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Ultrasonography (US) contrast imaging using US contrast agents has been widely applied for the diagnosis and differential diagnosis of tumors. Commercial US contrast agents have limited applications because of their large size and shorter imaging time. At the same time, the desired therapeutic purpose cannot be achieved by applying only conventional US contrast agents. The development of nanoscale US agents with US imaging and therapeutic functions has attracted increasing attention. In this study, we successfully developed DOX-loaded poly-1,6-hexanedithiol-sodium bicarbonate nanoparticles (DOX@HADT-SS-NaHCO3 NPs) with pH-responsive NaHCO3 and GSH-responsive disulfide linkages. DOX@HADT-SS-NaHCO3 NPs underwent acid-triggered decomposition of NaHCO3 to generate CO2 bubbles and a reduction of disulfide linkages to further promote the release of CO2 and DOX. The potential of DOX@HADT-SS-NaHCO3 NPs for contrast-enhanced US imaging and therapy of prostate cancer was thoroughly evaluated using in vitro agarose gel phantoms and a C4-2 tumor-bearing nude mice model. These polymeric NPs displayed significantly enhanced US contrast at acidic pH and antitumor efficacy. Therefore, the NaHCO3 and DOX-encapsulated polymeric NPs hold tremendous potential for effective US imaging and therapy of prostate cancer.

Objective To analyze the correlations between intraoperative ultrasound and MRI metrics of the spinal cord in degenerative cervical myelopathy and identify novel potential predictive ultrasonic indicators of neurological recovery for degenerative cervical myelopathy. Materials and Methods Twenty-two patients who underwent French-door laminoplasty for multilevel degenerative cervical myelopathy were followed up for 12 months. The Japanese Orthopedic Association (JOA) scores were assessed preoperatively and 12 months postoperatively. Maximum spinal cord compression and compression rates were measured and calculated using both intraoperative ultrasound imaging and preoperative T2-weight (T2W) MRI. Signal change rates of the spinal cord on preoperative T2W MRI and gray value ratios of dorsal and ventral spinal cord hyperechogenicity on intraoperative ultrasound imaging were measured and calculated. Correlations between intraoperative ultrasound metrics, MRI metrics, and the recovery rate JOA scores were analyzed using Spearman correlation analysis. Results The postoperative JOA scores improved significantly, with a mean recovery rate of 65.0 ± 20.3% (p < 0.001). No significant correlations were found between the operative ultrasound metrics and MRI metrics. The gray value ratios of the spinal cord hyperechogenicity was negatively correlated with the recovery rate of JOA scores (ρ = −0.638, p = 0.001), while the ventral and dorsal gray value ratios of spinal cord hyperechogenicity were negatively correlated with the recovery rate of JOA-motor scores (ρ = −0.582, p = 0.004) and JOA-sensory scores (ρ = −0.452, p = 0.035), respectively. The dorsal gray value ratio was significantly higher than the ventral gray value ratio (p < 0.001), while the recovery rate of JOA-motor scores was better than that of JOA-sensory scores at 12 months post-surgery (p = 0.028). Conclusion For degenerative cervical myelopathy, the correlations between intraoperative ultrasound and preoperative T2W MRI metrics were not significant. Gray value ratios of the spinal cord hyperechogenicity and dorsal and ventral spinal cord hyperechogenicity were significantly correlated with neurological recovery at 12 months postoperatively.

The goal of our study was to evaluate the differences between quantitative parameters of hepatocellular carcinoma (HCC) with or without portal vein tumor thrombosis (PVTT) on contrast-enhanced ultrasound (CEUS). Twenty-four patients with HCC with PVTT and 48 without PVTT underwent CEUS using sulfur hexafluoride microbubbles. Dynamic images were analyzed with quantification software. Time-intensity curves were obtained for HCC and surrounding liver parenchyma, and parameters including the intensity maximum (IMAX), rising time (RT), mean transit time and time to peak (TTP) were compared within and between the PVTT and control groups, respectively. RT and TTP of HCC were significantly faster than those of surrounding liver parenchyma in both the PVTT and control groups. IMAX of HCC was significantly stronger than that of surrounding liver in the control group, but not significantly different from that of liver parenchyma in the PVTT group. RT and TTP of HCC and surrounding liver were significantly faster in the PVTT group compared with the control group, whereas IMAX values of HCC in the PVTT group were lower than those in the control group. HCC with PVTT presents different hemodynamic parameters, with faster RT and TTP and lower IMAX than those for HCC without PVTT. Quantitative perfusion analysis of CEUS may be a potential method for predicting PVTT.

AIM To evaluate the usefulness of contrast-enhanced ultrasonography (CEUS) in differentiating malignant from benign peripheral pulmonary lesions, and to evaluate the feasibility, accuracy, and utility of CEUS-guided biopsy for peripheral pulmonary lesions. MATERIALS AND METHODS Thirty-three patients with histopathologically confirmed peripheral pulmonary lesions (22 malignant, 11 benign) were enrolled in this retrospective study. Conventional ultrasound (US) was first performed and then CEUS with a contrast-specific mode and sulfur hexafluoride-filled microbubble contrast agent. CEUS indices—time of enhancement (TE), time to peak (TP), extent of peak (EP), mean transit time (MTT), area under curve (AUC), and slope—were recorded and compared between the groups. The ability of CEUS and US to detect necrotic areas within lesions was also compared and the accuracy of CEUS-guided biopsy was calculated. RESULTS On CEUS, TE was significantly shorter in acute pneumonia lesions than in other types of lesions (p=0.03). Other indices were not significantly different between benign and malignant lesions. Detection of necrosis within lesions was significantly higher with CEUS than with US (51.5% versus 27.3%; p=0.04). The accuracy of CEUS-guided biopsy was 96.9% (32/33). CONCLUSION The study findings suggest that CEUS can identify necrotic areas within lesions, and thereby, play a useful role in imaging-guided biopsy. The present pilot study indicates that CEUS may help to identify acute pneumonia lesions from other types of pulmonary lesions. CEUS might be a useful additional technique for the diagnosis of lung lesions.

Objective To investigate the imaging features of focal splenic lesions (FSLs) on contrast-enhanced ultrasound (CEUS). Methods Thirty two patients with FSLs proved by pathology were retrospectively analyzed. CEUS was performed using intravenous bolus injection of 2.4 ml sulfur hexafluoride-filled microbubble contrast agent and real time scanning. There were hemangioma (n = 7), lymphoma (n = 8), true cyst (n = 3), infarction (n = 4), hematolymphangioma (n = 2), metastasis tumor (n = 2), and one for each of the following entities extramedullary hemopoiesis, hamartoma, tuberculosis, Langerhans’ cell histiocytosis, inflammatory pseudotumor and myxofibrosarcoma. Results Among 21 benign lesions, 4 infarctions and 3 cysts presented non-enhancement throughout CEUS scanning, and the other 14 lesions displayed various enhancement levels with 6 (42.9%) hyper-enhancement, 2 (14.3%) iso-enhancement and 6 (42.9%) hypo-enhancement in arterial phase and 11 (78.6%) hypo-enhancement, 1 (7.1%) iso-enhancement and 2 (14.3%) hyper-enhancement in late phase, respectively. The enhancement pattern included 9 (64.3%) homogeneous, 4 (28.6%) heterogeneous and 1 (7.1%) rim-like enhancement. As for the malignant FSLs, all the lesions became completely or extensively hypo-enhancement during the late phase no matter their vascularity during arterial phase. Conclusions The CEUS features reported in this series may enrich the knowledge for CEUS characterization of FSLs.

Background To evaluate the feasibility, accuracy, and utility of sonography (US) and CT fusion imaging guidance for radiofrequency ablation (RFA) of malignant liver tumors not visualized on conventional US. Methods Seventy-seven patients with hepatocellular carcinoma and 15 patients with metastatic liver cancer with a total of 136 lesions underwent RFA with US and CT fusion imaging guidance. The mean number of punctures, success rate of a single ablation session, local tumor progression rates, and long-term outcome were evaluated. Treatment efficacy was evaluated by dynamic CT and contrast-enhanced US 1 month after RFA. Results RFA was technically feasible in all patients, and no major complications occurred. The mean ± SD time needed to synchronize US and CT images was 13.9 ± 11.9 minutes (range, 5–55 minutes). The success rate of a single ablation session was 83.8% (114/136), and tumor residue was present in 7.4% of lesions (10/136). The mean number of treatment sessions was 1.2 ± 0.5 sessions. During follow-up, local tumor progression was observed for 15 (11.9%) lesions. Distant tumor recurrence was found in 51 (55.4%) patients. Conclusions US and CT fusion-assisted RFA is a safe and efficacious treatment for patients with hepatocellular carcinoma and metastatic liver cancer. © 2014 Wiley Periodicals, Inc. J Clin Ultrasound 42:321–330, 2014

Percutaneous ablative therapies (PAT) are valuable modalities for posthepatectomy recurrent hepatocellular carcinoma (RHCC), but its impact on long-term outcome and prognosis prediction have not been well documented. The present study aimed to analyze prognostic factors and to propose a prognosis-predicting model for RHCC treated with PAT. A total of 288 patients with posthepatectomy RHCC treated with percutaneous ethanol ablation, radiofrequency ablation, microwave ablation, or ethanol ablation combined with radiofrequency ablation were included. Survival and prognostic factors were analyzed. A prognosis-predicting model was created by quantifying and integrating all prognostic factors. Three-, 5-, and 7-year postablation survival rates were 37.8, 20.7, and 14.2 %, respectively. Multivariate analysis revealed that interval between recurrence and initial hepatectomy, tumor number, largest diameter of tumor, and Barcelona Clinic Liver Cancer stage at hepatectomy were independent prognostic factors for survival. A scoring system for prognostic factors was proposed, and summation of 4 prognostic factors (prognostic score) was ranged from 4 to 10. Prognostic score was classified into three strata, designated as prognostic classes A (score 4 and 5), B (score 6 and 7), and C (≥8). Three-, 5-, and 7-year postablation survival rates were 62.8, 39.4, and 26.9 % in class A, 36.9, 15.5, and 7.2 % in B, and 5.5, 0, and 0 % in class C, respectively (p = 0.00). Three-, 5-, 7-, and 10-year survival rates after initial hepatectomy were 82.4, 66.3, 52.1, and 36.4 % in class A, 51.6, 34.8, 20.7, and 6.6 % in class B, and 11.9, 7.8, 0, and 0 % in class C, respectively (p = 0.00). The prognostic model developed in the study could clearly predict different long-term outcomes for patients with posthepatectomy RHCC and thus help decide appropriate therapeutic strategy.

To retrospectively determine the accuracy of baseline ultrasound (BUS) and of contrast-enhanced ultrasound (CEUS) in the differential diagnosis of pancreatic solid-cystic lesions.Fifty-four pancreatic solid-cystic lesions in 52 patients were examined with BUS and CEUS, two different seniority radiologists read the images independently, Receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic value of BUS and CEUS in the diagnosis of benign or malignant pancreatic solid-cystic lesions, the diagnostic consistency between different seniority radiologists was evaluated by Kappa statistics.Among the 54 lesions, there were pancreatic cyst five cases, pancreatic pseudocyst twenty cases, pancreatic cystadenoma eight cases, pancreatic cystadenocarcinoma seven cases, intraductal papillary mucinous neoplasm of pancreas (IPMN) three cases, pancreatic carcinoma combined liquefied six cases, solid-pseudopallary tumor of pancreas (SPTP) three cases, pancreatic myopericytoma one case, pancreatic lymphangioma one case. After ROC analysis, the areas under the ROC curve (Az) were 0.752 by BUS, 0.928 by CEUS to resident radiologist, and 0.896 by BUS, 0.954 by CEUS to staff radiologist. The correct diagnosis rate of specific disease was 42.6% by BUS, 64.8% by CEUS to staff radiologist (P0.05), and 33.3% by BUS, 53.7% by CEUS to resident radiologist (P0.05). The interobserver agreement in CEUS is higher than that in BUS, the Kappa value was 0.889 ± 0.062 and 0.428 ± 0.126 respectively.Compared with BUS, CEUS can significantly enhance the diagnostic rate of pancreatic solid-cystic lesions.

To detect whether the efficacy of microwave ablation (MWA) could be improved by preinjected fluids in an ex vivo porcine liver model.Ablations were performed for 12 minutes using energy output of impedance-based (power output gradually rose to 200W, maintained until increases in tissue impedance of 20 Ω, reduced to 10W, and switched on again 15 seconds later) in radiofrequency ablation (RFA) or 80 W in MWA. Before ablation, 5 mL of ethanol, distilled water, 0.9% NaCl solution, or 10% NaCl solution (n = 6 each) was injected into the targeted liver tissue. Ablations without fluid injection served as control. The ablation diameter, volume, shape index, and temperature were recorded and compared.Preinjection of 0.9% or 10% NaCl solution resulted in larger coagulation volumes than that of the control group in RFA experiments (28.1 ± 2.9 cm(3), 45.3 ± 6.3 cm(3), 20.0 ± 2.5 cm(3), respectively; P.05). Ethanol and distilled water had no impact on coagulation volumes in RFA. Preinjection of ethanol or 10% NaCl solution created smaller coagulation volumes than that of the control group in MWA experiments (34.3 ± 2.0 cm(3), 33.9 ± 4.1 cm(3), 58.0 ± 6.6 cm(3), respectively; P.001). 0.9% NaCl solution and distilled water had no impact on coagulation volumes in MWA.In an ex vivo porcine liver, preinjected fluids do not benefit microwave ablation as those in radiofrequency ablation.

Objective: To investigate the potential usefulness of three-dimensional contrast-enhanced ultrasound (3D-CEUS) in evaluating the treatment response for liver cancer after local therapies. Methods: A total of 107 lesions in 95 consecutive patients with liver cancer underwent local therapies and thereafter received low acoustic power 3D-CEUS examination. The LOGIQ 9 ultrasound scanner and a volume transducer were used and the ultrasound contrast agent was SonoVue. The image quality of 3D-CEUS images was evaluated and the influence of 3D-CEUS to clinical outcome was investigated. Results: The image quality of 3D-CEUS was defined as high in 102 (102/107, 95.3%) lesions and common in 5 (5/107, 4.7%) lesions. 3D-CEUS did not change the diagnosis in any patient compared with 2D-CEUS. However, 3D-CEUS changed the management in 3 (2.8%) of 107 lesions, increased confidence but made no change in diagnosis in 85 (79.5%) lesions, added some information but did not change management or diagnosis in 15 (14.0%), and made no change in 4 (3.7%), respectively, in comparison with 2D-CEUS. Conclusion: 3D-CEUS enhances the diagnostic confidence in the majority of the patients and even changes the management in some patients. 3D-CEUS has potential usefulness in evaluating treatment response for liver cancer after local therapies.

Objective To compare the enhancement pattern of hilar cholangiocarcinoma on contrast-enhanced ultrasound (CEUS) with that on contrast-enhanced computed tomography (CECT). Methods Thirty-two consecutive patients with pathologically proven hilar cholangiocarcinomas were evaluated by both low mechanical index CEUS and CECT. The enhancement feature of the tumor, portal vein infiltration, and lesion conspicuity on them was investigated. Results In the arterial phase, the numbers of the lesions showing hyperenhancement, isoenhancement, and hypoenhancement, were 14 (43.8%), 14 (43.8%), and 4 (12.6%), on CEUS, and 12 (37.5%), 9 (28.1%), and 11 (34.4%), on CECT ( P = 0.162). In portal phase, the numbers of the lesions showing hypoenhancement, isoenhancement, and hyperenhancement were 30 (93.8%), 1 (3.1%), and 1 (3.1%), on CEUS, and 23 (71.9%), 8 (25.0%), and 1 (3.1%), on CECT ( P = 0.046). The detection rates for portal vein infiltration were 84.2% (16/19) for baseline ultrasound, 89.5% (17/19) for CEUS, and 78.9% (15/19) for CECT (all P > 0.05 between every two groups). CEUS significantly improved the lesion conspicuity in comparison with CECT. CEUS and CECT made correct diagnoses in 30 (93.8%) and 25 (78.1%) lesions prior to pathological examination ( P = 0.125). Conclusion The enhancement pattern of hilar cholangiocarcinoma on CEUS was similar with that on CECT in arterial phase, whereas in portal phase hilar cholangiocarcinoma shows hypoenhancement more likely on CEUS. CEUS and CECT lead to similar results in evaluating portal vein infiltration and diagnosis of this entity.

Purpose The objective of this study was to investigate the contrast-enhanced ultrasound (CEUS) imaging features of focal liver lesions (FLLs) in fatty liver. Method One hundred FLLs in 98 patients with fatty liver were evaluated with real-time CEUS. Results All malignant FLLs showed hyperenhancement in arterial phase and contrast washout in portal and late phases. Among the FLLs, 3.3% of hemangiomas, 12.5% of focal nodular hyperplasias (FNHs), and 2.5% of focal fatty sparing lesions showed contrast washout in the late phase. The sensitivity and specificity for the characterization of hepatocellular carcinoma, metastasis, hemangioma, FNH, and focal fatty sparing lesions were 100% and 95.6%, 60% and 100%, 93.3% and 98.6%, 87.5% and 97.8%, and 92.6% and 100%, respectively. Conclusions Correct characterization of FLLs in fatty liver by CEUS is possible based on their typical enhancement patterns.

We compared the enhancement pattern of 98 hepatocellular carcinoma nodules in 92 patients on contrast-enhanced ultrasound (CEUS) and contrast-enhanced computed tomography (CECT). Contrast-enhanced ultrasound was performed with SonoVue and a low mechanical index method. In arterial phase, 98 nodules were hyperenhancing on CEUS and 94 on CECT. In portal phase, 82 nodules were hypoenhancing on CEUS and 83 on CECT. Peripheral thin-rim-like enhancement was exhibited in 30 nodules on CEUS and 31 on CECT. Intratumoral vessels were visualized in 94 nodules on CEUS and 36 on CECT.

Percutaneous microwave ablation and radiofrequency ablation are two commonly used modalities for the treatment of hepatocellular carcinoma; however, comparisons of them have not been documented adequately.Of 102 patients with biopsy-proved hepatocellular carcinoma, 49 (98 nodules) were treated percutaneously with microwave ablation and 53 (72 nodules) with radiofrequency ablation. The local tumor control, complications related to treatment, and long-term results of the two modalities were compared retrospectively.The complete ablation rates were 94.9% (93/98) using microwave ablation vs 93.1% (67/72) using radiofrequency ablation (P = 0.75), and no significant differences were found either in the ablation of tumors of 3.0 cm or less (P = 1.00) or in those of more than 3.0 cm (P = 1.00) between the two modalities. The local recurrence rates were 11.8% (11/93) using microwave ablation vs 20.9% (14/67) using radiofrequency ablation (P = 0.12), and there were no significant differences between the two modalities either in tumors of 3.0 cm or less (P = 0.36) or in those of more than 3.0 cm (P = 0.82). The rates of major complications associated with microwave ablation and radiofrequency ablation were 8.2% (4/49) vs 5.7% (3/53; P = 0.71). The disease-free survival rates in the microwave ablation group were 45.9%, 26.9%, 26.9%, and 13.4% at 1, 2, 3, and 4 years, respectively, and those in the radiofrequency ablation group were 37.2%, 20.7%, and 15.5% at 1, 2 and 3 years, respectively (P = 0.53). The 1-, 2-, 3-, and 4-year cumulative survival rates for patients who underwent microwave ablation were 81.6%, 61.2%, 50.5%, and 36.8%, respectively, and for patients who underwent radiofrequency ablation the rates were 71.7%, 47.2%, 37.6%, and 24.2%, respectively (P = 0.12).Percutaneous microwave ablation and radiofrequency ablation are both effective methods in treating hepatocellular carcinomas. The local tumor control, complications related to treatment, and long-term survivals were equivalent for the two modalities.

Background Tumour ablation using a thermal energy source has shown promising results, and is particularly suitable for recurrent hepatocellular carcinoma (HCC). The present study evaluated long-term outcomes after percutaneous thermal ablation for recurrent HCC following liver resection. Methods Radiofrequency ablation or microwave ablation was used to treat a total of 124 tumour nodules (0·9–7·0 cm in diameter) in 72 patients with recurrent HCC. Results Complete ablation of 119 (96·0 per cent) of 124 tumour nodules was achieved. There was no treatment-related death and the major complication rate was 4 per cent. During a mean(s.d.) follow-up of 27·9(17·8) months, local recurrence developed in 16 (13·6 per cent) of 118 successfully treated tumour nodules. Distant recurrence developed in 60 (85 per cent) of 71 patients, of whom 26 had repeat metachronous distant recurrence. With repeated ablation for both local and distant recurrence, the 1-, 3- and 5-year overall survival rates after initial ablation were 75, 43 and 18 per cent respectively. Patients with a serum α-fetoprotein level greater than 200 ng/ml before treatment had significantly poorer survival than those with a lower level (P = 0·034) and multivariate analysis identified preablation AFP level as an independent prognostic factor (P = 0·054). Conclusion With their advantages of preservation of non-tumorous liver tissue and easy repetition, percutaneous thermal ablative therapies were particularly suitable for recurrent HCC and improved long-term survival.