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Malignant renal cell carcinoma (RCC) is a diverse set of diseases, which are independently difficult to characterize using conventional MRI and CT protocols due to low temporal resolution to study perfusion characteristics. Because different disease subtypes have different prognoses and involve varying treatment regimens, the ability to determine RCC subtype non-invasively is a clinical need. Contrast-enhanced ultrasound (CEUS) has been assessed as a tool to characterize kidney lesions based on qualitative and quantitative assessment of perfusion patterns, and we hypothesize that this technique might help differentiate disease subtypes. Twelve patients with RCC confirmed pathologically were imaged using contrast-enhanced ultrasound. Time intensity curves were generated and analyzed quantitatively using 10 characteristic metrics. Results showed that peak intensity ( p = 0.001) and time-to-80% on wash-out ( p = 0.004) provided significant differences between clear cell, papillary, and chromophobe RCC subtypes. These results suggest that CEUS may be a feasible test for characterizing RCC subtypes.
RATIONALE AND OBJECTIVES - The objective of this study was to evaluate and compare contrast-enhanced subharmonic and harmonic ultrasound as tools for characterizing solid renal masses and monitoring their response to cryoablation therapy.
MATERIALS AND METHODS - Sixteen patients undergoing percutaneous ablation of a renal mass provided informed consent to undergo ultrasound examinations the morning before and approximately 4 months after cryoablation. Ultrasound contrast parameters during pretreatment imaging were compared to biopsy results obtained during ablation (n = 13). Posttreatment changes were evaluated by a radiologist and compared to contrast-enhanced magnetic resonance imaging (MRI)/computed tomography (CT) follow-up.
RESULTS - All masses initially showed heterogeneous enhancement with both subharmonic and harmonic ultrasound. Early contrast washout in the mass relative to the cortex was observed in 6 of 9 malignant and 0 of 4 benign lesions in subharmonic mode and 8 of 9 malignant and 1 of 4 benign lesions in harmonic imaging. In cases where the lesion was adequately visualized at follow-up (n = 12), subharmonic and harmonic ultrasound showed accuracies of 83% and 75%, respectively, in predicting treatment outcome. Although harmonic imaging showed less overall error, no significant differences (P > .29) in ablation cavity volumes were observed between MRI/CT and either contrast-imaging mode.
CONCLUSIONS - Subharmonic and harmonic contrast-enhanced ultrasound may be a safe and accurate imaging alternative for characterizing renal masses and evaluating their response to cryoablation therapy. Although subharmonic imaging was more accurate in detecting effective cryoablation, harmonic imaging was superior in quantifying ablation cavity volumes.
Copyright © 2015 AUR. Published by Elsevier Inc. All rights reserved.
Bimodal imaging agents that combine magnetic resonance imaging (MRI) and nearinfrared (NIR) imaging formulated as nanoemulsions became increasingly popular for imaging inflammation in vivo. Quality of in vivo imaging using nanoemulsions is directly dependent on their integrity and stability. Here we report the design of nanoemulsions for bimodal imaging, where both photostability and colloidal stability are equally addressed. A highly chemically and photo stable quaterrylenediimide dye was introduced into perfluoro-15-crown-5 ether (PCE) nanoemulsions. The nanoemulsions were prepared with PCE and Miglyol 812N mixed at 1:1 v/v ratio as internal phase stabilized by non-ionic surfactants. Data shows exceptional colloidal stability demonstrated as unchanged droplet size (~130 nm) and polydispersity (<0.15) after 182 days follow up at both 4 and 25 °C. Nanoemulsions also sustained the exposure to mechanical and temperature stress, and prolonged exposure to light without changes in droplet size, (19)F signal or fluorescence signal. No toxicity was observed in vitro in model inflammatory cells upon 24 h exposure while confocal microscopy showed that nanoemulsions droplets accumulated in the cytoplasm. Overall, our data demonstrates that design of bimodal imaging agents requires consideration of stability of each imaging component and that of the nanosystem as a whole to achieve excellent imaging performance.
Copyright © 2014 Elsevier Ltd. All rights reserved.
A microfluidic cell co-culture platform that uses a liquid fluorocarbon oil barrier to separate cells into different culture chambers has been developed. Characterization indicates that the oil barrier could be effective for multiple days, and a maximum pressure difference between the oil barrier and aqueous media in the cell culture chamber could be as large as ~3.43 kPa before the oil barrier fails. Biological applications have been demonstrated with the separate transfection of two groups of primary hippocampal neurons with two different fluorescent proteins and subsequent observation of synaptic contacts between the neurons. In addition, the quality of the fluidic seal provided by the oil barrier is shown to be greater than that of an alternative solid-PDMS valve barrier design by testing the ability of each device to block low molecular weight CellTracker dyes used to stain cells in the culture chambers.
Perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) are used in a variety of consumer products and have been detected worldwide in human blood. Recent studies mainly of highly exposed populations have indicated that PFOA and PFOS may affect serum cholesterol levels, but the magnitude of the effect may be inconsistent across exposure levels. The aim of the present cross-sectional study was to investigate the association between plasma PFOA and PFOS and total cholesterol in a general, middle-aged Danish population. The study population comprised 753 individuals (663 men and 90 women), 50-65 years of age, nested within a Danish cohort of 57,053 participants. Blood samples were taken from all cohort members at enrolment (1993-1997) and stored in a biobank at -150°C. Plasma levels of PFOA and PFOS and serum levels of total cholesterol were measured. The associations between plasma PFOA and PFOS levels and total cholesterol levels were analysed by generalized linear models, both crude and adjusted for potential confounders. We observed statistically significant positive associations between both perfluorinated compounds and total cholesterol, e.g. a 4.4 [95% CI = 1.1-7.8] higher concentration of total cholesterol (mg/dL) per interquartile range of PFOA plasma level. Sex and prevalent diabetes appeared to modify the association between PFOA and PFOS, respectively, and cholesterol. In conclusion, this study indicated positive associations between plasma PFOA and PFOS levels and total cholesterol in a middle-aged Danish population, although whether the observed pattern of results reflects a causal association is unclear.
Because of small surface area to volume ratios nanoscale devices can exhibit dominant surface forces that can quickly degrade unlubricated contacting surfaces. While fluorinated materials have been widely used as lubricants, because of their low critical surface tension and high thermal and mechanical stability, fluorinated monolayer coatings, which are suitable for lubricating nanoscale devices, are less effective as lubricants. Although fluorinated monolayers are more stable than their hydrocarbon counterparts against elevated temperature and humidity, they are known to exhibit higher frictional forces. To overcome this issue, here we study mixed monolayers composed of both hydrocarbon and fluorocarbon chains. Hydrocarbon-based monolayers have been widely studied and shown to improve frictional properties and device life. To investigate the frictional behavior of mixed fluorocarbon/hydrocarbon monolayers, molecular dynamics simulations of pure hydrogenated and fluorinated chains and mixed fluorinated/hydrogenated chains on silica surfaces have been performed. The adhesion and friction between the nanoconfined monolayers as a function of normal load, chain length, and chemical composition of the monolayer coating have been investigated, and mixed fluorocarbon/hydrocarbon monolayers found to outperform both pure fluorocarbon and pure hydrocarbon monolayers. Surface coverage was found to have a significant effect on the performance of all systems studied with higher surface coverage resulting in lower frictional forces. The simulations also show that when the hydrocarbon chains in the monolayer are longer than the fluorocarbon chains, a liquidlike layer is formed by the longer hydrocarbon chains that protrudes above the shorter fluorocarbon chains and aids in friction reduction. A frictional load dependence is also seen in these mixed monolayer systems because of repulsive interactions between the fluorocarbon base layer and the hydrocarbon liquidlike layer. A chain length difference of eight carbons between the base layer and the liquidlike layer was found to provide the lowest friction, while both a larger (because of increased entanglement) and a smaller (insufficient atoms between the contacting base layers to form a liquidlike layer) chain length difference increased friction.
OBJECTIVE - To demonstrate the feasibility of simultaneous dual fundamental grayscale and subharmonic imaging on a modified commercial scanner.
MOTIVATION - The ability to generate signals at half the insonation frequency is exclusive to ultrasound contrast agents (UCA). Thus, subharmonic imaging (SHI; transmitting at f(0) and receiving at f(0)/2) provides improved visualization of UCA within the vasculature via suppression of the surrounding tissue echoes. While this capability has proven useful in a variety of clinical applications, the SHI suppression of surrounding tissue landmarks (which are needed for sonographic navigation) also limits it use as a primary imaging modality. In this paper we present results using a commercial ultrasound scanner modified to allow imaging in both grayscale (f(0)=4.0 MHz) and SHI (f(0)=2.5 MHz, f(0)/2=1.25 MHz) modes in real time.
METHODS - A Logiq 9 ultrasound scanner (GE Healthcare, Milwaukee, WI) with a 4C curvilinear probe was modified to provide this capability. Four commercially available UCA (Definity, Lantheus Medical Imaging, North Billerica, MA; Optison, GE Healthcare, Princeton, NJ; SonoVue, Bracco Imaging, Milan, Italy; and Sonazoid, GE Healthcare, Oslo, Norway) were all investigated in vitro over an acoustic output range of 3.34 MPa. In vivo the subharmonic response of Sonazoid was investigated in the portal veins of four canines (open abdominal cavity) and four patients with suspected portal hypertension.
RESULTS - In vitro, the four UCA showed an average maximum subharmonic amplitude of 44.1±5.4 dB above the noise floor with a maximum subharmonic amplitude of 48.6±1.6 dB provided by Sonazoid. The average in vivo maximum signal above the noise floor from Sonazoid was 20.8±2.3 dB in canines and 33.9±5.2 dB in humans. Subharmonic amplitude as a function of acoustic output in both groups matched the S-curve behavior of the agent observed in vitro. The dual grayscale imaging provided easier sonographic navigation, while the degree of tissue suppression in SHI mode varied greatly on a case by case basis.
CONCLUSIONS - These results demonstrate the feasibility of dual grayscale and SHI on a modified commercial scanner. The ability to simultaneously visualize both imaging modes in real time should improve the applicability of SHI as a future primary clinical imaging modality.
Copyright © 2011 Elsevier B.V. All rights reserved.
OBJECTIVES - To examine whether prenatal exposure to perfluorooctanesulfonate (PFOS) or perfluorooctanoate (PFOA) is associated with the occurrence of hospitalization for infectious diseases during early childhood.
METHODS - We randomly selected 1400 pregnant women and their offspring from the Danish National Birth Cohort (1996-2002) and measured PFOS and PFOA levels in maternal blood during early pregnancy. Hospitalizations for infection of the offspring were identified by the linkage to the National Hospital Discharge Register through 2008.
RESULTS - Hospitalizations due to infections were not associated with prenatal exposure to PFOA and PFOS. On the contrary, the relative risks of hospitalizations ranged from 0.71 to 0.84 for the three higher quartiles of maternal PFOA levels compared with the lowest, but no dose-response pattern was found. No clear pattern was observed when results were stratified by child's age at infection, with the exception of an inverse association between maternal PFC levels and risk of hospitalization during the child's first year of life.
CONCLUSIONS - These findings suggest that prenatal exposure to PFOA or PFOS is not associated with increased risk of infectious diseases leading to hospitalization in early childhood.
Copyright © 2010 Elsevier Inc. All rights reserved.
OBJECTIVE - The purpose of this article is to discuss and illustrate the use of contrast-enhanced transvaginal sonography for the early detection of ovarian cancer and suggest how this technique may best be used to distinguish benign from malignant ovarian masses.
CONCLUSION - Microbubble-enhanced transvaginal sonography can enhance the evaluation of ovarian masses by early detection of tumor microvascularity.
OBJECTIVE - The aim of this study was to evaluate diagnostic parameters to differentiate between benign versus malignant ovarian masses using contrast-enhanced transvaginal sonography (TVS).
METHODS - Thirty-three consecutive patients with 36 morphologically abnormal ovarian masses (solid or cystic with papillary excrescences, focally thickened walls, or irregular solid areas) smaller than 10 cm received a microbubble contrast agent intravenously while undergoing pulse inversion harmonic TVS. The following parameters were assessed: presence of contrast enhancement, time to peak enhancement, peak contrast enhancement, half wash-out time, and area under the enhancement curve (AUC). Tumor histologic analysis was used to distinguish benign from malignant ovarian tumors.
RESULTS - Twenty-six benign masses and 10 malignancies were studied. Of all examined criteria, an AUC of greater than 787 seconds(-1) was the most accurate diagnostic criterion for ovarian cancer, with 100.0% sensitivity and 96.2% specificity. Additionally, peak contrast enhancement of greater than 17.2 dB (90.0% sensitivity and 98.3% specificity) and half wash-out time of greater than 41.0 seconds (100.0% sensitivity and 92.3% specificity) proved to be useful.
CONCLUSIONS - Our data suggest that the AUC, peak enhancement, and half wash-out time had the greatest diagnostic accuracy for contrast-enhanced TVS in differentiation between benign and malignant ovarian masses.