Transrectal ultrasound examination of prostate cancer guided by fusion imaging of multiparametric MRI and TRUS: avoiding unnecessary mpMRI-guided targeted biopsy.

The purpose of this study was to explore transrectal ultrasound (TRUS) findings of prostate cancer (PCa) guided by multiparametric magnetic resonance imaging (mpMRI) and to improve the Prostate Imaging Reporting and Data System (PI-RADS) system for avoiding unnecessary mpMRI-guided targeted biopsy (TB). From January 2018 to October 2019, fusion mpMRI and TRUS-guided biopsies were performed in 162 consecutive patients. The study included 188 suspicious lesions on mpMRI in 156 patients, all of whom underwent mpMRI-TRUS fusion imaging-guided TB and 12-core transperineal systematic biopsy (SB). Univariate analyses were performed to investigate the relationship between TRUS features and PCa. Then, logistic regression analysis with generalized estimating equations was performed to determine the independent predictors of PCa and obtain the fitted probability of PCa. The detection rates of PCa based on TB alone, SB alone, and combined SB and TB were 55.9% (105 of 188), 52.6% (82 of 156), and 62.8% (98 of 156), respectively. The significant predictors of PCa on TRUS were hypoechogenicity (odds ratio [OR]: 9.595, P = 0.002), taller-than-wide shape (OR: 3.539, P = 0.022), asymmetric vascular structures (OR: 3.728, P = 0.031), close proximity to capsule (OR: 3.473, P = 0.040), and irregular margins (OR: 3.843, P = 0.041). We propose subgrouping PI-RADS score 3 into categories 3a, 3b, 3c, and 3d based on different numbers of TRUS predictors, as the creation of PI-RADS 3a (no suspicious ultrasound features) could avoid 16.7% of mpMRI-guided TBs. Risk stratification of PCa with mpMRI-TRUS fusion imaging-directed ultrasound features could avoid unnecessary mpMRI-TBs.

New horizon of ultrasound for screening and surveillance of non-alcoholic fatty liver disease spectrum.

Non-alcoholic fatty liver disease (NAFLD) affects almost one quarter of adults worldwide, and its progressive subtype, non-alcoholic steatohepatitis can progress to advanced fibrosis/cirrhosis and even hepatocellular carcinoma. It is critical to screen and grade NAFLD patients for management decisions to rationalize the utilization of medical resources. Conventional ultrasound is widely applied for NAFLD screening, however, some inherent weaknesses hinder its utility. This limitation has spurred the development of acoustic parameters-based quantitative ultrasound techniques that allow a more accurate evaluation of the histological features of NAFLD (e.g. steatosis, necroinflammation, fibrosis/cirrhosis). Herein, this paper reviews the research advances in emerging ultrasound techniques for screening and surveillance across NAFLD spectrum and summarize their principles, feasibility, accuracy, reproducibility, and limitations of each technique. The challenges and future directions are also discussed to advance clinical practice.

The first experience of ultrasound-guided percutaneous microwave ablation for extracranial schwannoma of the cervical vagus nerve in carotid space and treatment response evaluation with contrast-enhanced imaging: A case report.

Schwannoma is a benign tumor that originates from Schwann cells in the nerve sheathing of cranial, other peripheral, or autonomic nerves. Patients often present with painless mass as the chief complaint. The main symptoms of this tumor are related to its size and specific nerve origin. At present, the pretreatment diagnosis is mainly made by ultrasound, CT, MR, or biopsy, and the main treatment is surgical resection. We reported a new treatment method for cervical schwannoma in a 65-year-old woman with a history of non-small cell lung cancer (NSCLC). When the patient's neck mass was initially found with hoarseness and severe cough, it was considered as cervical lymph node metastasis of lung cancer due to her medical history. And she was diagnosed with schwannoma by core-needle biopsy after chemotherapy failed and the tumor shrank after the radiotherapy with no improvement of the clinical symptoms. After considering the physical condition, the patients were treated in our department for minimal invasiveness treatment. The patient was definitively diagnosed with cervical vagus schwannoma and was treated with ultrasound-guided microwave ablation of schwannoma under general anesthesia with systematic evaluation and improved preoperative examination. Her condition was stable, and the symptoms of severe cough disappeared after anesthesia resuscitation and the ablation. The tumor continued to shrink after the operation with no recurrence of cough symptoms. Ultrasound-guided percutaneous microwave ablation (MWA) for cervical vagus schwannomas might be a minimally invasive, effective, and relatively safe alternative to conventional treatment for those patients with severe symptoms.

Clinical Assessment of Differential Diagnostic Methods in Infants with Cholestasis due to Biliary Atresia or Non-Biliary Atresia.

The different methods in differentiating biliary atresia (BA) from non-BA-related cholestasis were evaluated in order to provide a practical basis for a rapid, early and accurate differential diagnosis of the diseases. 396 infants with cholestatic jaundice were studied prospectively during the period of May 2007 to June 2011. The liver function in all subjects was tested. All cases underwent abdominal ultrasonography and duodenal fluid examination. Most cases were subjected to hepatobiliary scintigraphy, magnetic resonance cholangiopancreatography (MRCP) and a percutaneous liver biopsy. The diagnosis of BA was finally made by cholangiography or histopathologic examination. The accuracy, sensitivity, specificity and predictive values of these various methods were compared. 178 patients (108 males and 70 females with a mean age of 58±30 days) were diagnosed as having BA. 218 patients (136 males and 82 females with a mean age of 61 ±24 days) were diagnosed as having non-BA etiologies of cholestasis jaundice during the follow-up period in which jaundice faded after treatment with medical therapy. For diagnosis of BA, clinical evaluation, hepatomegaly, stool color, serum gamma-glutamyltranspeptidase (GGT), duodenal juice color, bile acid in duodenal juice, ultrasonography (gallbladder), ultrasonography (griangular cord or strip-apparent hyperechoic foci), hepatobiliary scintigraphy, MRCP, liver biopsy had an accuracy of 76.0%, 51.8%, 84.3%, 70.0%, 92.4%, 98.0%, 90.4%, 67.2%, 85.3%, 83.2% and 96.6%, a sensitivity of 83.1%, 87.6%, 96.1%, 73.7%, 90.4%, 100%, 92.7%, 27.5%, 100%, 89.0% and 97.4%, a specificity of 70.2%, 77.5%, 74.8%, 67.0%, 94.0%, 96.3%, 88.5%, 99.5%, 73.3%, 75.4% and 94.3%, a positive predictive value of 69.0%, 72.6%, 75.7%, 64.6%, 92.5%, 95.7%, 86.8%, 98.0%, 75.4%, 82.6% and 98.0%, and a negative predictive value of 83.6%, 8.5%, 95.9%, 75.7%, 92.3%, 100%, 84.2%, 93.7%, 100%, 84.0% and 92.6%, respectively. It was concluded that all the differential diagnosis methods are useful. The test for duodenal drainage and elements is fast and accurate. It is helpful in the differential diagnosis of BA and non-BA etiologies of cholestasis. It shows good practical value clinically.

The diagnostic value of high-frequency ultrasonography in biliary atresia.

BACKGROUND: It is a globally challenging problem to differentially diagnose biliary atresia (BA) from other disease processes causing infantile cholestatic jaundice. The high-frequency ultrasonography (HUS) yields much improved spatial resolution and therefore, might show better image in BA diagnostic examination. The present study was to evaluate the HUS on the diagnosis of BA in infants with jaundice. METHODS: Fifty-one infants with neonatal jaundice were scanned with ultrasonography. Images included gallbladder, bile duct, right hepatic artery (RHA), portal vein (PV) and triangular cord (TC) sign, magnetic resonance imaging and additionally, laboratory tests and histopathology reports were assessed. RESULTS: Twenty-three BA and 28 non-BA cases were confirmed. The sensitivity, specificity, and accuracy of HUS were 91.3%, 92.9%, and 92.2%, respectively. All of these indices were significantly higher than those of conventional ultrasonography (P<0.01) and MR cholangiopancreatography (P<0.05). The HUS features, included a positive TC sign, an increased RHA diameter and RHA-diameter to portal-vein-diameter ratio (RHA/PV) and abnormal gallbladder, were important in the diagnosis of BA. CONCLUSION: HUS provided better imaging of BA and should be considered as a primary modality in the differential diagnosis of infantile jaundice.

Hydrolysis of magnetic amylase-imprinted poly(ethylene-co-vinyl alcohol) composite nanoparticles.

Molecularly imprinted polymers (MIPs) have frequently been employed as recognition elements in sensing applications, or for the controlled delivery of small molecule drugs. An equally important but less well studied application is the use of MIPs in the binding and immobilization of active enzymes. In this study, magnetic MIPs (MMIPs) recognizing the enzyme amylase were prepared using phase inversion of poly(ethylene-co-vinyl alcohol) (EVAL) solutions with 27-44 mol % ethylene in the presence of amylase. The size distribution, specific surface area, magnetization, and composition were characterized by dynamic light scattering (DLS), Brunauer-Emmett-Teller (BET) analysis, superconducting quantum interference devices (SQUID), and X-ray diffraction (XRD), respectively. The mean size of MMIPs was ~100 nm and the magnetization was 14.8 emu/g. The activities of both bound template and rebound enzyme was established by measuring glucose production via starch hydrolysis, at different temperatures, for MIPs with different compositions (wt % EVALs and mol % ethylene). The highest hydrolysis activity of MMIPs (obtained with 32 mol % ethylene) was found to be 1545.2 U/g. Finally, compared to the conventional catalysis process, MMIPs have the advantages of high surface area, suspension, easy removal from reaction, and rapid reload of enzyme. The good activity of amylase MMIPs persists after 50 cycles of starch hydrolysis.

Enhanced gene transduction into skeletal muscle of mice in vivo with pluronic block copolymers and ultrasound exposure.

The pluronic block copolymers are able to enhance the ultrasound-induced gene delivery in vitro. In the present study, the effects of pluronics on the efficiency of gene transfer into skeletal muscle in vivo under sonoporation were investigated. Plasmid DNA encoding green fluorescent protein (GFP) in combination with three different pluronics, F127, L61, and P85, was injected into the tibialis anterior (TA) muscle of mice with and without adjunct ultrasound (1 MHz, 3 W/cm(2) 1 min, 20% duty cycle). Mice were killed 1 week after injection. The TA muscles were removed and snap frozen immediately in isopentane cooled by liquid nitrogen and sections of 7 µm thick were cut. Transfection efficiency was assessed by counting the number of GFP-positive fibers under fluorescence microscopy, and tissue damage by hematoxylin and eosin staining. The results suggested that all three pluronics significantly enhanced transgene expression in skeletal muscle (P < 0.01), especially the P85 showed significantly higher efficiency than the other two pluronics (P < 0.05). Ultrasound synergistically enhanced the gene delivery efficiency with P85 (P < 0.01), but was unable to do so with F127 and L61 groups. In short, P85 displays significantly synergistic effect with ultrasound for enhancing plasmid DNA transduction in skeletal muscle of mice in vivo.

P85, Optison microbubbles and ultrasound cooperate in mediating plasmid DNA transfection in mouse skeletal muscles in vivo.

Pluronic block copolymers, a kind of non-ionic surfactant, also known as poloxamers, and ultrasound-targeted microbubble destruction have been respectively investigated as vectors for gene delivery in vitro and in vivo. However, they are limited for clinical application due to the relatively low transfer efficiency of each individual vector. In the present study, we explored if the combination of P85, a pluronic block copolymer, Optison, a microbubble contrast agent and ultrasound enhances the transfection of plasmid DNA in vivo using mouse skeletal muscle models. Plasmid encoding green fluorescent protein (GFP) was respectively conjugated with 0.05%P85, 10%Optison, or 0.05%P85 plus 10%Optison, and injected into mouse tibialis anterior (TA) muscles with or without ultrasound irradiation (1 MHz, 1 W/cm(2), 2 min and 20% duty cycle). Mice were sacrificed 1 week after injection. The TA muscles were collected and cryo-sectioned into a series of 7 µm slices. To assess the efficiency of plasmid DNA transfection, tissue sections were counterstained with DAPI and scored by counting the number of GFP-positive fibers. Meanwhile the area of damaged muscles was measured based on the tissues stained with hematoxylin and eosin. Both P85 and Optison significantly enhanced the delivery of plasmid DNA in mouse TA skeletal muscles (P<0.01 and P<0.05 respectively, compared to saline control). In combination with Ultrasound irradiation, P85 (P<0.01, compared to P85 alone) but not Optison (P>0.05, compared to Optison alone) exerted a more pronounced effect on the transfection efficiency. Furthermore P85-induced gene delivery was higher than that by Optison regardless of the presence of ultrasound (P<0.01). The highest transfection efficiency was observed when P85, Optison and ultrasound irradiation were administrated together (P<0.01, compared to any other treatment in this study). The area of damaged muscles was enlarged by ultrasound irradiation in the presence of Optison microbubbles (P<0.01, compared to those groups without ultrasound irradiation). These results suggest that P85, microbubbles and ultrasound irradiation synergistically enhance plasmid DNA delivery in mouse skeletal muscles in vivo.

Optical recognition of salivary proteins by use of molecularly imprinted poly(ethylene-co-vinyl alcohol)/quantum dot composite nanoparticles.

Molecularly imprinted polymers (MIPs) have long been studied for applications in biomolecule recognition and binding; compared with natural antibodies, they may offer advantages in cost and stability. We report on the development of MIPs that "self-report" concentrations of bound analytes via fluorescence changes in embedded quantum dots (QDots). Composite QDot/MIPs were prepared using phase inversion of poly(ethylene-co-vinyl alcohol) (EVAL) solutions with various ethylene mole ratios in the presence of salivary target molecules (e.g. amylase, lipase, and lysozyme). These major protein components of saliva have been implicated as possible biomarkers for pancreatic cancer. The optimum (highest imprinting effectiveness) ethylene mole ratios of the commercially available EVALs were found to be 32, 38, and 44 mol% for the imprinting of amylase, lipase, and lysozyme, respectively. QD fluorescence quenching was observed on binding of analytes to composite MIPs in a concentration-dependent manner, and was used to construct calibration curves. Finally, the composite MIP particles were used for the quantitative detection of amylase, lipase, and lysozyme in real samples (saliva) and compared with a commercial Architect ci 8200 chemical analysis system.

Pluronic block copolymers: novel functions in ultrasound-mediated gene transfer and against cell damage.

Pluronics have been investigated as vectors for drug and gene delivery in vitro and in vivo and were demonstrated to have high efficiency for gene transfer in vivo. However, they alone do not enhance gene transfer in vitro. We examined three pluronics, F127, L61 and P85, for their effects on ultrasound (US)-mediated gene transfer in three cell lines, 3T3-MDEI, C2C12 and CHO. The polymers showed differential effects on cell viability and transfection efficiency in a dose-dependent manner. All the polymers were unable to facilitate gene transfer when used alone, but enhanced US-mediated gene transfer significantly at concentrations around the critical micelle concentration in the three cell lines. F127 showed no significant toxicity at any concentration and protected the cells against US-mediated damage at a high concentration. L61 decreased cell viability significantly in a dose-dependent manner, whereas P85 showed mild toxicity when its concentration was at or above 0.05%.

Systemic delivery of antisense oligoribonucleotide restores dystrophin expression in body-wide skeletal muscles.

Antisense oligonucleotide-mediated alternative splicing has great potential for treatment of Duchenne muscular dystrophy (DMD) caused by mutations within nonessential regions of the dystrophin gene. We have recently shown in the dystrophic mdx mouse that exon 23, bearing a nonsense mutation, can be skipped after intramuscular injection of a specific 2'-O-methyl phosphorothioate antisense oligoribonucleotide (2OMeAO). This skipping created a shortened, but in-frame, transcript that is translated to produce near-normal levels of dystrophin expression. This expression, in turn, led to improved muscle function. However, because DMD affects muscles body-wide, effective treatment requires dystrophin induction ideally in all muscles. Here, we show that systemic delivery of specific 2OMeAOs, together with the triblock copolymer F127, induced dystrophin expression in all skeletal muscles but not in cardiac muscle of the mdx dystrophic mice. The highest dystrophin expression was detected in diaphragm, gastrocnemius, and intercostal muscles. Large numbers of fibers with near-normal level of dystrophin were observed in focal areas. Three injections of 2OMeAOs at weekly intervals enhanced the levels of dystrophin. Dystrophin mRNA lacking the targeted exon 23 remained detectable 2 weeks after injection. No evidence of tissue damage was detected after 2OMeAO and F127 treatment either by serum analysis or histological examination of liver, kidney, lung, and muscles. The simplicity and safety of the antisense protocol provide a realistic prospect for treatment of the majority of DMD mutations. We conclude that a significant therapeutic effect may be achieved by further optimization in dose and regime of administration of antisense oligonucleotide.

The value of color Doppler ultrasonography in monitoring normal orthotopic liver transplantation and postoperative complications.

OBJECTIVE: To assess the value of color Doppler ultrasonography in monitoring normal orthotopic liver transplantation and postoperative complications. METHODS: Forty-one patients after orthotopic liver transplantation were examined by using color Doppler flow imaging to observe the hepatic blood flow and change of ultrasonography of the hepatic parenchyma and bile duct. The measured indexes included maximum blood flow velocity, time-average blood flow velocity (TAV), resistance index (RI) and diameter of the bile duct. RESULTS: Among 41 patients, 17 (41.5%) suffered from liver transplant rejection. Of the 17 patients, 13 (76.4%) showed decrease of TAV of the portal vein, 15 (88.25%) low-amplitude single-phase serrated wave or negative biphasic wave of the hepatic vein, 9 (52.9%) increased hepatic arterial RI, and 5 (29.4%) slightly dilated bile duct. Sonography showed disappearance of the hepatic artery blood flow around the portal vein in 5 (12.2%) of the 41 patients with hepatic artery thrombosis in the postoperative period. Slight dilatation of the intrahepatic bile duct was found in 3 (7.3%) of the 41 patients in the early postoperational period and it normalized within 2 weeks. Ultrasonography of 20 patients (48.8%) revealed a visible dilatation of the intrahepatic bile duct, which was worsening gradually. The causes of bile duct dilatation included biliary stricture in 2 patients (10%), stone in 15 patients (75%) and others in 3 patients (15%). CONCLUSIONS: Color Doppler ultrasonography is valuable for monitoring normal liver transplantation and postoperative complications.