完全病灶至随访结束均未发生局部肿瘤进展。 结论在超声引导下胆囊旁肝肿瘤消融术中即时行超声造影检查能够通过反映胆囊壁血流灌注状态判断胆囊壁消融热损伤情况。     

Meta-Analysis: Contrast-Enhanced Ultrasound Versus Conventional Ultrasound for Differentiation of Benign and Malignant Breast Lesions

This meta-analysis aimed to compare the diagnostic performance of contrast-enhanced ultrasound (CEUS), conventional ultrasound (US) combined with CEUS (US?+?CEUS) and US for distinguishing breast lesions. From thorough literature research, studies that compared the diagnostic performance of CEUS versus US or US?+?CEUS versus US, using pathology results as the gold standard, were included. A total of 10 studies were included, of which 9 compared the diagnostic performance of CEUS and US, and 5 studies compared US?+?CEUS and US. In those comparing CEUS versus US, the pooled sensitivity was 0.93 (95% CI: 0.91–0.95) versus 0.87 (95% CI: 0.85–0.90) and pooled specificity was 0.86 (95% CI: 0.84–0.88) versus 0.72 (95% CI: 0.69–0.75). In studies comparing US?+?CEUS versus US, the pooled sensitivity was 0.94 (95% CI: 0.92–0.96) versus 0.87 (95% CI: 0.84–0.90) and pooled specificity was 0.86 (95% CI: 0.82–0.89) versus 0.80 (95% CI: 0.76–0.84). In terms of diagnosing breast malignancy, areas under the curve of the summary receiver operating characteristic (of both CEUS (p?=?0.003) and US?+?CEUS (p?=?0.000) were statistically higher than that of US. Both CEUS alone and US?+?CEUS had better diagnostic performance than US in differentiation of breast lesions, and US?+?CEUS also had low negative likelihood ratio.     

Contrast-Enhanced Ultrasound Findings and Differential Diagnosis of Hepatic Epithelioid Angiomyolipoma Compared with Hepatocellular Carcinoma

Hepatic epithelioid angiomyolipoma (EAML) has malignant potential that can easily be misdiagnosed as hepatocellular carcinoma (HCC), but the treatment options of these conditions are different. This retrospective study investigated whether contrast-enhanced ultrasound (CEUS) can differentiate EAML from HCC. We included 24 patients with pathologically confirmed EAML and 36 patients with HCC who underwent pre-operative conventional ultrasound and CEUS. The conventional ultrasound and CEUS features of the two groups were analyzed. Time intensity curves (TICs) were analyzed for all lesions using quantitative perfusion analysis software. This study found that significant differences existed between the EAML and HCC groups in terms of clinical features such as sex, age, symptoms, alpha-fetoprotein and history of hepatitis B virus infection (p < 0.05). Tumor size, number, border and echogenicity on conventional ultrasound were significantly different between EAML and HCC (p < 0.05). Regarding CEUS, EAML was more likely to have a centripetal enhancement pattern than HCC (p < 0.05). The tumor enhancement degree in the delayed phase in CEUS was significantly different between EAML and HCC (p < 0.05). Quantitative analysis of CEUS parameters revealed that the wash-in area under the curve (AUC) was larger in EAML than in HCC (p < 0.05). Time to peak was significantly shorter in EAML than in HCC (p < 0.05). The peak intensity was significantly stronger in EAML than in HCC (p < 0.05). Regarding the diagnostic performance of CEUS parameters that showed statistical significance on univariate analysis, the sensitivity and specificity for distinguishing EAML from HCC was 66.7%–100.0% and 55.6%–91.7%, respectively. Overall, CEUS could be valuable in differentiating EAML from HCC. Specific features such as the centripetal filling and prolonged enhancement patterns on CEUS, higher peak intensity, bigger wash-in AUC and shorter time to peak on TICs may contribute to a more confirmative differential diagnosis of EAML.     

Ultrasound Evaluation of Three Outcome Domains in the Follow-up of Urate-Lowering Therapy in Gout: An Observational Study

This prospective study was aimed at observing the changes in three ultrasound (US) outcome domains (urate deposition, joint inflammation and bone erosion) in gout patients within the 1 y on urate-lowering therapy. The elementary lesions, including tophus, double-contour (DC) sign, aggregates, synovitis and bone erosion of the bilateral knee, ankle and first metatarsophalangeal joints, were evaluated repeatedly by US before and after 3, 6 and 12 mo of treatment, and the effective rates of clearance of tophus, DC sign and aggregates in different time groups were compared. A Global OMERACT–EULAR Synovitis Score (GLOESS) was calculated for these three paired joints to observe the inflammation. Bone erosion was also scored. The correlation between serum uric acid levels and tophus size changes was analyzed. Our results indicated that the decrease in serum uric acid levels was not completely parallel to the decrease in tophus size. For tophus, there was no significant difference in the clearance rate between different time groups (χ² = 1.76, p = 0.392), while for DC sign and aggregates, there were significant differences (χ² = 21.48, p < 0.001, χ² = 7.75, p = 0.018). Meanwhile, GLOESS was significantly lower after 6 mo of therapy (χ² = 32.316, p < 0.001). Additionally, bone erosion had not improved after 1 y of treatment (Z = –1.633, p = 0.102). Thus, US is crucial for assessing response to urate-lowering therapy in gout.     

Quantification of Carotid Plaque Neovascularization Using Contrast-Enhanced Ultrasound With Histopathologic Validation

We sought to evaluate contrast-enhanced ultrasound (CEUS) imaging for the quantification of carotid plaque neovascularization. Seventeen patients underwent carotid endarterectomy after standard ultrasound and CEUS. Semiquantitative and quantitative analyses of contrast enhancement within the plaque were performed using a visual interpretation scale and quantitative analysis software, respectively. Enhancement intensity (dB) was measured at the plaque (EI_plaque). Each specimen was stained with CD34 and CD68 to assess for microvessels and macrophages, respectively. Semiquantitative CEUS analyses were correlated with neovascularization at histology (r = 0.70, p = 0.002). Quantitative analysis was also correlated with neovascularization at histology (EI_plaquer = 0.81, p < 0.001). EI_plaque (r = 0.64, p = 0.01) was correlated with the degree of enhancement as assessed visually. Semiquantitative and quantitative analyses were not correlated with macrophage infiltration at the plaque. Contrast enhancement in the carotid plaque was correlated with neovascularity at the histopathologic exam. Furthermore, semiquantitative and quantitative measurements were highly correlated with each other, suggesting that either can be used to detect intraplaque neovascularization.     

Value of Contrast-Enhanced Ultrasound Using Perflubutane Microbubbles for Diagnosing Liver Fibrosis and Cirrhosis in Rats

We determined the ability of contrast-enhanced ultrasound (CEUS) using perflubutane microbubbles to diagnose liver fibrosis and cirrhosis in rats using histology as the reference standard. Fibrosis was induced by oral administration of carbon tetrachloride to 32 Wistar rats. Features with baseline ultrasound (US) and enhancement level of liver and spleen with CEUS were obtained. In the post-vascular phase of CEUS, images of normal livers (n = 5) were significantly brighter than images of fibrotic (n = 6) and cirrhotic livers (n = 13) by quantitative analysis (all p < 0.05). The contrast between livers and spleens in rats with cirrhosis was quantitatively greater than that in normal rats and rats with fibrosis (all p < 0.05). Compared with US, CEUS improved sensitivity from 63% to 84% and accuracy from 71% to 88%. Specificity was 100% for both. The increased value of CEUS in diagnosing liver fibrosis and cirrhosis in rats supports its evaluation in clinical trials.     

Role of Lung Ultrasound in Adjusting Ultrafiltration Volume in Hemodialysis Patients

Chronic fluid over-hydration is common in dialysis patients. It is associated with mortality and cardiovascular events. Optimal methods for adjusting fluid volume status and ideal dry weight remain uncertain. The purpose of this study was to evaluate the usefulness of ultrasound in quantifying body water. In 35 hemodialysis patients, we performed ultrasound of the chest, pre-tibial skin tissue thickness (TT), heart and inferior vena cava (IVC) before and after dialysis. We compared B-line scores of lungs, IVC diameters and cardiac functions in pre-dialysis and post-dialysis groups. We then estimated the correlations between ultrasound parameters and ultrafiltration volumes. Ultrafiltration parameters were adjusted prospectively for subsequent dialysis. As a result, both extravascular and intravascular water decreased during ultrafiltration. The median numbers of B-line scores (10 [0–42] vs. 4 [0–30]; p < 0.001); mitral valve blood flow velocities E (0.83 ± 0.23 m/s vs. 0.70 ± 0.20 m/s; p < 0.001), A (0.93 ± 0.28 vs. 0.89 ± 0.23 m/s; p < 0.001) and E/e' (12.47 ± 4.92 vs. 10.37 ± 4.0; p < 0.001); IVC diameters at end-expiration (17.51 ± 3.33 mm vs. 14.26 ± 3.45 mm; p < 0.001); and right pre-tibial TT (2.86 ± 1.36 mm vs. 2.43 ± 1.24 mm; p < 0.001) decreased during dialysis. Ultrafiltration volume was most associated with B-line score (adjusting for age and sex) (β?=?–3.340; p?=?0.003). In addition, the B-line score after dialysis was significantly associated with left ventricular ejection fraction (r?=?–0.393; p?=?0.019) and TT (r?=?–0.447; p?=?0.007). Ultrafiltration volume was prospectively increased then if the B-line score was >6 in the previous dialysis. All patients tolerated the protocol well without any symptoms. Ultrafiltration volume was most associated with lung water, reflected by variation in B-line score. It was not associated with cardiac function, IVC diameter, IVC collapse rate or TT. Lung ultrasound is a useful imaging tool for dialysis patients.     

Clinical Application of Contrast-Enhanced Ultrasound Using High-Frequency Linear Probe in the Detection of Small Colorectal Liver Metastases

To compare the performance of contrast-enhanced ultrasound (CEUS) using high-frequency linear and convex probes in the detection of small colorectal liver metastases (CRLMs). A total of 85 patients with 143 small CRLMs were evaluated. High-frequency ultrasound (US) and CEUS detected significantly more superficial lesions within 60 mm below the skin than a convex probe (p <0.05). The detection rate decreased in the chemotherapy group, especially when using a convex probe for US (p <0.05). By combining convex and linear probes, detection rates of US and CEUS were significantly higher than that of a convex or a linear probe alone (p <0.05). High-frequency US and CEUS helped to improve detection of small CRLMs and reduce the influence of chemotherapy. For patients with a high risk of CRLMs and those after chemotherapy, we recommend first scanning the liver by using a convex probe and subsequently screening the surface area of the liver and suspicious small lesions by using a linear probe.     

Role of Contrast-Enhanced Ultrasound in Diagnosis of Thyroid Nodules in Acoustic Radiation Force Impulse “Gray Zone”

The aim of this study was to evaluate the clinical value of contrast-enhanced ultrasound (CEUS) in the diagnosis of thyroid nodules in the acoustic radiation force impulse (ARFI) “gray zone” (the shear wave velocity is in the range 2.5–3 m/s). ARFI was performed before thyroidectomy in 70 patients with 200 thyroid nodules, and then CEUS was performed in 40 thyroid nodules in the “gray zone.” The accuracy of ARFI for the 200 thyroid nodules was 82% (164/200). The accuracy of ARFI for the 40 “gray zone” thyroid nodules was 70% (28/40), whereas the accuracy of CEUS for the “gray zone” thyroid nodules was 90% (36/40). There was a significant difference in accuracy (p < 0.05). CEUS has better accuracy for thyroid nodules in the ARFI “gray zone.” CEUS supplemented ARFI in differential diagnosis of benign and malignant thyroid nodules.     

A Comprehensive Motion Compensation Method for In-Plane and Out-of-Plane Motion in Dynamic Contrast-Enhanced Ultrasound of Focal Liver Lesions

Contrast-enhanced ultrasound (CEUS) acquisitions of focal liver lesions are affected by motion, which has an impact on contrast signal quantification. We therefore developed and tested, in a large patient cohort, a motion compensation algorithm called the Iterative Local Search Algorithm (ILSA), which can correct for both periodic and non-periodic in-plane motion and can reject frames with out-of-plane motion. CEUS cines of 183 focal liver lesions in 155 patients from three hospitals were used to develop and test ILSA. Performance was evaluated through quantitative metrics, including the root mean square error and R² in fitting time–intensity curves and standard deviation value of B-mode intensities, computed across cine frames), and qualitative evaluation, including B-mode mean intensity projection images and parametric perfusion imaging. The median root mean square error significantly decreased from 0.032 to 0.024 (p < 0.001). Median R² significantly increased from 0.88 to 0.93 (p < 0.001). The median standard deviation value of B-mode intensities significantly decreased from 6.2 to 5.0 (p < 0.001). B-Mode mean intensity projection images revealed improved spatial resolution. Parametric perfusion imaging also exhibited improved spatial detail and better differentiation between lesion and background liver parenchyma. ILSA can compensate for all types of motion encountered during liver CEUS, potentially improving contrast signal quantification of focal liver lesions.     

The AMANDUS Project—Advanced Microperfusion Assessed Non-Union Diagnostics With Contrast-Enhanced Ultrasound (CEUS) for the Detection of Infected Lower Extremity Non-Unions

The pre-operative determination of infection plays a decisive role in non-union treatment. This study investigated in a large cohort the diagnostic potential of contrast-enhanced ultrasound (CEUS) as stand-alone method for the differentiation between aseptic and infected non-unions. Of 109 patients with lower extremity non-unions (tibia n = 78, femur n = 31) osseous perfusion with CEUS was prospectively assessed before revision surgery. The perfusion was quantified via time-intensity curves and peak enhancement (PE) (arbitrary unit [au]). Significant perfusion differences between aseptic and infected non-unions were evident (PE, p < 0.001). The sensitivity and specificity for the detection of infected tibial and femoral non-unions could be determined with 85.1% and 88.7% (cutoff PE: 81.2 au). CEUS illustrates tibial and femoral non-union perfusion in real time and discriminates reliably between aseptic and infected non-unions. Consequently, when CEUS is integrated into the diagnostic routine algorithm, non-union revision surgery can be planned more accurately as a single or multistep procedure.     

Sonographic Characteristics of Papillary Thyroid Carcinoma with Coexistent Hashimoto's Thyroiditis: Conventional Ultrasound,Acoustic Radiation Force Impulse Imaging and Contrast-Enhanced Ultrasound

Our objective was to provide the various sonographic characteristics of papillary thyroid carcinomas for Hashimoto's thyroiditis (HT) patients, including conventional ultrasound (US), acoustic radiation force impulse Virtual Touch imaging and quantification (ARFI-VTIQ) and contrast-enhanced ultrasound (CEUS). Sixty-nine HT patients with 85 thyroid nodules (TNs) (49 malignant and 36 benign) were enrolled in this study. We evaluated the size, shape, margin, echogenicity, presence of halo, calcification, vascularity and ARFI-VTIQ and CEUS parameters for each nodule and compared the findings with the reference standards of histopathological and/or cytologic results. Univariate analysis indicated that compared with benign TNs with HT, papillary thyroid carcinomas with HT more often had taller-than-wider shapes, ill-defined margins, microcalcifications, peripheral vascularity, relatively harder stiffness with a higher shear wave speed, hypo-enhancement, peak intensity index <1 and area under the curve index <1 at pre-operative US, ARFI-VTIQ and CEUS. Multivariate analysis revealed that ill-defined margins, microcalcifications and peak intensity index <1 are independent characteristics related to malignant TNs for their differentiation from benign TNs (all p < 0.05). Our study indicated that pre-operative multiparameter US characteristics may serve as a useful tool to identify malignant TNs in HT patients.     

The AMANDUS Project PART II—Advanced Microperfusion Assessed Non-Union Diagnostics with Contrast-Enhanced Ultrasound (CEUS): A Reliable Diagnostic Tool for the Management and Pre-operative Detection of Infected Upper-Limb Non-unions

The management of upper-limb non-unions can be challenging, especially when infection is existent. Thus, pre-operative detection of infection plays a relevant role in non-union treatment. This study investigated in a large cohort the diagnostic potential of contrast-enhanced ultrasound (CEUS) as stand-alone method for differentiating between aseptic and infected upper-limb non-unions. Osseous perfusion of 50 upper-extremity non-unions (radius/ulna, n = 20; humerus, n = 22; clavicle, n = 8) was prospectively assessed with CEUS before revision surgery. The perfusion was quantified via time-intensity curves and peak enhancement (in arbitrary units). Significant perfusion differences between aseptic and infected non-unions could be detected (peak enhancement, p < 0.001). The sensitivity and specificity for the detection of infected upper-limb non-unions were 80% and 94.3% (cutoff peak enhancement: 130.8 arbitrary units). CEUS reliably differentiates between aseptic and infected upper-limb non-unions. Consequently, CEUS should be integrated into the daily diagnostic routine algorithm to plan non-union revision surgery more precisely as a single- or multi-step procedure.     

Multimodal VEGF-Targeted Contrast-Enhanced Ultrasound and Photoacoustic Imaging of Rats with Inflammatory Arthritis: Using Dye-VEGF-Antibody-Loaded Microbubbles

Owing to the heavy health burdens from rheumatoid arthritis, a sensitive and objective imaging method is needed for early diagnosis and accurate evaluation of the disease. We aimed to fabricate vascular epithelial growth factor (VEGF)–targeted microbubbles (MBs) to evaluate the expression levels of VEGF within the inflammatory lesions of rats with adjuvant-induced arthritis (AIA) using a multimodal photoacoustic (PA)/ultrasound (US) imaging system. Fluorescein isothiocyanate–biotin double-labeled vascular endothelial growth factor receptor 2 antibodies and Cy5.5–biotin double-labeled VEGF2 antibodies were added to the avidin-labeled MBs to synthesize VEGF-targeted MBs. The antibodies could specifically bind to the MBs according to the flow cytometry and fluorescence imaging. In vitro experiments on the cellular uptake of the target MBs also validated the interaction of the VEGF antibodies and the MBs. Multimodal contrast-enhanced US (CEUS)/PA imaging was performed in sequence on the inflamed paws of the AIA rats with a single PA/US imaging system after the injection of the targeted MBs. The CEUS and PA signals were then quantified and verified by the pathologic results. A CEUS pattern of fast wash in and slow washout was observed in the AIA rats after injection of targeted MBs. Compared with AIA rats injected with unconnected VEGF antibodies and naked MBs, AIA rats injected with targeted MBs presented a higher peak intensity (p = 0.0079 and 0.0079 respectively) and a longer time to peak (p = 0.0117 and 0.0117, respectively). The PA signals were also significantly enhanced after injection of targeted MBs (p = 0.0112 and 0.0119, respectively), which was in accordance with the pathologic and immunohistochemical results. In conclusion, VEGF-targeted MBs can be used as agents for multimodal CEUS/PA imaging and to detect VEGF expression in the inflammatory lesions of AIA rats in vivo. This strategy may be useful in imaging evaluation of arthritis by identifying inflammation-related molecules in different imaging modes.