Theoretical study of closed-loop recycling liquid-liquid chromatography and experimental verification of the theory.

PubMed

Kostanyan, Artak E; Erastov, Andrey A

2016-09-02

The non-ideal recycling equilibrium-cell model including the effects of extra-column dispersion is used to simulate and analyze closed-loop recycling counter-current chromatography (CLR CCC). Previously, the operating scheme with the detector located before the column was considered. In this study, analysis of the process is carried out for a more realistic and practical scheme with the detector located immediately after the column. Peak equation for individual cycles and equations describing the transport of single peaks and complex chromatograms inside the recycling closed-loop, as well as equations for the resolution between single solute peaks of the neighboring cycles, for the resolution of peaks in the recycling chromatogram and for the resolution between the chromatograms of the neighboring cycles are presented. It is shown that, unlike conventional chromatography, increasing of the extra-column volume (the recycling line length) may allow a better separation of the components in CLR chromatography. For the experimental verification of the theory, aspirin, caffeine, coumarin and the solvent system hexane/ethyl acetate/ethanol/water (1:1:1:1) were used. Comparison of experimental and simulated processes of recycling and distribution of the solutes in the closed-loop demonstrated a good agreement between theory and experiment. Copyright © 2016 Elsevier B.V. All rights reserved.

High performance liquid chromatography column efficiency enhancement by zero dead volume recycling and practical approach using park and recycle arrangement.

PubMed

Minarik, Marek; Franc, Martin; Minarik, Milan

2018-06-15

A new instrumental approach to recycling HPLC is described. The concept is based on fast reintroduction of incremental peak sections back onto the separation column. The re-circulation is performed within a closed loop containing only the column and two synchronized switching valves. By having HPLC pump out of the cycle, the method minimizes peak broadening due to dead volume. As a result the efficiency is dramatically increased allowing for the most demanding analytical applications. In addition, a parking loop is employed for temporary storage of analytes from the middle section of the separated mixture prior to their recycling. Copyright © 2018 Elsevier B.V. All rights reserved.

40 CFR 799.6784 - TSCA water solubility: Column elution method; shake flask method.

Code of Federal Regulations, 2011 CFR

2011-07-01

....053 (3) The column should be connected to a recycling pump capable of controlling flows of... the carrier is not achieved due to partition effects on the surface of the carrier. (2) The loading of... this, the recycling pump is connected and the apparatus allowed to run until equilibration is...

40 CFR 799.6784 - TSCA water solubility: Column elution method; shake flask method.

Code of Federal Regulations, 2013 CFR

2013-07-01

....053 (3) The column should be connected to a recycling pump capable of controlling flows of... the carrier is not achieved due to partition effects on the surface of the carrier. (2) The loading of... this, the recycling pump is connected and the apparatus allowed to run until equilibration is...

40 CFR 799.6784 - TSCA water solubility: Column elution method; shake flask method.

Code of Federal Regulations, 2012 CFR

2012-07-01

....053 (3) The column should be connected to a recycling pump capable of controlling flows of... the carrier is not achieved due to partition effects on the surface of the carrier. (2) The loading of... this, the recycling pump is connected and the apparatus allowed to run until equilibration is...

40 CFR 799.6784 - TSCA water solubility: Column elution method; shake flask method.

Code of Federal Regulations, 2014 CFR

2014-07-01

....053 (3) The column should be connected to a recycling pump capable of controlling flows of... the carrier is not achieved due to partition effects on the surface of the carrier. (2) The loading of... this, the recycling pump is connected and the apparatus allowed to run until equilibration is...

The Fire Resistance Performance of Recycled Aggregate Concrete Columns with Different Concrete Compressive Strengths

PubMed Central

Dong, Hongying; Cao, Wanlin; Bian, Jianhui; Zhang, Jianwei

2014-01-01

In order to ascertain the fire resistance performance of recycled aggregate concrete (RAC) components with different concrete compressive strengths, four full-scaled concrete columns were designed and tested under high temperature. Two of the four specimens were constructed by normal concrete with compressive strength ratings of C20 and C30, respectively, while the others were made from recycled coarse aggregate (RCA) concrete of C30 and C40, respectively. Identical constant axial forces were applied to specimens while being subjected to simulated building fire conditions in a laboratory furnace. Several parameters from the experimental results were comparatively analyzed, including the temperature change, vertical displacement, lateral deflection, fire endurance, and failure characteristics of specimens. The temperature field of specimens was simulated with ABAQUS Software (ABAQUS Inc., Provindence, RI, USA) and the results agreed quite well with those from the experiments. Results show that the rate of heat transfer from the surface to the interior of the column increases with the increase of the concrete’s compressive strength for both RAC columns and normal concrete columns. Under the same initial axial force ratio, for columns with the same cross section, those with lower concrete compressive strengths demonstrate better fire resistance performance. The fire resistance performance of RAC columns is better than that of normal concrete columns, with the same concrete compressive strength. PMID:28788279

The Fire Resistance Performance of Recycled Aggregate Concrete Columns with Different Concrete Compressive Strengths.

PubMed

Dong, Hongying; Cao, Wanlin; Bian, Jianhui; Zhang, Jianwei

2014-12-08

In order to ascertain the fire resistance performance of recycled aggregate concrete (RAC) components with different concrete compressive strengths, four full-scaled concrete columns were designed and tested under high temperature. Two of the four specimens were constructed by normal concrete with compressive strength ratings of C20 and C30, respectively, while the others were made from recycled coarse aggregate (RCA) concrete of C30 and C40, respectively. Identical constant axial forces were applied to specimens while being subjected to simulated building fire conditions in a laboratory furnace. Several parameters from the experimental results were comparatively analyzed, including the temperature change, vertical displacement, lateral deflection, fire endurance, and failure characteristics of specimens. The temperature field of specimens was simulated with ABAQUS Software (ABAQUS Inc., Provindence, RI, USA) and the results agreed quite well with those from the experiments. Results show that the rate of heat transfer from the surface to the interior of the column increases with the increase of the concrete's compressive strength for both RAC columns and normal concrete columns. Under the same initial axial force ratio, for columns with the same cross section, those with lower concrete compressive strengths demonstrate better fire resistance performance. The fire resistance performance of RAC columns is better than that of normal concrete columns, with the same concrete compressive strength.

Systems and methods for reactive distillation with recirculation of light components

DOEpatents

Stickney, Michael J [Nassau Bay, TX; Jones, Jr., Edward M.

2011-07-26

Systems and methods for producing gas-to-liquids products using reactive distillation are provided. The method for producing gas-to-liquids products can include reacting a feedstock in a column having a distillation zone and a reaction zone to provide a bottoms stream and an overhead stream. A first portion of the overhead stream can be recycled to the column at the top of the reaction zone and second portion of the overhead stream can be recycled to the column at the bottom of the reaction zone.

Removing Chlorides From Metallurgical-Grade Silicon

NASA Technical Reports Server (NTRS)

Breneman, W. C.; Coleman, L. M.

1982-01-01

Process for making low-cost silicon for solar cells is further improved. Silane product recycled to feed stripper column converts some of heavy impurities to volatile ones that pass off at top of column with light wastes. Impurities--chlorides of arsenic, phosphorus, and boron-would otherwise be carried to subsequent distillations where they would be difficult to remove. Since only a small amount of silane is recycled, silicon production efficiency remains high.

Semi-industrial experimental study on bauxite separation using a cell-column integration process

NASA Astrophysics Data System (ADS)

Zhang, Ning-ning; Zhou, Chang-chun; Cong, Long-fei; Cao, Wen-long; Zhou, You

2016-01-01

The cyclonic-static micro-bubble flotation column (FCSMC) is a highly efficient mineral processing equipment. In this study, a cell-column (FCSMC) integration process was investigated for the separation of bauxite and its feasibility was analyzed on a theoretical basis. The properties of low-grade bauxite ore from Henan Province, China were analyzed. Parameters such as reagent dosage, scraping bubble time, and pressure of the circulating pump during the sorting process were investigated and optimized to improve the flotation efficiency. On the basis of these parameters, continuous separation experiments were conducted. Bauxite concentrate with an aluminum-to-silicon (A/S) mass ratio of 6.37 and a 77.63wt% recovery rate were achieved via a flow sheet consisting of "fast flotation using a flotation cell, one roughing flotation and one cleaning flotation using flotation columns". Compared with the full-flotation-cells process, the cell-column integration process resulted in an increase of the A/S ratio by 0.41 and the recovery rate by 17.58wt%. Cell-column integration separation technology represents a new approach for the separation of middle-to-low-grade bauxite ore.

Virus elimination during the recycling of chromatographic columns used during the manufacture of coagulation factors.

PubMed

Roberts, Peter L

2014-07-01

Various chromatographic procedures are used during the purification and manufacture of plasma products such as coagulation factors. These steps contribute to the overall safety of such products by removing potential virus contamination. Virus removal by two affinity chromatography procedures, i.e. monoclonal antibody chromatography and metal chelate chromatography (immobilised metal ion affinity chromatography), used during the manufacture of the high purity factor VIII (Replenate®) and factor IX (Replenine®-VF), respectively, has been investigated. In addition, as these columns are recycled after use, the effectiveness of the sanitisation procedures for preventing possible cross-contamination, has also been investigated. Both chromatographic steps proved effective for eliminating a range of model enveloped and non-enveloped viruses by 4 to >6 and 5 to >8 log for the monoclonal and metal chelate columns, respectively. The effectiveness of the relatively mild column sanitisation conditions used, i.e. ethanol for factor IX and acetic acid for factor VIII, was confirmed using non-spiked column runs. The chemicals used contributed to virus elimination by inactivation and/or by physical removal of the virus. In summary, these studies demonstrate that potential virus contamination between chromatographic runs can be prevented when an effective column recycling and sanitisation procedure is included. Copyright © 2014 The International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

Mechanical Behavior of Recycled Aggregate Concrete-Filled Steel Tubular Columns before and after Fire.

PubMed

Liu, Wenchao; Cao, Wanlin; Zhang, Jianwei; Wang, Ruwei; Ren, Lele

2017-03-09

Recycled aggregate concrete (RAC) is an environmentally friendly building material. This paper investigates the mechanical behavior of recycled aggregate concrete filled steel tube (RACFST) columns exposed to fire. Two groups of 12 columns were designed and tested, under axial compression, before and after fire, to evaluate the degradation of bearing capacity due to fire exposure. Six specimens were subjected to axial compression tests at room temperature and the other six specimens were subjected to axial compression tests after a fire exposure. The main parameters of the specimens include the wall thickness of the steel tube (steel content) and the type of concrete materials. Several parameters as obtained from the experimental results were compared and analyzed, including the load-bearing capacity, deformation capacity, and failure characteristics of the specimens. Meanwhile, rate of loss of bearing capacity of specimens exposed to fire were calculated based on the standards EC4 and CECS28:90. The results show that concrete material has a large influence on the rate of loss of bearing capacity in the case of a relatively lower steel ratio. While steel content has little effect on the rate of loss of bearing capacity of concrete-filled steel tube (CFST) columns after fire, it has a relatively large influence on the loss rate of bearing capacity of the RACFST columns. The loss of bearing capacity of the specimens from the experiment is more serious than that from the calculation. As the calculated values are less conservative, particular attention should be given to the application of recycled aggregate concrete in actual structures.

Mechanical Behavior of Recycled Aggregate Concrete-Filled Steel Tubular Columns before and after Fire

PubMed Central

Liu, Wenchao; Cao, Wanlin; Zhang, Jianwei; Wang, Ruwei; Ren, Lele

2017-01-01

Recycled aggregate concrete (RAC) is an environmentally friendly building material. This paper investigates the mechanical behavior of recycled aggregate concrete filled steel tube (RACFST) columns exposed to fire. Two groups of 12 columns were designed and tested, under axial compression, before and after fire, to evaluate the degradation of bearing capacity due to fire exposure. Six specimens were subjected to axial compression tests at room temperature and the other six specimens were subjected to axial compression tests after a fire exposure. The main parameters of the specimens include the wall thickness of the steel tube (steel content) and the type of concrete materials. Several parameters as obtained from the experimental results were compared and analyzed, including the load-bearing capacity, deformation capacity, and failure characteristics of the specimens. Meanwhile, rate of loss of bearing capacity of specimens exposed to fire were calculated based on the standards EC4 and CECS28:90. The results show that concrete material has a large influence on the rate of loss of bearing capacity in the case of a relatively lower steel ratio. While steel content has little effect on the rate of loss of bearing capacity of concrete-filled steel tube (CFST) columns after fire, it has a relatively large influence on the loss rate of bearing capacity of the RACFST columns. The loss of bearing capacity of the specimens from the experiment is more serious than that from the calculation. As the calculated values are less conservative, particular attention should be given to the application of recycled aggregate concrete in actual structures. PMID:28772634

The influence of distance between microbubbles on the fluid flow produced during ultrasound exposure

PubMed Central

Schutt, Carolyn E.; Ibsen, Stuart D.; Thrift, William; Esener, Sadik C.

2014-01-01

The collapse dynamics of lipid monolayer-coated microbubbles in the clinically-relevant size range under 6 μm in diameter have not been studied directly due to their small size obscuring the collapse visualization. This study investigates the influence of inter-microbubble distance on the shape of lipid debris clouds created by the collapse of the microbubble destroying the microbubble lipid monolayer. The shape was highly influenced by the fluid motion that occurred as the microbubbles collapsed. It was observed that at inter-microbubble distances smaller than 37 μm the microbubbles began to interact with one another resulting in distorted and ellipsoid-shaped debris clouds. At inter-microbubble distances less than 10 μm, significantly elongated debris clouds were observed that extended out from the original microbubble location in a single direction. These distortions show a significant distance-dependent interaction between microbubbles. It was observed that microbubbles in physical contact with one another behaved in the same manner as separate microbubbles less than 10 μm apart creating significantly elongated debris clouds. It can be hypothesized that small inter-microbubble distances influence the microbubble to collapse asymmetrically resulting in the creation of fluid jets that contribute to the formation of debris fields that are elongated in a single direction. PMID:25480086

Hydraulic and environmental behavior of recycled asphalt pavement in highway shoulder applications

DOT National Transportation Integrated Search

2017-10-01

Hydraulic conductivity of seven recycled asphalt pavement materials (RAPs) was evaluated through a series of constant-head tests, while their leaching potential was determined through batch leach tests and column leach tests. The contaminant transpor...

Recycling of drinking water treatment residue as an additional medium in columns for effective P removal from eutrophic surface water.

PubMed

Wang, Changhui; Wu, Yu; Bai, Leilei; Zhao, Yaqian; Yan, Zaisheng; Jiang, Helong; Liu, Xin

2018-07-01

This study assesses the feasibility of recycling drinking water treatment residue (DWTR) to treat eutrophic surface water in a one-year continuous flow column test. Heat-treated DWTR was used as an additional medium (2%-4%) in columns in case excessive organic matter and N were released from the DWTR to surface water. The results indicated that with minimal undesirable effects on other water properties, DWTR addition substantially enhanced P removal, rendering P concentrations in treated water oligotrophic and treated water unsuitable for Microcystis aeruginosa breeding. Long-term stable P removal by DWTR-column treatment was mainly attributed to the relatively low P levels in raw water (<0.108 mg L -1 ) and high P adsorption capability of DWTR, as confirmed by increases in amorphous Al/Fe in DWTR after the tests and low adsorption of P in the mobile forms. The major components of DWTR showed minimal changes, and potential metal pollution from DWTR was not a factor to consider during recycling. DWTR also enriched functional bacterial genera that benefitted biogeochemical cycles and multiple pollution control (e.g., Dechloromonas, Geobacter, Leucobacter, Nitrospira, Rhodoplanes, and Sulfuritalea); an apparent decrease in Mycobacterium with potential pathogenicity was observed in DWTR-columns. Regardless, limited denitrification of DWTR-columns was observed as a result of low bioavailability of C in surface water. This finding indicates that DWTR can be used with other methods to ensure denitrification for enhanced treatment effects. Overall, the use of DWTR as an additional medium in column systems can potentially treat eutrophic surface water. Copyright © 2018 Elsevier Ltd. All rights reserved.

Stress grading of recycled lumber and timber

Treesearch

Robert H. Falk; David Green

1999-01-01

This paper presents an overview of selected research at the Forest Products Laboratory (FPL) to characterize the grade distribution and engineering properties of lumber and timber recycled from deconstructed buildings on US. Army installations. The effects of splits on timber beam and column...

Effect of microbubble ligation to cells on ultrasound signal enhancement: implications for targeted imaging.

PubMed

Lankford, Miles; Behm, Carolyn Z; Yeh, James; Klibanov, Alexander L; Robinson, Peter; Lindner, Jonathan R

2006-10-01

Molecular imaging with contrast-enhanced ultrasound (CEU) relies on the detection of microbubbles retained in regions of disease. The aim of this study was to determine whether microbubble attachment to cells influences their acoustic signal generation and stability. Biotinylated microbubbles were attached to streptavidin-coated plates to derive density versus intensity relations during low- and high-power imaging. To assess damping from microbubble attachment to solid or cell surfaces, in vitro imaging was performed for microbubbles charge-coupled to methacrylate spheres and for vascular cell adhesion molecule-1-targeted microbubbles attached to endothelial cells. Signal enhancement on plates increased according to acoustic power and microbubble site density up to 300 mm. Microbubble signal was reduced by attachment to solid spheres during high- and low-power imaging but was minimally reduced by attachment to endothelial cells and only at low power. Attachment of targeted microbubbles to rigid surfaces results in damping and a reduction of their acoustic signal, which is not seen when microbubbles are attached to cells. A reliable concentration versus intensity relationship can be expected from microbubble attachment to 2-dimensional surfaces until a very high site density is reached.

Design and Control of Functional Microbubbles for Medical Applications of Ultrasound

NASA Astrophysics Data System (ADS)

Takagi, Shu; Osaki, Taichi; Ariyoshi, Takuya; Azuma, Takashi; Ichiyanagi, Mitsuhisa; Kinefuchi, Ikuya

2015-11-01

Microbubbles are used as a contrast agent for ultrasound diagnosis. It is also expected to be use for the treatment. One of the possible applications is microbubble DDS. For that purpose, microbubbles need to be well-controlled for the generating process and manipulation. In this talk, for the design and control of the functional microbubbles, an experimental study on generation and surface modification of microbubbles are explained. Using a T-junction type microchannel, small bubbles about 5 μm size are successfully generated. For the surface modification, Biotin-coated microbubbles are tried to adhere the Avidin-coated wall. Furthermore, the manipulation of the microbubbles using ultrasound is also discussed. Plane-wave and focused ultrasound is used to manipulate a microbubble and bubble clusters. The experimental results are shown in the presentation. Supported by JSPS KAKENHI Grant Number 15K13865.

Ultrasound-Targeted Microbubble Destruction to Deliver siRNA Cancer Therapy

PubMed Central

Carson, Andrew R; McTiernan, Charles F; Lavery, Linda; Grata, Michelle; Leng, Xiaoping; Wang, Jianjun; Chen, Xucai; Villanueva, Flordeliza S

2012-01-01

Microbubble contrast agents can specifically deliver nucleic acids to target tissues when exposed to ultrasound treatment parameters that mediate microbubble destruction. In this study, we evaluated whether microbubbles and ultrasound targeted microbubble destruction (UTMD) could be used to enhance delivery of EGFR-directed small inhibitory RNA (siRNA) to murine squamous cell carcinomas. Custom designed microbubbles efficiently bound siRNA and mediated RNAse protection. UTMD-mediated delivery of microbubbles loaded with EGFR-directed siRNA to murine squamous carcinoma cells in vitro reduced EGFR expression and EGF-dependent growth, relative to delivery of control siRNA. Similarly, serial UTMD-mediated delivery of EGFR siRNA to squamous cell carcinoma in vivo decreased EGFR expression and increased tumor doubling times, relative to controls receiving EGFR siRNA loaded microbubbles but not ultrasound or control siRNA loaded microbubbles and UTMD. Taken together, our results offer a preclinical proof of concept for customized microbubbles and UTMD to deliver gene-targeted siRNA for cancer therapy. PMID:23010078

Ligand conjugation to bimodal poly(ethylene glycol) brush layers on microbubbles.

PubMed

Chen, Cherry C; Borden, Mark A

2010-08-17

Using microbubbles as model systems, we examined molecular diffusion and binding to colloidal surfaces in bimodal poly(ethylene glycol) (PEG) brush layers. A microbubble is a gaseous colloidal particle with a diameter of less than 10 mum, of which the surface comprises amphiphilic phospholipids self-assembled to form a lipid monolayer shell. Due to the compressible gas core, microbubbles provide a sensitive acoustic response and are currently used as ultrasound contrast agents. Similar to the design of long circulating liposomes, PEG chains are typically incorporated into the shell of microbubbles to form a steric barrier against coalescence and adsorption of macromolecules to the microbubble surface. We introduced a buried-ligand architecture (BLA) design where the microbubble surface was coated with a bimodal PEG brush. After microbubbles were generated, fluorescent ligands with different molecular weights were conjugated to the tethered functional groups on the shorter PEG chains, while the longer PEG chains served as a shield to protect these ligands from exposure to the surrounding environment. BLA microbubbles reduced the binding of macromolecules (>10 kDa) to the tethers due to the steric hindrance of the PEG overbrush while allowing the uninhibited attachment of small molecules (<1 kDa). Roughly 40% less fluorescein-conjugated streptavidin (SA-FITC) bound to BLA microbubbles compared to exposed-ligand architecture (ELA) microbubbles. The binding of SA-FITC to BLA microbubbles suggested a possible phase separation between the lipid species on the surface leading to populations of revealed and concealed ligands. Ligand conjugation kinetics was independent of microbubble size, regardless of ligand size or microbubble architecture. We observed, for the first time, streptavidin-induced surface structure formation for ELA microbubbles and proposed that this phenomenon may be correlated to flow cytometry scattering measurements. We therefore demonstrated the feasibility of postlabeling for small-molecule ligands to BLA microbubbles to generate stealth targeted ultrasound contrast agents.

An optical system for detecting 3D high-speed oscillation of a single ultrasound microbubble

PubMed Central

Liu, Yuan; Yuan, Baohong

2013-01-01

As contrast agents, microbubbles have been playing significant roles in ultrasound imaging. Investigation of microbubble oscillation is crucial for microbubble characterization and detection. Unfortunately, 3-dimensional (3D) observation of microbubble oscillation is challenging and costly because of the bubble size—a few microns in diameter—and the high-speed dynamics under MHz ultrasound pressure waves. In this study, a cost-efficient optical confocal microscopic system combined with a gated and intensified charge-coupled device (ICCD) camera were developed to detect 3D microbubble oscillation. The capability of imaging microbubble high-speed oscillation with much lower costs than with an ultra-fast framing or streak camera system was demonstrated. In addition, microbubble oscillations along both lateral (x and y) and axial (z) directions were demonstrated. Accordingly, this system is an excellent alternative for 3D investigation of microbubble high-speed oscillation, especially when budgets are limited. PMID:24049677

PRETREATMENT AND FRACTIONATION OF CORN STOVER BY AMMONIA RECYCLE PERCOLATION PROCESS. (R831645)

EPA Science Inventory

Corn stover was pretreated with aqueous ammonia in a flow-through column reactor,
a process termed as Ammonia Recycle Percolation (ARP). The aqueous ammonia causes
swelling and efficient delignification of biomass at high temperatures. The ARP
process solubilizes abou...

Lung Surfactant Microbubbles Increase Lipophilic Drug Payload for Ultrasound-Targeted Delivery

PubMed Central

Sirsi, Shashank R.; Fung, Chinpong; Garg, Sumit; Tianning, Mary Y.; Mountford, Paul A.; Borden, Mark A.

2013-01-01

The cavitation response of circulating microbubbles to targeted ultrasound can be used for noninvasive, site-specific delivery of shell-loaded materials. One challenge for microbubble-mediated delivery of lipophilic compounds is the limitation of drug loading into the microbubble shell, which is commonly a single phospholipid monolayer. In this study, we investigated the use of natural lung surfactant extract (Survanta®, Abbott Nutrition) as a microbubble shell material in order to improve drug payload and delivery. Pulmonary surfactant extracts such as Survanta contain hydrophobic surfactant proteins (SP-B and SP-C) that facilitate lipid folding and retention on lipid monolayers. Here, we show that Survanta-based microbubbles exhibit wrinkles in bright-field microscopy and increased lipid retention on the microbubble surface in the form of surface-associated aggregates observed with fluorescence microscopy. The payload of a model lipophilic drug (DiO), measured by flow cytometry, increased by over 2-fold compared to lipid-coated microbubbles lacking SP-B and SP-C. Lung surfactant microbubbles were highly echogenic to contrast enhanced ultrasound imaging at low acoustic intensities. At higher ultrasound intensity, excess lipid was observed to be acoustically cleaved for localized release. To demonstrate targeting, a biotinylated lipopolymer was incorporated into the shell, and the microbubbles were subjected to a sequence of radiation force and fragmentation pulses as they passed through an avidinated hollow fiber. Lung surfactant microbubbles showed a 3-fold increase in targeted deposition of the model fluorescent drug compared to lipid-only microbubbles. Our results demonstrate that lung surfactant microbubbles maintain the acoustic responsiveness of lipid-coated microbubbles with the added benefit of increased lipophilic drug payload. PMID:23781287

Lung surfactant microbubbles increase lipophilic drug payload for ultrasound-targeted delivery.

PubMed

Sirsi, Shashank R; Fung, Chinpong; Garg, Sumit; Tianning, Mary Y; Mountford, Paul A; Borden, Mark A

2013-01-01

The cavitation response of circulating microbubbles to targeted ultrasound can be used for noninvasive, site-specific delivery of shell-loaded materials. One challenge for microbubble-mediated delivery of lipophilic compounds is the limitation of drug loading into the microbubble shell, which is commonly a single phospholipid monolayer. In this study, we investigated the use of natural lung surfactant extract (Survanta(®), Abbott Nutrition) as a microbubble shell material in order to improve drug payload and delivery. Pulmonary surfactant extracts such as Survanta contain hydrophobic surfactant proteins (SP-B and SP-C) that facilitate lipid folding and retention on lipid monolayers. Here, we show that Survanta-based microbubbles exhibit wrinkles in bright-field microscopy and increased lipid retention on the microbubble surface in the form of surface-associated aggregates observed with fluorescence microscopy. The payload of a model lipophilic drug (DiO), measured by flow cytometry, increased by over 2-fold compared to lipid-coated microbubbles lacking SP-B and SP-C. Lung surfactant microbubbles were highly echogenic to contrast enhanced ultrasound imaging at low acoustic intensities. At higher ultrasound intensity, excess lipid was observed to be acoustically cleaved for localized release. To demonstrate targeting, a biotinylated lipopolymer was incorporated into the shell, and the microbubbles were subjected to a sequence of radiation force and fragmentation pulses as they passed through an avidinated hollow fiber. Lung surfactant microbubbles showed a 3-fold increase in targeted deposition of the model fluorescent drug compared to lipid-only microbubbles. Our results demonstrate that lung surfactant microbubbles maintain the acoustic responsiveness of lipid-coated microbubbles with the added benefit of increased lipophilic drug payload.

RECYCLED MATERIALS FOR REPAIR AND REHABILITATION OF AGING CONCRETE STRUCTURES - PHASE I

EPA Science Inventory

Exterior wrapping of concrete columns initially was developed for seismic reinforcement in high-risk areas such as California. As the technology has gained acceptance, it is being considered for use in extending column life, reducing corrosion, and preventing spalling. All ...

Influence of the bubble-bubble interaction on destruction of encapsulated microbubbles under ultrasound.

PubMed

Yasui, Kyuichi; Lee, Judy; Tuziuti, Toru; Towata, Atsuya; Kozuka, Teruyuki; Iida, Yasuo

2009-09-01

Influence of the bubble-bubble interaction on the pulsation of encapsulated microbubbles has been studied by numerical simulations under the condition of the experiment reported by Chang et al. [IEEE Trans. Ultrason Ferroelectr. Freq. Control 48, 161 (2001)]. It has been shown that the natural (resonance) frequency of a microbubble decreases considerably as the microbubble concentration increases to relatively high concentrations. At some concentration, the natural frequency may coincide with the driving frequency. Microbubble pulsation becomes milder as the microbubble concentration increases except at around the resonance condition due to the stronger bubble-bubble interaction. This may be one of the reasons why the threshold of acoustic pressure for destruction of an encapsulated microbubble increases as the microbubble concentration increases. A theoretical model for destruction has been proposed.

Focal areas of increased lipid concentration on the coating of microbubbles during short tone-burst ultrasound insonification.

PubMed

Kooiman, Klazina; van Rooij, Tom; Qin, Bin; Mastik, Frits; Vos, Hendrik J; Versluis, Michel; Klibanov, Alexander L; de Jong, Nico; Villanueva, Flordeliza S; Chen, Xucai

2017-01-01

Acoustic behavior of lipid-coated microbubbles has been widely studied, which has led to several numerical microbubble dynamics models that incorporate lipid coating behavior, such as buckling and rupture. In this study we investigated the relationship between microbubble acoustic and lipid coating behavior on a nanosecond scale by using fluorescently labeled lipids. It is hypothesized that a local increased concentration of lipids, appearing as a focal area of increased fluorescence intensity (hot spot) in the fluorescence image, is related to buckling and folding of the lipid layer thereby highly influencing the microbubble acoustic behavior. To test this hypothesis, the lipid microbubble coating was fluorescently labeled. The vibration of the microbubble (n = 177; 2.3-10.3 μm in diameter) upon insonification at an ultrasound frequency of 0.5 or 1 MHz at 25 or 50 kPa acoustic pressure was recorded with the UPMC Cam, an ultra-high-speed fluorescence camera, operated at ~4-5 million frames per second. During short tone-burst excitation, hot spots on the microbubble coating occurred at relative vibration amplitudes > 0.3 irrespective of frequency and acoustic pressure. Around resonance, the majority of the microbubbles formed hot spots. When the microbubble also deflated acoustically, hot spot formation was likely irreversible. Although compression-only behavior (defined as substantially more microbubble compression than expansion) and subharmonic responses were observed in those microbubbles that formed hot spots, both phenomena were also found in microbubbles that did not form hot spots during insonification. In conclusion, this study reveals hot spot formation of the lipid monolayer in the microbubble's compression phase. However, our experimental results show that there is no direct relationship between hot spot formation of the lipid coating and microbubble acoustic behaviors such as compression-only and the generation of a subharmonic response. Hence, our hypothesis that hot spots are related to acoustic buckling could not be verified.

Acoustic Characterization and Enhanced Ultrasound Imaging of Long-Circulating Lipid-Coated Microbubbles.

PubMed

Li, Hongbo; Yang, Yanye; Zhang, Meimei; Yin, Liping; Tu, Juan; Guo, Xiasheng; Zhang, Dong

2018-05-01

A long-circulating lipid-coated ultrasound (US) contrast agent was fabricated to achieve a longer wash-out time and gain more resistance against higher-mechanical index sonication. Systemic physical, acoustic, and in vivo imaging experiments were performed to better understand the underlying mechanism enabling the improvement of contrast agent performance by adjusting the physical and acoustic properties of contrast agent microbubbles. By simply altering the gas core, a kind of US contrast agent microbubble was synthesized with a similar lipid-coating shell as SonoVue microbubbles (Bracco SpA, Milan, Italy) to achieve a longer wash-out time and higher inertial cavitation threshold. To bridge the structure-performance relationship of the synthesized microbubbles, the imaging performance of the microbubbles was assessed in vivo with SonoVue as a control group. The size distribution and inertial cavitation threshold of the synthesized microbubbles were characterized, and the shell parameters of the microbubbles were determined by acoustic attenuation measurements. All of the measurements were compared with SonoVue microbubbles. The synthesized microbubbles had a spherical shape, a smooth, consistent membrane, and a uniform distribution, with an average diameter of 1.484 μm. According to the measured attenuation curve, the synthesized microbubbles resonated at around 2.8 MHz. Although the bubble's shell elasticity (0.2 ± 0.09 N/m) was comparable with SonoVue, it had relatively greater viscosity and inertial cavitation because of the different gas core. Imaging studies showed that the synthesized microbubbles had a longer circulation time and a better chance of fighting against rapid collapse than SonoVue. Nano/micrometer long-circulating lipid-coated microbubbles could be fabricated by simply altering the core composition of SonoVue microbubbles with a higher-molecular weight gas. The smaller diameter and higher inertial cavitation threshold of the synthesized microbubbles might make it easier to access deep-seated organs and give prolonged imaging enhancement in the liver. © 2017 by the American Institute of Ultrasound in Medicine.

Experimental study of microbubble drag reduction on an axisymmetric body

NASA Astrophysics Data System (ADS)

Song, Wuchao; Wang, Cong; Wei, Yingjie; Zhang, Xiaoshi; Wang, Wei

2018-01-01

Microbubble drag reduction on the axisymmetric body is experimentally investigated in the turbulent water tunnel. Microbubbles are created by injecting compressed air through the porous medium with various average pore sizes. The morphology of microbubble flow and the size distribution of microbubble are observed by the high-speed visualization system. Drag measurements are obtained by the balance which is presented as the function of void ratio. The results show that when the air injection flow rate is high, uniformly dispersed microbubble flow is coalesced into an air layer with the larger increment rate of drag reduction ratio. The diameter distributions of microbubble under various conditions are submitted to normal distribution. Microbubble drag reduction can be divided into three distinguishable regions in which the drag reduction ratio experiences increase stage, rapid increase stage and stability stage, respectively, corresponding to the various morphologies of microbubble flow. Moreover, drag reduction ratio increases with the decreasing pore sizes of porous medium at the identical void ratio in the area of low speeds, while the effect of pore sizes on drag reduction is reduced gradually until it disappears with the increasing free stream speeds, which indicates that smaller microbubbles have better efficiency in drag reduction. This research results help to improve the understanding of microbubble drag reduction and provides helpful references for practical applications.

Numerical Study on Focusing of Ultrasounds in Microbubble-enhanced HIFU

NASA Astrophysics Data System (ADS)

Matsumoto, Yoichiro; Okita, Kohei; Takagi, Shu

2011-11-01

The injection of microbubbles into the target tissue enhances tissue heating in High-Intensity Focused Ultrasound therapy, via inertial cavitation. The control of the inertial cavitation is required to achieve the efficient tissue ablation. Microbubbles between a transducer and a target disturb the ultrasound propagation depending on the conditions. A method to clear such microbubbles has been proposed by Kajiyama et al. [Physics Procedia 3 (2010) 305-314]. In the method, the irradiation of intense ultrasounds with a burst waveform fragmentize microbubbles in the pathways before the irradiation of ultrasounds for tissue heating. The vitro experiment using a gel containing microbubbles has showed that the method enables to heat the target correctly by controlling the microbubble distribution. Following the experiment, we simulate the focusing of ultrasounds through a mixture containing microbubbles with considering the size and number density distributions in space. The numerical simulation shows that the movement of the heating region from the transducer side to the target by controlling the microbubble distributions. The numerical results elucidate well the experimental ones.

LyP-1 ultrasonic microbubbles targeting to cancer cell as tumor bio-acoustics markers or drug carriers: targeting efficiency evaluation in, microfluidic channels.

PubMed

Li, Xiang; Jin, Qiaofeng; Chen, Tan; Zhang, Baoyue; Zheng, Rongqin; Wang, Zhanhui; Zheng, Hairong

2009-01-01

Using ultrasonic contrast microbubbles as acoustic biomarkers and drug carrier vehicles by conjugating tumor specific antibody to microbubbles has shown great potential in ultrasonic tumor molecular imaging or drug-delivery and therapy. Microbubble probe targeting efficiency is one of the major challenges. In this study, we developed a novel method to evaluate the targeting capability and efficiency of microbubbles to cells, and more specifically, microbubbles binding LyP-1 (a cyclic nonapeptide acid peptide) target to cancer cell within a microfluidic system. The micro cell sieves within the microfludic channels could trap the tumor cells and enhance the microbubble's interaction with the cell. Assisted with the controllable fluid shear stress, the microbubble's targeting to the cell and the corresponding affinity efficiency could be quantitatively evaluated under a florescent microscope. The system provides a useful low-cost high efficient in vitro platform for studying microbubble-cell interaction for ultrasonic tumor molecular imaging or drug-delivery and therapy.

Multifunctional Polymer Microbubbles for Advanced Sentinel Lymph Node Imaging and Mapping

DTIC Science & Technology

2012-03-01

undesired PMA attached to microbubble surface. Figure 1: One-pot polymer -lipid microbubbles. (a) Synthesis of thiolated poly(acrylic acid) with...Award Number: W81XWH-11-1-0215 TITLE: Multifunctional Polymer Microbubbles for Advanced Sentinel...February 2012 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Multifunctional Polymer Microbubbles for Advanced Sentinel Lymph Node Imaging and Mapping 5b

HPLC separation of triacylglycerol positional isomers on a polymeric ODS column.

PubMed

Kuroda, Ikuma; Nagai, Toshiharu; Mizobe, Hoyo; Yoshimura, Nobuhito; Gotoh, Naohiro; Wada, Shun

2008-07-01

A polymeric ODS column was applied to the resolution of triacylglycerol positional isomers (TAG-PI), i.e. 1,3-dioleoyl-2-palmitoyl-glycerol (OPO) and 1,2-dioleoyl-3-palmitoyl-rac-glycerol (OOP), with a recycle HPLC system. To investigate the ODS column species and the column temperatures for the resolution of a TAG-PI pair, a mixture of OPO and OOP was subjected to an HPLC system equipped with a non-endcapped polymeric, endcapped monomeric, endcapped intermediate, or non-endcapped monomeric ODS column at three different column temperatures (40, 25, or 10 degrees C). Only the non-endcapped polymeric ODS column achieved the separation of OPO and OOP, and the lowest column temperature (10 degrees C) showed the best resolution for them. The other pair of TAG-PI, a mixture of 1,3-dipalmitoyl-2-oleoyl-glycerol (POP) and 1,2-dipalmitoyl-3-oleoyl-rac-glycerol (PPO) was also subjected to the system equipped with a non-endcapped polymeric or monomeric ODS column at five different column temperatures (40, 32, 25, 17, and 10 degrees C). Thus, POP and PPO were also separated on only the non-endcapped polymeric ODS column at 25 degrees C. However, no clear peak appeared at 10 degrees C. These results would indicate that the polymeric ODS stationary phase has an ability to recognize the structural differences between TAG-PI pairs. Also, the column temperature is a very important factor for separating the TAG-PI pair, and the optimal temperature would relate to the solubility of TAG-PI in the mobile phase. Furthermore, the recycle HPLC system provided measurements for the separation and analysis of TAG-PI pairs.

Ion-exchange chromatography separation applied to mineral recycle in closed systems

NASA Technical Reports Server (NTRS)

Ballou, E.; Spitze, L. A.; Wong, F. W.; Wydeven, T.; Johnson, C. C.

1981-01-01

As part of the controlled ecological life support system (CELSS) program, a study is being made of mineral separation on ion-exchange columns. The purpose of the mineral separation step is to allow minerals to be recycled from the oxidized waste products of plants, man, and animals for hydroponic food production. In the CELSS application, relatively large quantities of minerals in a broad concentration range must be recovered by the desired system, rather than the trace quantities and very low concentrations treated in analytical applications of ion-exchange chromatography. Experiments have been carried out to assess the parameters pertinent to the scale-up of ion-exchange chromatography and to determine feasibility. Preliminary conclusions are that the column scale-up is in a reasonable size range for the CELSS application. The recycling of a suitable eluent, however, remains a major challenge to the suitability of using ion exchange chromatography in closed systems.

Focal areas of increased lipid concentration on the coating of microbubbles during short tone-burst ultrasound insonification

PubMed Central

van Rooij, Tom; Qin, Bin; Mastik, Frits; Vos, Hendrik J.; Versluis, Michel; Klibanov, Alexander L.; de Jong, Nico; Villanueva, Flordeliza S.; Chen, Xucai

2017-01-01

Acoustic behavior of lipid-coated microbubbles has been widely studied, which has led to several numerical microbubble dynamics models that incorporate lipid coating behavior, such as buckling and rupture. In this study we investigated the relationship between microbubble acoustic and lipid coating behavior on a nanosecond scale by using fluorescently labeled lipids. It is hypothesized that a local increased concentration of lipids, appearing as a focal area of increased fluorescence intensity (hot spot) in the fluorescence image, is related to buckling and folding of the lipid layer thereby highly influencing the microbubble acoustic behavior. To test this hypothesis, the lipid microbubble coating was fluorescently labeled. The vibration of the microbubble (n = 177; 2.3–10.3 μm in diameter) upon insonification at an ultrasound frequency of 0.5 or 1 MHz at 25 or 50 kPa acoustic pressure was recorded with the UPMC Cam, an ultra-high-speed fluorescence camera, operated at ~4–5 million frames per second. During short tone-burst excitation, hot spots on the microbubble coating occurred at relative vibration amplitudes > 0.3 irrespective of frequency and acoustic pressure. Around resonance, the majority of the microbubbles formed hot spots. When the microbubble also deflated acoustically, hot spot formation was likely irreversible. Although compression-only behavior (defined as substantially more microbubble compression than expansion) and subharmonic responses were observed in those microbubbles that formed hot spots, both phenomena were also found in microbubbles that did not form hot spots during insonification. In conclusion, this study reveals hot spot formation of the lipid monolayer in the microbubble’s compression phase. However, our experimental results show that there is no direct relationship between hot spot formation of the lipid coating and microbubble acoustic behaviors such as compression-only and the generation of a subharmonic response. Hence, our hypothesis that hot spots are related to acoustic buckling could not be verified. PMID:28686673

Individual lipid encapsulated microbubble radial oscillations: Effects of fluid viscosity

PubMed Central

Helfield, Brandon; Chen, Xucai; Qin, Bin; Villanueva, Flordeliza S.

2016-01-01

Ultrasound-stimulated microbubble dynamics have been shown to be dependent on intrinsic bubble properties, including size and shell characteristics. The effect of the surrounding environment on microbubble response, however, has been less investigated. In particular, microbubble optimization studies are generally conducted in water/saline, characterized by a 1 cP viscosity, for application in the vasculature (i.e., 4 cP). In this study, ultra-high speed microscopy was employed to investigate fluid viscosity effects on phospholipid encapsulated microbubble oscillations at 1 MHz, using a single, eight-cycle pulse at peak negative pressures of 100 and 250 kPa. Microbubble oscillations were shown to be affected by fluid viscosity in a size- and pressure-dependent manner. In general, the oscillation amplitudes exhibited by microbubbles between 3 and 6 μm in 1 cP fluid were larger than in 4 cP fluid, reaching a maximum of 1.7-fold at 100 kPa for microbubbles 3.8 μm in diameter and 1.35-fold at 250 kPa for microbubbles 4.8 μm in diameter. Simulation results were in broad agreement at 250 kPa, however generally underestimated the effect of fluid viscosity at 100 kPa. This is the first experimental demonstration documenting the effects of surrounding fluid viscosity on microbubble oscillations, resulting in behavior not entirely predicted by current microbubble models. PMID:26827018

Ultra-high Speed Optical Imaging of Ultrasound-activated Microbubbles in Mesenteric Microvessels

NASA Astrophysics Data System (ADS)

Chen, Hong

Ultrasound contrast agent microbubbles have gained widespread applications in diagnostic and therapeutic ultrasound. Animal studies of bioeffects induced by ultrasound-activated microbubbles have demonstrated that microbubbles can cause microvessel damage. Much scientific attention has been attracted to such microvascular bioeffects, not only because of the related safety concerns, but also because of the potential useful applications of microbubbles in the intravascular delivery of drugs and genetic materials into target tissues. A significant challenge in using microbubbles in medical ultrasound is the lack of knowledge about how the microbubbles behave in blood vessels when exposed to ultrasound and how their interactions with ultrasound cause vascular damage. Although extensive studies were performed in the past to study the dynamics of microbubbles, most of those studies were performed in vitro and did not directly address the clinical environment in which microbubbles are injected into blood vessels. In this thesis work, a synchronized optical-acoustic system was set up for ultrahigh speed imaging of insonated microbubbles in microvessels. The recorded images revealed the formation of microjets penetrating the microbubbles, as well as vessel distention (motion outward against the surrounding tissue) and vessel invagination (motion inward toward the lumen) caused by the expansion and collapse of the microbubbles, respectively. Contrary to current paradigms which propose that microbubbles damage vessels either by distending them or by forming liquid jets impinging on them, microbubbles translation and jetting were in the direction away from the nearest vessel wall; furthermore, invagination typically exceeded distention in arterioles and venules. Vessel invagination was found to be associated with vascular damage. These studies suggest that vessel invagination may be a newly discovered potential mechanism for vascular damage by ultrasound-activated microbubbles. The dynamics of bubble-vessel interactions are coupled intimately with the viscoelastic properties of the microvessels. To probe these properties, a method based on the relaxation times of the invaginated microvessels was used to estimate the relaxation time constants of the microvessels. It was found that the time constants were on microsecond time scales, which provided insight into the unique and unknown viscoelastic properties of the microvessels.

Superhydrophobic Cones for Continuous Collection and Directional Transportation of CO2 Microbubbles in CO2 Supersaturated Solutions.

PubMed

Xue, Xiuzhan; Yu, Cunming; Wang, Jingming; Jiang, Lei

2016-12-27

Microbubbles are tiny bubbles with diameters below 50 μm. Because of their minute buoyant force, the microbubbles stagnate in aqueous media for a long time, and they sometimes cause serious damage. Most traditional methods chosen for elimination of gas bubbles utilize buoyancy forces including chemical methods and physical methods, and they only have a minor effect on microbubbles. Several approaches have been developed to collect and transport microbubbles in aqueous media. However, the realization of innovative strategies to directly collect and transport microbubbles in aqueous media remains a big challenge. In nature, both spider silk and cactus spines take advantage of their conical-shaped surface to yield the gradient of Laplace pressure and surface free energy for collecting fog droplets from the environment. Inspired by this, we introduce here the gradient of Laplace pressure and surface free energy to the interface of superhydrophobic copper cones (SCCs), which can continuously collect and directionally transport CO 2 microbubbles (from tip side to base side) in CO 2 -supersaturated solution. A gas layer was formed when the microbubbles encounter the SCCs. This offers a channel for microbubble directional transportation. The efficiency of microbubble transport is significantly affected by the apex angle of SCCs and the carbon dioxide concentration. The former provides different gradients of Laplace pressure as the driving force. The latter represents the capacity, which offers the quantity of CO 2 microbubbles for collection and transportation. We believe that this approach provides a simple and valid way to remove microbubbles.

An Experimental Study on the Stiffness of Size-Isolated Microbubbles Using Atomic Force Microscopy

PubMed Central

Chen, Cherry C.; Wu, Shih-Ying; Finan, John D.; Morrison, Barclay; Konofagou, Elisa E.

2014-01-01

To fully assess contrast-enhanced acoustic bioeffects in diagnostic and therapeutic procedures, the mechanical properties of microbubbles need to be considered. In the present study, direct measurements of the microbubble stiffness were performed using atomic force microscopy by applying nanoscale compressions (up to 25 nN/s) on size-isolated, lipid-coated microbubbles (diameter ranges of 4 to 6 μm and 6 to 8 μm). The stiffness was found to lie between 4 and 22 mN/m and to decrease exponentially with the microbubble size within the diameter range investigated. No cantilever spring constant effect was found on the measured stiffness. The Young’s modulus of the size-isolated microbubbles used in our study ranged between 0.4 and 2 MPa. Microstructures on the surface of the microbubbles were found to influence the overall microbubble elasticity. Our results indicated that more detailed theoretical models are needed to account for the size-dependent microbubble mechanical properties to accurately predict their acoustic behavior. The findings provided useful insights into guidance of cavitation-induced drug and gene delivery and could be used as part of the framework in studies on the shear stresses induced on the blood vessel walls by oscillating microbubbles. PMID:23475918

Enhanced cytotoxic effect of cisplatin using diagnostic ultrasound and microbubbles in vitro

NASA Astrophysics Data System (ADS)

Sasaki, Noboru; Nakamura, Kensuke; Murakami, Masahiro; Lim, Sue Yee; Ohta, Hiroshi; Yamasaki, Masahiro; Takiguchi, Mitsuyoshi

2012-10-01

Diagnostic ultrasound has accomplished drug and gene delivery by ultrasound targeted microbubble destruction (UTMD). However, the efficacy of delivery is still relatively low. Therefore, we optimized conditions of UTMD using diagnostic ultrasound and ultrasound contrast agent microbubbles. Canine thyroid adenocarcinoma cells were cultured in a 96-well plate. After addition of cisplatin and Sonazoid®, the plate was inverted to raise microbubbles near cells and incubated. Cells were exposed to diagnostic ultrasound using a linear probe operated in the contrast harmonic imaging mode. The center frequency was 2.5 MHz with a mechanical index of 1.33 and a frame rate of 48 frames/sec. Cytotoxic effect of cisplatin was evaluated 24h after exposure using trypan blue dye exclusion test. We optimized incubation duration, cisplatin concentration, and the relationship between microbubble concentration and exposure duration. The optimum enhancement was observed at incubation duration of 5min, cisplatin concentration of 1 μg/ml, and microbubble concentration of 2.4 × 105 microbubbles/ml. Exposure duration did not influence the enhancement at the microbubble concentration of 2.4 × 105 microbubbles/ml. Our results suggest that relative low concentrations of drug and microbubbles with short exposure duration might be sufficient for drug delivery by UTMD using diagnostic ultrasound.

Enzymatic amplification of a flow-injected thermometric enzyme-linked immunoassay for human insulin.

PubMed

Mecklenburg, M; Lindbladh, C; Li, H; Mosbach, K; Danielsson, B

1993-08-01

A flow-injected thermometric enzyme linked immunoassay for human insulin which employs the lactate dehydrogenase/lactate oxidase (LDH/LOD) substrate recycling system for signal amplification is described. The system is composed of two columns, an immunosorbent column containing immobilized anti-insulin antibodies for sensing and a recycling column containing immobilized LDH/LOD/Catalase for detection. The effect of flow rates, conjugate concentrations, and chromatographic support material upon the sensitivity of the assay are investigated. The assay has a detection limit of 0.025 microgram/ml and a linear range from 0.05 to 2 micrograms/ml. This corresponds to a 10-fold increase in sensitivity over the unamplified system. A recombinant human insulin-proinsulin conjugate was also tested. The results show that enzymatic amplification can be employed to increase the sensitivity and reproducibility of flow injection assay-based biosensors. The implications of these results upon on-line analysis are discussed.

TOPICAL REVIEW: Ultrasound contrast microbubbles in imaging and therapy: physical principles and engineering

NASA Astrophysics Data System (ADS)

Qin, Shengping; Caskey, Charles F.; Ferrara, Katherine W.

2009-03-01

Microbubble contrast agents and the associated imaging systems have developed over the past 25 years, originating with manually-agitated fluids introduced for intra-coronary injection. Over this period, stabilizing shells and low diffusivity gas materials have been incorporated in microbubbles, extending stability in vitro and in vivo. Simultaneously, the interaction of these small gas bubbles with ultrasonic waves has been extensively studied, resulting in models for oscillation and increasingly sophisticated imaging strategies. Early studies recognized that echoes from microbubbles contained frequencies that are multiples of the microbubble resonance frequency. Although individual microbubble contrast agents cannot be resolved—given that their diameter is on the order of microns—nonlinear echoes from these agents are used to map regions of perfused tissue and to estimate the local microvascular flow rate. Such strategies overcome a fundamental limitation of previous ultrasound blood flow strategies; the previous Doppler-based strategies are insensitive to capillary flow. Further, the insonation of resonant bubbles results in interesting physical phenomena that have been widely studied for use in drug and gene delivery. Ultrasound pressure can enhance gas diffusion, rapidly fragment the agent into a set of smaller bubbles or displace the microbubble to a blood vessel wall. Insonation of a microbubble can also produce liquid jets and local shear stress that alter biological membranes and facilitate transport. In this review, we focus on the physical aspects of these agents, exploring microbubble imaging modes, models for microbubble oscillation and the interaction of the microbubble with the endothelium.

Ultrasound contrast microbubbles in imaging and therapy: physical principles and engineering

PubMed Central

Qin, Shengping; Caskey, Charles F; Ferrara, Katherine W

2010-01-01

Microbubble contrast agents and the associated imaging systems have developed over the past twenty-five years, originating with manually-agitated fluids introduced for intra-coronary injection. Over this period, stabilizing shells and low diffusivity gas materials have been incorporated in microbubbles, extending stability in vitro and in vivo. Simultaneously, the interaction of these small gas bubbles with ultrasonic waves has been extensively studied, resulting in models for oscillation and increasingly sophisticated imaging strategies. Early studies recognized that echoes from microbubbles contained frequencies that are multiples of the microbubble resonance frequency. Although individual microbubble contrast agents cannot be resolved—given that their diameter is on the order of microns—nonlinear echoes from these agents are used to map regions of perfused tissue and to estimate the local microvascular flow rate. Such strategies overcome a fundamental limitation of previous ultrasound blood flow strategies; the previous Doppler-based strategies are insensitive to capillary flow. Further, the insonation of resonant bubbles results in interesting physical phenomena that have been widely studied for use in drug and gene delivery. Ultrasound pressure can enhance gas diffusion, rapidly fragment the agent into a set of smaller bubbles or displace the microbubble to a blood vessel wall. Insonation of a microbubble can also produce liquid jets and local shear stress that alter biological membranes and facilitate transport. In this review, we focus on the physical aspects of these agents, exploring microbubble imaging modes, models for microbubble oscillation and the interaction of the microbubble with the endothelium. PMID:19229096

Shrinking microbubbles with microfluidics: mathematical modelling to control microbubble sizes.

PubMed

Salari, A; Gnyawali, V; Griffiths, I M; Karshafian, R; Kolios, M C; Tsai, S S H

2017-11-29

Microbubbles have applications in industry and life-sciences. In medicine, small encapsulated bubbles (<10 μm) are desirable because of their utility in drug/oxygen delivery, sonoporation, and ultrasound diagnostics. While there are various techniques for generating microbubbles, microfluidic methods are distinguished due to their precise control and ease-of-fabrication. Nevertheless, sub-10 μm diameter bubble generation using microfluidics remains challenging, and typically requires expensive equipment and cumbersome setups. Recently, our group reported a microfluidic platform that shrinks microbubbles to sub-10 μm diameters. The microfluidic platform utilizes a simple microbubble-generating flow-focusing geometry, integrated with a vacuum shrinkage system, to achieve microbubble sizes that are desirable in medicine, and pave the way to eventual clinical uptake of microfluidically generated microbubbles. A theoretical framework is now needed to relate the size of the microbubbles produced and the system's input parameters. In this manuscript, we characterize microbubbles made with various lipid concentrations flowing in solutions that have different interfacial tensions, and monitor the changes in bubble size along the microfluidic channel under various vacuum pressures. We use the physics governing the shrinkage mechanism to develop a mathematical model that predicts the resulting bubble sizes and elucidates the dominant parameters controlling bubble sizes. The model shows a good agreement with the experimental data, predicting the resulting microbubble sizes under different experimental input conditions. We anticipate that the model will find utility in enabling users of the microfluidic platform to engineer bubbles of specific sizes.

A Sensitive TLRH Targeted Imaging Technique for Ultrasonic Molecular Imaging

PubMed Central

Hu, Xiaowen; Zheng, Hairong; Kruse, Dustin E.; Sutcliffe, Patrick; Stephens, Douglas N.; Ferrara, Katherine W.

2010-01-01

The primary goals of ultrasound molecular imaging are the detection and imaging of ultrasound contrast agents (microbubbles), which are bound to specific vascular surface receptors. Imaging methods that can sensitively and selectively detect and distinguish bound microbubbles from freely circulating microbubbles (free microbubbles) and surrounding tissue are critically important for the practical application of ultrasound contrast molecular imaging. Microbubbles excited by low frequency acoustic pulses emit wide-band echoes with a bandwidth extending beyond 20 MHz; we refer to this technique as TLRH (transmission at a low frequency and reception at a high frequency). Using this wideband, transient echo, we have developed and implemented a targeted imaging technique incorporating a multi-frequency co-linear array and the Siemens Antares® imaging system. The multi-frequency co-linear array integrates a center 5.4 MHz array, used to receive echoes and produce radiation force, and two outer 1.5 MHz arrays used to transmit low frequency incident pulses. The targeted imaging technique makes use of an acoustic radiation force sub-sequence to enhance accumulation and a TLRH imaging sub-sequence to detect bound microbubbles. The radiofrequency (RF) data obtained from the TLRH imaging sub-sequence are processsed to separate echo signatures between tissue, free microbubbles, and bound microbubbles. By imaging biotin-coated microbubbles targeted to avidin-coated cellulose tubes, we demonstrate that the proposed method has a high contrast-to-tissue ratio (up to 34 dB) and a high sensitivity to bound microbubbles (with the ratio of echoes from bound microbubbles versus free microbubbles extending up to 23 dB). The effects of the imaging pulse acoustic pressure, the radiation force sub-sequence and the use of various slow-time filters on the targeted imaging quality are studied. The TLRH targeted imaging method is demonstrated in this study to provide sensitive and selective detection of bound microbubbles for ultrasound molecularly-targeted imaging. PMID:20178897

Ultrasound-mediated vascular gene transfection by cavitation of endothelial-targeted cationic microbubbles.

PubMed

Xie, Aris; Belcik, Todd; Qi, Yue; Morgan, Terry K; Champaneri, Shivam A; Taylor, Sarah; Davidson, Brian P; Zhao, Yan; Klibanov, Alexander L; Kuliszewski, Michael A; Leong-Poi, Howard; Ammi, Azzdine; Lindner, Jonathan R

2012-12-01

Ultrasound-mediated gene delivery can be amplified by acoustic disruption of microbubble carriers that undergo cavitation. We hypothesized that endothelial targeting of microbubbles bearing cDNA is feasible and, through optimizing proximity to the vessel wall, increases the efficacy of gene transfection. Contrast ultrasound-mediated gene delivery is a promising approach for site-specific gene therapy, although there are concerns with the reproducibility of this technique and the safety when using high-power ultrasound. Cationic lipid-shelled decafluorobutane microbubbles bearing a targeting moiety were prepared and compared with nontargeted microbubbles. Microbubble targeting efficiency to endothelial adhesion molecules (P-selectin or intercellular adhesion molecule [ICAM]-1) was tested using in vitro flow chamber studies, intravital microscopy of tumor necrosis factor-alpha (TNF-α)-stimulated murine cremaster muscle, and targeted contrast ultrasound imaging of P-selectin in a model of murine limb ischemia. Ultrasound-mediated transfection of luciferase reporter plasmid charge coupled to microbubbles in the post-ischemic hindlimb muscle was assessed by in vivo optical imaging. Charge coupling of cDNA to the microbubble surface was not influenced by the presence of targeting ligand, and did not alter the cavitation properties of cationic microbubbles. In flow chamber studies, surface conjugation of cDNA did not affect attachment of targeted microbubbles at microvascular shear stresses (0.6 and 1.5 dyne/cm(2)). Attachment in vivo was also not affected by cDNA according to intravital microscopy observations of venular adhesion of ICAM-1-targeted microbubbles and by ultrasound molecular imaging of P-selectin-targeted microbubbles in the post-ischemic hindlimb in mice. Transfection at the site of high acoustic pressures (1.0 and 1.8 MPa) was similar for control and P-selectin-targeted microbubbles but was associated with vascular rupture and hemorrhage. At 0.6 MPa, there were no adverse bioeffects, and transfection was 5-fold greater with P-selectin-targeted microbubbles. We conclude that ultrasound-mediated transfection at safe acoustic pressures can be markedly augmented by endothelial juxtaposition. Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Ultrasound-Mediated Vascular Gene Transfection by Cavitation of Endothelial-Targeted Cationic Microbubbles

PubMed Central

Xie, Aris; Belcik, Todd; Qi, Yue; Morgan, Terry K.; Champaneri, Shivam A.; Taylor, Sarah; Davidson, Brian P.; Zhao, Yan; Klibanov, Alexander L.; Kuliszewski, Michael A.; Leong-Poi, Howard; Ammi, Azzdine; Lindner, Jonathan R.

2013-01-01

OBJECTIVES Ultrasound-mediated gene delivery can be amplified by acoustic disruption of microbubble carriers that undergo cavitation. We hypothesized that endothelial targeting of microbubbles bearing cDNA is feasible and, through optimizing proximity to the vessel wall, increases the efficacy of gene transfection. BACKGROUND Contrast ultrasound-mediated gene delivery is a promising approach for site-specific gene therapy, although there are concerns with the reproducibility of this technique and the safety when using high-power ultrasound. METHODS Cationic lipid-shelled decafluorobutane microbubbles bearing a targeting moiety were prepared and compared with nontargeted microbubbles. Microbubble targeting efficiency to endothelial adhesion molecules (P-selectin or intercellular adhesion molecule [ICAM]-1) was tested using in vitro flow chamber studies, intravital microscopy of tumor necrosis factor-alpha (TNF-α)–stimulated murine cremaster muscle, and targeted contrast ultrasound imaging of P-selectin in a model of murine limb ischemia. Ultrasound-mediated transfection of luciferase reporter plasmid charge coupled to microbubbles in the post-ischemic hindlimb muscle was assessed by in vivo optical imaging. RESULTS Charge coupling of cDNA to the microbubble surface was not influenced by the presence of targeting ligand, and did not alter the cavitation properties of cationic microbubbles. In flow chamber studies, surface conjugation of cDNA did not affect attachment of targeted microbubbles at microvascular shear stresses (0.6 and 1.5 dyne/cm2). Attachment in vivo was also not affected by cDNA according to intravital microscopy observations of venular adhesion of ICAM-1–targeted microbubbles and by ultrasound molecular imaging of P-selectin–targeted microbubbles in the post-ischemic hindlimb in mice. Transfection at the site of high acoustic pressures (1.0 and 1.8 MPa) was similar for control and P-selectin–targeted microbubbles but was associated with vascular rupture and hemorrhage. At 0.6 MPa, there were no adverse bioeffects, and transfection was 5-fold greater with P-selectin–targeted microbubbles. CONCLUSIONS We conclude that ultrasound-mediated transfection at safe acoustic pressures can be markedly augmented by endothelial juxtaposition. PMID:23236976

Sonoporation of endothelial cells by vibrating targeted microbubbles.

PubMed

Kooiman, Klazina; Foppen-Harteveld, Miranda; van der Steen, Antonius F W; de Jong, Nico

2011-08-25

Molecular imaging using ultrasound makes use of targeted microbubbles. In this study we investigated whether these microbubbles could also be used to induce sonoporation in endothelial cells. Lipid-coated microbubbles were targeted to CD31 and insonified at 1 MHz at low peak negative acoustic pressures at six sequences of 10 cycle sine-wave bursts. Vibration of the targeted microbubbles was recorded with the Brandaris-128 high-speed camera (~13 million frames per second). In total, 31 cells were studied that all had one microbubble (1.2-4.2 micron in diameter) attached per cell. After insonification at 80 kPa, 30% of the cells (n=6) had taken up propidium iodide, while this was 20% (n=1) at 120 kPa and 83% (n=5) at 200 kPa. Irrespective of the peak negative acoustic pressure, uptake of propidium iodide was observed when the relative vibration amplitude of targeted microbubbles was greater than 0.5. No relationship was found between the position of the microbubble on the cell and induction of sonoporation. This study shows that targeted microbubbles can also be used to induce sonoporation, thus making it possible to combine molecular imaging and drug delivery. Copyright © 2011 Elsevier B.V. All rights reserved.

Superharmonic microbubble Doppler effect in ultrasound therapy

NASA Astrophysics Data System (ADS)

Pouliopoulos, Antonios N.; Choi, James J.

2016-08-01

The introduction of microbubbles in focused ultrasound therapies has enabled a diverse range of non-invasive technologies: sonoporation to deliver drugs into cells, sonothrombolysis to dissolve blood clots, and blood-brain barrier opening to deliver drugs into the brain. Current methods for passively monitoring the microbubble dynamics responsible for these therapeutic effects can identify the cavitation position by passive acoustic mapping and cavitation mode by spectral analysis. Here, we introduce a new feature that can be monitored: microbubble effective velocity. Previous studies have shown that echoes from short imaging pulses had a Doppler shift that was produced by the movement of microbubbles. Therapeutic pulses are longer (>1 000 cycles) and thus produce a larger alteration of microbubble distribution due to primary and secondary acoustic radiation force effects which cannot be monitored using pulse-echo techniques. In our experiments, we captured and analyzed the Doppler shift during long therapeutic pulses using a passive cavitation detector. A population of microbubbles (5  ×  104-5  ×  107 microbubbles ml-1) was embedded in a vessel (inner diameter: 4 mm) and sonicated using a 0.5 MHz focused ultrasound transducer (peak-rarefactional pressure: 75-366 kPa, pulse length: 50 000 cycles or 100 ms) within a water tank. Microbubble acoustic emissions were captured with a coaxially aligned 7.5 MHz passive cavitation detector and spectrally analyzed to measure the Doppler shift for multiple harmonics above the 10th harmonic (i.e. superharmonics). A Doppler shift was observed on the order of tens of kHz with respect to the primary superharmonic peak and is due to the axial movement of the microbubbles. The position, amplitude and width of the Doppler peaks depended on the acoustic pressure and the microbubble concentration. Higher pressures increased the effective velocity of the microbubbles up to 3 m s-1, prior to the onset of broadband emissions, which is an indicator for high magnitude inertial cavitation. Although the microbubble redistribution was shown to persist for the entire sonication period in dense populations, it was constrained to the first few milliseconds in lower concentrations. In conclusion, superharmonic microbubble Doppler effects can provide a quantitative measure of effective velocities of a sonicated microbubble population and could be used for monitoring ultrasound therapy in real-time.

Superharmonic microbubble Doppler effect in ultrasound therapy

PubMed Central

Pouliopoulos, Antonios N; Choi, James J

2016-01-01

Abstract The introduction of microbubbles in focused ultrasound therapies has enabled a diverse range of non-invasive technologies: sonoporation to deliver drugs into cells, sonothrombolysis to dissolve blood clots, and blood-brain barrier opening to deliver drugs into the brain. Current methods for passively monitoring the microbubble dynamics responsible for these therapeutic effects can identify the cavitation position by passive acoustic mapping and cavitation mode by spectral analysis. Here, we introduce a new feature that can be monitored: microbubble effective velocity. Previous studies have shown that echoes from short imaging pulses had a Doppler shift that was produced by the movement of microbubbles. Therapeutic pulses are longer (>1 000 cycles) and thus produce a larger alteration of microbubble distribution due to primary and secondary acoustic radiation force effects which cannot be monitored using pulse-echo techniques. In our experiments, we captured and analyzed the Doppler shift during long therapeutic pulses using a passive cavitation detector. A population of microbubbles (5  ×  104–5  ×  107 microbubbles ml−1) was embedded in a vessel (inner diameter: 4 mm) and sonicated using a 0.5 MHz focused ultrasound transducer (peak-rarefactional pressure: 75–366 kPa, pulse length: 50 000 cycles or 100 ms) within a water tank. Microbubble acoustic emissions were captured with a coaxially aligned 7.5 MHz passive cavitation detector and spectrally analyzed to measure the Doppler shift for multiple harmonics above the 10th harmonic (i.e. superharmonics). A Doppler shift was observed on the order of tens of kHz with respect to the primary superharmonic peak and is due to the axial movement of the microbubbles. The position, amplitude and width of the Doppler peaks depended on the acoustic pressure and the microbubble concentration. Higher pressures increased the effective velocity of the microbubbles up to 3 m s−1, prior to the onset of broadband emissions, which is an indicator for high magnitude inertial cavitation. Although the microbubble redistribution was shown to persist for the entire sonication period in dense populations, it was constrained to the first few milliseconds in lower concentrations. In conclusion, superharmonic microbubble Doppler effects can provide a quantitative measure of effective velocities of a sonicated microbubble population and could be used for monitoring ultrasound therapy in real-time. PMID:27469394

Isolation and purification of diastereoisomeric flavonolignans from silymarin by binary-column recycling preparative high-performance liquid chromatography.

PubMed

Zhao, Weiquan; Yang, Guang; Zhong, Fanyi; Yang, Nan; Zhao, Xin; Qi, Yunpeng; Fan, Guorong

2014-09-01

Silymarin extracted from Silybum marianum (L.) Gaertn consists of a large number of flavonolignans, of which diastereoisomeric flavonolignans including silybin A and silybin B, and isosilybin A and isosilybin B are the main bioactive components, whose preparation from the crude extracts is still a difficult task. In this work, binary-column recycling preparative high-performance liquid chromatography systems without sample loop trapping, where two columns were switched alternately via one or two six-port switching valves, were established and successfully applied to the isolation and purification of the four diastereoisomeric flavonolignans from silymarin. The proposed system showed significant advantages over conventional preparative high-performance liquid chromatography with a single column in increasing efficiency and reducing the cost. To obtain the same amounts of products, the proposed system spends only one tenth of the time that the conventional system spends, and needs only one eleventh of the solvent that the conventional system consumes. Using the proposed system, the four diastereoisomers were successfully isolated from silymarin with purities over 98%. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The Effects of Pressure on Gases in Solution: Possible Insights to Improve Microbubble Filtration for Extracorporeal Circulation

PubMed Central

Herbst, Daniel P.

2013-01-01

Abstract: Improvements in micropore arterial line filter designs used for extracorporeal circulation are still needed because microbubbles larger than the rated pore sizes are being detected beyond the filter outlet. Linked to principles governing the function of micropore filters, fluid pressures contained in extracorporeal circuits also influence the behavior of gas bubbles and the extent to which they are carried in a fluid flow. To better understand the relationship between pressure and microbubble behavior, two ex vivo test circuits with and without inline resistance were designed to assess changes in microbubble load with changes in pressure. Ultrasound Doppler probes were used to measure and compare the quality and quantity of microbubbles generated in each test circuit. Analysis of microbubble load was separated into two distinct phases, the time periods during and immediately after bubble generation. Although microbubble number decreased similarly in both test circuits, changes in microbubble volume were significant only in the test circuit with inline resistance. The test circuit with inline resistance also showed a decrease in the rate of volume transferred across each ultrasound Doppler probe and the microbubble number and size range measured in the postbubble generation period. The present research proposes that fluid pressures contained in extracorporeal circuits may be used to affect gases in solution as a possible method to improve microbubble filtration during extracorporeal circulation. PMID:23930378

The effects of pressure on gases in solution: possible insights to improve microbubble filtration for extracorporeal circulation.

PubMed

Herbst, Daniel P

2013-06-01

Improvements in micropore arterial line filter designs used for extracorporeal circulation are still needed because microbubbles larger than the rated pore sizes are being detected beyond the filter outlet. Linked to principles governing the function of micropore filters, fluid pressures contained in extracorporeal circuits also influence the behavior of gas bubbles and the extent to which they are carried in a fluid flow. To better understand the relationship between pressure and microbubble behavior, two ex vivo test circuits with and without inline resistance were designed to assess changes in microbubble load with changes in pressure. Ultrasound Doppler probes were used to measure and compare the quality and quantity of microbubbles generated in each test circuit. Analysis of microbubble load was separated into two distinct phases, the time periods during and immediately after bubble generation. Although microbubble number decreased similarly in both test circuits, changes in microbubble volume were significant only in the test circuit with inline resistance. The test circuit with inline resistance also showed a decrease in the rate of volume transferred across each ultrasound Doppler probe and the microbubble number and size range measured in the postbubble generation period. The present research proposes that fluid pressures contained in extracorporeal circuits may be used to affect gases in solution as a possible method to improve microbubble filtration during extracorporeal circulation.

Phase contrast imaging of preclinical portal vein embolization with CO2 microbubbles.

PubMed

Tang, Rongbiao; Yan, Fuhua; Yang, Guo Yuan; Chen, Ke Min

2017-11-01

Preoperative portal vein embolization (PVE) is employed clinically to avoid postoperative liver insufficiency. Animal models are usually used to study PVE in terms of mechanisms and pathophysiological changes. PVE is formerly monitored by conventional absorption contrast imaging (ACI) with iodine contrast agent. However, the side effects induced by iodine can give rise to animal damage and death. In this study, the feasibility of using phase contrast imaging (PCI) to show PVE using homemade CO 2 microbubbles in living rats has been investigated. CO 2 gas was first formed from the reaction between citric acid and sodium bicarbonate. The CO 2 gas was then encapsulated by egg white to fabricate CO 2 microbubbles. ACI and PCI of CO 2 microbubbles were performed and compared in vitro. An additional increase in contrast was detected in PCI. PCI showed that CO 2 microbubbles gradually dissolved over time, and the remaining CO 2 microbubbles became larger. By PCI, the CO 2 microbubbles were found to have certain stability, suggesting their potential use as embolic agents. CO 2 microbubbles were injected into the main portal trunk to perform PVE in living rats. PCI exploited the differences in the refractive index and facilitated clear visualization of the PVE after the injection of CO 2 microbubbles. Findings from this study suggest that homemade CO 2 microbubbles-based PCI is a novel modality for preclinical PVE research.

Cardiac Gene Expression Knockdown Using Small Inhibitory RNA-Loaded Microbubbles and Ultrasound.

PubMed

Kopechek, Jonathan A; Carson, Andrew R; McTiernan, Charles F; Chen, Xucai; Klein, Edwin C; Villanueva, Flordeliza S

2016-01-01

RNA interference has potential therapeutic value for cardiac disease, but targeted delivery of interfering RNA is a challenge. Custom designed microbubbles, in conjunction with ultrasound, can deliver small inhibitory RNA to target tissues in vivo. The efficacy of cardiac RNA interference using a microbubble-ultrasound theranostic platform has not been demonstrated in vivo. Therefore, our objective was to test the hypothesis that custom designed microbubbles and ultrasound can mediate effective delivery of small inhibitory RNA to the heart. Microbubble and ultrasound mediated cardiac RNA interference was tested in transgenic mice displaying cardiac-restricted luciferase expression. Luciferase expression was assayed in select tissues of untreated mice (n = 14). Mice received intravenous infusion of cationic microbubbles bearing small inhibitory RNA directed against luciferase (n = 9) or control RNA (n = 8) during intermittent cardiac-directed ultrasound at mechanical index of 1.6. Simultaneous echocardiography in a separate group of mice (n = 3) confirmed microbubble destruction and replenishment during treatment. Three days post treatment, cardiac luciferase messenger RNA and protein levels were significantly lower in ultrasound-treated mice receiving microbubbles loaded with small inhibitory RNA directed against luciferase compared to mice receiving microbubbles bearing control RNA (23±7% and 33±7% of control mice, p<0.01 and p = 0.03, respectively). Passive cavitation detection focused on the heart confirmed that insonification resulted in inertial cavitation. In conclusion, small inhibitory RNA-loaded microbubbles and ultrasound directed at the heart significantly reduced the expression of a reporter gene. Ultrasound-targeted destruction of RNA-loaded microbubbles may be an effective image-guided strategy for therapeutic RNA interference in cardiac disease.

CO2 microbubble contrast enhancement in x-ray angiography.

PubMed

Kariya, S; Komemushi, A; Nakatani, M; Yoshida, R; Sawada, S; Tanigawa, N

2013-04-01

To demonstrate that carbon dioxide (CO2) microbubble contrast enhancement depicts blood vessels when used for x-ray examinations. Microbubbles were generated by cavitation of physiological saline to which CO2 gas had been added using an ejector-type microbubble generator. The input pressure values for CO2 gas and physiological saline that produced a large quantity of CO2 microbubbles were obtained in a phantom. In an animal study, angiography was performed in three swine using three types of contrast: CO2 microbubbles, conventional CO2 gas, and iodinated contrast medium. For CO2 microbubble contrast enhancement, physiological saline, and CO2 gas were supplied at the input pressures calculated in the phantom experiment. Regions of interest were set in the abdominal aorta, external iliac arteries, and background. The difference in digital values between each artery and the background was calculated. The input pressures obtained in the phantom experiment were 0.16 MPa for physiological saline and 0.5 MPa for CO2 gas, with physiological saline input volume being 8.1 ml/s. Three interventional radiologists all evaluated the depictions of all arteries as "present" in the CO2 microbubble contrast enhancement, conventional CO2 contrast enhancement, and iodinated contrast enhancement performed in three swine. Digital values for all vessels with microbubble CO2 contrast enhancement were higher than background values. In x-ray angiography, blood vessels can be depicted by CO2 microbubble contrast enhancement, in which a large quantity of CO2 microbubbles is generated within blood vessels. Copyright © 2012 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Polyplex-microbubble hybrids for ultrasound-guided plasmid DNA delivery to solid tumors.

PubMed

Sirsi, Shashank R; Hernandez, Sonia L; Zielinski, Lukasz; Blomback, Henning; Koubaa, Adel; Synder, Milo; Homma, Shunichi; Kandel, Jessica J; Yamashiro, Darrell J; Borden, Mark A

2012-01-30

Microbubble ultrasound contrast agents are being developed as image-guided gene carriers for targeted delivery in vivo. In this study, novel polyplex-microbubbles were synthesized, characterized and evaluated for systemic circulation and tumor transfection. Branched polyethylenimine (PEI; 25 kDa) was modified with polyethylene glycol (PEG; 5 kDa), thiolated and covalently attached to maleimide groups on lipid-coated microbubbles. The PEI-microbubbles demonstrated increasingly positive surface charge and DNA loading capacity with increasing maleimide content. The in vivo ultrasound contrast persistence of PEI-microbubbles was measured in the healthy mouse kidney, and a two-compartment pharmacokinetic model accounting for free and adherent microbubbles was developed to describe the anomalous time-intensity curves. The model suggested that PEI loading dramatically reduced free circulation and increased nonspecific adhesion to the vasculature. However, DNA loading to form polyplex-microbubbles increased circulation in the bloodstream and decreased nonspecific adhesion. PEI-microbubbles coupled to a luciferase bioluminescence reporter plasmid DNA were shown to transfect tumors implanted in the mouse kidney. Site-specific delivery was achieved using ultrasound applied over the tumor area following bolus injection of the DNA/PEI-microbubbles. In vivo imaging showed over 10-fold higher bioluminescence from the tumor region compared to untreated tissue. Ex vivo analysis of excised tumors showed greater than 40-fold higher expression in tumor tissue than non-sonicated control (heart) tissue. These results suggest that the polyplex-microbubble platform offers improved control of DNA loading and packaging suitable for ultrasound-guided tissue transfection. Copyright © 2011 Elsevier B.V. All rights reserved.

Molecular imaging with targeted contrast ultrasound.

PubMed

Piedra, Mark; Allroggen, Achim; Lindner, Jonathan R

2009-01-01

Molecular imaging with contrast-enhanced ultrasound uses targeted microbubbles that are retained in diseased tissue. The resonant properties of these microbubbles produce acoustic signals in an ultrasound field. The microbubbles are targeted to diseased tissue by using certain chemical constituents in the microbubble shell or by attaching disease-specific ligands such as antibodies to the microbubble. In this review, we discuss the applications of this technique to pathological states in the cerebrovascular system including atherosclerosis, tumor angiogenesis, ischemia, intravascular thrombus, and inflammation. Copyright 2009 S. Karger AG, Basel.

Spark channel propagation in a microbubble liquid

DOE Office of Scientific and Technical Information (OSTI.GOV)

Panov, V. A.; Vasilyak, L. M., E-mail: vasilyak@ihed.ras.ru; Vetchinin, S. P.

Experimental study on the development of the spark channel from the anode needle under pulsed electrical breakdown of isopropyl alcohol solution in water with air microbubbles has been performed. The presence of the microbubbles increases the velocity of the spark channel propagation and increases the current in the discharge gap circuit. The observed rate of spark channel propagation in microbubble liquid ranges from 4 to 12 m/s, indicating the thermal mechanism of the spark channel development in a microbubble liquid.

Microbubble Compositions, Properties and Biomedical Applications

PubMed Central

Sirsi, Shashank

2010-01-01

Over the last decade, there has been significant progress towards the development of microbubbles as theranostics for a wide variety of biomedical applications. The unique ability of microbubbles to respond to ultrasound makes them useful agents for contrast ultrasound imaging, molecular imaging, and targeted drug and gene delivery. The general composition of a microbubble is a gas core stabilized by a shell comprised of proteins, lipids or polymers. Each type of microbubble has its own unique advantages and can be tailored for specialized functions. In this review, different microbubbles compositions and physiochemical properties are discussed in the context of current progress towards developing novel constructs for biomedical applications, with specific emphasis on molecular imaging and targeted drug/gene delivery. PMID:20574549

Mapping microbubble viscosity using fluorescence lifetime imaging of molecular rotors

PubMed Central

Hosny, Neveen A.; Mohamedi, Graciela; Rademeyer, Paul; Owen, Joshua; Wu, Yilei; Tang, Meng-Xing; Eckersley, Robert J.; Stride, Eleanor; Kuimova, Marina K.

2013-01-01

Encapsulated microbubbles are well established as highly effective contrast agents for ultrasound imaging. There remain, however, some significant challenges to fully realize the potential of microbubbles in advanced applications such as perfusion mapping, targeted drug delivery, and gene therapy. A key requirement is accurate characterization of the viscoelastic surface properties of the microbubbles, but methods for independent, nondestructive quantification and mapping of these properties are currently lacking. We present here a strategy for performing these measurements that uses a small fluorophore termed a “molecular rotor” embedded in the microbubble surface, whose fluorescence lifetime is directly related to the viscosity of its surroundings. We apply fluorescence lifetime imaging to show that shell viscosities vary widely across the population of the microbubbles and are influenced by the shell composition and the manufacturing process. We also demonstrate that heterogeneous viscosity distributions exist within individual microbubble shells even with a single surfactant component. PMID:23690599

Microbubbles in Ultrasound-Triggered Drug and Gene Delivery

PubMed Central

Hernot, Sophie; Klibanov, Alexander L.

2008-01-01

Ultrasound contrast agents, in the form of gas-filled microbubbles, are becoming popular in perfusion monitoring; they are employed as molecular imaging agents. Microbubbles are manufactured from biocompatible materials, they can be injected intravenously, and some are approved for clinical use. Microbubbles can be destroyed by ultrasound irradiation. This destruction phenomenon can be applied to targeted drug delivery and enhancement of drug action. The ultrasonic field can be focused at the target tissues and organs; thus, selectivity of the treatment can be improved, reducing undesirable side effects. Microbubbles enhance ultrasound energy deposition in the tissues and serve as cavitation nuclei, increasing intracellular drug delivery. DNA delivery and successful tissue transfection is observed in the areas of the body where ultrasound is applied after intravascular administration of microbubbles and plasmid DNA. Accelerated blood clot dissolution in the areas of insonation by cooperative action of thrombolytic agents and microbubbles is demonstrated in several clinical trials. PMID:18486268

Sonochemotherapy: from bench to bedside

PubMed Central

Lammertink, Bart H. A.; Bos, Clemens; Deckers, Roel; Storm, Gert; Moonen, Chrit T. W.; Escoffre, Jean-Michel

2015-01-01

The combination of microbubbles and ultrasound has emerged as a promising method for local drug delivery. Microbubbles can be locally activated by a targeted ultrasound beam, which can result in several bio-effects. For drug delivery, microbubble-assisted ultrasound is used to increase vascular- and plasma membrane permeability for facilitating drug extravasation and the cellular uptake of drugs in the treated region, respectively. In the case of drug-loaded microbubbles, these two mechanisms can be combined with local release of the drug following destruction of the microbubble. The use of microbubble-assisted ultrasound to deliver chemotherapeutic agents is also referred to as sonochemotherapy. In this review, the basic principles of sonochemotherapy are discussed, including aspects such as the type of (drug-loaded) microbubbles used, the routes of administration used in vivo, ultrasound devices and parameters, treatment schedules and safety issues. Finally, the clinical translation of sonochemotherapy is discussed, including the first clinical study using sonochemotherapy. PMID:26217226

Acoustic cavitation of individual ultrasound contrast agent microbubbles confined in capillaries

NASA Astrophysics Data System (ADS)

Almaqwashi, Ali; McIntyre, David; Ammi, Azzdine

2011-10-01

Ultrasound targeted therapies mainly rely on the inertial cavitation of ultrasound contrast agent (UCA) microbubbles. Our objective is to determine the cavitation acoustic pressure threshold for the destruction of UCA microbubbles inside cellulose capillaries. Acoustic emission from individual Optison microbubbles confined inside a 200-μm diameter capillary was detected using a passive cavitation detection system. Excitation signals from a 2.25 MHz transmitter were applied to the microbubbles while their acoustic emission was detected by a broadband 15 MHz receiver. Time traces were recorded (100 MHz sampling, 12- bit), and frequency-domain analysis of the received signals was performed to characterize microbubble cavitation. The cavitation acoustic pressure threshold was found to be 1 MPa inside the capillary in comparison with ˜0.7 MPa previously reported for unconfined UCA microbubbles. This work provides a clearer understanding of the role of ultrasound contrast agent dynamics inside a capillary.

Microbubble Sizing and Shell Characterization Using Flow Cytometry

PubMed Central

Tu, Juan; Swalwell, Jarred E.; Giraud, David; Cui, Weicheng; Chen, Weizhong; Matula, Thomas J.

2015-01-01

Experiments were performed to size, count, and obtain shell parameters for individual ultrasound contrast microbubbles using a modified flow cytometer. Light scattering was modeled using Mie theory, and applied to calibration beads to calibrate the system. The size distribution and population were measured directly from the flow cytometer. The shell parameters (shear modulus and shear viscosity) were quantified at different acoustic pressures (from 95 to 333 kPa) by fitting microbubble response data to a bubble dynamics model. The size distribution of the contrast agent microbubbles is consistent with manufacturer specifications. The shell shear viscosity increases with increasing equilibrium microbubble size, and decreases with increasing shear rate. The observed trends are independent of driving pressure amplitude. The shell elasticity does not vary with microbubble size. The results suggest that a modified flow cytometer can be an effective tool to characterize the physical properties of microbubbles, including size distribution, population, and shell parameters. PMID:21622051

Acoustic monitoring method and system in laser-induced optical breakdown (LIOB)

DOEpatents

O'Donnell, Matthew [Ann Arbor, MI; Ye, Jing Yong [Ann Arbor, MI; Norris, Theodore B [Dexter, MI; Baker, Jr., James R.; Balogh, Lajos P [Ann Arbor, MI; Milas, Susanne M [Ann Arbor, MI; Emelianov, Stanislav Y [Ann Arbor, MI; Hollman, Kyle W [Fenton, MI

2008-05-06

An acoustic monitoring method and system in laser-induced optical breakdown (LIOB) provides information which characterize material which is broken down, microbubbles in the material, and/or the microenvironment of the microbubbles. In one embodiment of the invention, femtosecond laser pulses are focused just inside the surface of a volume of aqueous solution which may include dendrimer nanocomposite (DNC) particles. A tightly focused, high frequency, single-element ultrasonic transducer is positioned such that its focus coincides axially and laterally with this laser focus. When optical breakdown occurs, a microbubble forms and a shock or pressure wave is emitted (i.e., acoustic emission). In addition to this acoustic signal, the microbubble may be actively probed with pulse-echo measurements from the same transducer. After the microbubble forms, received pulse-echo signals have an extra pulse, describing the microbubble location and providing a measure of axial microbubble size. Wavefield plots of successive recordings illustrate the generation, growth, and collapse of microbubbles due to optical breakdown. These same plots can also be used to quantify LIOB thresholds.

The hydrodynamic and ultrasound-induced forces on microbubbles under high Reynolds number flow representative of the human systemic circulation

NASA Astrophysics Data System (ADS)

Clark, Alicia; Aliseda, Alberto

2016-11-01

Ultrasound contrast agents (UCAs) are micron-sized bubbles that are used in conjunction with ultrasound (US) in medical applications such as thrombolysis and targeted intravenous drug delivery. Previous work has shown that the Bjerknes force, due to the phase difference between the incoming US pressure wave and the bubble volume oscillations, can be used to manipulate the trajectories of microbubbles. Our work explores the behavior of microbubbles in medium sized blood vessels under both uniform and pulsatile flows at a range of physiologically relevant Reynolds and Womersley numbers. High speed images were taken of the microbubbles in an in-vitro flow loop that replicates physiological flow conditions. During the imaging, the microbubbles were insonified at different diagnostic ultrasound settings (varying center frequency, PRF, etc.). An in-house Lagrangian particle tracking code was then used to determine the trajectories of the microbubbles and, thus, a dynamic model for the microbubbles including the Bjerknes forces acting on them, as well as drag, lift, and added mass. Preliminary work has also explored the behavior of the microbubbles in a patient-specific model of a carotid artery bifurcation to demonstrate the feasibility of preferential steering of microbubbles towards the intracranial circulation with US.

Comparing the enhancement efficiency between liposomes and microbubbles for insulin pulmonary absorption.

PubMed

Xu, Yan-Yan; Lu, Cui-Tao; Fu, Hong-Xing; Zhao, Ying-Zheng; Yang, Wei; Li, Xing; Zhang, Lu; Li, Xiao-Kun; Zhang, Ming

2011-07-01

The present study investigated the enhancement efficiency between liposomes and microbubbles for insulin pulmonary absorption. Two types of phospholipid-based vesicle-liposomes and microbubbles-were prepared, and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) cytotoxicity test was used to evaluate their in vitro toxicity in A549 cells. Cellular uptake of insulin combined with liposomes or microbubbles was determined using A549 cells. With intratracheal insufflation of Sprague-Dawley rats, an insulin mixture with liposomes or microbubbles was administered to assess its potential for promoting drug pulmonary absorption. Both liposomes and microbubbles had a narrow and monodispersed size distribution with average diameter of 3.1 μm and 1.0 μm, respectively. From the MTT cytotoxicity test, a phospholipid-based vesicle concentration of <25% (vol/vol) in the final volume was the safe dosage range that could avoid severe cytotoxic effects. The intracellular uptake amount of insulin in the insulin-microbubble mixture was significantly higher than that in the insulin-liposome mixture. The minimum reductions of the blood glucose concentration produced by insulin-microbubble and insulin-liposome mixtures were 60.8% and 35.0% of the initial glucose levels, respectively, and their bioavailabilities relative to subcutaneous injection were 48.6% and 30.8%, respectively. Microbubbles have much better efficiency than liposomes in the rate and extent of insulin pulmonary absorption. Microbubbles might be recommended as a potential agent for enhancing protein intrapulmonary absorption.

Association schemes perspective of microbubble cluster in ultrasonic fields.

PubMed

Behnia, S; Yahyavi, M; Habibpourbisafar, R

2018-06-01

Dynamics of a cluster of chaotic oscillators on a network are studied using coupled maps. By introducing the association schemes, we obtain coupling strength in the adjacency matrices form, which satisfies Markov matrices property. We remark that in general, the stability region of the cluster of oscillators at the synchronization state is characterized by Lyapunov exponent which can be defined based on the N-coupled map. As a detailed physical example, dynamics of microbubble cluster in an ultrasonic field are studied using coupled maps. Microbubble cluster dynamics have an indicative highly active nonlinear phenomenon, were not easy to be explained. In this paper, a cluster of microbubbles with a thin elastic shell based on the modified Keller-Herring equation in an ultrasonic field is demonstrated in the framework of the globally coupled map. On the other hand, a relation between the microbubble elements is replaced by a relation between the vertices. Based on this method, the stability region of microbubbles pulsations at complete synchronization state has been obtained analytically. In this way, distances between microbubbles as coupling strength play the crucial role. In the stability region, we thus observe that the problem of study of dynamics of N-microbubble oscillators reduce to that of a single microbubble. Therefore, the important parameters of the isolated microbubble such as applied pressure, driving frequency and the initial radius have effective behavior on the synchronization state. Copyright © 2018 Elsevier B.V. All rights reserved.

Cardiac Gene Expression Knockdown Using Small Inhibitory RNA-Loaded Microbubbles and Ultrasound

PubMed Central

McTiernan, Charles F.; Chen, Xucai; Klein, Edwin C.; Villanueva, Flordeliza S.

2016-01-01

RNA interference has potential therapeutic value for cardiac disease, but targeted delivery of interfering RNA is a challenge. Custom designed microbubbles, in conjunction with ultrasound, can deliver small inhibitory RNA to target tissues in vivo. The efficacy of cardiac RNA interference using a microbubble-ultrasound theranostic platform has not been demonstrated in vivo. Therefore, our objective was to test the hypothesis that custom designed microbubbles and ultrasound can mediate effective delivery of small inhibitory RNA to the heart. Microbubble and ultrasound mediated cardiac RNA interference was tested in transgenic mice displaying cardiac-restricted luciferase expression. Luciferase expression was assayed in select tissues of untreated mice (n = 14). Mice received intravenous infusion of cationic microbubbles bearing small inhibitory RNA directed against luciferase (n = 9) or control RNA (n = 8) during intermittent cardiac-directed ultrasound at mechanical index of 1.6. Simultaneous echocardiography in a separate group of mice (n = 3) confirmed microbubble destruction and replenishment during treatment. Three days post treatment, cardiac luciferase messenger RNA and protein levels were significantly lower in ultrasound-treated mice receiving microbubbles loaded with small inhibitory RNA directed against luciferase compared to mice receiving microbubbles bearing control RNA (23±7% and 33±7% of control mice, p<0.01 and p = 0.03, respectively). Passive cavitation detection focused on the heart confirmed that insonification resulted in inertial cavitation. In conclusion, small inhibitory RNA-loaded microbubbles and ultrasound directed at the heart significantly reduced the expression of a reporter gene. Ultrasound-targeted destruction of RNA-loaded microbubbles may be an effective image-guided strategy for therapeutic RNA interference in cardiac disease. PMID:27471848

Theranostic Gd(III)-lipid microbubbles for MRI-guided focused ultrasound surgery.

PubMed

Feshitan, Jameel A; Vlachos, Fotis; Sirsi, Shashank R; Konofagou, Elisa E; Borden, Mark A

2012-01-01

We have synthesized a biomaterial consisting of Gd(III) ions chelated to lipid-coated, size-selected microbubbles for utility in both magnetic resonance and ultrasound imaging. The macrocyclic ligand DOTA-NHS was bound to PE headgroups on the lipid shell of pre-synthesized microbubbles. Gd(III) was then chelated to DOTA on the microbubble shell. The reaction temperature was optimized to increase the rate of Gd(III) chelation while maintaining microbubble stability. ICP-OES analysis of the microbubbles determined a surface density of 7.5 × 10(5) ± 3.0 × 10(5) Gd(III)/μm(2) after chelation at 50 °C. The Gd(III)-bound microbubbles were found to be echogenic in vivo during high-frequency ultrasound imaging of the mouse kidney. The Gd(III)-bound microbubbles also were characterized by magnetic resonance imaging (MRI) at 9.4 T by a spin-echo technique and, surprisingly, both the longitudinal and transverse proton relaxation rates were found to be roughly equal to that of no-Gd(III) control microbubbles and saline. However, the relaxation rates increased significantly, and in a dose-dependent manner, after sonication was used to fragment the Gd(III)-bound microbubbles into non-gas-containing lipid bilayer remnants. The longitudinal (r(1)) and transverse (r(2)) molar relaxivities were 4.0 ± 0.4 and 120 ± 18 mM(-1)s(-1), respectively, based on Gd(III) content. The Gd(III)-bound microbubbles may find application in the measurement of cavitation events during MRI-guided focused ultrasound therapy and to track the biodistribution of shell remnants. Copyright © 2011 Elsevier Ltd. All rights reserved.

Magnetic resonance properties of Gd(III)-bound lipid-coated microbubbles and their cavitation fragments.

PubMed

Feshitan, Jameel A; Boss, Michael A; Borden, Mark A

2012-10-30

Gas-filled microbubbles are potentially useful theranostic agents for magnetic resonance imaging-guided focused ultrasound surgery (MRIgFUS). Previously, MRI at 9.4 T was used to measure the contrast properties of lipid-coated microbubbles with gadolinium (Gd(III)) bound to lipid headgroups, which revealed that the longitudinal molar relaxivity (r(1)) increased after microbubble fragmentation. This behavior was attributed to an increase in water proton exchange with the Gd(III)-bound lipid fragments caused by an increase in the lipid headgroup area that accompanied the lipid shell monolayer-to-bilayer transition. In this article, we explore this mechanism by comparing the changes in r(1) and its transverse counterpart, r(2)*, after the fragmentation of microbubbles consisting of Gd(III) bound to two different locations on the lipid monolayer shell: the phosphatidylethanolamine (PE) lipid headgroup region or the distal region of the poly(ethylene glycol) (PEG) brush. Nuclear magnetic resonance (NMR) at 1.5 T was used to measure the contrast properties of the various microbubble constructs because this is the most common field strength used in clinical MRI. Results for the lipid-headgroup-labeled Gd(III) microbubbles revealed that r(1) increased after microbubble fragmentation, whereas r(2)* was unchanged. An analysis of PEG-labeled Gd(III) microbubbles revealed that both r(1) and r(2)* decreased after microbubble fragmentation. Further analysis revealed that the microbubble gas core enhanced the transverse MR signal (T(2)*) in a concentration-dependent manner but minimally affected the longitudinal (T(1)) signal. These results illustrate a new method for the use of NMR to measure the biomembrane packing structure and suggest that two mechanisms, proton-exchange enhancement by lipid membrane relaxation and magnetic field inhomogeneity imposed by the gas/liquid interface, may be used to detect and differentiate Gd(III)-labeled microbubbles and their cavitation fragments with MRI.

Nanoparticle Delivery Enhancement With Acoustically Activated Microbubbles

PubMed Central

Mullin, Lee B; Phillips, Linsey C; Dayton, Paul A

2013-01-01

The application of microbubbles and ultrasound to deliver nanoparticle carriers for drug and gene delivery is an area that has expanded greatly in recent years. Under ultrasound exposure, microbubbles can enhance nanoparticle delivery by increasing cellular and vascular permeability. In this review, the underlying mechanisms of enhanced nanoparticle delivery with ultrasound and microbubbles and various proposed delivery techniques are discussed. Additionally, types of nanoparticles currently being investigated in preclinical studies, as well as the general limitations and benefits of a microbubble-based approach to nanoparticle delivery are reviewed. PMID:23287914

Fabrication and characterization of an egg-shaped hollow fiber microbubble

NASA Astrophysics Data System (ADS)

Wang, Guanjun; Ruan, Yinlan; Jia, Pinggang; Gui, Zhiguo; Zhang, Pengcheng; Wang, Chao; Liu, Shen; Liao, Changrui; Yin, Guolu; Wang, Yiping

2017-04-01

In this paper, an egg-shaped microbubble is proposed and analyzed firstly, which is fabricated by the pressure-assisted arc discharge technique. By tailoring the arc parameters and the position of glass tube during the fabrication process, the thinnest wall of the fabricated microbubble could reach to the level of 873nm. Then, the fiber Fabry-Perot interference technique is used to analyze the deformation of microbubble that under different filling pressures. It is found that the endface of micro-bubble occurs compression when the inner pressure increasing from 4Kpa to 1400KPa. And the pressure sensitivity of such egg-shaped microbubble sample is14.3pm/Kpa. Results of this study could be good reference for developing new pressure sensors, etc.

Harmonic responses and cavitation activity of encapsulated microbubbles coupled with magnetic nanoparticles.

PubMed

Gu, Yuyang; Chen, Chuyi; Tu, Juan; Guo, Xiasheng; Wu, Hongyi; Zhang, Dong

2016-03-01

Encapsulated microbubbles coupled with magnetic nanoparticles, one kind of hybrid agents that can integrate both ultrasound and magnetic resonance imaging/therapy functions, have attracted increasing interests in both research and clinic communities. However, there is a lack of comprehensive understanding of their dynamic behaviors generated in diagnostic and therapeutic applications. In the present work, a hybrid agent was synthesized by integrating superparamagnetic iron oxide nanoparticles (SPIOs) into albumin-shelled microbubbles (named as SPIO-albumin microbubbles). Then, both the stable and inertial cavitation thresholds of this hybrid agent were measured at varied SPIO concentrations and ultrasound parameters (e.g., frequency, pressure amplitude, and pulse length). The results show that, at a fixed acoustic driving frequency, both the stable and inertial cavitation thresholds of SPIO-albumin microbubble should decrease with the increasing SPIO concentration and acoustic driving pulse length. The inertial cavitation threshold of SPIO-albumin microbubbles also decreases with the raised driving frequency, while the minimum sub- and ultra-harmonic thresholds appear at twice and two thirds resonance frequency, respectively. It is also noticed that both the stable and inertial cavitation thresholds of SonoVue microbubbles are similar to those measured for hybrid microbubbles with a SPIO concentration of 114.7 μg/ml. The current work could provide better understanding on the impact of the integrated SPIOs on the dynamic responses (especially the cavitation activities) of hybrid microbubbles, and suggest the shell composition of hybrid agents should be appropriately designed to improve their clinical diagnostic and therapeutic performances of hybrid microbubble agents. Copyright © 2015 Elsevier B.V. All rights reserved.

New insights into mechanisms of sonothrombolysis using ultra-high-speed imaging.

PubMed

Chen, Xucai; Leeman, Jonathan E; Wang, Jianjun; Pacella, John J; Villanueva, Flordeliza S

2014-01-01

Thrombotic arterial occlusion is the principal etiology for acute cardiovascular syndromes such as stroke, myocardial infarction and unstable angina. Exposing the thrombus to ultrasound and microbubbles facilitates thrombus disruption, making "sonothrombolysis" a potentially powerful therapeutic strategy for thromboembolic diseases. However, optimization of such a strategy, and hence clinical translation, is constrained by an incomplete understanding of mechanisms by which ultrasound-induced microbubble vibrations disrupt blood clots. We posit that previously reported sonothrombolytic efficacy using inertial cavitation regimes was due, at least in part, to mechanical clot disruption by oscillating microbubbles. To test this hypothesis, we optically characterized lipid microbubble interactions with thrombus in the presence of ultrasound using a recently developed ultra-high-speed microscopy imaging system to visualize microbubble acoustic behaviors at megahertz frame rates. A microscope/acoustic stage designed for the system allowed an experimentally created thrombus and microbubbles to be insonified at a co-localized acoustic and optical focus during synchronized high-speed imaging. Under inertial cavitation conditions, large-amplitude microbubble oscillations caused thrombus deformation and pitting. Acoustic radiation forces (Bjerknes forces) further augmented microbubble-thrombus interaction. These observations suggest that a direct mechanical effect of oscillating lipid microbubbles on an adjacent thrombus may play a role in mediating clot disruption in the presence of specific ultrasound conditions. Copyright © 2014 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Method of evaporation

NASA Technical Reports Server (NTRS)

Dufresne, Eugene R.

1987-01-01

Liquids, such as juices, milk, molten metal and the like are concentrated by forming uniformly-sized, small droplets in a precision droplet forming assembly and deploying the droplets in free fall downwardly as a central column within an evacuated column with cool walls. A portion of the solvent evaporates. The vapor flows to the wall, condenses, and usually flows down the wall as a film to condensate collector and drain. The vertical column of freely falling droplets enters the splash guard. The condensate can be collected, sent to other towers or recycled.

Current Status and Prospects for Microbubbles in Ultrasound Theranostics

PubMed Central

Martin, K. Heath

2013-01-01

Encapsulated microbubbles have been developed over the past two decades to provide both improvements in imaging as well as new therapeutic applications. Microbubble contrast agents are used currently for clinical imaging where increased sensitivity to blood flow is required, such as echocardiography. These compressible spheres oscillate in an acoustic field, producing nonlinear responses which can be uniquely distinguished from surrounding tissue, resulting in substantial enhancements in imaging signal-to-noise ratio. Furthermore, with sufficient acoustic energy the oscillation of microbubbles can mediate localized biological effects in tissue including the enhancement of membrane permeability or increased thermal energy deposition. Structurally, microbubbles are comprised of two principal components – an encapsulating shell and an inner gas core. This configuration enables microbubbles to be loaded with drugs or genes for additional therapeutic effect. Application of sufficient ultrasound energy can release this payload, resulting in site-specific delivery. Extensive pre-clinical studies illustrate that combining microbubbles and ultrasound can result in enhanced drug delivery or gene expression at spatially selective sites. Thus, microbbubles can be used for imaging, for therapy, or for both simultaneously. In this sense, microbubbles combined with acoustics may be one of the most universal theranostic tools. PMID:23504911

Acoustical properties of individual liposome-loaded microbubbles.

PubMed

Luan, Ying; Faez, Telli; Gelderblom, Erik; Skachkov, Ilya; Geers, Bart; Lentacker, Ine; van der Steen, Ton; Versluis, Michel; de Jong, Nico

2012-12-01

A comparison between phospholipid-coated microbubbles with and without liposomes attached to the microbubble surface was performed using the ultra-high-speed imaging camera (Brandaris 128). We investigated 73 liposome-loaded microbubbles (loaded microbubbles) and 41 microbubbles without liposome loading (unloaded microbubbles) with a diameter ranging from 3-10 μm at frequencies ranging from 0.6-3.8 MHz and acoustic pressures ranging from 5-100 kPa. The experimental data showed nearly the same shell elasticity for the loaded and unloaded bubbles, but the shell viscosity was higher for loaded bubbles compared with unloaded bubbles. For loaded bubbles, a higher pressure threshold for the bubble vibrations was noticed. In addition, an "expansion-only" behavior was observed for up to 69% of the investigated loaded bubbles, which mostly occurred at low acoustic pressures (≤30 kPa). Finally, fluorescence imaging showed heterogeneity of liposome distributions of the loaded bubbles. Copyright © 2012 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

``Recycling'' Geophysics: Monitoring and Isotopic Analysis of Engineered Biological Systems

NASA Astrophysics Data System (ADS)

Doherty, R.; Singh, K. P.; Ogle, N.; Ntarlagiannis, D.

2010-12-01

The emerging sub discipline of biogeophysics has provoked debate on the mechanisms of microbial processes that may contribute to geophysical signatures. At field scales geophysical signatures are often non unique due to the many parameters (physical, chemical, and biological) that are involved. It may be easier to apply geophysical techniques such as electrodic potential (EP), self potential (SP) and induced polarization (IP) to engineered biological systems where there is a degree of control over the design of the physical and chemical domain. Here we present results of a column experiment that was designed to anaerobically biodegrade dissolved organic matter in landfill leachate. The column utilises a recycled porous media (concrete) to help sequester organic carbon. Electrodic potential, self potential and induced polarisation are used in conjunction with chemical and isotopic techniques to monitor the effectiveness of this approach. Preliminary carbon and oxygen isotopic analysis on concrete from the column in contact with leachate show isotopic enrichment suggesting abiotic precipitation of carbonates.

Ultrasonic destruction of albumin microbubbles enhances gene transfection and expression in cardiac myocytes.

PubMed

Wang, Guo-zhong; Liu, Jing-hua; Lü, Shu-zheng; Lü, Yun; Guo, Cheng-jun; Zhao, Dong-hui; Fang, Dong-ping; He, Dong-fang; Zhou, Yuan; Ge, Chang-jiang

2011-05-01

It has been proven that ultrasonic destruction of microbubbles can enhance gene transfection efficiency into the noncardiac cells, but there are few reports about cardiac myocytes. Moreover, the exact mechanisms are not yet clear; whether the characteristic of microbubbles can affect the gene transfection efficiency or not is still controversial. This study was designed to investigate whether the ultrasound destruction of gene-loaded microbubbles could enhance the plasmids carried reporter gene transfection in primary cultured myocardial cell, and evaluate the effects of microbubbles characteristics on the transgene expression in cardiac myocytes. The β-galactosidase plasmids attached to the two types of microbubbles, air-contained sonicated dextrose albumin (ASDA) and perfluoropropane-exposed sonicated dextrose albumin (PESDA) were prepared. The gene transfection into cardiac myocytes was performed in vitro by naked plasmids, ultrasound exposure, ultrasonic destruction of gene-loaded microbubbles and calcium phosphate precipitation, and then the gene expression and cell viability were analyzed. The ultrasonic destruction of gene-loaded microbubbles enhanced gene expression in cardiac myocytes compared with naked plasmid transfection ((51.95 ± 2.41) U/g or (29.28 ± 3.65) U/g vs. (0.84 ± 0.21) U/g, P < 0.01), and ultrasonic destruction PESDA resulted in more significant gene expression than ASDA ((51.95 ± 2.41) U/g vs. (29.28 ± 3.65) U/g, P < 0.05). Ultrasonic destruction of microbubbles during calcium phosphate precipitation gene transfection enhanced β-galactosidase activity nearly 8-fold compared with calcium phosphate precipitation gene transfection alone ((111.35 ± 11.21) U/g protein vs. (14.13 ± 2.58) U/g protein, P < 0.01). Even 6 hours after calcium phosphate precipitation gene transfection, ultrasound-mediated microbubbles destruction resulted in more intense gene expression ((35.63 ± 7.65) U/g vs. (14.13 ± 2.58) U/g, P < 0.05). Ultrasonic destruction of microbubbles might be a promising method for the delivery of non-viral DNA into cardiac myocytes, and the gene tranfection is related to the characteristics of microbubbles.

Optical Verification of Microbubble Response to Acoustic Radiation Force in Large Vessels With In Vivo Results.

PubMed

Wang, Shiying; Wang, Claudia Y; Unnikrishnan, Sunil; Klibanov, Alexander L; Hossack, John A; Mauldin, F William

2015-11-01

The objective of this study was to optically verify the dynamic behaviors of adherent microbubbles in large blood vessel environments in response to a new ultrasound technique using modulated acoustic radiation force. Polydimethylsiloxane (PDMS) flow channels coated with streptavidin were used in targeted groups to mimic large blood vessels. The custom-modulated acoustic radiation force beam sequence was programmed on a Verasonics research scanner. In vitro experiments were performed by injecting a biotinylated lipid-perfluorobutane microbubble dispersion through flow channels. The dynamic response of adherent microbubbles was detected acoustically and simultaneously visualized using a video camera connected to a microscope. In vivo verification was performed in a large abdominal blood vessel of a murine model for inflammation with injection of biotinylated microbubbles conjugated with P-selectin antibody. Aggregates of adherent microbubbles were observed optically under the influence of acoustic radiation force. Large microbubble aggregates were observed solely in control groups without targeted adhesion. Additionally, the dispersion of microbubble aggregates were demonstrated to lead to a transient acoustic signal enhancement in control groups (a new phenomenon we refer to as "control peak"). In agreement with in vitro results, the control peak phenomenon was observed in vivo in a murine model. This study provides the first optical observation of microbubble-binding dynamics in large blood vessel environments with application of a modulated acoustic radiation force beam sequence. With targeted adhesion, secondary radiation forces were unable to produce large aggregates of adherent microbubbles. Additionally, the new phenomenon called control peak was observed both in vitro and in vivo in a murine model for the first time. The findings in this study provide us with a better understanding of microbubble behaviors in large blood vessel environments with application of acoustic radiation force and could potentially guide future beam sequence designs or signal processing routines for enhanced ultrasound molecular imaging.

The Use of Acoustic Radiation Force Decorrelation-Weighted Pulse Inversion for Enhanced Ultrasound Contrast Imaging.

PubMed

Herbst, Elizabeth B; Unnikrishnan, Sunil; Wang, Shiying; Klibanov, Alexander L; Hossack, John A; Mauldin, Frank William

2017-02-01

The use of ultrasound imaging for cancer diagnosis and screening can be enhanced with the use of molecularly targeted microbubbles. Nonlinear imaging strategies such as pulse inversion (PI) and "contrast pulse sequences" (CPS) can be used to differentiate microbubble signal, but often fail to suppress highly echogenic tissue interfaces. This failure results in false-positive detection and potential misdiagnosis. In this study, a novel acoustic radiation force (ARF)-based approach was developed for superior microbubble signal detection. The feasibility of this technique, termed ARF decorrelation-weighted PI (ADW-PI), was demonstrated in vivo using a subcutaneous mouse tumor model. Tumors were implanted in the hindlimb of C57BL/6 mice by subcutaneous injection of MC38 cells. Lipid-shelled microbubbles were conjugated to anti-VEGFR2 antibody and administered via bolus injection. An image sequence using ARF pulses to generate microbubble motion was combined with PI imaging on a Verasonics Vantage programmable scanner. ADW-PI images were generated by combining PI images with interframe signal decorrelation data. For comparison, CPS images of the same mouse tumor were acquired using a Siemens Sequoia clinical scanner. Microbubble-bound regions in the tumor interior exhibited significantly higher signal decorrelation than static tissue (n = 9, P < 0.001). The application of ARF significantly increased microbubble signal decorrelation (n = 9, P < 0.01). Using these decorrelation measurements, ADW-PI imaging demonstrated significantly improved microbubble contrast-to-tissue ratio when compared with corresponding CPS or PI images (n = 9, P < 0.001). Contrast-to-tissue ratio improved with ADW-PI by approximately 3 dB compared with PI images and 2 dB compared with CPS images. Acoustic radiation force can be used to generate adherent microbubble signal decorrelation without microbubble bursting. When combined with PI, measurements of the resulting microbubble signal decorrelation can be used to reconstruct images that exhibit superior suppression of highly echogenic tissue interfaces when compared with PI or CPS alone.

Optical Verification of Microbubble Response to Acoustic Radiation Force in Large Vessels with In Vivo Results

PubMed Central

Wang, Shiying; Wang, Claudia Y.; Unnikrishnan, Sunil; Klibanov, Alexander L.; Hossack, John A.; Mauldin, F. William

2015-01-01

Objectives To optically verify the dynamic behaviors of adherent microbubbles in large blood vessel environments in response to a new ultrasound technique using modulated acoustic radiation force. Materials and Methods Polydimethylsiloxane (PDMS) flow channels coated with streptavidin were used in targeted groups to mimic large blood vessels. The custom modulated acoustic radiation force beam sequence was programmed on a Verasonics research scanner. In vitro experiments were performed by injecting a biotinylated lipid-perfluorobutane microbubble dispersion through flow channels. The dynamic response of adherent microbubbles was detected acoustically and simultaneously visualized using a video camera connected to a microscope. In vivo verification was performed in a large abdominal blood vessel of a murine model for inflammation with injection of biotinylated microbubbles conjugated with P-selectin antibody. Results Aggregates of adherent microbubbles were observed optically under the influence of acoustic radiation force. Large microbubble aggregates were observed solely in control groups without targeted adhesion. Additionally, the dispersion of microbubble aggregates were demonstrated to lead to a transient acoustic signal enhancement in control groups (a new phenomenon we refer to as “control peak”). In agreement with in vitro results, the “control peak” phenomenon was observed in vivo in a murine model. Conclusions This study provides the first optical observation of microbubble binding dynamics in large blood vessel environments with application of a modulated acoustic radiation force beam sequence. With targeted adhesion, secondary radiation forces were unable to produce large aggregates of adherent microbubbles. Additionally, the new phenomenon called “control peak” was observed both in vitro and in vivo in a murine model for the first time. The findings in this study provide us with a better understanding of microbubble behaviors in large blood vessel environments with application of acoustic radiation force, and could potentially guide future beam sequence designs or signal processing routines for enhanced ultrasound molecular imaging. PMID:26135018

Magnetic targeting to enhance microbubble delivery in an occluded microarterial bifurcation

NASA Astrophysics Data System (ADS)

de Saint Victor, M.; Carugo, D.; Barnsley, L. C.; Owen, J.; Coussios, C.-C.; Stride, E.

2017-09-01

Ultrasound and microbubbles have been shown to accelerate the breakdown of blood clots both in vitro and in vivo. Clinical translation of this technology is still limited, however, in part by inefficient microbubble delivery to the thrombus. This study examines the obstacles to delivery posed by fluid dynamic conditions in occluded vasculature and investigates whether magnetic targeting can improve microbubble delivery. A 2D computational fluid dynamic model of a fully occluded Y-shaped microarterial bifurcation was developed to determine: (i) the fluid dynamic field in the vessel with inlet velocities from 1-100 mm s-1 (corresponding to Reynolds numbers 0.25-25) (ii) the transport dynamics of fibrinolytic drugs; and (iii) the flow behavior of microbubbles with diameters in the clinically-relevant range (0.6-5 µm). In vitro experiments were carried out in a custom-built microfluidic device. The flow field was characterized using tracer particles, and fibrinolytic drug transport was assessed using fluorescence microscopy. Lipid-shelled magnetic microbubbles were fluorescently labelled to determine their spatial distribution within the microvascular model. In both the simulations and experiments, the formation of laminar vortices and an abrupt reduction of fluid velocity were observed in the occluded branch of the bifurcation, severely limiting drug transport towards the occlusion. In the absence of a magnetic field, no microbubbles reached the occlusion, remaining trapped in the first vortex, within 350 µm from the bifurcation center. The number of microbubbles trapped within the vortex decreased as the inlet velocity increased, but was independent of microbubble size. Application of a magnetic field (magnetic flux density of 76 mT, magnetic flux density gradient of 10.90 T m-1 at the centre of the bifurcation) enabled delivery of microbubbles to the occlusion and the number of microbubbles delivered increased with bubble size and with decreasing inlet velocity.

Microcapsules: Reverse Sonoporation and Long-lasting, Safe Contrast

NASA Astrophysics Data System (ADS)

Wrenn, Steven; Dicker, Stephen; Small, Eleanor; Maghnouj, Abdelouahid; Hahn, Stephan A.; Mleczko, Michał; Hensel, Karin; Schmitz, Georg

We present a novel vehicle designed to serve the dual roles of enhanced ultrasound contrast and ultrasound-triggered drug delivery. The vehicle is comprised of a microcapsule that is filled with water in whose aqueous core a population of freely floating, phospholipid-coated microbubbles is suspended. At ultrasound intensities below the inertial cavitation threshold of the microbubbles, the microbubbles provide enhanced ultrasound contrast. The measured contrast is comparable in strength with SonoVue®. Encapsulation of microbubbles within microcapsules putatively eliminates - or at least significantly slows - dissolution of gas in the bulk aqueous medium, thereby avoiding disappearance of microbubbles that would otherwise occur due to pressure-induced gas diffusion across the surfactant monolayer coating the microbubble-water interface. Results suggest that our vehicle might provide longer lasting contrast in a clinical setting. We demonstrate that encapsulation of the microbubbles within microcapsules causes at least a doubling of the ultrasound intensity necessary to induce inertial cavitation. Moreover, no cell death was observed when cells were insonified in the presence of microbubble-containing microcapsules, whereas appreciable cell death occurs with unencapsulated microbubbles. These results point toward a potential safety benefit during ultrasound contrast imaging by using encapsulated microbubbles. Studies are underway to investigate the feasibility of ultrasound-triggered release of drug from the microcapsules, owing to inertial- or stable-cavitation, or both. Whereas leakage from polymeric microcapsule shells, such as poly(lactic acid), seemingly requires shell rupture and is exceedingly difficult to achieve, leakage across a lipid bilayer microcapsule shells appears feasible. Leakage across a bilayer shell has the additional benefit that the leakage mechanism can be tuned via phase behavior (liquid-ordered versus liquid-disordered) and cavitation mechanism (stable versus inertial).

Characterization of Contrast Agent Microbubbles for Ultrasound Imaging and Therapy Research.

PubMed

Mulvana, Helen; Browning, Richard J; Luan, Ying; de Jong, Nico; Tang, Meng-Xing; Eckersley, Robert J; Stride, Eleanor

2017-01-01

The high efficiency with which gas microbubbles can scatter ultrasound compared with the surrounding blood pool or tissues has led to their widespread employment as contrast agents in ultrasound imaging. In recent years, their applications have been extended to include super-resolution imaging and the stimulation of localized bio-effects for therapy. The growing exploitation of contrast agents in ultrasound and in particular these recent developments have amplified the need to characterize and fully understand microbubble behavior. The aim in doing so is to more fully exploit their utility for both diagnostic imaging and potential future therapeutic applications. This paper presents the key characteristics of microbubbles that determine their efficacy in diagnostic and therapeutic applications and the corresponding techniques for their measurement. In each case, we have presented information regarding the methods available and their respective strengths and limitations, with the aim of presenting information relevant to the selection of appropriate characterization methods. First, we examine methods for determining the physical properties of microbubble suspensions and then techniques for acoustic characterization of both suspensions and single microbubbles. The next section covers characterization of microbubbles as therapeutic agents, including as drug carriers for which detailed understanding of their surface characteristics and drug loading capacity is required. Finally, we discuss the attempts that have been made to allow comparison across the methods employed by various groups to characterize and describe their microbubble suspensions and promote wider discussion and comparison of microbubble behavior.

Intravascular ultrasound catheter to enhance microbubble-based drug delivery via acoustic radiation force.

PubMed

Kilroy, Joseph P; Klibanov, Alexander L; Wamhoff, Brian R; Hossack, John A

2012-10-01

Previous research has demonstrated that acoustic radiation force enhances intravascular microbubble adhesion to blood vessels in the presence of flow for moleculartargeted ultrasound imaging and drug delivery. A prototype acoustic radiation force intravascular ultrasound (ARFIVUS) catheter was designed and fabricated to displace a microbubble contrast agent in flow representative of conditions encountered in the human carotid artery. The prototype ARFIVUS transducer was designed to match the resonance frequency of 1.4- to 2.6-μm-diameter microbubbles modeled by an experimentally verified 1-D microbubble acoustic radiation force translation model. The transducer element was an elongated Navy Type I (hard) lead zirconate titanate (PZT) ceramic designed to operate at 3 MHz. Fabricated devices operated with center frequencies of 3.3 and 3.6 MHz with -6-dB fractional bandwidths of 55% and 50%, respectively. Microbubble translation velocities as high as 0.86 m/s were measured using a high-speed streak camera when insonating with the ARFIVUS transducer. Finally, the prototype was used to displace microbubbles in a flow phantom while imaging with a commercial 45-MHz imaging IVUS transducer. A sustained increase of 31 dB in average video intensity was measured following insonation with the ARFIVUS, indicating microbubble accumulation resulting from the application of acoustic radiation force.

Drug-Loaded Nanoemulsions/Microbubbles for Combined Tumor Imaging and Therapy

NASA Astrophysics Data System (ADS)

Rapoport, Natalya; Gao, Zhonggao; Kennedy, Ann

2007-05-01

A new class of multifunctional nanoparticles that combine properties of polymeric drug carriers, ultrasound imaging contrast agents, and enhancers of ultrasound-mediated intracellular drug delivery was developed. At room temperature, the developed systems comprise perfluorocarbon nanodroplets stabilized by the walls made of biodegradable block copolymers. The nanodroplets convert into microbubbles upon heating to physiological temperatures. The phase state of the systems and nanodroplet size may be controlled by the copolymer/perfluorocarbon volume ratio. Three areas observed in phase diagrams correspond to micelles; micelle/microbubble coexistence; and nano/microbubble coexistence. These systems manifest a relatively high drug loading capacity (about 15 % wt/wt). As indicated by biodistribution measurements and ultrasound imaging, the micelles and nanobubbles extravasate selectively into the tumor interstitia. Microbubble cavitate and collapse under the action of tumor-directed ultrasound, resulting in a dramatically enhanced intracellular drug uptake by the tumor cells. Upon intravenous injections, a long-lasting, strong and selective ultrasound contrast is observed in the tumor volume confirming nanobubble extravasation through the defected tumor microvasculature and suggesting their coalescence into larger, highly echogenic microbubbles in the tumor tissue. This effect is tumor-selective; no accumulation of echogenic microbubbles is observed in other organs. Tumor contrast increases in time confirming gradual accumulation of echogenic microbubbles in the tumor tissue, presumably via the enhanced penetration and retention (EPR) effect.

Next generation ultrasound platforms for theranostics.

PubMed

Oddo, Letizia; Cerroni, Barbara; Domenici, Fabio; Bedini, Angelico; Bordi, Federico; Chiessi, Ester; Gerbes, Stefan; Paradossi, Gaio

2017-04-01

Microbubbles are a well-established contrast agent which improves diagnostic ultrasound imaging. During the last decade research has focused on expanding their use to include molecular imaging, targeted therapy and imaging modalities other than ultrasound. However, bioadhesion of targeted microbubbles under physiological flow conditions is still difficult to achieve, the main challenge being connected to the poor stability of lipid microbubbles in the body's circulation system. In this article, we investigate the use of polymeric microbubbles based on a poly (vinyl alcohol) shell as an alternative to lipid microbubbles. In particular, we report on the development of microbubble shell modification, using mild reaction conditions, with the aim of designing a multifunctional platform to enable diagnosis and therapy. Superparamagnetic iron oxide nanoparticles and a near infrared fluorescent probe, indocyanine green, are coupled to the bubbles surface in order to support magnetic resonance and fluorescence imaging. Furthermore, anchoring cyclic arginyl-glycyl-aspartic acid (RGD) peptide, and cyclodextrin molecules, allows targeting and drug loading, respectively. Last but not least, shell topography is provided by atomic force microscopy. These applications and features, together with the high echogenicity of poly (vinyl alcohol) microbubbles, may offer a more stable alternative to lipid microbubbles for the development of a multimodal theranostic platform. Copyright © 2016 Elsevier Inc. All rights reserved.

Evaluation of Pollutant Leaching Potential of Coal Ashes for Recycling

NASA Astrophysics Data System (ADS)

Park, D.; Woo, N. C.; Kim, H.; Yoon, H.; Chung, D.

2011-12-01

By 2009, coal ashes produced from coal-based power plants in Korea have been reused as cement supplement materials; however, the rest is mostly disposed in landfills inside the plant properties. Continuous production of coal ashes and limited landfill sites require more recycles of coal ashes as base materials, specifically in constructions of roads and of huge industrial complex. Previous researches showed that coal ashes could contain various metals such as arsenic(As), chromium(Cr), lead(Pb), nickel(Ni), selenium(Se), etc. In this study, we collected four types of bottom ashes and two of fly ashes from four coal-based power plants. These ash samples were tested with distilled water through the column leaching process in oxidized conditions. The column test results were compared with those of total digestion, sequential extraction processes and TCLP. Concentrations of metals in outflows from columns are generally greater in fly ashes than in bottom ashes, specifically for As, Se, B, Sr and SO4. Only one fly ash (J2-F) shows high concentrations of arsenic and selenium in leachate. Sequential extraction results indicate that these metals are in readily soluble forms, such as adsorbed, carbonated, and reducible forms. Results of TCLP analysis indicate no potential contaminants leached from the ashes. In conclusion, recycling of coal combustion ashes could be encouraged with proper tests such as sequential and leaching experiments.

Risk mitigation by waste-based permeable reactive barriers for groundwater pollution control at e-waste recycling sites.

PubMed

Beiyuan, Jingzi; Tsang, Daniel C W; Yip, Alex C K; Zhang, Weihua; Ok, Yong Sik; Li, Xiang-Dong

2017-02-01

Permeable reactive barriers (PRBs) have proved to be a promising passive treatment to control groundwater contamination and associated human health risks. This study explored the potential use of low-cost adsorbents as PRBs media and assessed their longevity and risk mitigation against leaching of acidic rainfall through an e-waste recycling site, of which Cu, Zn, and Pb were the major contaminants. Batch adsorption experiments suggested a higher adsorption capacity of inorganic industrial by-products [acid mine drainage sludge (AMDS) and coal fly ash (CFA)] and carbonaceous recycled products [food waste compost (FWC) and wood-derived biochar] compared to natural inorganic minerals (limestone and apatite). Continuous leaching tests of sand columns with 10 wt% low-cost adsorbents were then conducted to mimic the field situation of acidic rainfall infiltration through e-waste-contaminated soils (collected from Qingyuan, China) by using synthetic precipitation leaching procedure (SPLP) solution. In general, Zn leached out first, followed by Cu, and finally delayed breakthrough of Pb. In the worst-case scenario (e.g., at initial concentrations equal to 50-fold of average SPLP result), the columns with limestone, apatite, AMDS, or biochar were effective for a relatively short period of about 20-40 pore volumes of leaching, after which Cu breakthrough caused non-cancer risk concern and later-stage Pb leaching considerably increased both non-cancer and lifetime cancer risk associated with portable use of contaminated water. In contrast, the columns with CFA or FWC successfully mitigated overall risks to an acceptable level for a prolonged period of 100-200 pore volumes. Therefore, with proper selection of low-cost adsorbents (or their mixture), waste-based PRBs is a technically feasible and economically viable solution to mitigate human health risk due to contaminated groundwater at e-waste recycling sites.

Counter-propagating wave interaction for contrast-enhanced ultrasound imaging

NASA Astrophysics Data System (ADS)

Renaud, G.; Bosch, J. G.; ten Kate, G. L.; Shamdasani, V.; Entrekin, R.; de Jong, N.; van der Steen, A. F. W.

2012-11-01

Most techniques for contrast-enhanced ultrasound imaging require linear propagation to detect nonlinear scattering of contrast agent microbubbles. Waveform distortion due to nonlinear propagation impairs their ability to distinguish microbubbles from tissue. As a result, tissue can be misclassified as microbubbles, and contrast agent concentration can be overestimated; therefore, these artifacts can significantly impair the quality of medical diagnoses. Contrary to biological tissue, lipid-coated gas microbubbles used as a contrast agent allow the interaction of two acoustic waves propagating in opposite directions (counter-propagation). Based on that principle, we describe a strategy to detect microbubbles that is free from nonlinear propagation artifacts. In vitro images were acquired with an ultrasound scanner in a phantom of tissue-mimicking material with a cavity containing a contrast agent. Unlike the default mode of the scanner using amplitude modulation to detect microbubbles, the pulse sequence exploiting counter-propagating wave interaction creates no pseudoenhancement behind the cavity in the contrast image.

Algae separation from urban landscape water using a high density microbubble layer enhanced by micro-flocculation.

PubMed

Chen, Shuwen; Xu, Jingcheng; Liu, Jia; Wei, Qiaoling; Li, Guangming; Huang, Xiangfeng

2014-01-01

Eutrophication of raw water results in outbreaks of algae, which hinders conventional water treatment. In this study, high density microbubble layers combined with micro-flocculation was adopted to remove algae from urban landscape water, and the effects of pressure, hydraulic loading, microbubble layer height and flocculation dosage on the removal efficiency for algae were studied. The greatest removal efficiency for algae, chemical oxygen demand, nitrogen and phosphorus was obtained at 0.42 MPa with hydraulic loading at 5 m/h and a flocculation dosage of 4 mg/L using a microbubble layer with a height of 130 cm. Moreover, the size, clearance distance and concentration of microbubbles were found to be affected by pressure and the height of the microbubble layer. Based on the study, this method was an alternative for algae separation from urban landscape water and water purification.

Ultrasound triggered drug delivery with liposomal nested microbubbles.

PubMed

Wallace, N; Wrenn, S P

2015-12-01

When ultrasound contrast agent microbubbles are nested within a liposome, damage to the liposome membrane caused by both stable and inertial cavitation of the microbubble allows for release of the aqueous core of the liposome. Triggered release was not accomplished unless microbubbles were present within the liposome. Leakage was tested using fluorescence assays developed specifically for this drug delivery vehicle and qualitative measurements using an optical microscope. These studies were done using a 1 MHz focused ultrasound transducer while varying parameters including peak negative ultrasound pressure, average liposome diameter, and microbubble concentration. Two regimes exist for membrane disruption caused by cavitating microbubbles. A faster release rate, as well as permanent membrane damage are seen for samples exposed to high pressure (2.1-3.7 MPa). A slower release rate and dilation/temporary poration are characteristic of stable cavitation for low pressure studies (0.54-1.7 MPa). Copyright © 2015 Elsevier B.V. All rights reserved.

Probing microbubble targeting with atomic force microscopy.

PubMed

Sboros, V; Glynos, E; Ross, J A; Moran, C M; Pye, S D; Butler, M; McDicken, W N; Brown, S B; Koutsos, V

2010-10-01

Microbubble science is expanding beyond ultrasound imaging applications to biological targeting and drug/gene delivery. The characteristics of molecular targeting should be tested by a measurement system that can assess targeting efficacy and strength. Atomic force microscopy (AFM) is capable of piconewton force resolution, and is reported to measure the strength of single hydrogen bonds. An in-house targeted microbubble modified using the biotin-avidin chemistry and the CD31 antibody was used to probe cultures of Sk-Hep1 hepatic endothelial cells. We report that the targeted microbubbles provide a single distribution of adhesion forces with a median of 93pN. This interaction is assigned to the CD31 antibody-antigen unbinding event. Information on the distances between the interaction forces was obtained and could be important for future microbubble fabrication. In conclusion, the capability of single microbubbles to target cell lines was shown to be feasible with AFM.

Ultrasound wave propagation in tissue and scattering from microbubbles for echo particle image velocimetry technique.

PubMed

Mukdadi, Osama; Shandas, Robin

2004-01-01

Nonlinear wave propagation in tissue can be employed for tissue harmonic imaging, ultrasound surgery, and more effective tissue ablation for high intensity focused ultrasound (HIFU). Wave propagation in soft tissue and scattering from microbubbles (ultrasound contrast agents) are modeled to improve detectability, signal-to-noise ratio, and contrast harmonic imaging used for echo particle image velocimetry (Echo-PIV) technique. The wave motion in nonlinear material (tissue) is studied using KZK-type parabolic evolution equation. This model considers ultrasound beam diffraction, attenuation, and tissue nonlinearity. Time-domain numerical model is based on that originally developed by Lee and Hamilton [J. Acoust. Soc. Am 97:906-917 (1995)] for axi-symmetric acoustic field. The initial acoustic waveform emitted from the transducer is assumed to be a broadband wave modulated by Gaussian envelope. Scattering from microbubbles seeded in the blood stream is characterized. Hence, we compute the pressure field impinges the wall of a coated microbubble; the dynamics of oscillating microbubble can be modeled using Rayleigh-Plesset-type equation. Here, the continuity and the radial-momentum equation of encapsulated microbubbles are used to account for the lipid layer surrounding the microbubble. Numerical results show the effects of tissue and microbubble nonlinearities on the propagating pressure wave field. These nonlinearities have a strong influence on the waveform distortion and harmonic generation of the propagating and scattering waves. Results also show that microbubbles have stronger nonlinearity than tissue, and thus improves S/N ratio. These theoretical predictions of wave phenomena provide further understanding of biomedical imaging technique and provide better system design.

Usage of CO2 microbubbles as flow-tracing contrast media in X-ray dynamic imaging of blood flows.

PubMed

Lee, Sang Joon; Park, Han Wook; Jung, Sung Yong

2014-09-01

X-ray imaging techniques have been employed to visualize various biofluid flow phenomena in a non-destructive manner. X-ray particle image velocimetry (PIV) was developed to measure velocity fields of blood flows to obtain hemodynamic information. A time-resolved X-ray PIV technique that is capable of measuring the velocity fields of blood flows under real physiological conditions was recently developed. However, technical limitations still remained in the measurement of blood flows with high image contrast and sufficient biocapability. In this study, CO2 microbubbles as flow-tracing contrast media for X-ray PIV measurements of biofluid flows was developed. Human serum albumin and CO2 gas were mechanically agitated to fabricate CO2 microbubbles. The optimal fabricating conditions of CO2 microbubbles were found by comparing the size and amount of microbubbles fabricated under various operating conditions. The average size and quantity of CO2 microbubbles were measured by using a synchrotron X-ray imaging technique with a high spatial resolution. The quantity and size of the fabricated microbubbles decrease with increasing speed and operation time of the mechanical agitation. The feasibility of CO2 microbubbles as a flow-tracing contrast media was checked for a 40% hematocrit blood flow. Particle images of the blood flow were consecutively captured by the time-resolved X-ray PIV system to obtain velocity field information of the flow. The experimental results were compared with a theoretically amassed velocity profile. Results show that the CO2 microbubbles can be used as effective flow-tracing contrast media in X-ray PIV experiments.

Aptamer-crosslinked microbubbles: smart contrast agents for thrombin-activated ultrasound imaging.

PubMed

Nakatsuka, Matthew A; Mattrey, Robert F; Esener, Sadik C; Cha, Jennifer N; Goodwin, Andrew P

2012-11-27

Thrombosis, or malignant blood clotting, is associated with numerous cardiovascular diseases and cancers. A microbubble contrast agent is presented that produces ultrasound harmonic signal only when exposed to elevated thrombin levels. Initially silent microbubbles are activated in the presence of both thrombin-spiked and freshly clotting blood in three minutes with detection limits of 20 nM thrombin and 2 aM microbubbles. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The use of Acoustic Radiation Force decorrelation-weighted pulse inversion (ADW-PI) for enhanced ultrasound contrast imaging

PubMed Central

Herbst, Elizabeth; Unnikrishnan, Sunil; Wang, Shiying; Klibanov, Alexander L.; Hossack, John A.; Mauldin, F. William

2016-01-01

Objectives The use of ultrasound imaging for cancer diagnosis and screening can be enhanced with the use of molecularly targeted microbubbles. Nonlinear imaging strategies such as pulse inversion (PI) and “contrast pulse sequences” (CPS) can be used to differentiate microbubble signal, but often fail to suppress highly echogenic tissue interfaces. This failure results in false positive detection and potential misdiagnosis. In this study, a novel Acoustic Radiation Force (ARF) based approach was developed for superior microbubble signal detection. The feasibility of this technique, termed ARF-decorrelation-weighted PI (ADW-PI), was demonstrated in vivo using a subcutaneous mouse tumor model. Materials and Methods Tumors were implanted in the hindlimb of C57BL/6 mice by subcutaneous injection of MC38 cells. Lipid-shelled microbubbles were conjugated to anti-VEGFR2 antibody and administered via bolus injection. An image sequence using ARF pulses to generate microbubble motion was combined with PI imaging on a Verasonics Vantage programmable scanner. ADW-PI images were generated by combining PI images with inter-frame signal decorrelation data. For comparison, CPS images of the same mouse tumor were acquired using a Siemens Sequoia clinical scanner. Results Microbubble-bound regions in the tumor interior exhibited significantly higher signal decorrelation than static tissue (n = 9, p < 0.001). The application of ARF significantly increased microbubble signal decorrelation (n = 9, p < 0.01). Using these decorrelation measurements, ADW-PI imaging demonstrated significantly improved microbubble contrast-to-tissue ratio (CTR) when compared to corresponding CPS or PI images (n = 9, p < 0.001). CTR improved with ADW-PI by approximately 3 dB compared to PI images and 2 dB compared to CPS images. Conclusions Acoustic radiation force can be used to generate adherent microbubble signal decorrelation without microbubble bursting. When combined with pulse inversion, measurements of the resulting microbubble signal decorrelation can be used to reconstruct images that exhibit superior suppression of highly echogenic tissue interfaces when compared to PI or CPS alone. PMID:27495188

Targeting property and toxicity of a novel ultrasound contrast agent microbubble carrying the targeting and drug-loaded complex FA-CNTs-PTX on MCF7 cells.

PubMed

Zhang, Jie; Zhang, Yu; Liu, Junxi; Li, Guozhong; Wen, Zhaohui; Zhao, Yue; Zhang, Xiangyu; Liu, Fenghua

2017-10-01

The application of ultrasound contrast agents not only is confined to the enhancement of ultrasound imaging but also has started to be used as a drug system for diagnosis and treatment. In this paper, Span60 and PEG1500 were used as membrane materials, and a new targeting and drug-loading multifunctional ultrasound contrast agent microbubble enveloping the FA-CNTs-PTX complex was successfully prepared by acoustic cavitation. With the breast cancer cell line MCF7 as the research target, the effects of the microbubble with FA-CNTs-PTX on the proliferation and toxicity of MCF7 cells were studied using a CCK-8 and AO/EB double-staining method. The influences of the microbubbles with FA-CNTs-PTX on the cellular morphology and apoptosis period of the MCF7 cells were detected using an inverted fluorescence microscope. The apoptosis of MCF7 cells induced by the microbubbles with FA-CNTs-PTX was investigated with flow cytometry and an annexin and PI double staining fluorescence quantitative analysis. The results indicated that the ultrasound contrast agent microbubble with FA-CNTs-PTX remarkably inhibited the proliferation of MCF7 cells, which was mainly controlled by the drug loading rate and the nanometer size of the microbubbles. Moreover, the proliferative inhibition rate of the microbubbles with FA-CNTs-PTX was related to the cell apoptosis period of MCF7 cells. Its inhibition degree on the proliferation of MCF7 cells was higher than that of the hepatoma HepG2 cells. The apoptosis rate of MCF7 cells induced by the microbubbles with FA-CNTs-PTX was higher than that of normal human umbilical vein endothelial cells (HUVECs), and the microbubbles with FA-CNTs-PTX could target the MCF7 cells. Copyright © 2017 Elsevier B.V. All rights reserved.

Size distributions of micro-bubbles generated by a pressurized dissolution method

NASA Astrophysics Data System (ADS)

Taya, C.; Maeda, Y.; Hosokawa, S.; Tomiyama, A.; Ito, Y.

2012-03-01

Size of micro-bubbles is widely distributed in the range of one to several hundreds micrometers and depends on generation methods, flow conditions and elapsed times after the bubble generation. Although a size distribution of micro-bubbles should be taken into account to improve accuracy in numerical simulations of flows with micro-bubbles, a variety of the size distribution makes it difficult to introduce the size distribution in the simulations. On the other hand, several models such as the Rosin-Rammler equation and the Nukiyama-Tanazawa equation have been proposed to represent the size distribution of particles or droplets. Applicability of these models to the size distribution of micro-bubbles has not been examined yet. In this study, we therefore measure size distribution of micro-bubbles generated by a pressurized dissolution method by using a phase Doppler anemometry (PDA), and investigate the applicability of the available models to the size distributions of micro-bubbles. Experimental apparatus consists of a pressurized tank in which air is dissolved in liquid under high pressure condition, a decompression nozzle in which micro-bubbles are generated due to pressure reduction, a rectangular duct and an upper tank. Experiments are conducted for several liquid volumetric fluxes in the decompression nozzle. Measurements are carried out at the downstream region of the decompression nozzle and in the upper tank. The experimental results indicate that (1) the Nukiyama-Tanasawa equation well represents the size distribution of micro-bubbles generated by the pressurized dissolution method, whereas the Rosin-Rammler equation fails in the representation, (2) the bubble size distribution of micro-bubbles can be evaluated by using the Nukiyama-Tanasawa equation without individual bubble diameters, when mean bubble diameter and skewness of the bubble distribution are given, and (3) an evaluation method of visibility based on the bubble size distribution and bubble number density is proposed, and the evaluated visibility agrees well with the visibility measured in the upper tank.

Investigation of microbubble response to long pulses used in ultrasound-enhanced drug delivery.

PubMed

Mannaris, Christophoros; Averkiou, Michalakis A

2012-04-01

In current drug delivery approaches, microbubbles and drugs can be co-administered while ultrasound is applied. The mechanism of microbubble interaction with ultrasound, the drug and the cells is not fully understood. The aim of this study was to investigate microbubble response to long ultrasonic pulses used in drug delivery approaches. Two different in vitro set-ups were considered: with the microbubbles diluted in an enclosure and with the microbubbles flowing in a capillary tube. Acoustic streaming, which influences the observed bubble response, was observed in "typical" drug delivery conditions in the first set-up. With the capillary set-up, streaming effects were avoided and accurate bubble responses were recorded. The diffraction pattern of the source greatly influences the bubble response and in different locations of the field different bubble responses are observed. At low nondestructive pressures, microbubbles can oscillate for thousands of cycles repeatedly. At high acoustic pressures (at 1 MHz), most bubble activity disappeared within about 100 μs despite the length of the pulse, mainly due to violent bubble destruction and subsequent accelerated diffusion. Copyright © 2012 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Drug-carrying microbubbles as a theranostic tool in convection-enhanced delivery for brain tumor therapy.

PubMed

Chen, Pin-Yuan; Yeh, Chih-Kuang; Hsu, Po-Hung; Lin, Chung-Yin; Huang, Chiung-Yin; Wei, Kuo-Chen; Liu, Hao-Li

2017-06-27

Convection-enhanced delivery (CED) is a promising technique for infusing a therapeutic agent through a catheter with a pressure gradient to create bulk flow for improving drug spread into the brain. So far, gadopentetate dimeglumine (Gd-DTPA) is the most commonly applied surrogate agent for predicting drug distribution through magnetic resonance imaging (MRI). However, Gd-DTPA provides only a short observation duration, and concurrent infusion provides an indirect measure of the exact drug distribution. In this study, we propose using microbubbles as a contrast agent for MRI monitoring, and evaluate their use as a drug-carrying vehicle to directly monitor the infused drug. Results show that microbubbles can provide excellent detectability through MRI relaxometry and accurately represent drug distribution during CED infusion. Compared with the short half-life of Gd-DTPA (1-2 hours), microbubbles allow an extended observation period of up to 12 hours. Moreover, microbubbles provide a sufficiently high drug payload, and glioma mice that underwent a CED infusion of microbubbles carrying doxorubicin presented considerable tumor growth suppression and a significantly improved survival rate. This study recommends microbubbles as a new theranostic tool for CED procedures.

Microbubble and ultrasound radioenhancement of bladder cancer

PubMed Central

Tran, W T; Iradji, S; Sofroni, E; Giles, A; Eddy, D; Czarnota, G J

2012-01-01

Background: Tumour vasculature is an important component of tumour growth and survival. Recent evidence indicates tumour vasculature also has an important role in tumour radiation response. In this study, we investigated ultrasound and microbubbles to enhance the effects of radiation. Methods: Human bladder cancer HT-1376 xenografts in severe combined immuno-deficient mice were used. Treatments consisted of no, low and high concentrations of microbubbles and radiation doses of 0, 2 and 8 Gy in short-term and longitudinal studies. Acute response was assessed 24 h after treatment and longitudinal studies monitored tumour response weekly up to 28 days using power Doppler ultrasound imaging for a total of 9 conditions (n=90 animals). Results: Quantitative analysis of ultrasound data revealed reduced blood flow with ultrasound-microbubble treatments alone and further when combined with radiation. Tumours treated with microbubbles and radiation revealed enhanced cell death, vascular normalisation and areas of fibrosis. Longitudinal data demonstrated a reduced normalised vascular index and increased tumour cell death in both low and high microbubble concentrations with radiation. Conclusion: Our study demonstrated that ultrasound-mediated microbubble exposure can enhance radiation effects in tumours, and can lead to enhanced tumour cell death. PMID:22790798

A Review of Microbubble and its Applications in Ozonation

NASA Astrophysics Data System (ADS)

Shangguan, Yufei; Yu, Shuili; Gong, Chao; Wang, Yue; Yang, Wangzhen; Hou, Li-an

2018-03-01

Ozonation has been demonstrated to be an effective technology for the oxidation of organic matters in water treatment. But the low solubility and low mass transfer efficiency limit the application. Microbubble technology has the potential of enhancing gas-liquid mass transfer efficiency, thus it can be applied in ozonation process. The applications of microbubble ozonation have shown advantages over macro bubble ozonation in mass transfer and reaction rate. Microbubble ozonation will be a promising treatment both in water and wastewater treatment.

Passive acoustic mapping of magnetic microbubbles for cavitation enhancement and localization.

PubMed

Crake, Calum; Victor, Marie de Saint; Owen, Joshua; Coviello, Christian; Collin, Jamie; Coussios, Constantin-C; Stride, Eleanor

2015-01-21

Magnetic targeting of microbubbles functionalized with superparamagnetic nanoparticles has been demonstrated previously for diagnostic (B-mode) ultrasound imaging and shown to enhance gene delivery in vitro and in vivo. In the present work, passive acoustic mapping (PAM) was used to investigate the potential of magnetic microbubbles for localizing and enhancing cavitation activity under focused ultrasound. Suspensions of magnetic microbubbles consisting of 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), air and 10 nm diameter iron oxide nanoparticles were injected into a tissue mimicking phantom at different flow velocities (from 0 to 50 mm s(-1)) with or without an applied magnetic field. Microbubbles were excited using a 500 kHz single element focused transducer at peak negative focal pressures of 0.1-1.0 MPa, while a 64 channel imaging array passively recorded their acoustic emissions. Magnetic localization of microbubble-induced cavitation activity was successfully achieved and could be resolved using PAM as a shift in the spatial distribution and increases in the intensity and sustainability of cavitation activity under the influence of a magnetic field. Under flow conditions at shear rates of up to 100 s(-1) targeting efficacy was maintained. Application of a magnetic field was shown to consistently increase the energy of cavitation emissions by a factor of 2-5 times over the duration of exposures compared to the case without targeting, which was approximately equivalent to doubling the injected microbubble dose. These results suggest that magnetic targeting could be used to localize and increase the concentration of microbubbles and hence cavitation activity for a given systemic dose of microbubbles or ultrasound intensity.

Microbubble gas volume: A unifying dose parameter in blood-brain barrier opening by focused ultrasound.

PubMed

Song, Kang-Ho; Fan, Alexander C; Hinkle, Joshua J; Newman, Joshua; Borden, Mark A; Harvey, Brandon K

2017-01-01

Focused ultrasound with microbubbles is being developed to transiently, locally and noninvasively open the blood-brain barrier (BBB) for improved pharmaceutical delivery. Prior work has demonstrated that, for a given concentration dose, microbubble size affects both the intravascular circulation persistence and extent of BBB opening. When matched to gas volume dose, however, the circulation half-life was found to be independent of microbubble size. In order to determine whether this holds true for BBB opening as well, we independently measured the effects of microbubble size (2 vs. 6 µm diameter) and concentration, covering a range of overlapping gas volume doses (1-40 µL/kg). We first demonstrated precise targeting and a linear dose-response of Evans Blue dye extravasation to the rat striatum for a set of constant microbubble and ultrasound parameters. We found that dye extravasation increased linearly with gas volume dose, with data points from both microbubble sizes collapsing to a single line. A linear trend was observed for both the initial sonication (R 2 =0.90) and a second sonication on the contralateral side (R 2 =0.68). Based on these results, we conclude that microbubble gas volume dose, not size, determines the extent of BBB opening by focused ultrasound (1 MHz, ~0.5 MPa at the focus). This result may simplify planning for focused ultrasound treatments by constraining the protocol to a single microbubble parameter - gas volume dose - which gives equivalent results for varying size distributions. Finally, using optimal parameters determined for Evan Blue, we demonstrated gene delivery and expression using a viral vector, dsAAV1-CMV-EGFP, one week after BBB disruption, which allowed us to qualitatively evaluate neuronal health.

Targeted microbubbles: a novel application for the treatment of kidney stones.

PubMed

Ramaswamy, Krishna; Marx, Vanessa; Laser, Daniel; Kenny, Thomas; Chi, Thomas; Bailey, Michael; Sorensen, Mathew D; Grubbs, Robert H; Stoller, Marshall L

2015-07-01

Kidney stone disease is endemic. Extracorporeal shockwave lithotripsy was the first major technological breakthrough where focused shockwaves were used to fragment stones in the kidney or ureter. The shockwaves induced the formation of cavitation bubbles, whose collapse released energy at the stone, and the energy fragmented the kidney stones into pieces small enough to be passed spontaneously. Can the concept of microbubbles be used without the bulky machine? The logical progression was to manufacture these powerful microbubbles ex vivo and inject these bubbles directly into the collecting system. An external source can be used to induce cavitation once the microbubbles are at their target; the key is targeting these microbubbles to specifically bind to kidney stones. Two important observations have been established: (i) bisphosphonates attach to hydroxyapatite crystals with high affinity; and (ii) there is substantial hydroxyapatite in most kidney stones. The microbubbles can be equipped with bisphosphonate tags to specifically target kidney stones. These bubbles will preferentially bind to the stone and not surrounding tissue, reducing collateral damage. Ultrasound or another suitable form of energy is then applied causing the microbubbles to induce cavitation and fragment the stones. This can be used as an adjunct to ureteroscopy or percutaneous lithotripsy to aid in fragmentation. Randall's plaques, which also contain hydroxyapatite crystals, can also be targeted to pre-emptively destroy these stone precursors. Additionally, targeted microbubbles can aid in kidney stone diagnostics by virtue of being used as an adjunct to traditional imaging methods, especially useful in high-risk patient populations. This novel application of targeted microbubble technology not only represents the next frontier in minimally invasive stone surgery, but a platform technology for other areas of medicine. © 2014 The Authors BJU International © 2014 BJU International Published by John Wiley & Sons Ltd.

Modeling photothermal and acoustical induced microbubble generation and growth.

PubMed

Krasovitski, Boris; Kislev, Hanoch; Kimmel, Eitan

2007-12-01

Previous experimental studies showed that powerful heating of nanoparticles by a laser pulse using energy density greater than 100 mJ/cm(2), could induce vaporization and generate microbubbles. When ultrasound is introduced at the same time as the laser pulse, much less laser power is required. For therapeutic applications, generation of microbubbles on demand at target locations, e.g. cells or bacteria can be used to induce hyperthermia or to facilitate drug delivery. The objective of this work is to develop a method capable of predicting photothermal and acoustic parameters in terms of laser power and acoustic pressure amplitude that are needed to produce stable microbubbles; and investigate the influence of bubble coalescence on the thresholds when the microbubbles are generated around nanoparticles that appear in clusters. We develop and solve here a combined problem of momentum, heat and mass transfer which is associated with generation and growth of a microbubble, filled with a mixture of non-vaporized gas (air) and water vapor. The microbubble's size and gas content vary as a result of three mechanisms: gas expansion or compression, evaporation or condensation on the bubble boundary, and diffusion of dissolved air in the surrounding water. The simulations predict that when ultrasound is applied relatively low threshold values of laser and ultrasound power are required to obtain a stable microbubble from a single nanoparticle. Even lower power is required when microbubbles are formed by coalescence around a cluster of 10 nanoparticles. Laser pulse energy density of 21 mJ/cm(2) is predicted for instance together with acoustic pressure of 0.1 MPa for a cluster of 10 or 62 mJ/cm(2) for a single nanoparticle. Those values are well within the safety limits, and as such are most appealing for targeted therapeutic purposes.

Ultrafast 2-dimensional image monitoring and array-based passive cavitation detection for ultrasound contrast agent destruction in a variably sized region.

PubMed

Xu, Shanshan; Hu, Hong; Jiang, Hujie; Xu, Zhi'an; Wan, Mingxi

2014-11-01

A combined approach was proposed, based on programmable ultrasound equipment, to simultaneously monitor surviving microbubbles and detect cavitation activity during microbubble destruction in a variably sized region for use in ultrasound contrast agent (UCA)-enhanced therapeutic ultrasound applications. A variably sized focal region wherein the acoustic pressure was above the UCA fragmentation threshold was synthesized at frequencies of 3, 4, 5, and 6 MHz with a linear broadband imaging probe. The UCAs' temporal and spatial distribution during the microbubbles' destruction was monitored in a 2-dimensional imaging plane at 5 MHz and a frame rate of 400 Hz, and simultaneously, broadband noise emissions during the microbubbles' fragmentation were extracted by using the backscattered signals produced by the focused release bursts (ie, destruction pulses) themselves. Afterward, the temporal evolution of broadband noise emission, the surviving microbubbles in a region of interest (ROI), and the destruction area in a static UCA suspension were computed. Then the inertial cavitation dose, destruction rate of microbubbles in the ROI, and area of the destruction region were determined. It was found that an increasing pulse length and a decreasing transmit aperture and excitation frequency were correlated with an increased inertial cavitation dose, microbubble destruction rate, and destruction area. Furthermore, it was obvious that the microbubble destruction rate was significantly correlated with the inertial cavitation dose (P < .05). In addition, the intensity decrease in the ROI was significantly correlated with the destruction area (P < .05). By the proposed strategy, microbubbles could be destroyed in a variably sized region, and destruction efficiency as well as the corresponding inertial cavitation dose could be regulated by manipulating the transmission parameters. © 2014 by the American Institute of Ultrasound in Medicine.

Are microbubbles free flowing tracers through the Myocardium? Comparison of indicator-dilution curves obtained from dye dilution and echo contrast using harmonic power Doppler imaging.

PubMed

Tiemann, K; Schlosser, T; Pohl, C; Bimmel, D; Wietasch, G; Hoeft, A; Likungu, J; Vahlhaus, C; Kuntz, S; Nanda, N C; Becher, H; Lüderitz, B

2000-01-01

Harmonic power Doppler imaging (H-PDI) has been introduced into the field of contrast echocardiography as a contrast-specific imaging modality. However, there has been considerable skepticism as to whether H-PDI would be quantifiable, because it depends on the destruction of microbubbles and has more complex signal processing than gray scale imaging. The aim of the present study was to evaluate the relationship between the concentration of microbubbles and the resulting H-PDI signals even under conditions where bubble destruction is most likely. Furthermore, we evaluated whether microbubbles of Levovist freely pass the microcirculation, which is a prerequisite for the assessment of myocardial blood flow. A strong positive correlation was found between the H-PDI signals and the amount of microbubbles up to the onset of acoustic shadowing (r = 0. 968, P<0.001). Time-intensity curves for H-PDI of air-filled microbubbles were compared with time-concentration curves of indocyanine green (ICG) in both a flow phantom and a working heart setup. The mean transit times (MTTs) through the myocardium of both agents were compared after a bolus injection into the left coronary artery. A close correlation was observed between 1/MTT and flow in both setups (r>0.98, P<0.0001). However, at high flow rates, the MTTs of the microbubbles were slightly, albeit not significantly, faster than those of indocyanine green. We conclude that microbubbles fulfill the prerequisites of free flowing tracers through the myocardium. Furthermore, H-PDI technology allows a reliable assessment of time-concentration curves of air-filled microbubbles up to the onset of acoustic shadowing.

Microbubble-assisted optofluidic control using a photothermal waveguide

NASA Astrophysics Data System (ADS)

Cheng, YuPeng; Yang, JianXin; Li, ZongBao; Zhu, DeBin; Cai, Xiang; Hu, Xiaowen; Huang, Wen; Xing, XiaoBo

2017-10-01

A convenient and easily controllable microfluidic system was proposed based on a photothermal device. Here, graphene oxide was assembled on an optical waveguide, which could serve as a miniature heat source to generate a microbubble and to control dynamic behaviors of flow by adjusting optical power at the micrometer scale. Micro/nanoparticles were used to demonstrate the trace of fluid flow around the microbubble, which displayed the ability of the flow to capture, transmit, and rotate particles in thermal convection. Correspondingly, three-dimensional theoretical simulation combining thermodynamics with hydrodynamics analyzed the distribution of the velocity field induced by the microbubble for collection and driving of particles. Furthermore, the photothermal waveguide would be developed into a microbubble-based device in the manipulation or transmission of micro/nanoparticles.

Temperature sensor based on high-Q polymethylmethacrylate optical microbubble

NASA Astrophysics Data System (ADS)

He, Chunhong; Sun, Huijin; Mo, Jun; Yang, Chao; Feng, Guoying; Zhou, Hao; Zhou, Shouhuan

2018-07-01

A new flexible method to fabricate a temperature sensor based on polymethylmethacrylate (PMMA) optical microbubbles, using a volume-controllable pipette, is demonstrated. The high quality factor of the cavity is guaranteed by the smooth wall of the microbubble. The shape and refractive index of the microbubbles change with the surrounding temperature, which leads to the obvious displacement of the whispering gallery mode transmission spectrum. As the surrounding temperature increases, the spectrum undergoes a significant blue shift, hence the microresonator can be used for temperature sensing. A sensitivity of 39 pm °C‑1 is obtained in a PMMA microbubble with a diameter of 740 µm. This work suggests a new convenient approach to achieving high-quality flexible microscale sensors.

Bubble column and CFD simulation for chemical recycling of polyethylene terephthalate

NASA Astrophysics Data System (ADS)

Alzuhairi, Mohammed

2018-05-01

Computational Fluid Dynamics (CFD) is an important simulation tool, which uses powerful computer to get optimal design in industrial processes. New approach technique of bubble column for three phases has been used with respect to chemical recycling of Polyethylene Terephthalate (PET). The porous ceramic has been used in thin plate (5 mm) with a narrow pore size distribution. Excellent agreement between CFD has been predicted and experimental profiles of hold-up and velocity close to wall have been observed for a column diameter 0.08 m, column height 0.15 m (HD), and superficial gas velocity (VG) 0.05 m/s. The main purpose of the current study is to highlight depolymerization of PET chemically by using the close system of Ethylene Glycol, PET-Catalyzed, and Nitrogen glycolysis process in bubble column of three phases technique by using Nano catalyst, SiO2 with various weight percent (0.01, 0.02, 0.05, 0.1, 0.2, and 0.5) based on PET weight and preheated Nitrogen up to 100° C by extra heater in bubble column reactor. The depolymerization time could be reduced in order to improve heat and mass transfer in comparison with the traditional methods. Little amount not exceeding 0.01% of Nano SiO2 is enough for completing depolymerization. The final product of PET depolymerization has full characterization by FTIR, AFM, CHN tests and has been used as a vital additive for Bitumen, it has been investigated as a moisture-proof, water seepage-proof material, and as a tough resistant to environmental conditions.

Combined optical sizing and acoustical characterization of single freely-floating microbubbles

NASA Astrophysics Data System (ADS)

Luan, Ying; Renaud, Guillaume; Raymond, Jason L.; Segers, Tim; Lajoinie, Guillaume; Beurskens, Robert; Mastik, Frits; Kokhuis, Tom J. A.; van der Steen, Antonius F. W.; Versluis, Michel; de Jong, Nico

2016-12-01

In this study we present a combined optical sizing and acoustical characterization technique for the study of the dynamics of single freely-floating ultrasound contrast agent microbubbles exposed to long burst ultrasound excitations up to the milliseconds range. A co-axial flow device was used to position individual microbubbles on a streamline within the confocal region of three ultrasound transducers and a high-resolution microscope objective. Bright-field images of microbubbles passing through the confocal region were captured using a high-speed camera synchronized to the acoustical data acquisition to assess the microbubble response to a 1-MHz ultrasound burst. Nonlinear bubble vibrations were identified at a driving pressure as low as 50 kPa. The results demonstrate good agreement with numerical simulations based on the shell-buckling model proposed by Marmottant et al. [J. Acoust. Soc. Am. 118, 3499-3505 (2005)]. The system demonstrates the potential for a high-throughput in vitro characterization of individual microbubbles.

Mechanisms for microvascular damage induced by ultrasound-activated microbubbles

NASA Astrophysics Data System (ADS)

Chen, Hong; Brayman, Andrew A.; Evan, Andrew P.; Matula, Thomas J.

2012-10-01

To provide insight into the mechanisms of microvascular damage induced by ultrasound-activated microbubbles, experimental studies were performed to correlate microvascular damage to the dynamics of bubble-vessel interactions. High-speed photomicrography was used to record single microbubbles interacting with microvessels in ex vivo tissue, under the exposure of short ultrasound pulses with a center frequency of 1 MHz and peak negative pressures (PNP) ranging from 0.8-4 MPa. Vascular damage associated with observed bubble-vessel interactions was either indicated directly by microbubble extravasation or examined by transmission electron microscopy (TEM) analyses. As observed previously, the high-speed images revealed that ultrasound-activated microbubbles could cause distention and invagination of adjacent vessel walls, and could form liquid jets in microvessels. Vessel distention, invagination, and liquid jets were associated with the damage of microvessels whose diameters were smaller than those of maximally expanded microbubbles. However, vessel invagination appeared to be the dominant mechanism for the damage of relative large microvessels.

Mechanisms for microvascular damage induced by ultrasound-activated microbubbles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen Hong; Brayman, Andrew A.; Evan, Andrew P.

To provide insight into the mechanisms of microvascular damage induced by ultrasound-activated microbubbles, experimental studies were performed to correlate microvascular damage to the dynamics of bubble-vessel interactions. High-speed photomicrography was used to record single microbubbles interacting with microvessels in ex vivo tissue, under the exposure of short ultrasound pulses with a center frequency of 1 MHz and peak negative pressures (PNP) ranging from 0.8-4 MPa. Vascular damage associated with observed bubble-vessel interactions was either indicated directly by microbubble extravasation or examined by transmission electron microscopy (TEM) analyses. As observed previously, the high-speed images revealed that ultrasound-activated microbubbles could cause distentionmore » and invagination of adjacent vessel walls, and could form liquid jets in microvessels. Vessel distention, invagination, and liquid jets were associated with the damage of microvessels whose diameters were smaller than those of maximally expanded microbubbles. However, vessel invagination appeared to be the dominant mechanism for the damage of relative large microvessels.« less

Time-resolved nanoseconds dynamics of ultrasound contrast agent microbubbles manipulated and controlled by optical tweezers

NASA Astrophysics Data System (ADS)

Garbin, Valeria; Cojoc, Dan; Ferrari, Enrico; Di Fabrizio, Enzo; Overvelde, Marlies L. J.; Versluis, Michel; van der Meer, Sander M.; de Jong, Nico; Lohse, Detlef

2006-08-01

Optical tweezers enable non-destructive, contact-free manipulation of ultrasound contrast agent (UCA) microbubbles, which are used in medical imaging for enhancing the echogenicity of the blood pool and to quantify organ perfusion. The understanding of the fundamental dynamics of ultrasound-driven contrast agent microbubbles is a first step for exploiting their acoustical properties and to develop new diagnostic and therapeutic applications. In this respect, optical tweezers can be used to study UCA microbubbles under controlled and repeatable conditions, by positioning them away from interfaces and from neighboring bubbles. In addition, a high-speed imaging system is required to record the dynamics of UCA microbubbles in ultrasound, as their oscillations occur on the nanoseconds timescale. In this work, we demonstrate the use of an optical tweezers system combined with a high-speed camera capable of 128-frame recordings at up to 25 million frames per second (Mfps), for the study of individual UCA microbubble dynamics as a function of the distance from solid interfaces.

Effect of microbubbled water on the removal of a biofilm attached to orthodontic appliances--an in vitro study.

PubMed

Mukumoto, Mio; Ohshima, Tomoko; Ozaki, Miwa; Konishi, Hirokazu; Maeda, Nobuko; Nakamura, Yoshiki

2012-01-01

Orthodontic appliances often cause oral diseases such as dental caries and gingivitis due to the attachment of an oral biofilm. However, there are few reliable methods to remove the biofilm from the orthodontic appliances. The aim of this study was to investigate the effects of microbubbled water on the removal of biofilms made with Streptococcus mutans or Candida albicans on orthodontic appliances. The orthodontic appliances with biofilm were immersed with microbubbled water and the remaining biofilm on the appliances was detected and measured using a micro-plate reader and an absorbance meter. The microbubbled water had a sufficient effect on the removal of biofilm from orthodontic appliances. The effects of microbubbled water were significantly higher than those of tap water (S. mutans: p<0.05, C. albicans: p<0.01). The results of this study suggest that microbubbled water is effective in the removal of biofilm from the mouth of orthodontic patients.

Continuous Nanoparticle Assembly by a Modulated Photo-Induced Microbubble for Fabrication of Micrometric Conductive Patterns.

PubMed

Armon, Nina; Greenberg, Ehud; Layani, Michael; Rosen, Yitzchak S; Magdassi, Shlomo; Shpaisman, Hagay

2017-12-20

The laser-induced microbubble technique (LIMBT) has recently been developed for micro-patterning of various materials. In this method, a laser beam is focused on a dispersion of nanoparticles leading to the formation of a microbubble due to laser heating. Convection currents around the microbubble carry nanoparticles so that they become pinned to the bubble/substrate interface. The major limitation of this technique is that for most materials, a noncontinuous deposition is formed. We show that continuous patterns can be formed by preventing the microbubble from being pinned to the deposited material. This is done by modulating the laser so that the construction and destruction of the microbubble are controlled. When the method is applied to a dispersion of Ag nanoparticles, continuous electrically conductive lines are formed. Furthermore, the line width is narrower than that achieved by the standard nonmodulated LIMBT. This approach can be applied to the direct-write fabrication of micron-size conductive patterns in electronic devices without the use of photolithography.

Microbubbles induce renal hemorrhage when exposed to diagnostic ultrasound in anesthetized rats.

PubMed

Wible, James H; Galen, Karen P; Wojdyla, Jolette K; Hughes, Michael S; Klibanov, Alexander L; Brandenburger, Gary H

2002-01-01

The generation of ultrasound (US) bioeffects using a clinical imaging system is controversial. We tested the hypothesis that the presence of microbubbles in the US field of a medical imager induces biologic effects. Both kidneys of anesthetized rats were insonified for 5 min using a medical imaging system after the administration of microbubbles. One kidney was insonified using a continuous mode (30 Hz) and the opposite kidney was insonified using an intermittent (1 Hz) technique. The microbubbles were exposed to three different transducer frequencies and four transducer output powers. After insonification, the animals were euthanized, the kidneys were removed and their gross appearance scored under "blinded" conditions using a defined scale. After the administration of microbubbles, US imaging of the kidney caused hemorrhage in the renal tissue. The severity and area of hemorrhage increased with an increase in the transducer power and a decrease in the transducer frequency. Intermittent insonification in the presence of microbubbles produced a greater degree of renal hemorrhage than continuous imaging techniques.

Fluid viscosity affects the fragmentation and inertial cavitation threshold of lipid encapsulated microbubbles

PubMed Central

Helfield, Brandon; Black, John J.; Qin, Bin; Pacella, John; Chen, Xucai; Villanueva, Flordeliza S.

2015-01-01

Ultrasound and microbubble optimization studies for therapeutic applications are often conducted in water/saline, with a fluid viscosity of 1 cP. In an in vivo context, microbubbles are situated in blood, a more viscous fluid (~4 cP). In this study, ultra-high speed microscopy and passive cavitation approaches were employed to investigate the effect of fluid viscosity on microbubble behavior at 1 MHz subject to high pressures (0.25 – 2 MPa). The propensity for individual microbubble (n=220) fragmentation was shown to significantly decrease in 4 cP fluid as compared to 1 cP fluid, despite achieving similar maximum radial excursions. Microbubble populations diluted in 4 cP fluid exhibited decreased wideband emissions (up to 10.2 times), and increasingly distinct harmonic emission peaks (e.g. ultraharmonic) with increasing pressure as compared to 1 cP fluid. These results suggest that in vitro studies should consider an evaluation using physiologic viscosity perfusate before transitioning to in vivo evaluations. PMID:26674676

Salvaging deep anterior lamellar keratoplasty with microbubble incision technique in failed "big bubble" cases: an update study.

PubMed

Banerjee, Sanjib; Li, He J; Tsaousis, Konstantinos T; Tabin, Geoffrey C

2016-11-04

To report the achievement rate of bare Descemet membrane (DM) dissection with the help of microbubble incision technique in eyes with failed big bubble formation and to investigate the mechanism of the microbubble rescue technique through ex vivo imaging of human cadaver corneas. This retrospective clinical study included 80 eyes of 80 patients that underwent deep anterior lamellar keratoplasty (DALK). In 22/80 (27.5%) cases, big bubble dissection failed. After puncturing the microbubbles, viscodissection helped to achieve separation of DM from the remaining stroma. In addition, an ex vivo study with human cadaver cornea specimens, gross photography, and anterior segment optical coherence tomography imaging was accomplished ex vivo to explore the mechanism of this method. Microbubble dissection technique led to successful DALK in 19 of 22 cases of failed big bubble. Microperforation occurred in 3 eyes. Deep anterior lamellar keratoplasty was completed without any complications in 2 out of the 3 eyes with microperforation. In 1 eye, conversion to penetrating keratoplasty was required. Microbubble-guided viscodissection achieved 95.4% (21/22) success in exposing bare DM in failed big-bubble cases of DALK. Anterior segment optical coherence tomography imaging results of cadaver eyes showed where these microbubbles were concentrated and their related size. Microbubble-guided DALK should be considered an effective rescue technique in achieving bare DM in eyes with failed big bubble. Our ex vivo experiment illustrated the possible alterations in cornea anatomy during this technique.

Quantitative investigation of the edge enhancement in in-line phase contrast projections and tomosynthesis provided by distributing microbubbles on the interface between two tissues: a phantom study

NASA Astrophysics Data System (ADS)

Wu, Di; Donovan Wong, Molly; Li, Yuhua; Fajardo, Laurie; Zheng, Bin; Wu, Xizeng; Liu, Hong

2017-12-01

The objective of this study was to quantitatively investigate the ability to distribute microbubbles along the interface between two tissues, in an effort to improve the edge and/or boundary features in phase contrast imaging. The experiments were conducted by employing a custom designed tissue simulating phantom, which also simulated a clinical condition where the ligand-targeted microbubbles are self-aggregated on the endothelium of blood vessels surrounding malignant cells. Four different concentrations of microbubble suspensions were injected into the phantom: 0%, 0.1%, 0.2%, and 0.4%. A time delay of 5 min was implemented before image acquisition to allow the microbubbles to become distributed at the interface between the acrylic and the cavity simulating a blood vessel segment. For comparison purposes, images were acquired using three system configurations for both projection and tomosynthesis imaging with a fixed radiation dose delivery: conventional low-energy contact mode, low-energy in-line phase contrast and high-energy in-line phase contrast. The resultant images illustrate the edge feature enhancements in the in-line phase contrast imaging mode when the microbubble concentration is extremely low. The quantitative edge-enhancement-to-noise ratio calculations not only agree with the direct image observations, but also indicate that the edge feature enhancement can be improved by increasing the microbubble concentration. In addition, high-energy in-line phase contrast imaging provided better performance in detecting low-concentration microbubble distributions.

Comparison of microbubble presence in the right heart during mechanochemical and radiofrequency ablation for varicose veins.

PubMed

Moon, K H; Dharmarajah, B; Bootun, R; Lim, C S; Lane, Tra; Moore, H M; Sritharan, K; Davies, A H

2017-07-01

Objective Mechanochemical ablation is a novel technique for ablation of varicose veins utilising a rotating catheter and liquid sclerosant. Mechanochemical ablation and radiofrequency ablation have no reported neurological side-effect but the rotating mechanism of mechanochemical ablation may produce microbubbles. Air emboli have been implicated as a cause of cerebrovascular events during ultrasound-guided foam sclerotherapy and microbubbles in the heart during ultrasound-guided foam sclerotherapy have been demonstrated. This study investigated the presence of microbubbles in the right heart during varicose vein ablation by mechanochemical abaltion and radiofrequency abaltion. Methods Patients undergoing great saphenous vein ablation by mechanochemical abaltion or radiofrequency ablation were recruited. During the ablative procedure, the presence of microbubbles was assessed using transthoracic echocardiogram. Offline blinded image quantification was performed using International Consensus Criteria grading guidelines. Results From 32 recruited patients, 28 data sets were analysed. Eleven underwent mechanochemical abaltion and 17 underwent radiofrequency abaltion. There were no neurological complications. In total, 39% (11/28) of patients had grade 1 or 2 microbubbles detected. Thirty-six percent (4/11) of mechanochemical abaltion patients and 29% (5/17) of radiofrequency ablation patients had microbubbles with no significant difference between the groups ( p=0.8065). Conclusion A comparable prevalence of microbubbles between mechanochemical abaltion and radiofrequency ablation both of which are lower than that previously reported for ultrasound-guided foam sclerotherapy suggests that mechanochemical abaltion may not confer the same risk of neurological events as ultrasound-guided foam sclerotherapy for treatment of varicose veins.

The Behavior of Lipid Debris Left on Cell Surfaces from Microbubble Based Ultrasound Molecular Imaging

PubMed Central

Ibsen, Stuart; Shi, Guixin; Schutt, Carolyn; Shi, Linda; Suico, Kyle-David; Benchimol, Michael; Serra, Viviana; Simberg, Dmitri; Berns, Michael; Esener, Sadik

2014-01-01

Lipid monolayer coated microbubbles are currently being developed to identify vascular regions that express certain surface proteins as part of the new technique of ultrasound molecular imaging. The microbubbles are functionalized with targeting ligands which bind to the desired cells holding the microbubbles in place as the remaining unbound microbubbles are eliminated from circulation. Subsequent scanning with ultrasound can detect the highly reflectant microbubbles that are left behind. The ultrasound scanning and detection process results in the destruction of the microbubble, creating lipid fragments from the monolayer. Here we demonstrate that microbubbles targeted to 4T1 murine breast cancer cells and human umbilical cord endothelial cells leave behind adhered fragments of the lipid monolayer after exposure to ultrasound with peak negative pressures of 0.18 and 0.8 MPa. Most of the observed fragments were large enough to be resistant to receptor mediated endocytosis. The fragments were not observed to incorporate into the lipid membrane of the cell over a period of 96 min. They were not observed to break into smaller pieces or significantly change shape but they were observed to undergo translation and rotation across the cell surface as the cells migrated over the substrate. These large fragments will apparently remain on the surface of the targeted cells for significant periods of time and need to be considered for their potential effects on blood flow through the microcapillaries and potential for immune system recognition. PMID:25059435

Precipitation Recycling and the Vertical Distribution of Local and Remote Sources of Water for Precipitation

NASA Technical Reports Server (NTRS)

Bosilovich, Michael G.; Atlas, Robert (Technical Monitor)

2002-01-01

Precipitation recycling is defined as the amount of water that evaporates from a region that precipitates within the same region. This is also interpreted as the local source of water for precipitation. In this study, the local and remote sources of water for precipitation have been diagnosed through the use of passive constituent tracers that represent regional evaporative sources along with their transport and precipitation. We will discuss the differences between this method and the simpler bulk diagnostic approach to precipitation recycling. A summer seasonal simulation has been analyzed for the regional sources of the United States Great Plains precipitation. While the tropical Atlantic Ocean (including the Gulf of Mexico) and the local continental sources of precipitation are most dominant, the vertically integrated column of water contains substantial water content originating from the Northern Pacific Ocean, which is not precipitated. The vertical profiles of regional water sources indicate that local Great Plains source of water dominates the lower troposphere, predominantly in the PBL. However, the Pacific Ocean source is dominant over a large portion of the middle to upper troposphere. The influence of the tropical Atlantic Ocean is reasonably uniform throughout the column. While the results are not unexpected given the formulation of the model's convective parameterization, the analysis provides a quantitative assessment of the impact of local evaporation on the occurrence of convective precipitation in the GCM. Further, these results suggest that local source of water is not well mixed throughout the vertical column.

Benthic flux measurements of Hg species in a northern Adriatic lagoon environment (Marano and Grado Lagoon, Italy)

NASA Astrophysics Data System (ADS)

Emili, Andrea; Acquavita, Alessandro; Koron, Neža; Covelli, Stefano; Faganeli, Jadran; Horvat, Milena; Žižek, Suzana; Fajon, Vesna

2012-11-01

As part of the "MIRACLE" project, the biogeochemical cycling of mercury (Hg) at the sediment-water interface was studied in the field in the Marano and Grado Lagoon (Northern Adriatic Sea). Seasonal investigations were conducted at selected experimental sites, where Manila Clams (Tapes philippinarum) were previously seeded. Measurements were performed seasonally during three campaigns, using two benthic chambers, one transparent and one dark, to evaluate the effect of light on Hg cycling. Total dissolved Hg (THg), methylmercury (MeHg), and dissolved gaseous Hg (DGM) species were considered. Diurnal benthic fluxes were found to significantly exceed the diffusive fluxes at all stations. The assessment of the annual recycling of Hg species from sediments to the water column showed that up to 99% of MeHg is recycled annually to the water column, while Hg recycling ranges from 30 to 60%. MeHg poses the higher risk for potential bioaccumulation in clams, but it is partially mitigated by Hg reduction, which seems to be an important process leading to evasion losses of Hg from these environments. Estimated benthic fluxes suggest that Hg recycling at the sediment-water interface is more active in the Grado sector. Hence, based on the estimated release of MeHg from sediments, it is suggested that the western sector seems to be more suitable for clam farming and the extension of rearing activities.

Biosurfactants for Microbubble Preparation and Application

PubMed Central

Xu, Qingyi; Nakajima, Mitsutoshi; Liu, Zengshe; Shiina, Takeo

2011-01-01

Biosurfactants can be classified by their chemical composition and their origin. This review briefly describes various classes of biosurfactants based on their origin and introduces a few of the most widely used biosurfactants. The current status and future trends in biosurfactant production are discussed, with an emphasis on those derived from plants. Following a brief introduction of the properties of microbubbles, recent progress in the application of microbubble technology to molecular imaging, wastewater treatment, and aerobic fermentation are presented. Several studies on the preparation, characterization and applications of biosurfactant-based microbubbles are reviewed. PMID:21339998

Theranostic Oxygen Delivery Using Ultrasound and Microbubbles

PubMed Central

Kwan, James J.; Kaya, Mehmet; Borden, Mark A.; Dayton, Paul A.

2012-01-01

Means to overcome tumor hypoxia have been the subject of clinical investigations since the 1960's; however these studies have yet to find a treatment which is widely accepted. It has been known for nearly a century that hypoxic cells are more resistant to radiotherapy than aerobic cells, and tumor hypoxia is a major factor leading to the resistance of tumors to radiation treatment as well as several cytotoxic agents. In this manuscript, the application of ultrasound combined with oxygen-carrier microbubbles is demonstrated as a method to locally increase dissolved oxygen. Microbubbles can also be imaged by ultrasound, thus providing the opportunity for image-guided oxygen delivery. Simulations of gas diffusion and microbubble gas exchange show that small amounts (down to 5 vol%) of a low-solubility osmotic gas can substantially increase microbubble persistence and therefore production rates and stability of oxygen-carrier microbubbles. Simulations also indicate that the lipid shell can be engineered with long-chain lipids to increase oxygen payload during in vivo transit. Experimental results demonstrate that the application of ultrasound to destroy the microbubbles significantly enhances the local oxygen release. We propose this technology as an application for ultrasound image-guided release of oxygen directly to hypoxic tissue, such as tumor sites to enhance radiotherapy. PMID:23382774

In Vivo Demonstration of Cancer Molecular Imaging with Ultrasound Radiation Force and Buried-Ligand Microbubbles

PubMed Central

Borden, Mark A.; Streeter, Jason E.; Sirsi, Shashank R.; Dayton, Paul A.

2015-01-01

In designing targeted contrast agent materials for imaging, the need to present a targeting ligand for recognition and binding by the target is counterbalanced by the need to minimize interactions with plasma components and to avoid recognition by the immune system. We have previously reported on a microbubble imaging probe for ultrasound molecular imaging that uses a buried-ligand surface architecture to minimize unwanted interactions and immunogenicity. Here we examine for the first time the utility of this approach for in vivo molecular imaging. In accordance with previous results, we showed a threefold increase in circulation persistence through the tumor of a fibrosarcoma model in comparison with controls. The buried-ligand microbubbles were then activated for targeted adhesion through the application of noninvasive ultrasound radiation forces applied specifically to the tumor region. Using a clinical ultrasound scanner, microbubbles were activated, imaged, and silenced. The results showed visually conspicuous images of tumor neovasculature and a twofold increase in ultrasound radiation force enhancement of acoustic contrast intensity for buried-ligand microbubbles, whereas no such increase was found for exposed-ligand microbubbles. We therefore conclude that the use of acoustically active buried-ligand microbubbles for ultrasound molecular imaging bridges the demand for low immunogenicity with the necessity of maintaining targeting efficacy and imaging conspicuity in vivo. PMID:23981781

Leaching standards for mineral recycling materials--a harmonized regulatory concept for the upcoming German Recycling Decree.

PubMed

Susset, Bernd; Grathwohl, Peter

2011-02-01

In this contribution we give a first general overview of results of recent studies in Germany which focused on contaminant leaching from various materials and reactive solute transport in the unsaturated soil zone to identify the key factors for groundwater risk assessment. Based on these results we developed new and improved existing methods for groundwater risk assessment which are used to derive a new regulatory concept for the upcoming "Decree for the Requirements of the Use of Alternative Mineral Building Materials in Technical Constructions and for the Amendment of the Federal Soil Protection and Contaminated Sites Ordinance" of the German Federal Ministry of Environment. The new concept aims at a holistic and scientifically sound assessment of the use of mineral recycling materials (e.g., mineral waste, excavated soils, slag and ashes, recycling products, etc.) in technical constructions (e.g., road dams) and permanent applications (e.g., backfilling and landscaping) which is based on a mechanistic understanding of leaching and transport processes. Fundamental for risk assessment are leaching standards for the mineral recycling materials. For each application of mineral recycling materials specific maximum concentrations of a substance in the seepage water at the bottom of an application were calculated. Technical boundary conditions and policy conventions derived from the "German precautionary groundwater and soil protection policy" were accounted to prevent adverse environmental effects on the media soil and groundwater. This includes the concentration decline of highly soluble substances (e.g., chloride and sulphate), retardation or attenuation of solutes, accumulation of contaminants in sub-soils and the hydraulic properties of recycling materials used for specific applications. To decide whether the use of a mineral recycling material is possible in a specific application, the leaching qualities were evaluated based on column percolation tests with various samples and compared with application-specific maximum concentrations. In the upcoming federal decree this simplified concept is realized using detailed tables which classify the leaching quality of mineral recycling materials and demonstrate potential application. A quality assurance system will be mandatory which defines specific testing programs (material properties and limit concentrations to be tested, number and schedule of testing) for the different mineral recycling materials using standardized methods (column percolation test). Copyright © 2010 Elsevier Ltd. All rights reserved.

Type of adsorbent and column height in adsorption process of used cooking oil

NASA Astrophysics Data System (ADS)

Hasnelly, Hervelly, Taufik, Yusman; Melany, Ivo Nila

2015-12-01

The purpose of this research was to find out the best adsorbent and column height that can adsorb color and soluble impurities substances in used cooking oil. This research was meant for knowledge development of refined cooking oil technology. The used of this research was giving out information on the recycling process of used cooking oil. Research design used 2 × 2 factorial pattern in randomized group design with 6 repetitions. The first factor is adsorbent type (J) that consist of activated carbon (J1) and Zeolit (J2). The second factor is column height (K) with variations of 15 cm (k1) and 20 cm (k2). Chemical analysis parameter are free fatty acid, water content and saponification value. Physical parameter measurement was done on color with Hunter Lab system analysis and viscosity using viscometer method. Chemical analysis result of preliminary research on used cooking oil showed water content of 1,9%, free fatty acid 1,58%, saponification value 130,79 mg KOH/g oil, viscosity 0,6 d Pas and color with L value of -27,60, a value 1,04 and b value 1,54. Result on main research showed that adsorbent type only gave effect on water content whereas column height and its interaction was not gave significant effect on water content. Interaction between adsorbent type (J) and column height (K) gave significant effect to free fatty acid, saponification value, viscosity and color for L, a and b value of recycled cooking oil.

Cationic microbubbles and antibiotic-free miniplasmid for sustained ultrasound-mediated transgene expression in liver.

PubMed

Manta, Simona; Renault, Gilles; Delalande, Anthony; Couture, Olivier; Lagoutte, Isabelle; Seguin, Johanne; Lager, Franck; Houzé, Pascal; Midoux, Patrick; Bessodes, Michel; Scherman, Daniel; Bureau, Michel-Francis; Marie, Corinne; Pichon, Chantal; Mignet, Nathalie

2017-09-28

Despite the increasing number of clinical trials in gene therapy, no ideal methods still allow non-viral gene transfer in deep tissues such as the liver. We were interested in ultrasound (US)-mediated gene delivery to provide long term liver expression. For this purpose, new positively charged microbubbles were designed and complexed with pFAR4, a highly efficient small length miniplasmid DNA devoid of antibiotic resistance sequence. Sonoporation parameters, such as insonation time, acoustic pressure and duration of plasmid injection were controlled under ultrasound imaging guidance. The optimization of these various parameters was performed by bioluminescence optical imaging of luciferase reporter gene expression in the liver. Mice were injected with 50μg pFAR4-LUC either alone, or complexed with positively charged microbubbles, or co-injected with neutral MicroMarker™ microbubbles, followed by low ultrasound energy application to the liver. Injection of the pFAR4 encoding luciferase alone led to a transient transgene expression that lasted only for two days. The significant luciferase signal obtained with neutral microbubbles decreased over 2days and reached a plateau with a level around 1 log above the signal obtained with pFAR4 alone. With the newly designed positively charged microbubbles, we obtained a much stronger bioluminescence signal which increased over 2days. The 12-fold difference (p<0.05) between MicroMarker™ and our positively charged microbubbles was maintained over a period of 6months. Noteworthy, the positively charged microbubbles led to an improvement of 180-fold (p<0.001) as regard to free pDNA using unfocused ultrasound performed at clinically tolerated ultrasound amplitude. Transient liver damage was observed when using the cationic microbubble-pFAR4 complexes and the optimized sonoporation parameters. Immunohistochemistry analyses were performed to determine the nature of cells transfected. The pFAR4 miniplasmid complexed with cationic microbubbles allowed to transfect mostly hepatocytes compared to its co-injection with MicroMarker™ which transfected more preferentially endothelial cells. Copyright © 2017 Elsevier B.V. All rights reserved.

Ultra-low-dose Ultrasound Molecular Imaging for the Detection of Angiogenesis in a Mouse Murine Tumor Model: How Little Can We See?

PubMed Central

Wang, Shiying; Herbst, Elizabeth B.; Mauldin, F. William; Diakova, Galina B.; Klibanov, Alexander L.; Hossack, John A.

2016-01-01

Objectives The objective of this study is to evaluate the minimum microbubble dose for ultrasound molecular imaging to achieve statistically significant detection of angiogenesis in a mouse model. Materials and Methods The pre-burst minus post-burst method was implemented on a Verasonics ultrasound research scanner using a multi-frame compounding pulse inversion imaging sequence. Biotinylated lipid (distearoyl phosphatidylcholine, DSPC-based) microbubbles that were conjugated with anti-vascular endothelial growth factor 2 (VEGFR2) antibody (MBVEGFR2) or isotype control antibody (MBControl) were injected into mice carrying adenocarcinoma xenografts. Different injection doses ranging from 5 × 104 to 1 × 107 microbubbles per mouse were evaluated to determine the minimum diagnostically effective dose. Results The proposed imaging sequence was able to achieve statistically significant detection (p < 0.05, n = 5) of VEGFR2 in tumors with a minimum MBVEGFR2 injection dose of only 5 × 104 microbubbles per mouse (DSPC at 0.053 ng/g mouse body mass). Non-specific adhesion of MBControl at the same injection dose was negligible. Additionally, the targeted contrast ultrasound signal of MBVEGFR2 decreased with lower microbubble doses, while non-specific adhesion of MBControl increased with higher microbubble doses. Conclusions 5 × 104 microbubbles per animal is now the lowest injection dose on record for ultrasound molecular imaging to achieve statistically significant detection of molecular targets in vivo. Findings in this study provide us with further guidance for future developments of clinically translatable ultrasound molecular imaging applications using a lower dose of microbubbles. PMID:27654582

Focused ultrasound and microbubbles for enhanced extravasation.

PubMed

Böhmer, M R; Chlon, C H T; Raju, B I; Chin, C T; Shevchenko, T; Klibanov, A L

2010-11-20

The permeability of blood vessels for albumin can be altered by using ultrasound and polymer or lipid-shelled microbubbles. The region in which the microbubbles were destroyed with focused ultrasound was quantified in gel phantoms as a function of pressure, number of cycles and type of microbubble. At 2MPa the destruction took place in a fairly wide area for a lipid-shelled agent, while for polymer-shelled agents at this setting, distinct destruction spots with a radius of only 1mm were obtained. When microbubbles with a thicker shell were used, the pressure above which the bubbles were destroyed shifts to higher values. In vivo both lipid and polymer microbubbles increased the extravasation of the albumin binding dye Evans Blue, especially in muscle leading to about 6-8% of the injected dose to extravasate per gram muscle tissue 30 min after start of the treatment, while no Evans Blue could be detected in muscle in the absence of microbubbles. Variation in the time between ultrasound treatment and Evans Blue injection, demonstrated that the time window for promoting extravasation is at least an hour at the settings used. In MC38 tumors, extravasation already occurred without ultrasound and only a trend towards enhancement with about a factor of 2 could be established with a maximum percentage injected dose per gram of 3%. Ultrasound mediated microbubble destruction especially enhances the extravasation in the highly vascularized outer part of the MC38 tumor and adjacent muscle and would, therefore, be most useful for release of, for instance, anti-angiogenic drugs. Copyright © 2010 Elsevier B.V. All rights reserved.

Ultrasonic bubbles in medicine: influence of the shell.

PubMed

Postema, Michiel; Schmitz, Georg

2007-04-01

Ultrasound contrast agents consist of microscopically small bubbles encapsulated by an elastic shell. These microbubbles oscillate upon ultrasound insonification, and demonstrate highly nonlinear behavior, ameliorating their detectability. (Potential) medical applications involving the ultrasonic disruption of contrast agent microbubble shells include release-burst imaging, localized drug delivery, and noninvasive blood pressure measurement. To develop and enhance these techniques, predicting the cracking behavior of ultrasound-insonified encapsulated microbubbles has been of importance. In this paper, we explore microbubble behavior in an ultrasound field, with special attention to the influence of the bubble shell. A bubble in a sound field can be considered a forced damped harmonic oscillator. For encapsulated microbubbles, the presence of a shell has to be taken into account. In models, an extra damping parameter and a shell stiffness parameter have been included, assuming that Hooke's Law holds for the bubble shell. At high acoustic amplitudes, disruptive phenomena have been observed, such as microbubble fragmentation and ultrasonic cracking. We analyzed the occurrence of ultrasound contrast agent fragmentation, by simulating the oscillating behavior of encapsulated microbubbles with various sizes in a harmonic acoustic field. Fragmentation occurs exclusively during the collapse phase and occurs if the kinetic energy of the collapsing microbubble is greater than the instantaneous bubble surface energy, provided that surface instabilities have grown big enough to allow for break-up. From our simulations it follows that the Blake critical radius is not a good approximation for a fragmentation threshold. We demonstrated how the phase angle differences between a damped radially oscillating bubble and an incident sound field depend on shell parameters.

Microbubble responses to a similar mechanical index with different real-time perfusion imaging techniques.

PubMed

Porter, Thomas R; Oberdorfer, Joseph; Rafter, Patrick; Lof, John; Xie, Feng

2003-08-01

The purpose of this study was to determine differences in contrast enhancement and microbubble destruction rates with current commercially available low-mechanical index (MI) real-time perfusion imaging modalities. A tissue-mimicking phantom was developed that had vessels at 3 cm (near field) and 9 cm (far field) from a real-time transducer. Perfluorocarbon-exposed sonicated dextrose albumin microbubbles (PESDA) were injected proximal to a mixing chamber, and then passed through these vessels while the region was insonified with either pulses of alternating polarity with pulse inversion Doppler (PID) or pulses of alternating amplitude by power modulation (PM) at MIs of 0.1, 0.2 and 0.3. Effluent microbubble concentration, contrast intensity and the slope of digital contrast intensity vs. time were measured. Our results demonstrated that microbubble destruction already occurs with PID at an MI of 0.1. Contrast intensity seen with PID was less than with PM. Therefore, differences in contrast enhancement and microbubble destruction rates occur at a similar MI setting when using different real-time pulse sequence schemes.

High-frequency ultrasound-guided disruption of glycoprotein VI-targeted microbubbles targets atheroprogressison in mice.

PubMed

Metzger, Katja; Vogel, Sebastian; Chatterjee, Madhumita; Borst, Oliver; Seizer, Peter; Schönberger, Tanja; Geisler, Tobias; Lang, Florian; Langer, Harald; Rheinlaender, Johannes; Schäffer, Tilman E; Gawaz, Meinrad

2015-01-01

Targeted contrast-enhanced ultrasound (CEU) using microbubble agents is a promising non-invasive imaging technique to evaluate atherosclerotic lesions. In this study, we decipher the diagnostic and therapeutic potential of targeted-CEU with soluble glycoprotein (GP)-VI in vivo. Microbubbles were conjugated with the recombinant fusion protein GPVI-Fc (MBGPVI) that binds with high affinity to atherosclerotic lesions. MBGPVI or control microbubbles (MBC) were intravenously administered into ApoE(-/-) or wild type mice and binding of the microbubbles to the vessel wall was visualized by high-resolution CEU. CEU molecular imaging signals of MBGPVI were substantially enhanced in the aortic arch and in the truncus brachiocephalicus in ApoE(-/-) as compared to wild type mice. High-frequency ultrasound (HFU)-guided disruption of MBGPVI enhanced accumulation of GPVI in the atherosclerotic lesions, which may interfere with atheroprogression. Thus, we establish targeted-CEU with soluble GPVI as a novel non-invasive molecular imaging method for atherosclerosis. Further, HFU-guided disruption of GPVI-targeted microbubbles is an innovate therapeutic approach that potentially prevents progression of atherosclerotic disease. Copyright © 2014 Elsevier Ltd. All rights reserved.

Fluid Viscosity Affects the Fragmentation and Inertial Cavitation Threshold of Lipid-Encapsulated Microbubbles.

PubMed

Helfield, Brandon; Black, John J; Qin, Bin; Pacella, John; Chen, Xucai; Villanueva, Flordeliza S

2016-03-01

Ultrasound and microbubble optimization studies for therapeutic applications are often conducted in water/saline, with a fluid viscosity of 1 cP. In an in vivo context, microbubbles are situated in blood, a more viscous fluid (∼4 cP). In this study, ultrahigh-speed microscopy and passive cavitation approaches were employed to investigate the effect of fluid viscosity on microbubble behavior at 1 MHz subject to high pressures (0.25-2 MPa). The propensity for individual microbubble (n = 220) fragmentation was found to significantly decrease in 4-cP fluid compared with 1-cP fluid, despite achieving similar maximum radial excursions. Microbubble populations diluted in 4-cP fluid exhibited decreased wideband emissions (up to 10.2 times), and increasingly distinct harmonic emission peaks (e.g., ultraharmonic) with increasing pressure, compared with those in 1-cP fluid. These results suggest that in vitro studies should consider an evaluation using physiologic viscosity perfusate before transitioning to in vivo evaluations. Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

The effect of lipid monolayer in-plane rigidity on in vivo microbubble circulation persistence

PubMed Central

Garg, Sumit; Thomas, Alex A.; Borden, Mark A.

2013-01-01

The goal of this study was to increase in vivo microbubble circulation persistence for applications in medical imaging and targeted drug delivery. Our approach was to investigate the effect of lipid monolayer in-plane rigidity to reduce the rate of microbubble dissolution, while holding constant the microbubble size, concentration and surface architecture. We first estimated the impact of acyl chain length of the main diacyl phosphatidyl-choline (PC) lipid and inter-lipid distance on the cohesive surface energy and, based on these results, we hypothesized that microbubble stability and in vivo ultrasound contrast persistence would increase monotonically with increasing acyl chain length. We therefore measured microbubble in vitro stability to dilution with and without ultrasound exposure, as well as in vivo ultrasound contrast persistence. All measurements showed a sharp rise in stability between DPPC (C16:0) and DSPC (C18:0), which correlates to the wrinkling transition, which signals the onset of significant surface shear and gas permeation resistance, observed in prior single-bubble dissolution studies. Further evidence for the effect of the wrinkling transition came from an in vitro and in vivo stability comparison of microbubbles coated with pure DPPC with those of lung surfactant extract. Microbubble stability against dilution without ultrasound and in vivo ultrasound contrast persistence showed a monotonic increase with acyl chain length from DSPC to DBPC (C22:0). However, we also observed that stability dropped precipitously for all measurements on further increasing lipid acyl chain length from DBPC to DLiPC (C24:0). This result suggests that hydrophobic mismatch between the main PC lipid and the lipopolymer emulsifier, DSPE-PEG5000, may drive a less stable surface microstructure. Overall, these results support our general hypothesis of the role of in-plane rigidity for increasing the lifetime of microbubble circulation. PMID:23787108

Inertial cavitation threshold of nested microbubbles.

PubMed

Wallace, N; Dicker, S; Lewin, Peter; Wrenn, S P

2015-04-01

Cavitation of ultrasound contrast agents (UCAs) promotes both beneficial and detrimental bioeffects in vivo (Radhakrishnan et al., 2013) [1]. The ability to determine the inertial cavitation threshold of UCA microbubbles has potential application in contrast imaging, development of therapeutic agents, and evaluation of localized effects on the body (Ammi et al., 2006) [2]. This study evaluates a novel UCA and its inertial cavitation behavior as determined by a home built cavitation detection system. Two 2.25 MHz transducers are placed at a 90° angle to one another where one transducer is driven by a high voltage pulser and the other transducer receives the signal from the oscillating microbubble. The sample chamber is placed in the overlap of the focal region of the two transducers where the microbubbles are exposed to a pulser signal consisting of 600 pulse trains per experiment at a pulse repetition frequency of 5 Hz where each train has four pulses of four cycles. The formulation being analyzed is comprised of an SF6 microbubble coated by a DSPC PEG-3000 monolayer nested within a poly-lactic acid (PLA) spherical shell. The effect of varying shell diameters and microbubble concentration on cavitation threshold profile for peak negative pressures ranging from 50 kPa to 2 MPa are presented and discussed in this paper. The nesting shell decreases inertial cavitation events from 97.96% for an un-nested microbubble to 19.09% for the same microbubbles nested within a 2.53 μm shell. As shell diameter decreases, the percentage of inertially cavitating microbubbles also decreases. For nesting formulations with average outer capsule diameters of 20.52, 14.95, 9.95, 5.55, 2.53, and 1.95 μm, the percentage of sample destroyed at 1 MPa was 51.02, 38.94, 33.25, 25.27, 19.09, and 5.37% respectively. Copyright © 2015 Elsevier B.V. All rights reserved.

Effects of the microbubble shell physicochemical properties on ultrasound-mediated drug delivery to the brain.

PubMed

Wu, Shih-Ying; Chen, Cherry C; Tung, Yao-Sheng; Olumolade, Oluyemi O; Konofagou, Elisa E

2015-08-28

Lipid-shelled microbubbles have been used in ultrasound-mediated drug delivery. The physicochemical properties of the microbubble shell could affect the delivery efficiency since they determine the microbubble mechanical properties, circulation persistence, and dissolution behavior during cavitation. Therefore, the aim of this study was to investigate the shell effects on drug delivery efficiency in the brain via blood-brain barrier (BBB) opening in vivo using monodisperse microbubbles with different phospholipid shell components. The physicochemical properties of the monolayer were varied by using phospholipids with different hydrophobic chain lengths (C16, C18, and C24). The dependence on the molecular size and acoustic energy (both pressure and pulse length) were investigated. Our results showed that a relatively small increase in the microbubble shell rigidity resulted in a significant increase in the delivery of 40-kDa dextran, especially at higher pressures. Smaller (3kDa) dextran did not show significant difference in the delivery amount, suggesting that the observed shell effect was molecular size-dependent. In studying the impact of acoustic energy on the shell effects, it was found that they occurred most significantly at pressures causing microbubble destruction (450kPa and 600kPa); by increasing the pulse length to deliver the 40-kDa dextran, the difference between C16 and C18 disappeared while C24 still achieved the highest delivery efficiency. These indicated that the acoustic energy could be used to modulate the shell effects. The acoustic cavitation emission revealed the physical mechanisms associated with different shells. Overall, lipid-shelled microbubbles with long hydrophobic chain length could achieve high delivery efficiency for larger molecules especially with high acoustic energy. Our study, for the first time, offered evidence directly linking the microbubble monolayer shell with their efficacy for drug delivery in vivo. Copyright © 2015 Elsevier B.V. All rights reserved.

Trapping of a micro-bubble by non-paraxial Gaussian beam: computation using the FDTD method.

PubMed

Sung, Seung-Yong; Lee, Yong-Gu

2008-03-03

Optical forces on a micro-bubble were computed using the Finite Difference Time Domain method. Non-paraxial Gaussian beam equation was used to represent the incident laser with high numerical aperture, common in optical tweezers. The electromagnetic field distribution around a micro-bubble was computed using FDTD method and the electromagnetic stress tensor on the surface of a micro-bubble was used to compute the optical forces. By the analysis of the computational results, interesting relations between the radius of the circular trapping ring and the corresponding stability of the trap were found.

Multifunctional microbubbles and nanobubbles for photoacoustic and ultrasound imaging

PubMed Central

Kim, Chulhong; Qin, Ruogu; Xu, Jeff S.; Wang, Lihong V.; Xu, Ronald

2010-01-01

We develop a novel dual-modal contrast agent—encapsulated-ink poly(lactic-co-glycolic acid) (PLGA) microbubbles and nanobubbles—for photoacoustic and ultrasound imaging. Soft gelatin phantoms with embedded tumor simulators of encapsulated-ink PLGA microbubbles and nanobubbles in various concentrations are clearly shown in both photoacoustic and ultrasound images. In addition, using photoacoustic imaging, we successfully image the samples positioned below 1.8-cm-thick chicken breast tissues. Potentially, simultaneous photoacoustic and ultrasound imaging enhanced by encapsulated-dye PLGA microbubbles or nanobubbles can be a valuable tool for intraoperative assessment of tumor boundaries and therapeutic margins. PMID:20210423

Resonance and streaming of armored microbubbles

NASA Astrophysics Data System (ADS)

Spelman, Tamsin; Bertin, Nicolas; Stephen, Olivier; Marmottant, Philippe; Lauga, Eric

2015-11-01

A new experimental technique involves building a hollow capsule which partially encompasses a microbubble, creating an ``armored microbubble'' with long lifespan. Under acoustic actuation, such bubble produces net streaming flows. In order to theoretically model the induced flow, we first extend classical models of free bubbles to describe the streaming flow around a spherical body for any known axisymmetric shape oscillation. A potential flow model is then employed to determine the resonance modes of the armored microbubble. We finally use a more detailed viscous model to calculate the surface shape oscillations at the experimental driving frequency, and from this we predict the generated streaming flows.

Lipid microbubbles as a vehicle for targeted drug delivery using focused ultrasound-induced blood-brain barrier opening.

PubMed

Sierra, Carlos; Acosta, Camilo; Chen, Cherry; Wu, Shih-Ying; Karakatsani, Maria E; Bernal, Manuel; Konofagou, Elisa E

2017-04-01

Focused ultrasound in conjunction with lipid microbubbles has fully demonstrated its ability to induce non-invasive, transient, and reversible blood-brain barrier opening. This study was aimed at testing the feasibility of our lipid-coated microbubbles as a vector for targeted drug delivery in the treatment of central nervous system diseases. These microbubbles were labeled with the fluorophore 5-dodecanoylaminfluorescein. Focused ultrasound targeted mouse brains in vivo in the presence of these microbubbles for trans-blood-brain barrier delivery of 5-dodecanoylaminfluorescein. This new approach, compared to previously studies of our group, where fluorescently labeled dextrans and microbubbles were co-administered, represents an appreciable improvement in safety outcome and targeted drug delivery. This novel technique allows the delivery of 5-dodecanoylaminfluorescein at the region of interest unlike the alternative of systemic exposure. 5-dodecanoylaminfluorescein delivery was assessed by ex vivo fluorescence imaging and by in vivo transcranial passive cavitation detection. Stable and inertial cavitation doses were quantified. The cavitation dose thresholds for estimating, a priori, successful targeted drug delivery were, for the first time, identified with inertial cavitation were concluded to be necessary for successful delivery. The findings presented herein indicate the feasibility and safety of the proposed microbubble-based targeted drug delivery and that, if successful, can be predicted by cavitation detection in vivo.

Measurement of radial artery contrast intensity to assess cardiac microbubble behavior.

PubMed

Sosnovik, David E; Januzzi, James L; Church, Charles C; Mertsch, Judith A; Sears, Andrea L; Fetterman, Robert C; Walovitch, Richard C; Picard, Michael H

2003-12-01

We sought to determine whether analysis of the contrast signal from the radial artery is better able to reflect changes in left ventricular (LV) microbubble dynamics than the signal from the LV itself. Assessment of microbubble behavior from images of the LV may be affected by attenuation from overlying microbubbles and nonuniform background signal intensities. The signal intensity from contrast in a peripheral artery is not affected by these artifacts and may, thus, be more accurate. After injection of a contrast bolus into a peripheral vein, signal intensity was followed simultaneously in the LV and radial artery. The measurements were repeated using continuous, triggered, low and high mechanical index harmonic imaging of the LV. Peak and integrated signal intensities ranged from 25 dB and 1550 dB/s, respectively, with radial artery imaging to 5.6 dB and 471 dB/s with ventricular imaging. Although differences in microbubble behavior during the different imaging protocols could be determined from both the LV and radial artery curves, analysis of the radial artery curves yielded more consistent and robust differences. The signal from microbubbles in the radial artery is not affected by shadowing and is, thus, a more accurate reflection of microbubble behavior in the LV than the signal from the LV itself. This may have important implications for the measurement of myocardial perfusion by contrast echocardiography.

Hydrodynamic Forces on Microbubbles under Ultrasound Excitation

NASA Astrophysics Data System (ADS)

Clark, Alicia; Aliseda, Alberto

2014-11-01

Ultrasound (US) pressure waves exert a force on microbubbles that can be used to steer them in a flow. To control the motion of microbubbles under ultrasonic excitation, the coupling between the volume oscillations induced by the ultrasound pressure and the hydrodynamic forces needs to be well understood. We present experimental results for the motion of small, coated microbubbles, with similar sizes and physico-chemical properties as clinically-available ultrasound contrast agents (UCAs). The size distribution for the bubbles, resulting from the in-house manufacturing process, was characterized by analysis of high magnification microscopic images and determined to be bimodal. More than 99% of the volume is contained in microbubbles less than 10 microns in diameter, the size of a red blood cell. The motion of the microbubbles in a pulsatile flow, at different Reynolds and Womersley numbers, is studied from tracking of high-speed shadowgraphy. The influence of ultrasound forcing, at or near the resonant frequency of the bubbles, on the hydrodynamic forces due to the pulsatile flow is determined from the experimental measurements of the trajectories. Previous evidence of a sign reversal in Saffman lift is the focus of particular attention, as this is frequently the only hydrodynamic force acting in the direction perpendicular to the flow pathlines. Application of the understanding of this physical phenomenon to targeted drug delivery is analyzed in terms of the transport of the microbubbles. NSF GRFP.

Lipid microbubbles as a vehicle for targeted drug delivery using focused ultrasound-induced blood–brain barrier opening

PubMed Central

Sierra, Carlos; Acosta, Camilo; Chen, Cherry; Wu, Shih-Ying; Karakatsani, Maria E; Bernal, Manuel

2016-01-01

Focused ultrasound in conjunction with lipid microbubbles has fully demonstrated its ability to induce non-invasive, transient, and reversible blood–brain barrier opening. This study was aimed at testing the feasibility of our lipid-coated microbubbles as a vector for targeted drug delivery in the treatment of central nervous system diseases. These microbubbles were labeled with the fluorophore 5-dodecanoylaminfluorescein. Focused ultrasound targeted mouse brains in vivo in the presence of these microbubbles for trans-blood–brain barrier delivery of 5-dodecanoylaminfluorescein. This new approach, compared to previously studies of our group, where fluorescently labeled dextrans and microbubbles were co-administered, represents an appreciable improvement in safety outcome and targeted drug delivery. This novel technique allows the delivery of 5-dodecanoylaminfluorescein at the region of interest unlike the alternative of systemic exposure. 5-dodecanoylaminfluorescein delivery was assessed by ex vivo fluorescence imaging and by in vivo transcranial passive cavitation detection. Stable and inertial cavitation doses were quantified. The cavitation dose thresholds for estimating, a priori, successful targeted drug delivery were, for the first time, identified with inertial cavitation were concluded to be necessary for successful delivery. The findings presented herein indicate the feasibility and safety of the proposed microbubble-based targeted drug delivery and that, if successful, can be predicted by cavitation detection in vivo. PMID:27278929

Characterization of non-endcapped polymeric ODS column for the separation of triacylglycerol positional isomers.

PubMed

Gotoh, Naohiro; Matsumoto, Yumiko; Yuji, Hiromi; Nagai, Toshiharu; Mizobe, Hoyo; Ichioka, Kenji; Kuroda, Ikuma; Noguchi, Noriko; Wada, Shun

2010-01-01

The characteristics of a non-endcapped polymeric ODS column for the resolution of triacylglycerol positional isomers (TAG-PI) were examined using a recycle HPLC-atmospheric pressure chemical ionization/mass spectrometry system. A pair of TAG-PI containing saturated fatty acids at least 12 carbons was separated. Except for TAG-PI containing elaidic acid, pairs of TAG-PI containing three unsaturated fatty acids were not separated, even by recycle runs. These results indicate that the resolution of TAG-PI on a non-endcapped polymeric ODS stationary phase is realized by the recognition of the linear structure of the fatty acid and the binding position of the saturated fatty acid in TAG-PI. Chain length was also an important factor for resolution. This method may be a useful and simple for measuring the abundance ratio of TAG-PI containing saturated fatty acids in natural oils.

Integrated protein analysis platform based on column switch recycling size exclusion chromatography, microenzymatic reactor and microRPLC-ESI-MS/MS.

PubMed

Yuan, Huiming; Zhou, Yuan; Zhang, Lihua; Liang, Zhen; Zhang, Yukui

2009-10-30

An integrated platform with the combination of proteins and peptides separation was established via the unit of on-line proteins digestion, by which proteins were in sequence separated by column switch recycling size exclusion chromatography (csrSEC), on-line digested by an immobilized trypsin microreactor, trapped and desalted by two parallel C8 precolumns, separated by microRPLC with the linear gradient of organic modifier concentration, and identified by ESI-MS/MS. A 6-protein mixture, with Mr ranging from 10 kDa to 80 kDa, was used to evaluate the performance of the integrated platform, and all proteins were identified with sequence coverage over 5.67%. Our experimental results demonstrate that such an integrated platform is of advantages such as good time compatibility, high peak capacity, and facile automation, which might be a promising approach for proteome study.

Efficiency of jet grout columns and sand-recycled material mixtures for mitigating liquefaction damage

NASA Astrophysics Data System (ADS)

Kerem Ertek, M.; Demir, Gökhan; Köktan, Utku

2017-04-01

Liquefaction is an important seismic phenomena that has to be assessed and consequently makes it essential to take measures in order to reduce related hazards. There are several ways to assess liquefaction potential analytically and some constitutive models implemented in FEM softwares presenting cyclic behaviour of sand making it possible to observe shear strain or excess pore pressure ratio which are measures to hold a view about liquefaction occurrence. According to various studies in the literature, post-earthquake inspections show that the measures in terms of grouting, piled rafts and sand mixtures with different non-liquefiable materials reduce liquefaction related damage. This paper aims to provide a brief information about effectiveness of jet-grout columns and recycled material-sand mixtures against liquefaction by the help of numerical analyses performed with MIDAS GTS NX software with regard to generation of shear strains. Key words: liquefaction, numerical analyses, jet-grout, sand mixtures

Micro- and nanobubbles: a versatile non-viral platform for gene delivery.

PubMed

Cavalli, Roberta; Bisazza, Agnese; Lembo, David

2013-11-18

Micro- and nanobubbles provide a promising non-viral strategy for ultrasound mediated gene delivery. Microbubbles are spherical gas-filled structures with a mean diameter of 1-8 μm, characterised by their core-shell composition and their ability to circulate in the bloodstream following intravenous injection. They undergo volumetric oscillations or acoustic cavitation when insonified by ultrasound and, most importantly, they are able to resonate at diagnostic frequencies. It is due to this behaviour that microbubbles are currently being used as ultrasound contrast agents, but their use in therapeutics is still under investigation. For example, microbubbles could play a role in enhancing gene delivery to cells: when combined with clinical ultrasound exposure, microbubbles are able to favour gene entry into cells by cavitation. Two different delivery strategies have been used to date: DNA can be co-administered with the microbubbles (i.e. the contrast agent) or 'loaded' in purposed-built bubble systems - indeed a number of different technological approaches have been proposed to associate genes within microbubble structures. Nanobubbles, bubbles with sizes in the nanometre order of magnitude, have also been developed with the aim of obtaining more efficient gene delivery systems. Their small sizes allow the possibility of extravasation from blood vessels into the surrounding tissues and ultrasound-targeted site-specific release with minimal invasiveness. In contrast, microbubbles, due to their larger sizes, are unable to extravasate, thus and their targeting capacity is limited to specific antigens present within the vascular lumen. This review provides an overview of the use of microbubbles as gene delivery systems, with a specific focus on recent research into the development of nanosystems. In particular, ultrasound delivery mechanisms, formulation parameters, gene-loading approaches and the advantages of nanometric systems will be described. Copyright © 2013 Elsevier B.V. All rights reserved.

Augmentation of limb perfusion and reversal of tissue ischemia produced by ultrasound-mediated microbubble cavitation.

PubMed

Belcik, J Todd; Mott, Brian H; Xie, Aris; Zhao, Yan; Kim, Sajeevani; Lindner, Nathan J; Ammi, Azzdine; Linden, Joel M; Lindner, Jonathan R

2015-04-01

Ultrasound can increase tissue blood flow, in part, through the intravascular shear produced by oscillatory pressure fluctuations. We hypothesized that ultrasound-mediated increases in perfusion can be augmented by microbubble contrast agents that undergo ultrasound-mediated cavitation and sought to characterize the biological mediators. Contrast ultrasound perfusion imaging of hindlimb skeletal muscle and femoral artery diameter measurement were performed in nonischemic mice after unilateral 10-minute exposure to intermittent ultrasound alone (mechanical index, 0.6 or 1.3) or ultrasound with lipid microbubbles (2×10(8) IV). Studies were also performed after inhibiting shear- or pressure-dependent vasodilator pathways, and in mice with hindlimb ischemia. Ultrasound alone produced a 2-fold increase (P<0.05) in muscle perfusion regardless of ultrasound power. Ultrasound-mediated augmentation in flow was greater with microbubbles (3- and 10-fold higher than control for mechanical index 0.6 and 1.3, respectively; P<0.05), as was femoral artery dilation. Inhibition of endothelial nitric oxide synthase attenuated flow augmentation produced by ultrasound and microbubbles by 70% (P<0.01), whereas inhibition of adenosine-A2a receptors and epoxyeicosatrienoic acids had minimal effect. Limb nitric oxide production and muscle phospho-endothelial nitric oxide synthase increased in a stepwise fashion by ultrasound and ultrasound with microbubbles. In mice with unilateral hindlimb ischemia (40%-50% reduction in flow), ultrasound (mechanical index, 1.3) with microbubbles increased perfusion by 2-fold to a degree that was greater than the control nonischemic limb. Increases in muscle blood flow during high-power ultrasound are markedly amplified by the intravascular presence of microbubbles and can reverse tissue ischemia. These effects are most likely mediated by cavitation-related increases in shear and activation of endothelial nitric oxide synthase. © 2015 American Heart Association, Inc.

AUGMENTATION OF LIMB PERFUSION AND REVERSAL OF TISSUE ISCHEMIA PRODUCED BY ULTRASOUND-MEDIATED MICROBUBBLE CAVITATION

PubMed Central

Belcik, J. Todd; Mott, Brian H.; Xie, Aris; Zhao, Yan; Kim, Sajeevani; Lindner, Nathan J.; Ammi, Azzdine; Linden, Joel M.; Lindner, Jonathan R.

2015-01-01

Background Ultrasound can increase tissue blood flow in part through the intravascular shear produced by oscillatory pressure fluctuations. We hypothesized that ultrasound-mediated increases in perfusion can be augmented by microbubble contrast agents that undergo ultrasound-mediated cavitation, and sought to characterize the biologic mediators. Methods and Results Contrast ultrasound perfusion imaging of hindlimb skeletal muscle and femoral artery diameter measurement were performed in non-ischemic mice after unilateral 10 min exposure to intermittent ultrasound alone (mechanical index [MI] 0.6 or 1.3) or ultrasound with lipid microbubbles (2×108 I.V.). Studies were also performed after inhibiting shear- or pressure-dependent vasodilator pathways, and in mice with hindlimb ischemia. Ultrasound alone produced a 2-fold increase (p<0.05) in muscle perfusion regardless of ultrasound power. Ultrasound-mediated augmentation in flow was greater with microbubbles (3-fold and 10-fold higher than control for MI 0.6 and 1.3, respectively; p<0.05), as was femoral artery dilation. Inhibition of endothelial nitric oxide synthase (eNOS) attenuated flow augmentation produced by ultrasound and microbubbles by 70% (p<0.01), whereas inhibition of adenosine-A2a receptors and epoxyeicosatrienoic acids had minimal effect. Limb nitric oxide (NO) production and muscle phospho-eNOS increased in a stepwise fashion by ultrasound and ultrasound with microbubbles. In mice with unilateral hindlimb ischemia (40–50% reduction in flow), ultrasound (MI 1.3) with microbubbles increased perfusion by 2-fold to a degree that was greater than the control non-ischemic limb. Conclusions Increases in muscle blood flow during high-power ultrasound are markedly amplified by the intravascular presence of microbubbles and can reverse tissue ischemia. These effects are most likely mediated by cavitation-related increases in shear and activation of eNOS. PMID:25834183

Engineering evaluation of 55-year-old timber columns recycled from an industrial military building

Treesearch

Robert H. Falk; David Green; Douglas Rammer; Scott F. Lantz

2000-01-01

A large sample of timber was collected from a 548,000-ft.2 (50,900-m2) World War II era industrial military building containing approximately 1, 875,000 board feet (4,400 m3) of lumber and timber. Sixty 12-foot- (3.6-m-) long, nominal 8- by 8-inches (190-by 190-mm) Douglas-fir columns were tested at the USDA Forest Service, Forest Products Laboratory, and the results...

Algal cell disruption using microbubbles to localize ultrasonic energy

PubMed Central

Krehbiel, Joel D.; Schideman, Lance C.; King, Daniel A.; Freund, Jonathan B.

2015-01-01

Microbubbles were added to an algal solution with the goal of improving cell disruption efficiency and the net energy balance for algal biofuel production. Experimental results showed that disruption increases with increasing peak rarefaction ultrasound pressure over the range studied: 1.90 to 3.07 MPa. Additionally, ultrasound cell disruption increased by up to 58% by adding microbubbles, with peak disruption occurring in the range of 108 microbubbles/ml. The localization of energy in space and time provided by the bubbles improve efficiency: energy requirements for such a process were estimated to be one-fourth of the available heat of combustion of algal biomass and one-fifth of currently used cell disruption methods. This increase in energy efficiency could make microbubble enhanced ultrasound viable for bioenergy applications and is expected to integrate well with current cell harvesting methods based upon dissolved air flotation. PMID:25311188

Effect of Micro-Bubbles in Water on Beam Patterns of Parametric Array

NASA Astrophysics Data System (ADS)

Hashiba, Kunio; Masuzawa, Hiroshi

2003-05-01

The improvement in efficiency of a parametric array by nonlinear oscillation of micro-bubbles in water is studied in this paper. The micro-bubble oscillation can increase the nonlinear coefficient of the acoustic medium. The amplitude of the difference-frequency wave along the longitudinal axis and its beam patterns in the field including the layer with micro-bubbles were analyzed using a Khokhlov-Zabolotskaya-Kuznetsov (KZK) equation. As a result, the largest improvement in efficiency was obtained and a narrow parametric beam was formed by forming a layer with micro-bubbles in front of a parametric sound radiator as thick as about the shock formation distance. If the layer becomes significantly thicker than the distance, the beam of the difference-frequency wave in the far-field will become broader. If the layer is significantly thinner than the distance, the intensity level of the wave in the far-field will be too low.

Methylene blue microbubbles as a model dual-modality contrast agent for ultrasound and activatable photoacoustic imaging

NASA Astrophysics Data System (ADS)

Jeon, Mansik; Song, Wentao; Huynh, Elizabeth; Kim, Jungho; Kim, Jeesu; Helfield, Brandon L.; Leung, Ben Y. C.; Goertz, David E.; Zheng, Gang; Oh, Jungtaek; Lovell, Jonathan F.; Kim, Chulhong

2014-01-01

Ultrasound and photoacoustic imaging are highly complementary modalities since both use ultrasonic detection for operation. Increasingly, photoacoustic and ultrasound have been integrated in terms of hardware instrumentation. To generate a broadly accessible dual-modality contrast agent, we generated microbubbles (a standard ultrasound contrast agent) in a solution of methylene blue (a standard photoacoustic dye). This MB2 solution was formed effectively and was optimized as a dual-modality contrast solution. As microbubble concentration increased (with methylene blue concentration constant), photoacoustic signal was attenuated in the MB2 solution. When methylene blue concentration increased (with microbubble concentration held constant), no ultrasonic interference was observed. Using an MB2 solution that strongly attenuated all photoacoustic signal, high powered ultrasound could be used to burst the microbubbles and dramatically enhance photoacoustic contrast (>800-fold increase), providing a new method for spatiotemporal control of photoacoustic signal generation.

Gene therapy for cardiovascular disease mediated by ultrasound and microbubbles

PubMed Central

2013-01-01

Gene therapy provides an efficient approach for treatment of cardiovascular disease. To realize the therapeutic effect, both efficient delivery to the target cells and sustained expression of transgenes are required. Ultrasound targeted microbubble destruction (UTMD) technique has become a potential strategy for target-specific gene and drug delivery. When gene-loaded microbubble is injected, the ultrasound-mediated microbubble destruction may spew the transported gene to the targeted cells or organ. Meanwhile, high amplitude oscillations of microbubbles increase the permeability of capillary and cell membrane, facilitating uptake of the released gene into tissue and cell. Therefore, efficiency of gene therapy can be significantly improved. To date, UTMD has been successfully investigated in many diseases, and it has achieved outstanding progress in the last two decades. Herein, we discuss the current status of gene therapy of cardiovascular diseases, and reviewed the progress of the delivery of genes to cardiovascular system by UTMD. PMID:23594865

Methylene blue microbubbles as a model dual-modality contrast agent for ultrasound and activatable photoacoustic imaging.

PubMed

Jeon, Mansik; Song, Wentao; Huynh, Elizabeth; Kim, Jungho; Kim, Jeesu; Helfield, Brandon L; Leung, Ben Y C; Goertz, David E; Zheng, Gang; Oh, Jungtaek; Lovell, Jonathan F; Kim, Chulhong

2014-01-01

Ultrasound and photoacoustic imaging are highly complementary modalities since both use ultrasonic detection for operation. Increasingly, photoacoustic and ultrasound have been integrated in terms of hardware instrumentation. To generate a broadly accessible dual-modality contrast agent, we generated microbubbles (a standard ultrasound contrast agent) in a solution of methylene blue (a standard photoacoustic dye). This MB2 solution was formed effectively and was optimized as a dual-modality contrast solution. As microbubble concentration increased (with methylene blue concentration constant), photoacoustic signal was attenuated in the MB2 solution. When methylene blue concentration increased (with microbubble concentration held constant), no ultrasonic interference was observed. Using an MB2 solution that strongly attenuated all photoacoustic signal, high powered ultrasound could be used to burst the microbubbles and dramatically enhance photoacoustic contrast (>800-fold increase), providing a new method for spatiotemporal control of photoacoustic signal generation.

Detection of recycled marine sediment components in crater lake fluids using 129I

NASA Astrophysics Data System (ADS)

Fehn, U.; Snyder, G. T.; Varekamp, J. C.

2002-06-01

Crater lakes provide time-integrated samples of volcanic fluids, which may carry information on source components. We tested under what circumstances 129I concentrations can be used for the detection of a signal derived from the recycling of marine sediments in subduction zone magmatism. The 129I system has been successfully used to determine origin and pathways in other volcanic fluids, but the application of this system to crater lakes is complicated by the presence of anthropogenic 129I, related to recent nuclear activities. Results are reported from four crater lakes, associated with subducting crust varying in age between 23 and 98 Ma. The 129I/I ratios determined for Copahue, Argentina, (129I/I=700×10-15) and White Island, New Zealand, (129I/I=284×10-15) demonstrate the presence of iodine in the crater lakes that was derived from recycled marine sediments. A comparison to the ages of the subducted sediments in these two cases indicates that the ratios likely reflect iodine remobilization from the entire sediment column that was undergoing subduction. While the 129I signals in Poás and Rincón de la Vieja, Costa Rica also demonstrate the presence of recycled iodine, the relatively high percentage of meteoric water in these lakes prevents a reliable determination of source ages. The observed high concentrations of iodine and 129I/I ratios substantially below current surface values strongly argue for the presence of recycled marine components in the arc magmas of all four cases. Components from subducted marine sediments can be quantified and related to specific parts of the sediment column in cases where the iodine concentration in the lake waters exceeds 5 μM.

Efficacy of washing treatments in the reduction of postharvest decay of chestnuts (Castanea crenata 'Tsukuba') during storage

Treesearch

Uk Lee; Sukhyun Joo; Ned B. Klopfenstein; Mee-Sook Kim

2016-01-01

This research evaluated the influence of different washing treatments (i.e., tap water, ozone, microbubbles, and ozone combined with microbubbles) on post-harvest decay of chestnuts (Castanea crenata ‘Tsukuba’) during storage. Overall, treatments with ozone and microbubbles significantly reduced the decay frequency and the associated microbial populations (...

Chirp resonance spectroscopy of single lipid-coated microbubbles using an "acoustical camera".

PubMed

Renaud, G; Bosch, J G; van der Steen, A F W; de Jong, N

2012-12-01

An acoustical method was developed to study the resonance of single lipid-coated microbubbles. The response of 127 SonoVue microbubbles to a swept sine excitation between 0.5 and 5.5 MHz with a peak acoustic pressure amplitude of 70 kPa was measured by means of a 25 MHz probing wave. The relative amplitude modulation in the signal scattered in response to the probing wave is approximately equal to the radial strain induced by the swept sine excitation. An average damping coefficient of 0.33 and an average resonance frequency of 2.5 MHz were measured. Microbubbles experienced an average peak radial strain of 20%.

Ultrasound and Microbubble Guided Drug Delivery: Mechanistic Understanding and Clinical Implications

PubMed Central

Wang, Tzu-Yin; Wilson, Katheryne E.; Machtaler, Steven; Willmann, Jürgen K.

2014-01-01

Ultrasound mediated drug delivery using microbubbles is a safe and noninvasive approach for spatially localized drug administration. This approach can create temporary and reversible openings on cellular membranes and vessel walls (a process called “sonoporation”), allowing for enhanced transport of therapeutic agents across these natural barriers. It is generally believed that the sonoporation process is highly associated with the energetic cavitation activities (volumetric expansion, contraction, fragmentation, and collapse) of the microbubble. However, a thorough understanding of the process was unavailable until recently. Important progress on the mechanistic understanding of sonoporation and the corresponding physiological responses in vitro and in vivo has been made. Specifically, recent research shed light on the cavitation process of microbubbles and fluid motion during insonation of ultrasound, on the spatio-temporal interactions between microbubbles and cells or vessel walls, as well as on the temporal course of the subsequent biological effects. These findings have significant clinical implications on the development of optimal treatment strategies for effective drug delivery. In this article, current progress in the mechanistic understanding of ultrasound and microbubble mediated drug delivery and its implications for clinical translation is discussed. PMID:24372231

Sonothrombolysis of Intra-Catheter Aged Venous Thrombi Using Microbubble Enhancement and Guided Three Dimensional Ultrasound Pulses

PubMed Central

Kutty, Shelby; Xie, Feng; Gao, Shunji; Drvol, Lucas K; Lof, John; Fletcher, Scott E; Radio, Stanley J; Danford, David A; Hammel, James M; Porter, Thomas R

2010-01-01

Central venous and arterial catheters are a major source of thrombo-embolic disease in children. We hypothesized that guided high mechanical index (MI) impulses from diagnostic three-dimensional (3D) ultrasound during an intravenous microbubble infusion could dissolve these thrombi. An in vitro system simulating intra-catheter thrombi was created and then treated with guided high MI impulses from 3D ultrasound, utilizing low MI microbubble sensitive imaging pulse sequence schemes to detect the microbubbles (Perflutren Lipid Microsphere, Definity®, Lantheus). Ten aged thrombi over 24 hours old were tested using 3D ultrasound coupled with a continuous diluted microbubble infusion (Group A), and ten with 3D ultrasound alone (Group B). Mean thrombus age was 28.6 hours (range 26.6–30.3). Groups A exhibited a 55 ± 19 % reduction in venous thrombus size, compared to 31±10 % for Group B (p=0.008). Feasibility testing was performed in 4 pigs, establishing a model to further investigate the efficacy. Sonothrombolysis of aged intra-catheter venous thrombi can be achieved with commercially available microbubbles and guided high MI ultrasound from a diagnostic 3D transducer. PMID:20696549

Fabrication of Indocyanine Green and 2H, 3H-perfluoropentane loaded microbubbles for fluorescence and ultrasound imaging

NASA Astrophysics Data System (ADS)

He, Yutong; Wu, Qiang; Ma, Rong; Chang, Shufang; Shao, Pengfei; Xu, Ronald

2016-03-01

As a near-infrared (NIR) fluorescence dye, Indocyanine Green (ICG) has not gained broader clinical applications, owing to its multiple limitations such as concentration-dependent aggregation, low fluorescence quantum yield, poor physicochemical stability and rapid elimination from the body. In the meanwhile, 2H,3H-perfluoropentane (H-PFP) has been widely studied in ultrasound imaging as a vehicle for targeted delivery of contrast agents and drugs. We synthesized a novel dual-modal fluorescence and ultrasound contrast agent by encapsulating ICG and H-PFP in lipid microbubbles using a liquid-driven coaxial flow focusing (LDCFF) process. Uniform microbubbles with the sizes ranging from 1-10um and great ICG loading efficiency was achieved by this method. Our benchtop experiments showed that ICG/H-PFP microbubbles exhibited less aggregation, increased fluorescence intensity and more stable photostability compared to free ICG aqueous solution. Our phantom experiments demonstrated that ICG/H-PFP microbubbles enhanced the imaging contrasts in fluorescence imaging and ultrasonography. Our animal experiments indicated that ICG/H-PFP microbubbles extended the ICG life time and facilitated dual mode fluorescence and ultrasound imaging in vivo.

Steering Microbubbles in Physiologically Realistic Flows Using the Bjerknes Force

NASA Astrophysics Data System (ADS)

Clark, Alicia; Aliseda, Alberto

2017-11-01

Ultrasound contrast agents (UCAs) are lipid-coated microbubbles that are used to increase contrast in ultrasound imaging due to their ability to scatter sound. Additionally, UCAs can be used in conjunction with ultrasound in medical applications such as targeted drug delivery and thrombolysis. These applications utilize the Bjerknes force, an ultrasound-induced force caused by the phase difference between the incoming ultrasound pressure wave and the microbubble volume oscillations. The dynamics of microbubbles under ultrasound excitation have been studied thoroughly in stagnant fluid baths; however, understanding of the fundamental physics of microbubbles in physiologically realistic flows is lacking. An in vitroexperiment that reproduces the dynamics (Reynolds and Womersley numbers) of a medium-sized blood vessel was used to explore the behavior of microbubbles. Using Lagrangian tracking, the trajectory of each individual bubble was reconstructed using information obtained from high speed imaging. The balance of hydrodynamic forces (lift, drag, added mass, etc.) against the primary Bjerknes force was analyzed. The results show that an increase in ultrasound pulse repetition frequency leads to a linear increase in the Bjerknes force and the increase in the force is quadratic with the amplitude of the excitation.

Acoustic force measurements on polymer-coated microbubbles in a microfluidic device

PubMed Central

Memoli, Gianluca; Fury, Christopher R.; Baxter, Kate O.; Gélat, Pierre N.; Jones, Philip H.

2017-01-01

This work presents an acoustofluidic device for manipulating coated microbubbles, designed for the simultaneous use of optical and acoustical tweezers. A comprehensive characterization of the acoustic pressure in the device is presented, obtained by the synergic use of different techniques in the range of acoustic frequencies where visual observations showed aggregation of polymer-coated microbubbles. In absence of bubbles, the combined use of laser vibrometry and finite element modelling supported a non-invasive measurement of the acoustic pressure and an enhanced understanding of the system resonances. Calibrated holographic optical tweezers were used for direct measurements of the acoustic forces acting on an isolated microbubble, at low driving pressures, and to confirm the spatial distribution of the acoustic field. This allowed quantitative acoustic pressure measurements by particle tracking, using polystyrene beads, and an evaluation of the related uncertainties. This process facilitated the extension of tracking to microbubbles, which have a negative acoustophoretic contrast factor, allowing acoustic force measurements on bubbles at higher pressures than optical tweezers, highlighting four peaks in the acoustic response of the device. Results and methodologies are relevant to acoustofluidic applications requiring a precise characterization of the acoustic field and, in general, to biomedical applications with microbubbles or deformable particles. PMID:28599556

EFFECTS OF ACIDIC PRECIPITATION ON BENTHOS

EPA Science Inventory

The community of organisms, the benthos, which inhabit aquatic sediments interact with biological and chemical components of the water column by processing detritus, recycling inorganic nutrients, mixing sediments, and serving as a principal food source for fish, waterfowl, and r...

Design and Implementation of a Hall Effect Sensor Array Applied to Recycling Hard Drive Magnets

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kisner, Roger; Lenarduzzi, Roberto; Killough, Stephen M

Rare earths are an important resource for many electronic components and technologies. Examples abound including Neodymium magnets used in mobile devices and computer hard drives (HDDs), and a variety of renewable energy technologies (e.g., wind turbines). Approximately 21,000 metric tons of Neodymium is processed annually with less than 1% being recycled. An economic system to assist in the recycling of magnet material from post-consumer goods, such as Neodymium Iron Boron magnets commonly found in hard drives is presented. A central component of this recycling measurement system uses an array of 128 Hall Effect sensors arranged in two columns to detectmore » the magnetic flux lines orthogonal to the HDD. Results of using the system to scan planar shaped objects such as hard drives to identify and spatially locate rare-earth magnets for removal and recycling from HDDs are presented. Applications of the sensor array in other identification and localization of magnetic components and assemblies will be presented.« less

Integrated process of distillation with side reactors for synthesis of organic acid esters

DOE Office of Scientific and Technical Information (OSTI.GOV)

Panchal, Chandrakant B; Prindle, John C; Kolah, Aspri

An integrated process and system for synthesis of organic-acid esters is provided. The method of synthesizing combines reaction and distillation where an organic acid and alcohol composition are passed through a distillation chamber having a plurality of zones. Side reactors are used for drawing off portions of the composition and then recycling them to the distillation column for further purification. Water is removed from a pre-reactor prior to insertion into the distillation column. An integrated heat integration system is contained within the distillation column for further purification and optimizing efficiency in the obtaining of the final product.

Benthic flux of metals and nutrients into the water column of Lake Coeur d'Alene, Idaho report of an August, 1999, pilot study

USGS Publications Warehouse

Kuwabara, James S.; Berelson, William M.; Balistrieri, Laurie S.; Woods, Paul F.; Topping, Brent R.; Steding, Douglas J.; Krabbenhoft, David P.

2000-01-01

A field study was conducted between August 16-27, 1999, to provide the first direct measurements of the benthic flux of dissolved (0.2-micron filtered) solutes between the bottom sediment and water column at two sites in Lake Coeur d'Alene, Idaho. Trace metals (namely, cadmium, copper, manganese, mercury species, and zinc) and nutrients (namely, ammonia, nitrate plus nitrite, oxygen, orthophosphate and silica) were solutes of primary interest. Benthic flux (sometimes referred to as internal recycling) represents the transport of dissolved chemical species between the water column and the underlying sediment.

Improving ultrasound gene transfection efficiency by controlling ultrasound excitation of microbubbles

PubMed Central

Fan, Z.; Chen, D.; Deng, C.X.

2013-01-01

Ultrasound application in the presence of microbubbles has shown great potential for non-viral gene transfection via transient disruption of cell membrane (sonoporation). However, improvement of its efficiency has largely relied on empirical approaches without consistent and translatable results. The goal of this study is to develop a rational strategy based on new results obtained using novel experimental techniques and analysis to improve sonoporation gene transfection. We conducted experiments using targeted microbubbles that were attached to cell membrane to facilitate sonoporation. We quantified the dynamic activities of microbubbles exposed to pulsed ultrasound and the resulting sonoporation outcome and identified distinct regimes of characteristic microbubble behaviors: stable cavitation, coalescence and translation, and inertial cavitation. We found that inertial cavitation generated the highest rate of membrane poration. By establishing direct correlation of ultrasound-induced bubble activities with intracellular uptake and pore size, we designed a ramped pulse exposure scheme for optimizing microbubble excitation to improve sonoporation gene transfection. We implemented a novel sonoporation gene transfection system using an aqueous two phase system (ATPS) for efficient use of reagents and high throughput operation. Using plasmid coding for the green fluorescence protein (GFP), we achieved a sonoporation transfection efficiency in rate aortic smooth muscle cells (RASMCs) of 6.9% ± 2.2% (n = 9), comparable with lipofection (7.5% ± 0.8%, n = 9). Our results reveal characteristic microbubble behaviors responsible for sonoporation and demonstrated a rational strategy to improve sonoporation gene transfection. PMID:23770009

CHANGES IN LIPID-ENCAPSULATED MICROBUBBLE POPULATION DURING CONTINUOUS INFUSION AND METHODS TO MAINTAIN CONSISTENCY

PubMed Central

KAYA, MEHMET; GREGORY, THOMAS S.; DAYTON, PAUL A.

2009-01-01

Stabilized microbubbles are utilized as ultrasound contrast agents. These micron-sized gas capsules are injected into the bloodstream to provide contrast enhancement during ultrasound imaging. Some contrast imaging strategies, such as destruction-reperfusion, require a continuous injection of microbubbles over several minutes. Most quantitative imaging strategies rely on the ability to administer a consistent dose of contrast agent. Because of the buoyancy of these gas-filled agents, their spatial distribution within a syringe changes over time. The population of microbubbles that is pumped from a horizontal syringe outlet differs from initial population as the microbubbles float to the syringe top. In this manuscript, we study the changes in the population of a contrast agent that is pumped from a syringe due to microbubble floatation. Results are presented in terms of change in concentration and change in mean diameter, as a function of time, suspension medium, and syringe diameter. Data illustrate that the distribution of contrast agents injected from a syringe changes in both concentration and mean diameter over several minutes without mixing. We discuss the application of a mixing system and viscosity agents to keep the contrast solution more evenly distributed in a syringe. These results are significant for researchers utilizing microbubble contrast agents in continuous-infusion applications where it is important to maintain consistent contrast agent delivery rate, or in situations where the injection syringe cannot be mixed immediately prior to administration. PMID:19632760

Ideal versus real automated twin column recycling chromatography process.

PubMed

Gritti, Fabrice; Leal, Mike; McDonald, Thomas; Gilar, Martin

2017-07-28

The full baseline separation of two compounds (selectivity factors α<1.03) is either impractical (too long analysis times) or even impossible when using a single column of any length given the pressure limitations of current LC instruments. The maximum efficiency is that of an infinitely long column operated at infinitely small flow rates. It is determined by the maximum allowable system pressure, the column permeability (particle size), the viscosity of the eluent, and the intensity of the effective diffusivity of the analytes along the column. Alternatively, the twin-column recycling separation process (TCRSP) can overcome the efficiency limit of the single-column approach. In the TCRSP, the sample mixture may be transferred from one to a second (twin) column until its band has spread over one column length. Basic theory of chromatography is used to confirm that the speed-resolution performance of the TCRSP is intrinsically superior to that of the single-column process. This advantage is illustrated in this work by developing an automated TCRSP for the challenging separation of two polycyclic aromatic hydrocarbon (PAH) isomers (benzo[a]anthracene and chrysene) in the reversed-phase retention mode at pressure smaller than 5000psi. The columns used are the 3.0mm×150mm column packed with 3.5μm XBridge BEH-C 18 material (α=1.010) and the 3.0mm or 4.6mm×150mm columns packed with the same 3.5μm XSelect HSST 3 material (α=1.025). The isocratic mobile phase is an acetonitrile-water mixture (80/20, v/v). Remarkably, significant differences are observed between the predicted retention times and efficiencies of the ideal TCRSP (given by the number of cycles multiplied by the retention time and efficiency of one column) and those of the real TCRSP. The fundamental explanation lies in the pressure-dependent retention of these PAHs or in the change of their partial molar volume as they are transferred from the mobile to the stationary phase. A revisited retention and efficiency model is then built to predict the actual performance of real TCRSPs. The experimental and calculated resolution data are found in very good agreement for a change, Δv m =-10cm 3 /mol, of the partial molar volume of the two PAH isomers upon transfer from the acetonitrile-water eluent mixture to the silica-C 18 stationary phase. Copyright © 2017 Elsevier B.V. All rights reserved.

Ultrasound mediated nanoparticle drug delivery

NASA Astrophysics Data System (ADS)

Mullin, Lee B.

Ultrasound is not only a powerful diagnostic tool, but also a promising therapeutic technology that can be used to improve localized drug delivery. Microbubble contrast agents are micron sized encapsulated gas filled bubbles that are administered intravenously. Originally developed to enhance ultrasound images, microbubbles are highly echogenic due to the gas core that provides a detectable impedance difference from the surrounding medium. The core also allows for controlled response of the microbubbles to ultrasound pulses. Microbubbles can be pushed using acoustic radiation force and ruptured using high pressures. Destruction of microbubbles can increase permeability at the cellular and vascular level, which can be advantageous for drug delivery. Advances in drug delivery methods have been seen with the introduction of nanoparticles, nanometer sized objects often carrying a drug payload. In chemotherapy, nanoparticles can deliver drugs to tumors while limiting systemic exposure due to abnormalities in tumor vasculature such large gaps between endothelial cells that allow nanoparticles to enter into the interstitial space; this is referred to as the enhanced permeability and retention (EPR) effect. However, this effect may be overestimated in many tumors. Additionally, only a small percentage of the injected dose accumulates in the tumor, which most the nanoparticles accumulating in the liver and spleen. It is hypothesized that combining the acoustic activity of an ultrasound contrast agent with the high payload and extravasation ability of a nanoparticle, localized delivery to the tumor with reduced systemic toxicity can be achieved. This method can be accomplished by either loading nanoparticles onto the shell of the microbubble or through a coadministration method of both nanoparticles and microbubbles. The work presented in this dissertation utilizes novel and commercial nanoparticle formulations, combined with microbubbles and a variety of ultrasound systems. Ultrasound parameters are optimized to achieve maximum cell internalization of molecules and increased nanoparticle delivery to a cell layer on a coverslip. In-vivo studies demonstrate the possibility of using a lower dose of paclitaxel to slow tumor growth rates, increase doxorubicin concentration in tumor tissue, and enhance tumor delivery of fluorescent molecules through treatments that combine nanoparticles with ultrasound and microbubbles.

Application of colloidal gas aphron suspensions produced from Sapindus mukorossi for arsenic removal from contaminated soil.

PubMed

Mukhopadhyay, Soumyadeep; Mukherjee, Sumona; Hashim, Mohd Ali; Sen Gupta, Bhaskar

2015-01-01

Colloidal gas aphron dispersions (CGAs) can be described as a system of microbubbles suspended homogenously in a liquid matrix. This work examines the performance of CGAs in comparison to surfactant solutions for washing low levels of arsenic from an iron rich soil. Sodium Dodecyl Sulfate (SDS) and saponin, a biodegradable surfactant, obtained from Sapindus mukorossi or soapnut fruit were used for generating CGAs and solutions for soil washing. Column washing experiments were performed in down-flow and up flow modes at a soil pH of 5 and 6 using varying concentration of SDS and soapnut solutions as well as CGAs. Soapnut CGAs removed more than 70% arsenic while SDS CGAs removed up to 55% arsenic from the soil columns in the soil pH range of 5-6. CGAs and solutions showed comparable performances in all the cases. CGAs were more economical since it contains 35% of air by volume, thereby requiring less surfactant. Micellar solubilization and low pH of soapnut facilitated arsenic desorption from soil column. FT-IR analysis of effluent suggested that soapnut solution did not interact chemically with arsenic thereby facilitating the recovery of soapnut solution by precipitating the arsenic. Damage to soil was minimal arsenic confirmed by metal dissolution from soil surface and SEM micrograph. Copyright © 2014 Elsevier Ltd. All rights reserved.

Acoustic Studies on Nanodroplets, Microbubbles and Liposomes

NASA Astrophysics Data System (ADS)

Kumar, Krishna Nandan

Microbubbles and droplets are nanometer to micron size biocompatible particles which are primarily used for drug delivery and contrast imaging. Our aim is to broaden the use of microbubbles from contrast imaging to other applications such as measuring blood pressure. The other goal is to develop in situ contrast agents (phase shift droplets) which can be used for applications such as cancer tumor imaging. Therefore, the focus is on developing and validating the concept using experimental and theoretical methods. Below is an overview of each of the projects performed on droplets and microbubbles. Phase shift droplets vaporizable by acoustic stimulation offer many advantages over microbubbles as contrast agents due to their higher stability and possibility of smaller sizes. In this study, the acoustic droplet vaporization (ADV) threshold of a suspension of PFP droplets (400-3000nm) was acoustically measured as a function of the excitation frequency by examining the scattered signals, fundamental, sub- and second-harmonic. This work presents the experimental methodology to determine ADV threshold. The threshold increases with frequency: 1.25 MPa at 2.25 MHz, 2.0 MPa at 5 MHz and 2.5 MPa at 10 MHz. The scattered response from droplets was also found to match well with that of independently prepared lipid-coated microbubble suspension in magnitude as well as trends above the threshold value. Additionally, we have employed classical nucleation theory (CNT) to investigate the ADV, specifically the threshold value of the peak negative pressure required for vaporization. The theoretical analysis predicts that the ADV threshold increases with increasing surface tension of the droplet core and frequency of excitation, while it decreases with increasing temperature and droplet size. The predictions are in qualitative agreement with experimental observations. A technique to measure the ambient pressure using microbubbles was developed. Here we are presenting the results of an in vitro study aimed at developing an ultrasound-aided noninvasive pressure estimation technique using contrast agents-DefinityRTM, a lipid coated microbubble, and an experimental PLA (Poly lactic acid) microbubbles. Scattered responses from these bubbles have been measured in vitro as a function of ambient pressure using a 3.5 MHz acoustic excitation of varying amplitude. At an acoustic pressure of 670 kPa, Definity RTM microbubbles showed a linear decrease in subharmonic signal with increasing ambient pressure, registering a 12dB reduction at an overpressure of 120 mm Hg. Ultrasound contrast microbubbles experience widely varying ambient blood pressure in different organs, which can also change due to diseases. Pressure change can alter the material properties of the encapsulation of these microbubbles. Here the characteristic rheological parameters of contrast agent Definity and Targestar are determined by varying the ambient pressure (in a physiologically relevant range 0-200 mmHg). Four different interfacial rheological models are used to characterize the microbubbles. Both the contrast agents show an increase in their interfacial dilatational viscosity and interfacial dilatational elasticity with ambient pressure. It has been well established that liposomes prepared following a careful multi-step procedure can be made echogenic. Our group as well as others experimentally demonstrated that freeze-drying in the presence of mannitol is a crucial component to ensure echogenicity. Here, we showed that freeze-dried aqueous solutions of excipients such as mannitol, meso-erythritol, glycine, and glucose that assume a crystalline state, when dispersed in water creates bubbles and are echogenic even without any lipids. We also present an explanation for the bubble generation process because of dissolution of mannitol.

Hybrid integration of III-V semiconductor lasers on silicon waveguides using optofluidic microbubble manipulation

PubMed Central

Jung, Youngho; Shim, Jaeho; Kwon, Kyungmook; You, Jong-Bum; Choi, Kyunghan; Yu, Kyoungsik

2016-01-01

Optofluidic manipulation mechanisms have been successfully applied to micro/nano-scale assembly and handling applications in biophysics, electronics, and photonics. Here, we extend the laser-based optofluidic microbubble manipulation technique to achieve hybrid integration of compound semiconductor microdisk lasers on the silicon photonic circuit platform. The microscale compound semiconductor block trapped on the microbubble surface can be precisely assembled on a desired position using photothermocapillary convective flows induced by focused laser beam illumination. Strong light absorption within the micro-scale compound semiconductor object allows real-time and on-demand microbubble generation. After the assembly process, we verify that electromagnetic radiation from the optically-pumped InGaAsP microdisk laser can be efficiently coupled to the single-mode silicon waveguide through vertical evanescent coupling. Our simple and accurate microbubble-based manipulation technique may provide a new pathway for realizing high precision fluidic assembly schemes for heterogeneously integrated photonic/electronic platforms as well as microelectromechanical systems. PMID:27431769

Novel chitosan derivative for temperature and ultrasound dual-sensitive liposomal microbubble gel.

PubMed

Chen, Daquan; Yu, Hongyun; Mu, Hongjie; Wei, Junhua; Song, Zhenkun; Shi, Hong; Liang, Rongcai; Sun, Kaoxiang; Liu, Wanhui

2013-04-15

In this study, a novel liposome-loaded microbubble gel based on N-cholesteryl hemisuccinate-O-sulfate chitosan (NCHOSC) was designed. The structure of the NCHOSC was characterized by FTIR and (1)H NMR. The liposomal microbubble gel based on NCHOSC with a high encapsulation efficiency of curcumin was formed and improved the solubility of curcumin. The diameter of most liposomal microbubble was about 950 nm. The temperature-sensitive CS/GP gel could be formulated at room temperature and would form a gel at body temperature. Simultaneously, the ultrasound-sensitive induced release of curcumin was 85% applying ultrasound. The results of cytotoxicity assay indicated that encapsulated curcumin in Cur-LM or Cur-LM-G was less toxic. The anti-tumor efficacy in vivo suggested that Cur-LM-G by ultrasound suppressed tumor growth most efficiently. These findings have shed some light on the potential NCHOSC material used to liposome-loaded microbubble gel for temperature and ultrasound dual-sensitive drug delivery. Copyright © 2013 Elsevier Ltd. All rights reserved.

Encapsulated microbubbles and echogenic liposomes for contrast ultrasound imaging and targeted drug delivery

PubMed Central

Paul, Shirshendu; Nahire, Rahul; Mallik, Sanku; Sarkar, Kausik

2014-01-01

Micron- to nanometer-sized ultrasound agents, like encapsulated microbubbles and echogenic liposomes, are being developed for diagnostic imaging and ultrasound mediated drug/gene delivery. This review provides an overview of the current state of the art of the mathematical models of the acoustic behavior of ultrasound contrast microbubbles. We also present a review of the in vitro experimental characterization of the acoustic properties of microbubble based contrast agents undertaken in our laboratory. The hierarchical two-pronged approach of modeling contrast agents we developed is demonstrated for a lipid coated (Sonazoid™) and a polymer shelled (poly D-L-lactic acid) contrast microbubbles. The acoustic and drug release properties of the newly developed echogenic liposomes are discussed for their use as simultaneous imaging and drug/gene delivery agents. Although echogenicity is conclusively demonstrated in experiments, its physical mechanisms remain uncertain. Addressing questions raised here will accelerate further development and eventual clinical approval of these novel technologies. PMID:26097272

Introduction to the ultrasound targeted microbubble destruction technique.

PubMed

Walton, Chad B; Anderson, Cynthia D; Boulay, Rachel; Shohet, Ralph V

2011-06-12

In UTMD, bioactive molecules, such as negatively charged plasmid DNA vectors encoding a gene of interest, are added to the cationic shells of lipid microbubble contrast agents. In mice these vector-carrying microbubbles can be administered intravenously or directly to the left ventricle of the heart. In larger animals they can also be infused through an intracoronary catheter. The subsequent delivery from the circulation to a target organ occurs by acoustic cavitation at a resonant frequency of the microbubbles. It seems likely that the mechanical energy generated by the microbubble destruction results in transient pore formation in or between the endothelial cells of the microvasculature of the targeted region. As a result of this sonoporation effect, the transfection efficiency into and across the endothelial cells is enhanced, and transgene-encoding vectors are deposited into the surrounding tissue. Plasmid DNA remaining in the circulation is rapidly degraded by nucleases in the blood, which further reduces the likelihood of delivery to non-sonicated tissues and leads to highly specific target-organ transfection.

Dissolution of used nuclear fuel using recycled nitric acid

DOE Office of Scientific and Technical Information (OSTI.GOV)

Almond, Philip M.; Daniel, Jr., William E.; Rudisill, Tracy S.

An evaluation was performed on the feasibility of using HB-Line anion exchange column waste streams from Alternate Feedstock 2 (AFS-2) processing for the dissolver solution for used nuclear fuel (UNF) processing. The targeted UNF for dissolution using recycled solution are fuels similar to the University of Missouri Research Reactor (MURR) fuel. Furthermore, the objectives of this experimental program were to validate the feasibility of using impure dissolver solutions with the MURR dissolution flowsheet to verify they would not significantly affect dissolution of the UNF in a detrimental manner.

Dissolution of used nuclear fuel using recycled nitric acid

DOE PAGES

Almond, Philip M.; Daniel, Jr., William E.; Rudisill, Tracy S.

2017-03-20

An evaluation was performed on the feasibility of using HB-Line anion exchange column waste streams from Alternate Feedstock 2 (AFS-2) processing for the dissolver solution for used nuclear fuel (UNF) processing. The targeted UNF for dissolution using recycled solution are fuels similar to the University of Missouri Research Reactor (MURR) fuel. Furthermore, the objectives of this experimental program were to validate the feasibility of using impure dissolver solutions with the MURR dissolution flowsheet to verify they would not significantly affect dissolution of the UNF in a detrimental manner.

Multifunctional Polymer Microbubbles for Advanced Sentinel Lymph Node Imaging and Mapping

DTIC Science & Technology

2012-06-01

of thiolated poly(acrylic acid) with fluorescein attached. (b) Bright field image of large bubbles stabilized by polymer and phospholipid...Page 1 of 6 AD_________________ Award Number: W81XWH-11-1-0215 TITLE:   Multifunctional Polymer Microbubbles for Advanced... Polymer Microbubbles for Advanced Sentinel Lymph Node Imaging and Mapping 5b. GRANT NUMBER W81XWH-11-1-0215   5c. PROGRAM ELEMENT NUMBER 6

Transportation of single cell and microbubbles by phase-shift introduced to standing leaky surface acoustic waves

PubMed Central

Meng, Long; Cai, Feiyan; Zhang, Zidong; Niu, Lili; Jin, Qiaofeng; Yan, Fei; Wu, Junru; Wang, Zhanhui; Zheng, Hairong

2011-01-01

A microfluidic device was developed to precisely transport a single cell or multiple microbubbles by introducing phase-shifts to a standing leaky surface acoustic wave (SLSAW). The device consists of a polydimethyl-siloxane (PDMS) microchannel and two phase-tunable interdigital transducers (IDTs) for the generation of the relative phase for the pair of surface acoustic waves (SAW) propagating along the opposite directions forming a standing wave. When the SAW contacts the fluid medium inside the microchannel, some of SAW energy is coupled to the fluid and the SAW becomes the leaky surface wave. By modulating the relative phase between two IDTs, the positions of pressure nodes of the SLSAW in the microchannel change linearly resulting in the transportation of a single cell or microbubbles. The results also reveal that there is a good linear relationship between the relative phase and the displacement of a single cell or microbubbles. Furthermore, the single cell and the microbubbles can be transported over a predetermined distance continuously until they reach the targeted locations. This technique has its distinct advantages, such as precise position-manipulation, simple to implement, miniature size, and noninvasive character, which may provide an effective method for the position-manipulation of a single cell and microbubbles in many biological and biomedical applications. PMID:22662056

Ultrasound image-guided therapy enhances antitumor effect of cisplatin.

PubMed

Sasaki, Noboru; Kudo, Nobuki; Nakamura, Kensuke; Lim, Sue Yee; Murakami, Masahiro; Kumara, W R Bandula; Tamura, Yu; Ohta, Hiroshi; Yamasaki, Masahiro; Takiguchi, Mitsuyoshi

2014-01-01

The aim of this study was to clarify whether ultrasound image-guided cisplatin delivery with an intratumor microbubble injection enhances the antitumor effect in a xenograft mouse model. Canine thyroid adenocarcinoma cells were used for all experiments. Before in vivo experiments, the cisplatin and microbubble concentration and ultrasound exposure time were optimized in vitro. For in vivo experiments, cells were implanted into the back of nude mice. Observed by a diagnostic ultrasound machine, a mixture of cisplatin and ultrasound contrast agent, Sonazoid, microbubbles was injected directly into tumors. The amount of injected cisplatin and microbubbles was 1 μg/tumor and 1.2 × 10(7) microbubbles/tumor, respectively, with a total injected volume of 20 μl. Using the same diagnostic machine, tumors were exposed to ultrasound for 15 s. The treatment was repeated four times. The combination of cisplatin, microbubbles, and ultrasound significantly delayed tumor growth as compared with no treatment (after 18 days, 157 ± 55 vs. 398 ± 49 mm(3), P = 0.049). Neither cisplatin alone nor the combination of cisplatin and ultrasound delayed tumor growth. The treatment did not decrease the body weight of mice. Ultrasound image-guided anticancer drug delivery may enhance the antitumor effects of drugs without obvious side effects.

Sonoporation, drug delivery, and gene therapy.

PubMed

Liang, H-D; Tang, J; Halliwell, M

2010-01-01

Ultrasound is a very effective modality for drug delivery and gene therapy because energy that is non-invasively transmitted through the skin can be focused deeply into the human body in a specific location and employed to release drugs at that site. Ultrasound cavitation, enhanced by injected microbubbles, perturbs cell membrane structures to cause sonoporation and increases the permeability to bioactive materials. Cavitation events also increase the rate of drug transport in general by augmenting the slow diffusion process with convective transport processes. Drugs and genes can be incorporated into microbubbles, which in turn can target a specific disease site using ligands such as the antibody. Drugs can be released ultrasonically from microbubbles that are sufficiently robust to circulate in the blood and retain their cargo of drugs until they enter an insonated volume of tissue. Local drug delivery ensures sufficient drug concentration at the diseased region while limiting toxicity for healthy tissues. Ultrasound-mediated gene delivery has been applied to heart, blood vessel, lung, kidney, muscle, brain, and tumour with enhanced gene transfection efficiency, which depends on the ultrasonic parameters such as acoustic pressure, pulse length, duty cycle, repetition rate, and exposure duration, as well as microbubble properties such as size, gas species, shell material, interfacial tension, and surface rigidity. Microbubble-augmented sonothrombolysis can be enhanced further by using targeting microbubbles.

Ultrasound-mediated microbubble enhancement of radiation therapy studied using three-dimensional high-frequency power Doppler ultrasound.

PubMed

Kwok, Sheldon J J; El Kaffas, Ahmed; Lai, Priscilla; Al Mahrouki, Azza; Lee, Justin; Iradji, Sara; Tran, William Tyler; Giles, Anoja; Czarnota, Gregory J

2013-11-01

Tumor responses to high-dose (>8 Gy) radiation therapy are tightly connected to endothelial cell death. In the study described here, we investigated whether ultrasound-activated microbubbles can locally enhance tumor response to radiation treatments of 2 and 8 Gy by mechanically perturbing the endothelial lining of tumors. We evaluated vascular changes resulting from combined microbubble and radiation treatments using high-frequency 3-D power Doppler ultrasound in a breast cancer xenograft model. We compared treatment effects and monitored vasculature damage 3 hours, 24 hours and 7 days after treatment delivery. Mice treated with 2 Gy radiation and ultrasound-activated microbubbles exhibited a decrease in vascular index to 48 ± 10% at 24 hours, whereas vascular indices of mice treated with 2 Gy radiation alone or microbubbles alone were relatively unchanged at 95 ± 14% and 78 ± 14%, respectively. These results suggest that ultrasound-activated microbubbles enhance the effects of 2 Gy radiation through a synergistic mechanism, resulting in alterations of tumor blood flow. This novel therapy may potentiate lower radiation doses to preferentially target endothelial cells, thus reducing effects on neighboring normal tissue and increasing the efficacy of cancer treatments. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

Ablation of synovial pannus using microbubble-mediated ultrasonic cavitation in antigen-induced arthritis in rabbits.

PubMed

Qiu, Li; Jiang, Yong; Zhang, Lingyan; Wang, Lei; Luo, Yan

2012-12-01

To investigate the ablative effectiveness of microbubble-mediated ultrasonic cavitation for treating synovial pannus and to determine a potential mechanism using the antigen-induced arthritis model (AIA). Ultrasonic ablation was performed on the knee joints of AIA rabbits using optimal ultrasonic ablative parameters. Rabbits with antigen-induced arthritis were randomly assigned to 4 groups: (1) the ultrasound (US) + microbubble group; (2) the US only group; (3) the microbubble only group, and (4) the control group. At 1 h and 14 days after the first ablation, contrast-enhanced ultrasonography (CEUS) monitoring and pathology synovitis score were used to evaluate the therapeutic effects. Synovial necrosis and microvascular changes were also measured. After the ablation treatment, the thickness of synovium and parameters of time intensity curve including derived peak intensity and area under curve were measured using CEUS, and the pathology synovitis score in the ultrasound + microbubble group was significantly lower than that found in the remaining groups. No damage was observed in the surrounding normal tissues. The mechanism underlying the ultrasonic ablation was related to microthrombosis and microvascular rupture that resulted in synovial necrosis. The results suggest that microbubble-mediated ultrasonic cavitation should be applied as a non-invasive strategy for the treatment of synovial pannus in arthritis under optimal conditions.

Unilateral Opening of Rat Blood-Brain Barrier Assisted by Diagnostic Ultrasound Targeted Microbubbles Destruction.

PubMed

Xu, Yali; Cui, Hai; Zhu, Qiong; Hua, Xing; Xia, Hongmei; Tan, Kaibin; Gao, Yunhua; Zhao, Jing; Liu, Zheng

2016-01-01

Objective. Blood-brain barrier (BBB) is a key obstacle that prevents the medication from blood to the brain. Microbubble-enhanced cavitation by focused ultrasound can open the BBB and proves to be valuable in the brain drug delivery. The study aimed to explore the feasibility, efficacy, and safety of unilateral opening of BBB using diagnostic ultrasound targeted microbubbles destruction in rats. Methods. A transtemporal bone irradiation of diagnostic ultrasound and intravenous injection of lipid-coated microbubbles were performed at unilateral hemisphere. Pathological changes were monitored. Evans Blue extravasation grades, extraction from brain tissue, and fluorescence optical density were quantified. Lanthanum nitrate was traced by transmission electron microscopy. Results. After diagnostic ultrasound mediated microbubbles destruction, Evans Blue extravasation and fluorescence integrated optical density were significantly higher in the irradiated hemisphere than the contralateral side (all p < 0.01). Erythrocytes extravasations were demonstrated in the ultrasound-exposed hemisphere (4 ± 1, grade 2) while being invisible in the control side. Lanthanum nitrate tracers leaked through interendothelial cleft and spread to the nerve fiber existed in the irradiation side. Conclusions. Transtemporal bone irradiation under DUS mediated microbubble destruction provides us with a more accessible, safer, and higher selective BBB opening approach in rats, which is advantageous in brain targeted drugs delivery.

Microfluidics-based microbubbles in methylene blue solution for photoacoustic and ultrasound imaging

NASA Astrophysics Data System (ADS)

Das, Dhiman; Sivasubramanian, Kathyayini; Yang, Chun; Pramanik, Manojit

2018-02-01

Contrast agents which can be used for more than one bio-imaging technique has gained a lot of attention from researchers in recent years. In this work, a microfluidic device employing a flow-focusing junction, is used for the continuous generation of monodisperse nitrogen microbubbles in methylene blue, an optically absorbing organic dye, for dual-modal photoacoustic and ultrasound imaging. Using an external phase of polyoxyethylene glycol 40 stearate (PEG 40), a non-ionic surfactant, and 50% glycerol solution at a flow rate of 1 ml/hr and gas pressure at 1.75 bar, monodisperse nitrogen microbubbles of diameter 7 microns were obtained. The external phase also contained methylene blue hydrate at a concentration of 1 gm/litre. The monodisperse microbubbles produced a strong ultrasound signal as expected. It was observed that the signal-to-noise (SNR) ratio of the photoacoustic signal for the methylene blue solution in the presence of the monodisperse microbubbles was 68.6% lower than that of methylene blue solution in the absence of microbubbles. This work is of significance because using microfluidics, we can precisely control the bubbles' production rate and bubble size which increases ultrasound imaging efficiency. A uniform size distribution of the bubbles will have narrower resonance frequency bandwidth which will respond well to specific ultrasound frequencies.

Enhancing surface methane fluxes from an oligotrophic lake: exploring the microbubble hypothesis.

PubMed

McGinnis, Daniel F; Kirillin, Georgiy; Tang, Kam W; Flury, Sabine; Bodmer, Pascal; Engelhardt, Christof; Casper, Peter; Grossart, Hans-Peter

2015-01-20

Exchange of the greenhouse gases carbon dioxide (CO2) and methane (CH4) across inland water surfaces is an important component of the terrestrial carbon (C) balance. We investigated the fluxes of these two gases across the surface of oligotrophic Lake Stechlin using a floating chamber approach. The normalized gas transfer rate for CH4 (k600,CH4) was on average 2.5 times higher than that for CO2 (k600,CO2) and consequently higher than Fickian transport. Because of its low solubility relative to CO2, the enhanced CH4 flux is possibly explained by the presence of microbubbles in the lake’s surface layer. These microbubbles may originate from atmospheric bubble entrainment or gas supersaturation (i.e., O2) or both. Irrespective of the source, we determined that an average of 145 L m(–2) d(–1) of gas is required to exit the surface layer via microbubbles to produce the observed elevated k600,CH4. As k600 values are used to estimate CH4 pathways in aquatic systems, the presence of microbubbles could alter the resulting CH4 and perhaps C balances. These microbubbles will also affect the surface fluxes of other sparingly soluble gases in inland waters, including O2 and N2.

The effect of microbubbles on gas-liquid mass transfer coefficient and degradation rate of COD in wastewater treatment.

PubMed

Yao, Kangning; Chi, Yong; Wang, Fei; Yan, Jianhua; Ni, Mingjiang; Cen, Kefa

2016-01-01

A commonly used aeration device at present has the disadvantages of low mass transfer rate because the generated bubbles are several millimeters in diameter which are much bigger than microbubbles. Therefore, the effect of a microbubble on gas-liquid mass transfer and wastewater treatment process was investigated. To evaluate the effect of each bubble type, the volumetric mass transfer coefficients for microbubbles and conventional bubbles were determined. The volumetric mass transfer coefficient was 0.02905 s(-1) and 0.02191 s(-1) at a gas flow rate of 0.67 L min(-1) in tap water for microbubbles and conventional bubbles, respectively. The degradation rate of simulated municipal wastewater was also investigated, using aerobic activated sludge and ozone. Compared with the conventional bubble generator, the chemical oxygen demand (COD) removal rate was 2.04, 5.9, 3.26 times higher than those of the conventional bubble contactor at the same initial COD concentration of COD 200 mg L(-1), 400 mg L(-1), and 600 mg L(-1), while aerobic activated sludge was used. For the ozonation process, the rate of COD removal using microbubble generator was 2.38, 2.51, 2.89 times of those of the conventional bubble generator. Based on the results, the effect of initial COD concentration on the specific COD degradation rate were discussed in different systems. Thus, the results revealed that microbubbles could enhance mass transfer in wastewater treatment and be an effective method to improve the degradation of wastewater.

Ultrasound imaging of the mouse pancreatic duct using lipid microbubbles

NASA Astrophysics Data System (ADS)

Banerjee, B.; McKeown, K. R.; Skovan, B.; Ogram, E.; Ingram, P.; Ignatenko, N.; Paine-Murrieta, G.; Witte, R.; Matsunaga, T. O.

2012-03-01

Research requiring the murine pancreatic duct to be imaged is often challenging due to the difficulty in selectively cannulating the pancreatic duct. We have successfully catheterized the pancreatic duct through the common bile duct in severe combined immune deficient (SCID) mice and imaged the pancreatic duct with gas filled lipid microbubbles that increase ultrasound imaging sensitivity due to exquisite scattering at the gas/liquid interface. A SCID mouse was euthanized by CO2, a midline abdominal incision made, the common bile duct cut at its midpoint, a 2 cm, 32 gauge tip catheter was inserted about 1 mm into the duct and tied with suture. The duodenum and pancreas were excised, removed in toto, embedded in agar and an infusion pump was used to instill normal saline or lipid-coated microbubbles (10 million / ml) into the duct. B-mode images before and after infusion of the duct with microbubbles imaged the entire pancreatic duct (~ 1 cm) with high contrast. The microbubbles were cavitated by high mechanical index (HMI) ultrasound for imaging to be repeated. Our technique of catheterization and using lipid microbubbles as a contrast agent may provide an effective, affordable technique of imaging the murine pancreatic duct; cavitation with HMI ultrasound would enable repeated imaging to be performed and clustering of targeted microbubbles to receptors on ductal cells would allow pathology to be localized accurately. This research was supported by the Experimental Mouse Shared Service of the AZ Cancer Center (Grant Number P30CA023074, NIH/NCI and the GI SPORE (NIH/NCI P50 CA95060).

Two-dimensional longitudinal strain assessment in the presence of myocardial contrast agents is only feasible with speckle-tracking after microbubble destruction.

PubMed

Cavalcante, João L; Collier, Patrick; Plana, Juan C; Agler, Deborah; Thomas, James D; Marwick, Thomas H

2012-12-01

Longitudinal strain (LS) imaging is an important tool for the quantification of left ventricular function and deformation, but its assessment is challenging in the presence of echocardiographic contrast agents (CAs). The aim of this study was to test the hypothesis that destruction of microbubbles using high mechanical index (MI) could allow the measurement of LS. LS was measured using speckle strain (speckle-tracking LS [STLS]) and Velocity Vector Imaging (VVI) before and after CA administration in 30 consecutive patients. Low MI was used for left ventricular opacification and three-dimensional high MI for microbubble destruction. Four different settings were tested over 60 sec: (1) baseline LS without contrast, (2) LS after CA administration with low MI (0.3), (3) LS after CA administration with high MI (0.9), and (4) LS after microbubble destruction with high MI and three-dimensional imaging. Baseline feasibility of LS assessment (99.3% and 98.2% with STLS and VVI, respectively) was reduced after CA administration using STLS at low (69%, P < .0001) and high (95.4%, P = .0002) MI as well as with VVI (93.8%, P = .004, and 84.7%, P < .0001, respectively). STLS assessment was feasible with high MI after microbubble destruction (1.7% of uninterpretable segments vs 0.7%, P = .26) but not using VVI (7.2% vs 1.8%, P < .001). Regardless of which microbubbles or image settings were used, VVI was associated with significant variability and overestimation of global LS (for low MI, +4.7%, P < .01; for high MI, +3.3%, P < .001; for high MI after microbubble destruction, +1.3%, P = .04). LS assessment is most feasible without contrast. If a CA is necessary, the calculation of LS is feasible using the speckle-tracking method, if three-dimensional imaging is used as a tool for microbubble destruction 1 min after CA administration. Copyright © 2012. Published by Mosby, Inc.

Material Recycling and Waste Minimization by Freeze Crystallization. Phase 1

DTIC Science & Technology

1995-05-01

or centrifuge for recovery. DESIGN PARAMETERS - Crystallizer Gives direct scale-up information. - Eutectic Salt Separation Gives direct scale-up...because of sfer rates and crystal kinetics, differences in crystallizer construction. - Eutectic Salt Separation No ability in this system. - Wash Columns

Photothermal generation of microbubbles on plasmonic nanostructures inside microfluidic channels

NASA Astrophysics Data System (ADS)

Li, Jingting; Li, Ming; Santos, Greggy M.; Zhao, Fusheng; Shih, Wei-Chuan

2016-03-01

Microbubbles have been utilized as micro-pumps, micro-mixers, micro-valves, micro-robots and surface cleaners. Various generation techniques can be found in the literature, including resistive heating, hydrodynamic methods, illuminating patterned metal films and noble metal nanoparticles of Au or Ag. We present photothermal microbubble generation by irradiating nanoporous gold disk covered microfluidic channels. The size of the microbubble can be controlled by adjusting the laser power. The dynamics of both bubble growth and shrinkage are studied. The advantages of this technique are flexible bubble generation locations, long bubble lifetimes, no need for light-adsorbing dyes, high controllability over bubble size, low power consumption, etc. This technique has the potential to provide new flow control functions in microfluidic devices.

Microenvironment Induced Spheroid to Sheeting Transition of Immortalized Human Keratinocytes (HaCaT) Cultured in Microbubbles Formed in Polydimethylsiloxane

PubMed Central

Chandrasekaran, Siddarth; Giang, Ut-Binh; King, Michael R.; DeLouise, Lisa A

2011-01-01

The in vivo cellular microenvironment is regulated by a complex interplay of soluble factors and signaling molecules secreted by cells and it plays a critical role in the growth and development of normal and diseased tissues. In vitro systems that can recapitulate the microenvironment at the cellular level are needed to investigate the influence of autocrine signaling and extracellular matrix effects on tissue homeostasis, regeneration, and disease development and progression. In this study we report the use of microbubble technology as a means to culture cells in a controlled microenvironment in which cells can influence their function through autocrine signaling. Microbubbles (MB) are small spherical cavities about 100–300 µm in diameter formed in hydrophobic polymer polydimethylsiloxane (PDMS) with ~60–100 µm circular openings and aspect ratio ~3.5. We demonstrate that the unique architecture of the microbubble compartment is advantaged for cell culture using HaCaT cells, an immortalized keratinocyte cell line. We observe that HaCaT cells, seeded in microbubbles (15–20 cells / MB) and cultured under standard conditions, adopt a compact 3-D spheroidal morphology. Within 2–3 days, the cells transition to a sheeting morphology. Through experimentation and simulation we show that this transition in morphology is due to the unique architecture of the microbubble compartment which enables cells to condition their local microenvironment. The small media volume per cell and the development of shallow concentration gradients allow factors secreted by the cells to rise to bioactive levels. The kinetics of the morphology transition depends on the number of cells seeded per microbubble; higher cell seeding induces a more rapid transition. HaCaT cells seeded onto PDMS cured in 96-well plates also form compact spheroids but they do not transition to a sheeting morphology even after several weeks of culture. The importance of soluble factor accumulation in driving this morphology transition in microbubbles is supported by the observation that spheroids do not form when cells - seeded into microbubbles or onto PDMS cured in 96 well plates - are cultured in media conditioned by HaCaT cells grown in standard tissue culture plate. We observed that the addition of TGF-β1 to the growth media induced cells to proliferate in a sheeting morphology from the onset both on PDMS cured in 96-well plates and in microbubbles. TGF-β1 is a morphogen known to regulate epithelial-to-mesenchymal transition (EMT). Studies of the role of Ca2+ concentration and changes in Ecadherin expression additionally support an EMT-like HaCaT morphology transition. These findings taken together validate the microbubble compartment as a unique cell culture platform that can potentially transform investigative studies in cell biology and in particular the tumor microenvironment. Targeting the tumor microenvironment is an emerging area of anti-cancer therapy. PMID:21724250

BEHAVIOR AND ASSIMILATION OF ORGANIC AND INORGANIC PRIOIRTY POLLUTANTS CODISPOSED WITH MUNICIPAL REFUSE - VOLUME II - APPENDICES

EPA Science Inventory

Organic and inorganic priority pollutants codisposed with municipal solid waste (MSW) in ten pilot-scale simulated landfill columns, operated under single pass leaching or leachate recycle, were capable of being attenuated by microbially-mediated landfill stabilization processes....

Comparison of the release of constituents from granular materials under batch and column testing.

PubMed

Lopez Meza, Sarynna; Garrabrants, Andrew C; van der Sloot, Hans; Kosson, David S

2008-01-01

Column leaching testing can be considered a better basis for assessing field impact data than any other available batch test method and thus provides a fundamental basis from which to estimate constituent release under a variety of field conditions. However, column testing is time-intensive compared to the more simplified batch testing, and may not always be a viable option when making decisions for material reuse. Batch tests are used most frequently as a simple tool for compliance or quality control reasons. Therefore, it is important to compare the release that occurs under batch and column testing, and establish conservative interpretation protocols for extrapolation from batch data when column data are not available. Five different materials (concrete, construction debris, aluminum recycling residue, coal fly ash and bottom ash) were evaluated via batch and column testing, including different column flow regimes (continuously saturated and intermittent unsaturated flow). Constituent release data from batch and column tests were compared. Results showed no significant difference between the column flow regimes when constituent release data from batch and column tests were compared. In most cases batch and column testing agreed when presented in the form of cumulative release. For arsenic in carbonated materials, however, batch testing underestimates the column constituent release for most LS ratios and also on a cumulative basis. For cases when As is a constituent of concern, column testing may be required.

Microembolism and catheter ablation I: a comparison of irrigated radiofrequency and multielectrode-phased radiofrequency catheter ablation of pulmonary vein ostia.

PubMed

Haines, David E; Stewart, Mark T; Dahlberg, Sarah; Barka, Noah D; Condie, Cathy; Fiedler, Gary R; Kirchhof, Nicole A; Halimi, Franck; Deneke, Thomas

2013-02-01

Cerebral diffusion-weighted MRI lesions have been observed after catheter ablation of atrial fibrillation. We hypothesized that conditions predisposing to microembolization could be identified using a porcine model of pulmonary vein ablation and an extracorporeal circulation loop. Ablations of the pulmonary veins were performed in 18 swine with echo monitoring. The femoral artery and vein were cannulated and an extracorporeal circulation loop with 2 ultrasonic bubble detectors and a 73-μm filter were placed in series. Microemboli and microbubbles were compared between ablation with an irrigated radiofrequency system (Biosense-Webster) and a phased radiofrequency multielectrode system (pulmonary vein ablation catheter [PVAC], Medtronic, Inc, Carlsbad, CA) in unipolar and 3 blended unipolar/bipolar modes. Animal pathology was examined. The size and number of microbubbles observed during ablation ranged from 30 to 180 μm and 0 to 3253 bubbles per ablation. Microbubble volumes with PVAC (29.1 nL) were greater than with irrigated radiofrequency (0.4 nL; P=0.045), and greatest with type II or III microbubbles on transesophageal echocardiography. Ablation with the PVAC showed fewest microbubbles in the unipolar mode (P=0.012 versus bipolar). The most occurred during bipolar energy delivery with overlap of proximal and distal electrodes (median microbubble volume, 1744 nL; interquartile range, 737-4082 nL; maximum, 19 516 nL). No cerebral MRI lesions were seen, but 2 animals had renal embolization. Left atrial ablation with irrigated radiofrequency and PVAC catheters in swine is associated with microbubble and microembolus production. Avoiding overlap of electrodes 1 and 10 on PVAC should reduce the microembolic burden associated with this procedure.

Acoustic Characterization of a Vessel-on-a-Chip Microfluidic System for Ultrasound-Mediated Drug Delivery.

PubMed

Beekers, Ines; van Rooij, Tom; Verweij, Martin D; Versluis, Michel; de Jong, Nico; Trietsch, Sebastiaan J; Kooiman, Klazina

2018-04-01

Ultrasound in the presence of gas-filled microbubbles can be used to enhance local uptake of drugs and genes. To study the drug delivery potential and its underlying physical and biological mechanisms, an in vitro vessel model should ideally include 3-D cell culture, perfusion flow, and membrane-free soft boundaries. Here, we propose an organ-on-a-chip microfluidic platform to study ultrasound-mediated drug delivery: the OrganoPlate. The acoustic propagation into the OrganoPlate was determined to assess the feasibility of controlled microbubble actuation, which is required to study the microbubble-cell interaction for drug delivery. The pressure field in the OrganoPlate was characterized non-invasively by studying experimentally the well-known response of microbubbles and by simulating the acoustic wave propagation in the system. Microbubble dynamics in the OrganoPlate were recorded with the Brandaris 128 ultrahigh-speed camera (17 million frames/s) and a control experiment was performed in an OptiCell, an in vitro monolayer cell culture chamber that is conventionally used to study ultrasound-mediated drug delivery. When insonified at frequencies between 1 and 2 MHz, microbubbles in the OrganoPlate experienced larger oscillation amplitudes resulting from higher local pressures. Microbubbles responded similarly in both systems when insonified at frequencies between 2 and 4 MHz. Numerical simulations performed with a 3-D finite-element model of ultrasound propagation into the OrganoPlate and the OptiCell showed the same frequency-dependent behavior. The predictable and homogeneous pressure field in the OrganoPlate demonstrates its potential to develop an in vitro 3-D cell culture model, well suited to study ultrasound-mediated drug delivery.

Transient permeabilization of cell membranes by ultrasound-exposed microbubbles is related to formation of hydrogen peroxide.

PubMed

Juffermans, L J M; Dijkmans, P A; Musters, R J P; Visser, C A; Kamp, O

2006-10-01

In the present study, we addressed the interactions among ultrasound, microbubbles, and living cells as well as consequent arising bioeffects. We specifically investigated whether hydrogen peroxide (H(2)O(2)) is involved in transient permeabilization of cell membranes in vitro after ultrasound exposure at low diagnostic power, in the presence of stable oscillating microbubbles, by measuring the generation of H(2)O(2) and Ca(2+) influx. Ultrasound, in the absence or presence of SonoVue microbubbles, was applied to H9c2 cells at 1.8 MHz with a mechanical index (MI) of 0.1 or 0.5 during 10 s. This was repeated every minute, for a total of five times. The production of H(2)O(2) was measured intracellularly with CM-H(2)DCFDA. Cell membrane permeability was assessed by measuring real-time changes in intracellular Ca(2+) concentration with fluo-4 using live-cell fluorescence microscopy. Ultrasound, in the presence of microbubbles, caused a significant increase in intracellular H(2)O(2) at MI 0.1 of 50% and MI 0.5 of 110% compared with control (P < 0.001). Furthermore, we found increases in intracellular Ca(2+) levels at both MI 0.1 and MI 0.5 in the presence of microbubbles, which was not detected in the absence of extracellular Ca(2+). In addition, in the presence of catalase, Ca(2+) influx immediately following ultrasound exposure was completely blocked at MI 0.1 (P < 0.01) and reduced by 50% at MI 0.5 (P < 0.001). Finally, cell viability was not significantly affected, not even 24 h later. These results implicate a role for H(2)O(2) in transient permeabilization of cell membranes induced by ultrasound-exposed microbubbles.

The stable microbubble test for determining continuous positive airway pressure (CPAP) success in very preterm infants receiving nasal CPAP from birth.

PubMed

Bhatia, Risha; Morley, Colin J; Argus, Brenda; Tingay, David G; Donath, Susan; Davis, Peter G

2013-01-01

Very preterm infants can be treated with nasal continuous positive airway pressure (CPAP) from birth, but some fail. A rapid test, such as the stable microbubble test (SMT) on gastric aspirate, may identify those who can be managed successfully using CPAP. To determine if SMT can identify soon after birth, very preterm infants who may be successfully managed on CPAP alone. Stable microbubbles (diameter <15 µm) were counted in gastric aspirates taken <1 h of age from infants <30 weeks' gestation, who received CPAP from birth. Infants failed CPAP if intubated at <72 h of age. Clinicians were masked to SMT results. A receiver operating characteristic curve was generated to determine the relationship between number of microbubbles/mm(2) and subsequent intubation. 68 infants of mean (SD) 28.1 (1.4) weeks' gestation received CPAP in the delivery room at a median (interquartile range) pressure 7 (6-8) cmH2O and FiO2 0.25 (0.21-0.3). Gastric aspirates were taken at a median (interquartile range) age of 0.5 (0.3-0.6) hours. The best cut-off point for predicting CPAP success or failure was a SMT count of 8 microbubbles/mm(2). The area under the receiver operating characteristic curve was 0.8 (95% CI 0.7-0.9). A SMT count ≥8 microbubbles/mm(2) had a sensitivity of 53%, a specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 60% for predicting CPAP success. Infants treated with CPAP from birth, who had SMT counts ≥8 microbubbles/mm(2) on their gastric aspirate, did not fail CPAP. Copyright © 2013 S. Karger AG, Basel.

Circulating Magnetic Microbubbles for Localized Real-Time Control of Drug Delivery by Ultrasonography-Guided Magnetic Targeting and Ultrasound

PubMed Central

Chertok, Beata; Langer, Robert

2018-01-01

Image-guided and target-selective modulation of drug delivery by external physical triggers at the site of pathology has the potential to enable tailored control of drug targeting. Magnetic microbubbles that are responsive to magnetic and acoustic modulation and visible to ultrasonography have been proposed as a means to realize this drug targeting strategy. To comply with this strategy in vivo, magnetic microbubbles must circulate systemically and evade deposition in pulmonary capillaries, while also preserving magnetic and acoustic activities in circulation over time. Unfortunately, challenges in fabricating magnetic microbubbles with such characteristics have limited progress in this field. In this report, we develop magnetic microbubbles (MagMB) that display strong magnetic and acoustic activities, while also preserving the ability to circulate systemically and evade pulmonary entrapment. Methods: We systematically evaluated the characteristics of MagMB including their pharmacokinetics, biodistribution, visibility to ultrasonography and amenability to magneto-acoustic modulation in tumor-bearing mice. We further assessed the applicability of MagMB for ultrasonography-guided control of drug targeting. Results: Following intravenous injection, MagMB exhibited a 17- to 90-fold lower pulmonary entrapment compared to previously reported magnetic microbubbles and mimicked circulation persistence of the clinically utilized Definity microbubbles (>10 min). In addition, MagMB could be accumulated in tumor vasculature by magnetic targeting, monitored by ultrasonography and collapsed by focused ultrasound on demand to activate drug deposition at the target. Furthermore, drug delivery to target tumors could be enhanced by adjusting the magneto-acoustic modulation based on ultrasonographic monitoring of MagMB in real-time. Conclusions: Circulating MagMB in conjunction with ultrasonography-guided magneto-acoustic modulation may provide a strategy for tailored minimally-invasive control over drug delivery to target tissues. PMID:29290812

Floating treatment wetlands for domestic wastewater treatment.

PubMed

Faulwetter, J L; Burr, M D; Cunningham, A B; Stewart, F M; Camper, A K; Stein, O R

2011-01-01

Floating islands are a form of treatment wetland characterized by a mat of synthetic matrix at the water surface into which macrophytes can be planted and through which water passes. We evaluated two matrix materials for treating domestic wastewater, recycled plastic and recycled carpet fibers, for chemical oxygen demand (COD) and nitrogen removal. These materials were compared to pea gravel or open water (control). Experiments were conducted in laboratory scale columns fed with synthetic wastewater containing COD, organic and inorganic nitrogen, and mineral salts. Columns were unplanted, naturally inoculated, and operated in batch mode with continuous recirculation and aeration. COD was efficiently removed in all systems examined (>90% removal). Ammonia was efficiently removed by nitrification. Removal of total dissolved N was ∼50% by day 28, by which time most remaining nitrogen was present as NO(3)-N. Complete removal of NO(3)-N by denitrification was accomplished by dosing columns with molasses. Microbial communities of interest were visualized with denaturing gradient gel electrophoresis (DGGE) by targeting specific functional genes. Shifts in the denitrifying community were observed post-molasses addition, when nitrate levels decreased. The conditioning time for reliable nitrification was determined to be approximately three months. These results suggest that floating treatment wetlands are a viable alternative for domestic wastewater treatment.

Environmental risk related to specific processes during scrap computer recycling and disposal.

PubMed

Li, Jinhui; Shi, Pixing; Shan, Hongshan; Xie, Yijun

2012-12-01

The purpose of this work was to achieve a better understanding of the generation of toxic chemicals related to specific processes in scrap computer recycling and disposal, such as thermal recycling of printed circuit boards (PCBs) and the landfilling or dumping of cathode ray tubes (CRTs). Tube furnace pyrolysis was carried out to simulate different thermal treatment conditions for the identification of the by-products and potential environmental risk from thermal recycling ofPCBs. The Toxicity Characteristic Leaching Procedure (TCLP) and a column test were used to study the leaching characteristics of lead from waste CRT glass, which is one of the most important environmental concerns arising from the disposal of e-waste. The results indicate that more attention should be paid to the benzene series when recycling PCBs under thermal conditions, especially for workers without any personal protection equipment. The impact of immersion on the leaching of lead from CRT leaded glass was more effective than the impact of washing only by acid rain. Thus when waste leaded glass has to be stored for some reason, the storage facility should be dry.

Trapping and mixing of particles in water using a microbubble attached to an NSOM fiber probe.

PubMed

Taylor, Rod; Hnatovsky, C

2004-03-08

Low power cw laser radiation at lambda=1.32microm was coupled into a chemically etched,metalized Near-Field Scanning Optical Microscopy (NSOM) fiber probe to generate a stable microbubble in water as well as in other fluids.The microbubble,which was attached to the end face of the fiber probe,was used to trap, manipulate and mix micron sized glass,latex and fluorescent particles as well as biological material.

Testing the 'microbubble effect' using the Cavitron technique to measure xylem water extraction curves.

PubMed

Pivovaroff, Alexandria L; Burlett, Régis; Lavigne, Bruno; Cochard, Hervé; Santiago, Louis S; Delzon, Sylvain

2016-01-01

Plant resistance to xylem cavitation is a major drought adaptation trait and is essential to characterizing vulnerability to climate change. Cavitation resistance can be determined with vulnerability curves. In the past decade, new techniques have increased the ease and speed at which vulnerability curves are produced. However, these new techniques are also subject to new artefacts, especially as related to long-vesselled species. We tested the reliability of the 'flow rotor' centrifuge technique, the so-called Cavitron, and investigated one potential mechanism behind the open vessel artefact in centrifuge-based vulnerability curves: the microbubble effect. The microbubble effect hypothesizes that microbubbles introduced to open vessels, either through sample flushing or injection of solution, travel by buoyancy or mass flow towards the axis of rotation where they artefactually nucleate cavitation. To test the microbubble effect, we constructed vulnerability curves using three different rotor sizes for five species with varying maximum vessel length, as well as water extraction curves that are constructed without injection of solution into the rotor. We found that the Cavitron technique is robust to measure resistance to cavitation in tracheid-bearing and short-vesselled species, but not for long-vesselled ones. Moreover, our results support the microbubble effect hypothesis as the major cause for the open vessel artefact in long-vesselled species. Published by Oxford University Press on behalf of the Annals of Botany Company.

Preliminary study on forming microbubble-surrounded cells as carriers for cellular therapy and evaluation of ultrasound controllability by fluorescence imaging

NASA Astrophysics Data System (ADS)

Demachi, Fumi; Murayama, Yuta; Hosaka, Naoto; Mochizuki, Takashi; Masuda, Kohji; Enosawa, Shin; Chiba, Toshio; Oda, Yusuke; Suzuki, Ryo; Maruyama, Kazuo

2015-07-01

Although various cellular immune therapies have been proposed and developed, because the therapeutic cells disperse upon injection into blood flow, there is a limitation on the accumulation of the cells to the target area. We previously reported our attempts to actively control microbubbles in artificial blood vessels, and here we propose a new method of carrying therapeutic cells for cellular therapy using microbubbles and ultrasound. When microbubbles and their aggregations attach to the surface of therapeutic cells, the acoustic force needed to propel the cells is increased because of the size expansion and the boundary in acoustic impedance on the cell surface. We fabricated a cylindrical chamber including two ultrasound transducers to emit a suspension of microbubbles (TF-BLs, transferrin-bubble liposomes) on the cells (Colon-26) to enhance the adhesion of microbubbles on the cells. We found that the optimum conditions for producing BL-surrounded cells were a sound pressure of 100 kPa-pp, an exposure time of 30 s, and a TF-BL concentration of 0.33 mg lipid/mL, when the cell concentration was constant at 0.77 × 105/mL in phosphate-buffered saline. Using these BL-surrounded cells, we confirmed the controllability of the cells under ultrasound exposure, where the displacement increased in proportion to the sound pressure and was not confirmed with the original cells.

Resonance frequencies of lipid-shelled microbubbles in the regime of nonlinear oscillations

PubMed Central

Doinikov, Alexander A.; Haac, Jillian F.; Dayton, Paul A.

2009-01-01

Knowledge of resonant frequencies of contrast microbubbles is important for the optimization of ultrasound contrast imaging and therapeutic techniques. To date, however, there are estimates of resonance frequencies of contrast microbubbles only for the regime of linear oscillation. The present paper proposes an approach for evaluating resonance frequencies of contrast agent microbubbles in the regime of nonlinear oscillation. The approach is based on the calculation of the time-averaged oscillation power of the radial bubble oscillation. The proposed procedure was verified for free bubbles in the frequency range 1–4 MHz and then applied to lipid-shelled microbubbles insonified with a single 20-cycle acoustic pulse at two values of the acoustic pressure amplitude, 100 kPa and 200 kPa, and at four frequencies: 1.5, 2.0, 2.5, and 3.0 MHz. It is shown that, as the acoustic pressure amplitude is increased, the resonance frequency of a lipid-shelled microbubble tends to decrease in comparison with its linear resonance frequency. Analysis of existing shell models reveals that models that treat the lipid shell as a linear viscoelastic solid appear may be challenged to provide the observed tendency in the behavior of the resonance frequency at increasing acoustic pressure. The conclusion is drawn that the further development of shell models could be improved by the consideration of nonlinear rheological laws. PMID:18977009

Advances in ultrasound-targeted microbubble-mediated gene therapy for liver fibrosis.

PubMed

Huang, Cuiyuan; Zhang, Hong; Bai, Ruidan

2017-07-01

Hepatic fibrosis develops as a wound-healing scar in response to acute and chronic liver inflammation and can lead to cirrhosis in patients with chronic hepatitis B and C. The condition arises due to increased synthesis and reduced degradation of extracellular matrix (ECM) and is a common pathological sequela of chronic liver disease. Excessive deposition of ECM in the liver causes liver dysfunction, ascites, and eventually upper gastrointestinal bleeding as well as a series of complications. However, fibrosis can be reversed before developing into cirrhosis and has thus been the subject of extensive researches particularly at the gene level. Currently, therapeutic genes are imported into the damaged liver to delay or prevent the development of liver fibrosis by regulating the expression of exogenous genes. One technique of gene delivery uses ultrasound targeting of microbubbles combined with therapeutic genes where the time and intensity of the ultrasound can control the release process. Ultrasound irradiation of microbubbles in the vicinity of cells changes the permeability of the cell membrane by its cavitation effect and enhances gene transfection. In this paper, recent progress in the field is reviewed with emphasis on the following aspects: the types of ultrasound microbubbles, the construction of an ultrasound-mediated gene delivery system, the mechanism of ultrasound microbubble-mediated gene transfer and the application of ultrasound microbubbles in the treatment of liver fibrosis.

High pulse repetition frequency ultrasound system for ex vivo measurement of mechanical properties of crystalline lenses with laser-induced microbubble interrogated by acoustic radiation force

PubMed Central

Yoon, Sangpil; Aglyamov, Salavat; Karpiouk, Andrei; Emelianov, Stanislav

2012-01-01

A high pulse repetition frequency ultrasound system for ex vivo measurement of mechanical properties of animal crystalline lens was developed and validated. We measured the bulk displacement of laser-induced microbubbles created at different positions within the lens using nanosecond laser pulses. An impulsive acoustic radiation force was applied to the microbubble, and spatio-temporal measurements of the microbubble displacement were assessed using a custom-made high pulse repetition frequency ultrasound system consisting of two 25 MHz focused ultrasound transducers. One of these transducers was used to emit a train of ultrasound pulses and another transducer was used to receive the ultrasound echoes reflected from the microbubble. The developed system was operating at 1 MHz pulse repetition frequency. Based on measured motion of the microbubble, the Young’s moduli of surrounding tissue were reconstructed and the values were compared with those measured using indentation test. Measured values of Young’s moduli of 4 bovine lenses ranged from 2.6±0.1 to 26±1.4 kPa and there was good agreement between the two methods. Therefore, our studies, utilizing the high pulse repetition frequency ultrasound system, suggest that the developed approach can be used to assess the mechanical properties of ex vivo crystalline lenses. Furthermore, the potential of the presented approach for in vivo measurements is discussed. PMID:22797709

In vivo characterization of ultrasound contrast agents: microbubble spectroscopy in a chicken embryo.

PubMed

Faez, Telli; Skachkov, Ilya; Versluis, Michel; Kooiman, Klazina; de Jong, Nico

2012-09-01

The dynamics of coated microbubbles was studied in an in vivo model. Biotinylated lipid-coated microbubbles were prepared in-house and were injected into a chick embryo chorioallantoic membrane (CAM) model on the fifth day of incubation. The microbubbles, ranging between 1.0 and 3.5 μm in diameter, were insonified in the frequency range of 4-7 MHz. Two amplitudes of acoustic pressure were applied: 300 kPa and 400 kPa. The fundamental and subharmonic responses were recorded optically with an ultra-fast camera (Brandaris 128) at 20 million frames per second. A subharmonic response was observed for 44% of the studied bubbles. From the data the frequency of the maximum fundamental and subharmonic response was derived for each individual bubble and resulted in the resonance curves of the microbubbles. All the bubbles showed shell (strain) hardening behavior for a higher acoustic pressure. We conclude that the subharmonic oscillations observed in this study belonged to the transmit at resonance (TR) regime. Copyright © 2012 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Intravascular forward-looking ultrasound transducers for microbubble-mediated sonothrombolysis.

PubMed

Kim, Jinwook; Lindsey, Brooks D; Chang, Wei-Yi; Dai, Xuming; Stavas, Joseph M; Dayton, Paul A; Jiang, Xiaoning

2017-06-14

Effective removal or dissolution of large blood clots remains a challenge in clinical treatment of acute thrombo-occlusive diseases. Here we report the development of an intravascular microbubble-mediated sonothrombolysis device for improving thrombolytic rate and thus minimizing the required dose of thrombolytic drugs. We hypothesize that a sub-megahertz, forward-looking ultrasound transducer with an integrated microbubble injection tube is more advantageous for efficient thrombolysis by enhancing cavitation-induced microstreaming than the conventional high-frequency, side-looking, catheter-mounted transducers. We developed custom miniaturized transducers and demonstrated that these transducers are able to generate sufficient pressure to induce cavitation of lipid-shelled microbubble contrast agents. Our technology demonstrates a thrombolysis rate of 0.7 ± 0.15 percent mass loss/min in vitro without any use of thrombolytic drugs.

Rupture loop annex ion exchange RLAIX vault deactivation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ham, J.E.; Harris, D.L., Westinghouse Hanford

This engineering report documents the deactivation, stabilization and final conditions of the Rupture Loop Annex Ion Exchange (RLAIX) Vault located northwest of the 309 Building`s Plutonium Recycle Test Reactor (PRTR). Twelve ion exchange columns, piping debris, and column liquid were removed from the vault, packaged and shipped for disposal. The vault walls and floor were decontaminated, and portions of the vault were painted to fix loose contamination. Process piping and drains were plugged, and the cover blocks and rain cover were installed. Upon closure,the vault was empty, stabilized, isolated.

WE-D-210-04: Radiation-Induced Polymerization of Ultrasound Contrast Agents in View of Non-Invasive Dosimetry in External Beam Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Callens, M; Verboven, E; Van Den Abeele, K

2015-06-15

Purpose: Ultrasound contrast agents (UCA’s) based on gas-filled microbubbles encapsulated by an amphiphilic shell are well established as safe and effective echo-enhancers in diagnostic imaging. In view of an alternative application of UCA’s, we investigated the use of targeted microbubbles as radiation sensors for external beam radiation therapy. As radiation induces permanent changes in the microbubble’s physico-chemical properties, a robust measure of these changes can provide a direct or indirect estimate of the applied radiation dose. For instance, by analyzing the ultrasonic dispersion characteristics of microbubble distributions before and after radiation treatment, an estimate of the radiation dose at themore » location of the irradiated volume can be made. To increase the radiation sensitivity of microbubbles, polymerizable diacetylene molecules can be incorporated into the shell. This study focuses on characterizing the acoustic response and quantifying the chemical modifications as a function of radiation dose. Methods: Lipid/diacetylene microbubbles were irradiated with a 6 MV photon beam using dose levels in the range of 0–150 Gy. The acoustic response of the microbubbles was monitored by ultrasonic through-transmission measurements in the range of 500 kHz to 20 MHz, thereby providing the dispersion relations of the phase velocity, attenuation and nonlinear coefficient. In addition, the radiation-induced chemical modifications were quantified using UV-VIS spectroscopy. Results: UV-VIS spectroscopy measurements indicate that ionizing radiation induces the polymerization of diacetylenes incorporated in the microbubble shell. The polymer yield strongly depends on the shell composition and the radiation-dose. The acoustic response is inherently related to the visco-elastic properties of the shell and is strongly influenced by the shell composition and the physico-chemical changes in the environment. Conclusion: Diacetylene-containing microbubbles are polymerizable under influence of ionizing radiation and are a promising design concept within the development of a novel non-invasive in-vivo radiation dosimeter for external beam radiation therapy. This work was funded by the Research Foundation - Flanders (FWO)« less

Simulation and optimization of continuous extractive fermentation with recycle system

NASA Astrophysics Data System (ADS)

Widjaja, Tri; Altway, Ali; Rofiqah, Umi; Airlangga, Bramantyo

2017-05-01

Extractive fermentation is continuous fermentation method which is believed to be able to substitute conventional fermentation method (batch). The recovery system and ethanol refinery will be easier. Continuous process of fermentation will make the productivity increase although the unconverted sugar in continuous fermentation is still in high concentration. In order to make this process more efficient, the recycle process was used. Increasing recycle flow will enhance the probability of sugar to be re-fermented. However, this will make ethanol enter fermentation column. As a result, the accumulated ethanol will inhibit the growth of microorganism. This research aims to find optimum conditions of solvent to broth ratio (S:B) and recycle flow to fresh feed ratio in order to produce the best yield and productivity. This study employed optimization by Hooke Jeeves method using Matlab 7.8 software. The result indicated that optimum condition occured in S: B=2.615 and R: F=1.495 with yield = 50.2439 %.

A green strategy for desorption of trihalomethanes adsorbed by humin and reuse of the fixed bed column.

PubMed

Cunha, G C; Romão, L P C; Santos, M C; Costa, A S; Alexandre, M R

2012-03-30

The objective of the present work was to develop a thermal desorption method for the removal of trihalomethanes (THM) adsorbed by humin, followed by multiple recycling of the fixed bed column in order to avoid excessive consumption of materials and reduce operating costs. The results obtained for adsorption on a fixed bed column confirmed the effectiveness of humin as an adsorbent, extracting between 45.9% and 90.1% of the total THM (TTHM). In none of the tests was the column fully saturated after 10h. Experiments involving thermal desorption were used to evaluate the potential of the technique for column regeneration. The adsorptive capacity of the humin bed increased significantly (p<0.05) between the first and fifth desorption cycle, by 18.9%, 18.1%, 24.2%, 20.2% and 24.2% for CHBr(3), CHBr(2)Cl, CHBrCl(2), CHCl(3) and TTHM, respectively. Copyright © 2011 Elsevier B.V. All rights reserved.

Pancreatic cancer cell detection by targeted lipid microbubbles and multiphoton imaging

NASA Astrophysics Data System (ADS)

Cromey, Benjamin; McDaniel, Ashley; Matsunaga, Terry; Vagner, Josef; Kieu, Khanh Quoc; Banerjee, Bhaskar

2018-04-01

Surgical resection of pancreatic cancer represents the only chance of cure and long-term survival in this common disease. Unfortunately, determination of a cancer-free margin at surgery is based on one or two tiny frozen section biopsies, which is far from ideal. Not surprisingly, cancer is usually left behind and is responsible for metastatic disease. We demonstrate a method of receptor-targeted imaging using peptide ligands, lipid microbubbles, and multiphoton microscopy that could lead to a fast and accurate way of examining the entire cut surface during surgery. Using a plectin-targeted microbubble, we performed a blinded in-vitro study to demonstrate avid binding of targeted microbubbles to pancreatic cancer cells but not noncancerous cell lines. Further work should lead to a much-needed point-of-care diagnostic test for determining clean margins in oncologic surgery.

Optical Fluorescent Imaging to Monitor Temporal Effects of Microbubble-Mediated Ultrasound Therapy

PubMed Central

Sorace, Anna G.; Saini, Reshu; Rosenthal, Eben; Warram, Jason M.; Zinn, Kurt R.; Hoyt, Kenneth

2013-01-01

Microbubble-mediated ultrasound therapy can noninvasively enhance drug delivery to localized regions in the body. This technique can be beneficial in cancer therapy, but currently there are limitations to tracking the therapeutic effects. The purpose of this experiment was to investigate the potential of fluorescent imaging for monitoring the temporal effects of microbubble-mediated ultrasound therapy. Mice were implanted with 2LMP breast cancer cells. The animals underwent microbubble-mediated ultrasound therapy in the presence of Cy5.5 fluorescent-labeled IgG antibody (large molecule) or Cy5.5 dye (small molecule) and microbubble contrast agents. Control animals were administered fluorescent molecules only. Animals were transiently imaged in vivo at 1, 10, 30, and 60 min post therapy using a small animal optical imaging system. Tumors were excised and analyzed ex vivo. Tumors were homogenized and emulsion imaged for Cy5.5 fluorescence. Monitoring in vivo results showed significant influx of dye into the tumor (p < 0.05) using the small molecule, but not in the large molecule group (p > 0.05). However, after tumor emulsion, significantly higher dye concentration was detected in therapy group tumors for both small and large molecule groups in comparison to their control counterparts (p < 0.01). This paper explores a noninvasive optical imaging method for monitoring the effects of microbubble-mediated ultrasound therapy in a cancer model. It provides temporal information following the process of increasing extravasation of molecules into target tumors. PMID:23357902

Optical fluorescent imaging to monitor temporal effects of microbubble-mediated ultrasound therapy.

PubMed

Sorace, Anna G; Saini, Reshu; Rosenthal, Eben; Warram, Jason M; Zinn, Kurt R; Hoyt, Kenneth

2013-02-01

Microbubble-mediated ultrasound therapy can noninvasively enhance drug delivery to localized regions in the body. This technique can be beneficial in cancer therapy, but currently there are limitations to tracking the therapeutic effects. The purpose of this experiment was to investigate the potential of fluorescent imaging for monitoring the temporal effects of microbubble-mediated ultrasound therapy. Mice were implanted with 2LMP breast cancer cells. The animals underwent microbubble-mediated ultrasound therapy in the presence of Cy5.5 fluorescent-labeled IgG antibody (large molecule) or Cy5.5 dye (small molecule) and microbubble contrast agents. Control animals were administered fluorescent molecules only. Animals were transiently imaged in vivo at 1, 10, 30, and 60 min post therapy using a small animal optical imaging system. Tumors were excised and analyzed ex vivo. Tumors were homogenized and emulsion imaged for Cy5.5 fluorescence. Monitoring in vivo results showed significant influx of dye into the tumor (p < 0.05) using the small molecule, but not in the large molecule group (p > 0.05). However, after tumor emulsion, significantly higher dye concentration was detected in therapy group tumors for both small and large molecule groups in comparison to their control counterparts (p <0.01). This paper explores a noninvasive optical imaging method for monitoring the effects of microbubble-mediated ultrasound therapy in a cancer model. It provides temporal information following the process of increasing extravasation of molecules into target tumors.

[Effect of low-dose focused ultrasound pre-irradiation versus microbubbles for enhancing high-intensity focused ultrasound ablation of VX2 hepatic tumor in rabbits].

PubMed

Zhang, Yi; Yang, Chao; Zou, Jian-Zhong; Chen, Fei; Ou, Xia; Zou, Hai-Rong; Wang, Yan

2016-10-20

To compare the effect of low-dose focused ultrasound pre-irradiation and microbubbles for enhancing the ablation effect of high intensity focused ultrasound (HIFU) on VX 2 hepatic tumor in rabbits. Fifty-five rabbits bearing VX 2 hepatic tumor were randomly divided into low-dose pre-irradiation + HIFU ablation group, microbubbles+HIFU ablation group, and HIFU ablation group for corresponding treatments. The pathological changes in the tumors after low-dose irradiation, time for HIFU ablation, tumor volume with coagulative necrosis, energy efficiency factor (EEF), pathological changes in the ablated tumor, and sound channel of HIFU ablation were observed. Tumor cell edema, vacuolar changes in the cytoplasm and tumor interstitial vascular congestion were observed 24 h after low-dose pre-irradiation. The ablation time were significantly shorter, coagulative necrosis volume was larger, and EEF was lower in low-dose irradiation + HIFU ablation group and microbubbles+HIFU ablation group than in simple HIFU ablation group (P<0.05), but the differences between the former two groups were not significant. The effectiveness and stability of the synergistic effect of low-dose pre-irradiation were inferior to microbubbles, but the former ensured a better safety of the sound channel. Low-dose irradiation has comparable synergistic effect in HIFU with microbubbles with such advantages as non-invasiveness, high concentration and good safety, and can be a potentially new method to enhance the efficiency of HIFU.

Real time observation of the ultrasound stimulated disintegration of optically trapped microbubbles in proximity to biological cells

NASA Astrophysics Data System (ADS)

Prentice, Paul; MacDonald, Michael P.; Cuschieri, Alfred; Dholakia, Kishan; Campbell, Paul

2005-08-01

Cells that are exposed to varying amounts of ultrasonic energy in the presence of ultrasound contrast agent (UCA) may undergo either permanent cell membrane damage (lethal sonoporation), or a transient enhancement of membrane permeability (reversible or non lethal sonoporation). The merits of each mode are clear; lethal sonoporation constitutes a significant tumour therapy weapon, whilst its less intrusive counterpart, reversible sonoporation, represents an effective non-invasive targeted drug delivery technique. Our working hypothesis for understanding this problem was that the root cause and effect in sonoporation involves the interaction of individual cells with single microbubbles, and to that end we devised an experiment that facilitates video rate observation of this specific scenario under well defined optical control. Specifically, we have constructed an innovative hybridization apparatus involving holographic optical trapping of single and multiple UCA microbubbles, together with the facility to irradiate with MHz pulsed ultrasound energy in the presence cancerous cells. This approach allows the isolation of a target microbubble from a resident population and the relocation to a [controllable] predetermined position relative to a cell within a monolayer. Frame extraction from standard framing rate video microscopy demonstrates the individuality of single microbubble-cell interactions. We describe a fluorescence microscopy protocol that will allow future study of the potential to deliver molecular species to cells, the dependence of the delivery on the initial microbubble-cell distance and to determine the targeted cell survival.

Liver haemostasis using microbubble-enhanced ultrasound at a low acoustic intensity.

PubMed

Zhao, Xiaochen; Li, Lu; Zhao, Hongzhi; Li, Tao; Wu, Shengzheng; Zhong, Yu; Zhao, Yang; Liu, Zheng

2012-02-01

To explore the haemostatic effects of microbubble-enhanced ultrasound (MEUS) at a very low acoustic intensity on the bleeding liver of rabbits. Liver incisions made on 20 rabbits were treated with a pulsed therapeutic ultrasound transducer. The transducer was operated at 831 KHz with an acoustic intensity of 0.4 W/cm(2). The treatment was coordinated with intravenous injection of microbubbles. Ultrasound only and sham treatment served as the controls. Visual bleeding score and 10-min bleeding volume were evaluated for haemostatic efficacy. Contrast-enhanced ultrasound (CEUS) was performed to assess the liver perfusion. Nine treated livers were harvested for acute histological examination. Regarding the bleeding incisions made on rabbit livers, the haemorrhage stopped immediately after 2 min of MEUS treatment but bleeding continued in the controls treated by ultrasound or microbubble injection alone. The bleeding scores and the 10-min haemorrhagic volumes dropped significantly in the MEUS group compared with those of the controls (p < 0.01). The mechanism of MEUS haemostasis appears to involve the extensive swelling of hepatocytes and the haemorrhage of the portal area, which formed a joint compression on the regional liver circulation. Low acoustic intensity MEUS might provide a novel method for liver haemostasis. • This animal experiment demonstrates a novel method of controlling hepatic haemorrhage • The treatment uses therapeutic ultrasound during enhancement with intravenous microbubbles • This combined therapy was more effective than ultrasound or intravenous microbubbles alone • More work is required with larger animals before potential human trials.

Pulse sequences for uniform perfluorocarbon droplet vaporization and ultrasound imaging.

PubMed

Puett, C; Sheeran, P S; Rojas, J D; Dayton, P A

2014-09-01

Phase-change contrast agents (PCCAs) consist of liquid perfluorocarbon droplets that can be vaporized into gas-filled microbubbles by pulsed ultrasound waves at diagnostic pressures and frequencies. These activatable contrast agents provide benefits of longer circulating times and smaller sizes relative to conventional microbubble contrast agents. However, optimizing ultrasound-induced activation of these agents requires coordinated pulse sequences not found on current clinical systems, in order to both initiate droplet vaporization and image the resulting microbubble population. Specifically, the activation process must provide a spatially uniform distribution of microbubbles and needs to occur quickly enough to image the vaporized agents before they migrate out of the imaging field of view. The development and evaluation of protocols for PCCA-enhanced ultrasound imaging using a commercial array transducer are described. The developed pulse sequences consist of three states: (1) initial imaging at sub-activation pressures, (2) activating droplets within a selected region of interest, and (3) imaging the resulting microbubbles. Bubble clouds produced by the vaporization of decafluorobutane and octafluoropropane droplets were characterized as a function of focused pulse parameters and acoustic field location. Pulse sequences were designed to manipulate the geometries of discrete microbubble clouds using electronic steering, and cloud spacing was tailored to build a uniform vaporization field. The complete pulse sequence was demonstrated in the water bath and then in vivo in a rodent kidney. The resulting contrast provided a significant increase (>15 dB) in signal intensity. Copyright © 2014 Elsevier B.V. All rights reserved.

A high pulse repetition frequency ultrasound system for the ex vivo measurement of mechanical properties of crystalline lenses with laser-induced microbubbles interrogated by acoustic radiation force.

PubMed

Yoon, Sangpil; Aglyamov, Salavat; Karpiouk, Andrei; Emelianov, Stanislav

2012-08-07

A high pulse repetition frequency ultrasound system for an ex vivo measurement of mechanical properties of an animal crystalline lens was developed and validated. We measured the bulk displacement of laser-induced microbubbles created at different positions within the lens using nanosecond laser pulses. An impulsive acoustic radiation force was applied to the microbubble, and spatio-temporal measurements of the microbubble displacement were assessed using a custom-made high pulse repetition frequency ultrasound system consisting of two 25 MHz focused ultrasound transducers. One of these transducers was used to emit a train of ultrasound pulses and another transducer was used to receive the ultrasound echoes reflected from the microbubble. The developed system was operating at 1 MHz pulse repetition frequency. Based on the measured motion of the microbubble, Young's moduli of surrounding tissue were reconstructed and the values were compared with those measured using the indentation test. Measured values of Young's moduli of four bovine lenses ranged from 2.6 ± 0.1 to 26 ± 1.4 kPa, and there was good agreement between the two methods. Therefore, our studies, utilizing the high pulse repetition frequency ultrasound system, suggest that the developed approach can be used to assess the mechanical properties of ex vivo crystalline lenses. Furthermore, the potential of the presented approach for in vivo measurements is discussed.

An iterative fullwave simulation approach to multiple scattering in media with randomly distributed microbubbles

NASA Astrophysics Data System (ADS)

Joshi, Aditya; Lindsey, Brooks D.; Dayton, Paul A.; Pinton, Gianmarco; Muller, Marie

2017-05-01

Ultrasound contrast agents (UCA), such as microbubbles, enhance the scattering properties of blood, which is otherwise hypoechoic. The multiple scattering interactions of the acoustic field with UCA are poorly understood due to the complexity of the multiple scattering theories and the nonlinear microbubble response. The majority of bubble models describe the behavior of UCA as single, isolated microbubbles suspended in infinite medium. Multiple scattering models such as the independent scattering approximation can approximate phase velocity and attenuation for low scatterer volume fractions. However, all current models and simulation approaches only describe multiple scattering and nonlinear bubble dynamics separately. Here we present an approach that combines two existing models: (1) a full-wave model that describes nonlinear propagation and scattering interactions in a heterogeneous attenuating medium and (2) a Paul-Sarkar model that describes the nonlinear interactions between an acoustic field and microbubbles. These two models were solved numerically and combined with an iterative approach. The convergence of this combined model was explored in silico for 0.5 × 106 microbubbles ml-1, 1% and 2% bubble concentration by volume. The backscattering predicted by our modeling approach was verified experimentally with water tank measurements performed with a 128-element linear array transducer. An excellent agreement in terms of the fundamental and harmonic acoustic fields is shown. Additionally, our model correctly predicts the phase velocity and attenuation measured using through transmission and predicted by the independent scattering approximation.

Continuous High-solids corn liquefaction and fermentation with stripping of ethanol

USDA-ARS?s Scientific Manuscript database

Removal of ethanol from the fermentor during fermentation can increase productivity and reduce the costs for dewatering the product and coproduct. One approach is to recycle the fermentor contents through a stripping column, where a non-condensable gas removes ethanol to a condenser. Previous resear...

Nitric acid recycling and copper nitrate recovery from effluent.

PubMed

Jô, L F; Marcus, R; Marcelin, O

2014-01-01

The recycling of nitric acid and copper nitrate contained in an industrial effluent was studied. The experiments conducted on such a medium showed that the presence of copper nitrate significantly improves nitric acid-water separation during distillation in an azeotropic medium. At the temperature of the azeotrope, however, this metal salt starts to precipitate, making the medium pasty, thus inhibiting the nitric acid extraction process. The optimisation of parameters such as column efficiency and adding water to the boiler at the azeotrope temperature are recommended in this protocol in order to collect the various components while avoiding the formation of by-products: NOx compounds. Thus, the absence of column, along with the addition of a small volume of water at a temperature of 118 °C, significantly increases the yield, allowing 94 % nitric acid to be recovered at the end of the process, along with the residual copper nitrate. The resulting distillate, however, is sufficiently dilute to not be used as is. Rectification is required to obtain concentrated nitric acid at 15 mol·l(-1), along with a weakly acidic distillate from the distillation front. This latter is quenched using potassium hydroxide and is used as a fertiliser solution for horticulture or sheltered market gardening. This process thus allows complete recycling of all the medium's components, including that of the distillate resulting from the nitric acid rectification operation.

Ultrasound contrast agent fabricated from microbubbles containing instant adhesives, and its ultrasound imaging ability

NASA Astrophysics Data System (ADS)

Makuta, T.; Tamakawa, Y.

2012-04-01

Non-invasive surgery techniques and drug delivery system with acoustic characteristics of ultrasound contrast agent have been studied intensively in recent years. Ultrasound contrast agent collapses easily under the blood circulating and the ultrasound irradiating because it is just a stabilized bubble without solid-shell by surface adsorption of surfactant or lipid. For improving the imaging stability, we proposed the fabrication method of the hollow microcapsule with polymer shell, which can be fabricated just blowing vapor of commonly-used instant adhesive (Cyanoacrylate monomer) into water as microbubbles. Therefore, the cyanoacrylate vapor contained inside microbubble initiates polymerization on the gasliquid interface soon after microbubbles are generated in water. Consequently, hollow microspheres coated by cyanoacrylate thin film are generated. In this report, we revealed that diameter distributions of microbubbles and microcapsules were approximately same and most of them were less than 10 μm, that is, smaller than blood capillary. In addition, we also revealed that hollow microcapsules enhanced the acoustic signal especially in the harmonic contrast imaging and were broken or agglomerated under the ultrasound field. As for the yield of hollow microcapsules, we revealed that sodium dodecyl sulfate addition to water phase instead of deoxycolic acid made the fabrication yield increased.

Low-amplitude non-linear volume vibrations of single microbubbles measured with an "acoustical camera".

PubMed

Renaud, Guillaume; Bosch, Johan G; Van Der Steen, Antonius F W; De Jong, Nico

2014-06-01

Contrast-enhanced ultrasound imaging is based on the detection of non-linear vibrational responses of a contrast agent after its intravenous administration. Improving contrast-enhanced images requires an accurate understanding of the vibrational response to ultrasound of the lipid-coated gas microbubbles that constitute most ultrasound contrast agents. Variations in the volume of microbubbles provide the most efficient radiation of ultrasound and, therefore, are the most important bubble vibrations for medical diagnostic ultrasound imaging. We developed an "acoustical camera" that measures the dynamic volume change of individual microbubbles when excited by a pressure wave. In the work described here, the technique was applied to the characterization of low-amplitude non-linear behaviors of BR14 microbubbles (Bracco Research, Geneva, Switzerland). The amplitude dependence of the resonance frequency and the damping, the prevalence of efficient subharmonic and ultraharmonic vibrations and the amplitude dependence of the response at the fundamental frequency and at the second harmonic frequency were investigated. Because of the large number of measurements, we provide a statistical characterization of the low-amplitude non-linear properties of the contrast agent. Copyright © 2014 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Effects of boundary proximity on monodispersed microbubbles in ultrasonic fields

NASA Astrophysics Data System (ADS)

Dzaharudin, F.; Ooi, A.; Manasseh, R.

2017-12-01

Microbubbles have demonstrated the potential to redraw the boundaries of biomedical applications and revolutionize diagnostic and therapeutic applications. However, the ability to distinguish the acoustic response from a cluster of microbubbles in close proximity to the vessel endothelial cell from those that are not is a challenge that needs to be addressed. To address this, the present paper modifies the Keller-Miksis model to include the effects of a boundary. The acoustic responses are analysed via techniques from dynamical systems theory such as Poincaré plots and bifurcation diagrams. It is found that the presence of a boundary causes an intermittent route to chaos while microbubbles far from the boundary result in a period-doubling route to chaos as the single control parameter pressure amplitude is varied. The route to chaos is altered via antimonotinicity with increasing bubble-wall distance. It has also been found that the effects of coupling are significant as it alters the chaotic threshold to occur at lower driving pressure amplitudes. The results also suggest that the increase in coupling effects between microbubbles near a boundary lowers the pressure amplitude required for chaos and lowers the natural frequency of the cluster.

Enhanced cell killing and apoptosis of oral squamous cell carcinoma cells with ultrasound in combination with cetuximab coated albumin microbubbles.

PubMed

Narihira, Kyoichi; Watanabe, Akiko; Sheng, Hong; Endo, Hitomi; Feril, Loreto B; Irie, Yutaka; Ogawa, Koichi; Moosavi-Nejad, Seyedeh; Kondo, Seiji; Kikuta, Toshihiro; Tachibana, Katsuro

2018-03-01

Targeted microbubbles have the potential to be used for ultrasound (US) therapy and diagnosis of various cancers. In the present study, US was irradiated to oral squamous cell carcinoma cells (HSC-2) in the presence of cetuximab-coated albumin microbubbles (CCAM). Cell killing rate with US treatment at 0.9 W/cm 2 and 1.0 W/cm 2 in the presence of CCAM was greater compared to non-targeted albumin microbubbles (p < .05). On the other hand, selective cell killing was not observed in human myelomonocytic lymphoma cell line (U937) that had no affinity to cetuximab. Furthermore, US irradiation in the presence of CCAM showed a fivefold increase of cell apoptotic rate for HSC-2 cells (21.0 ± 3.8%) as compared to U937 cells (4.0 ± 0.8%). Time-signal intensity curve in a tissue phantom demonstrated clear visualisation of CCAM with conventional US imaging device. Our experiment verifies the hypothesis that CCAM was selective to HSC-2 cells and may be applied as a novel therapeutic/diagnostic microbubble for oral squamous cell carcinoma.

Reparable Cell Sonoporation in Suspension: Theranostic Potential of Microbubble.

PubMed

Nejad, S Moosavi; Hosseini, Hamid; Akiyama, Hidenori; Tachibana, Katsuro

2016-01-01

The conjunction of low intensity ultrasound and encapsulated microbubbles can alter the permeability of cell membrane, offering a promising theranostic technique for non-invasive gene/drug delivery. Despite its great potential, the biophysical mechanisms of the delivery at the cellular level remains poorly understood. Here, the first direct high-speed micro-photographic images of human lymphoma cell and microbubble interaction dynamics are provided in a completely free suspension environment without any boundary parameter defect. Our real-time images and theoretical analyses prove that the negative divergence side of the microbubble's dipole microstreaming locally pulls the cell membrane, causing transient local protrusion of 2.5 µm in the cell membrane. The linear oscillation of microbubble caused microstreaming well below the inertial cavitation threshold, and imposed 35.3 Pa shear stress on the membrane, promoting an area strain of 0.12%, less than the membrane critical areal strain to cause cell rupture. Positive transfected cells with pEGFP-N1 confirm that the interaction causes membrane poration without cell disruption. The results show that the overstretched cell membrane causes reparable submicron pore formation, providing primary evidence of low amplitude (0.12 MPa at 0.834 MHz) ultrasound sonoporation mechanism.

Modeling of a Reaction-Distillation-Recycle System to Produce Dimethyl Ether through Methanol Dehydration

NASA Astrophysics Data System (ADS)

Muharam, Y.; Zulkarnain, L. M.; Wirya, A. S.

2018-03-01

The increase in the dimethyl ether yield through methanol dehydration due to a recycle integration to a reaction-distillation system was studied in this research. A one-dimensional phenomenological model of a methanol dehydration reactor and a shortcut model of distillation columns were used to achieve the aim. Simulation results show that 10.7 moles/s of dimethyl ether is produced in a reaction-distillation system with the reactor length being 4 m, the reactor inlet pressure being 18 atm, the reactor inlet temperature being 533 K, the reactor inlet velocity being 0.408 m/s, and the distillation pressure being 8 atm. The methanol conversion is 90% and the dimethyl ether yield is 48%. The integration of the recycle stream to the system increases the dimethyl ether yield by 8%.

High Efficiency Molecular Delivery with Sequential Low-Energy Sonoporation Bursts

PubMed Central

Song, Kang-Ho; Fan, Alexander C.; Brlansky, John T.; Trudeau, Tammy; Gutierrez-Hartmann, Arthur; Calvisi, Michael L.; Borden, Mark A.

2015-01-01

Microbubbles interact with ultrasound to induce transient microscopic pores in the cellular plasma membrane in a highly localized thermo-mechanical process called sonoporation. Theranostic applications of in vitro sonoporation include molecular delivery (e.g., transfection, drug loading and cell labeling), as well as molecular extraction for measuring intracellular biomarkers, such as proteins and mRNA. Prior research focusing mainly on the effects of acoustic forcing with polydisperse microbubbles has identified a “soft limit” of sonoporation efficiency at 50% when including dead and lysed cells. We show here that this limit can be exceeded with the judicious use of monodisperse microbubbles driven by a physiotherapy device (1.0 MHz, 2.0 W/cm2, 10% duty cycle). We first examined the effects of microbubble size and found that small-diameter microbubbles (2 µm) deliver more instantaneous power than larger microbubbles (4 & 6 µm). However, owing to rapid fragmentation and a short half-life (0.7 s for 2 µm; 13.3 s for 6 µm), they also deliver less energy over the sonoporation time. This translates to a higher ratio of FITC-dextran (70 kDa) uptake to cell death/lysis (4:1 for 2 µm; 1:2 for 6 µm) in suspended HeLa cells after a single sonoporation. Sequential sonoporations (up to four) were consequently employed to increase molecular delivery. Peak uptake was found to be 66.1 ± 1.2% (n=3) after two sonoporations when properly accounting for cell lysis (7.0 ± 5.6%) and death (17.9 ± 2.0%), thus overcoming the previously reported soft limit. Substitution of TRITC-dextran (70 kDa) on the second sonoporation confirmed the effects were multiplicative. Overall, this study demonstrates the possibility of utilizing monodisperse small-diameter microbubbles as a means to achieve multiple low-energy sonoporation bursts for efficient in vitro cellular uptake and sequential molecular delivery. PMID:26681986

Observation of contrast agent response to chirp insonation with a simultaneous optical-acoustical system.

PubMed

Sun, Yang; Zhao, Shukui; Dayton, Paul A; Ferrara, Katherine W

2006-06-01

Rayleigh-Plesset analysis, ultra-high speed photography, and single bubble acoustical recordings previously were applied independently to characterize the radial oscillation and resulting echoes from a microbubble in response to an ultrasonic pulse. In addition, high-speed photography has shown that microbubbles are destroyed over a single pulse or pulse train by diffusion and fragmentation. In order to develop a single model to characterize microbubble echoes based on oscillatory and destructive characteristics, an optical-acoustical system was developed to simultaneously record the optical image and backscattered echo from each microbubble. Combined observation provides the opportunity to compare predictions for oscillation and echoes with experimental results and identify discrepancies due to diffusion or fragmentation. Optimization of agents and insonating pulse parameters may be facilitated with this system. The mean correlation of the predicted and experimental radius-time curves and echoes exceeds 0.7 for the parameters studied here. An important application of this new system is to record and analyze microbubble response to a long pulse in which diffusion is shown to occur over the pulse duration. The microbubble response to an increasing or decreasing chirp is evaluated using this new tool. For chirp insonation beginning with the lower center frequency, low-frequency modulation of the oscillation envelope was obvious. However, low-frequency modulation was not observed in the radial oscillation produced by decreasing chirp insonation. Comparison of the echoes from similar sized microbubbles following increasing and decreasing chirp insonation demonstrated that the echoes were not time-reversed replicas. Using a transmission pressure of 620 kPa, the -6 dB echo length was 0.9 and 1.1 micros for increasing and decreasing chirp insonation, respectively (P = 0.02). The mean power in the low-frequency portion of the echoes was 8 (mV)2 and 13 (mV)2 for increasing and decreasing chirp insonation, respectively (P = 0.01).

Observation of contrast agent response to chirp insonation with a simultaneous optical-acoustical system

PubMed Central

Sun, Yang; Zhao, Shukui; Dayton, Paul A.; Ferrara, Katherine W.

2006-01-01

Rayleigh-Plesset analysis, ultra-high speed photography, and single bubble acoustical recordings have previously been applied independently to characterize the radial oscillation and resulting echoes from a microbubble in response to an ultrasonic pulse. In addition, high speed photography has shown that microbubbles are destroyed over a single pulse or pulse train by diffusion and fragmentation. In order to develop a single model to characterize microbubble echoes based on oscillatory and destructive characteristics, an optical-acoustical system was developed to simultaneously record the optical image and backscattered echo from each microbubble. Combined observation provides the opportunity to compare predictions for oscillation and echoes with experimental results and identify discrepancies due to diffusion or fragmentation. Optimization of agents and insonating pulse parameters may be facilitated with this system. The mean correlation of the predicted and experimental radius-time curves and echoes exceeds 0.7 for the parameters studied here. An important application of this new system is to record and analyze microbubble response to a long pulse where diffusion is shown to occur over the pulse duration. The microbubble response to an increasing or decreasing chirp is evaluated using this new tool. For chirp insonation beginning with the lower center frequency, low frequency modulation of the oscillation envelope was obvious. However, low frequency modulation was not observed in the radial oscillation produced by decreasing chirp insonation. Comparison of the echoes from similar sized microbubbles following increasing and decreasing chirp insonation demonstrated that the echoes were not time-reversed replicas. Using a transmission pressure of 620 kPa, the −6 dB echo length was 0.9 and 1.1 μs for increasing and decreasing chirp insonation, respectively (P = 0.02). The mean power in the low frequency portion of the echoes was 8 (mV)2 and 13 (mV)2 for increasing and decreasing chirp insonation, respectively, (P = 0.01). PMID:16846145

TREATMENT OF MICROVASCULAR MICRO-EMBOLIZATION USING MICROBUBBLES AND LONG-TONE-BURST ULTRASOUND: AN IN VIVO STUDY

PubMed Central

Pacella, John J.; Brands, Judith; Schnatz, Frederick G.; Black, John J.; Chen, Xucai; Villanueva, Flordeliza S.

2015-01-01

Despite epicardial coronary artery reperfusion by percutaneous coronary intervention, distal micro-embolization into the coronary microcirculation limits myocardial salvage during acute myocardial infarction. Thrombolysis using ultrasound and microbubbles (sonothrombolysis) is an approach that induces microbubble oscillations to cause clot disruption and restore perfusion. We sought to determine whether this technique could restore impaired tissue perfusion caused by thrombotic microvascular obstruction. In 16 rats, an imaging transducer was placed on the biceps femoris muscle, perpendicular to a single-element 1-MHz treatment transducer. Ultrasound contrast perfusion imaging was performed at baseline and after micro-embolization. Therapeutic ultrasound (5000 cycles, pulse repetition frequency = 5 0.33 Hz, 1.5 MPa) was delivered to nine rats for two 10-min sessions during intra-arterial infusion of lipid-encapsulated microbubbles; seven control rats received no ultrasound–microbubble therapy. Ultrasound contrast perfusion imaging was repeated after each treatment or control period, and microvascular volume was measured as peak video intensity. There was a 90% decrease in video intensity after micro-embolization (from 8.6 ± 4.8 to 0.7 ± 0.8 dB, p < 0.01). The first and second ultrasound–microbubble sessions were respectively followed by video intensity increases of 5.8 ± 5.1 and 8.7 ± 5.7 dB (p < 0.01, compared with micro-embolization). The first and second control sessions, respectively, resulted in no significant increase in video intensity (2.4 ± 2.3 and 3.6 ± 4.9) compared with micro-embolization (0.6 ± 0.7 dB). We have developed an in vivo model that simulates the distal thrombotic microvascular obstruction that occurs after primary percutaneous coronary intervention. Long-pulse-length ultrasound with microbubbles has a therapeutic effect on microvascular perfusion and may be a valuable adjunct to reperfusion therapy for acute myocardial infarction. PMID:25542487

Reversible and irreversible vascular bioeffects induced by ultrasound and microbubbles in chorioallantoic membrane model

NASA Astrophysics Data System (ADS)

Tarapacki, Christine; Kuebler, Wolfgang M.; Tabuchi, Arata; Karshafian, Raffi

2017-03-01

Background: The application of ultrasound and microbubbles at therapeutic conditions has been shown to improve delivery of molecules, cause vasoconstriction, modulate blood flow and induce a vascular shut down in in vivo cancerous tissues. The underlying mechanism has been associated with the interaction of ultrasonically-induced microbubble oscillation and cavitation with the blood vessel wall. In this study, the effect of ultrasound and microbubbles on blood flow and vascular architecture was studied using a fertilized chicken egg CAM (chorioallantoic membrane) model. Methods: CAM at day 12 of incubation (Hamburger-Hamilton stage 38-40) were exposed to ultrasound at varying acoustic pressures (160, 240 and 320 kPa peak negative pressure) in the presence of Definity microbubbles and 70 kDa FITC dextran fluorescent molecules. A volume of 50 µL Definity microbubbles were injected into a large anterior vein of the CAM prior to ultrasound exposure. The ultrasound treatment sequence consisted of 5 s exposure at 500 kHz frequency, 8 cycles and 1 kHz pulse repetition frequency with 5 s off for a total exposure of 2 minutes. Fluorescent videos and images of the CAM vasculature were acquired using intravital microscopy prior, during and following the ultrasound exposure. Perfusion was quantified by measuring the length of capillaries in a region of interest using Adobe Illustrator. Results and Discussion: The vascular bioeffects induced by USMB increased with acoustic peak negative pressure. At 160 kPa, no visible differences were observed compared to the control. At 240 kPa, a transient decrease in perfusion with subsequent recovery within 15 minutes was observed, whereas at 320 kPa, the fluorescent images showed an irreversible vascular damage. The study indicates that a potential mechanism for the transient decrease in perfusion may be related to blood coagulation. The results suggest that ultrasound and microbubbles can induce reversible and irreversible vascular changes depending on the ultrasound exposure pressure.

Parametric array technique for microbubble excitation.

PubMed

Vos, Hendrik J; Goertz, David E; van der Steen, Antonius F W; de Jong, Nico

2011-05-01

This study investigates the use of an acoustic parametric array as a means for microbubble excitation. The excitation wave is generated during propagation in a nonlinear medium of two high-frequency carrier waves, whereby the frequency of the excitation wave is the difference frequency of the carrier waves. Carrier waves of around 10 and 25 MHz are used to generate low-frequency waves between 0.5 and 3.5 MHz at amplitudes in the range of 25 to 80 kPa in water. We demonstrate with high-speed camera observations that it is possible to induce microbubble oscillations with the low frequency signal arising from the nonlinear propagation process. As an application, we determined the resonance frequency of Definity contrast agent microbubbles with radius ranging from 1.5 to 5 μm by sweeping the difference frequency in the range from 0.5 to 3.5 MHz.

Pancreatic cancer cell detection by targeted lipid microbubbles and multiphoton imaging.

PubMed

Cromey, Benjamin; McDaniel, Ashley; Matsunaga, Terry; Vagner, Josef; Kieu, Khanh Quoc; Banerjee, Bhaskar

2018-04-01

Surgical resection of pancreatic cancer represents the only chance of cure and long-term survival in this common disease. Unfortunately, determination of a cancer-free margin at surgery is based on one or two tiny frozen section biopsies, which is far from ideal. Not surprisingly, cancer is usually left behind and is responsible for metastatic disease. We demonstrate a method of receptor-targeted imaging using peptide ligands, lipid microbubbles, and multiphoton microscopy that could lead to a fast and accurate way of examining the entire cut surface during surgery. Using a plectin-targeted microbubble, we performed a blinded in-vitro study to demonstrate avid binding of targeted microbubbles to pancreatic cancer cells but not noncancerous cell lines. Further work should lead to a much-needed point-of-care diagnostic test for determining clean margins in oncologic surgery. (2018) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE).

Conformal drug delivery and instantaneous monitoring based on an inverse synthesis method at a diagnostic ultrasound platform

NASA Astrophysics Data System (ADS)

Xu, Shanshan; Zong, Yujin; Liu, Xiaodong; Lu, Mingzhu; Wan, Mingxi

2017-03-01

In this paper, based on a programmable diagnostic ultrasound scanner, a combined approach was proposed, in which a variable-sized focal region wherein the acoustic pressure is above the ultrasound contrast agents (UCA) fragmentation threshold is synthesized by reasonably matching the excitation voltage and the transmit aperture of the linear array at 5MHz, the UCAs' temporal and spatial distribution before and after the microbubbles fragmentation is monitored using the plane-wave transmission and reception at 400Hz and, simultaneously, the broadband noise emission during the microbubbles fragmentation is extracted using the backscattering of focused release bursts (destruction pulse) themselves on the linear array. Then, acquired radio frequency (RF) data are processed to draw parameters which can be correlated with the indicator of broadband noise emission level, namely inertial cavitation dose (ICD) and microbubble fragmentation efficiency, namely decay rate of microbubbles.

Microbubble-enhanced ultrasound to demonstrate urethral transection in a case of penile fracture.

PubMed

Czarnecki, Oliver; von Stempel, Conrad Brice; Sangster, Pippa; Walkden, Miles

2017-09-23

A 47-year-old man attended the emergency department following trauma during sexual intercourse after which he developed penile swelling and haematuria several hours later. A penile fracture was suspected but given the slightly atypical history, ultrasound was performed to look for a fracture. Given the history of haematuria, both a standard Doppler ultrasound and a microbubble-enhanced retrograde ultrasound urethrogram were performed. The Doppler confirmed the suspected diagnosis of penile fracture, and microbubble urethrogram demonstrated a urethral injury. This facilitated prompt surgical treatment and helped guide the surgical approach. Retrograde microbubble enhanced ultrasound urethrogram is a novel technique that can be used in conjunction with standard ultrasound to confirm the presence of a concurrent urethral rupture in penile fracture. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Modeling Encapsulated Microbubble Dynamics at High Pressure Amplitudes

NASA Astrophysics Data System (ADS)

Heyse, Jan F.; Bose, Sanjeeb; Iaccarino, Gianluca

2017-11-01

Encapsulated microbubbles are commonly used in ultrasound contrast imaging and are of growing interest in therapeutic applications where local cavitation creates temporary perforations in cell membranes allowing for enhanced drug delivery. Clinically used microbubbles are encapsulated by a shell commonly consisting of protein, polymer, or phospholipid; the response of these bubbles to externally imposed ultrasound waves is sensitive to the compressibility of the encapsulating shell. Existing models approximate the shell compressibility via an effective surface tension (Marmottant et al. 2005). We present simulations of microbubbles subjected to high amplitude ultrasound waves (on the order of 106 Pa) and compare the results with the experimental measurements of Helfield et al. (2016). Analysis of critical points (corresponding to maximum and minimum expansion) in the governing Rayleigh-Plesset equation is used to make estimates of the parameters used to characterize the effective surface tension of the encapsulating shell. Stanford Graduate Fellowship.

Characteristics of carbon nanotubes based micro-bubble generator for thermal jet printing.

PubMed

Zhou, Wenli; Li, Yupeng; Sun, Weijun; Wang, Yunbo; Zhu, Chao

2011-12-01

We propose a conceptional thermal printhead with dual microbubble generators mounted parallel in each nozzle chamber, where multiwalled carbon nanotubes are adopted as heating elements with much higher energy efficiency than traditional approaches using noble metals or polysilicon. Tailing effect of droplet can be excluded by appropriate control of grouped bubble generations. Characteristics of the corresponding micro-fabricated microbubble generators were comprehensively studied before the formation of printhead. Electrical properties of the microheaters on glass substrate in air and performance of bubble generation underwater focusing on the relationships between input power, device resistance and bubble behavior were probed. Proof-of-concept bubble generations grouped to eliminate the tailing effect of droplet were performed indicating precise pattern with high resolution could be realized by this kind of printhead. Experimental results revealed guidance to the geometric design of the printhead as well as its fabrication margin and the electrical control of the microbubble generators.

Harmonic vibro-acoustography.

PubMed

Chen, Shigao; Kinnick, Randall R; Greenleaf, James F; Fatemi, Mostafa

2007-07-01

Vibro-acoustography is an imaging method that uses the radiation force of two interfering ultrasound beams of slightly different frequency to probe an object. An image is made using the acoustic emission resulted from the object vibration at the difference frequency. In this paper, the feasibility of imaging objects at twice the difference frequency (harmonic acoustic emission) is studied. Several possible origins of harmonic acoustic emission are explored. As an example, it is shown that microbubbles close to resonance can produce significant harmonic acoustic emission due to its high nonlinearity. Experiments demonstrate that, compared to the fundamental acoustic emission, harmonic acoustic emission greatly improves the contrast between microbubbles and other objects in vibro-acoustography (an improvement of 17-23 dB in these experiments). Applications of this technique include imaging the nonlinearity of the object and selective detection of microbubbles for perfusion imaging. The impact of microbubble destruction during the imaging process also is discussed.

Vascular applications of contrast-enhanced ultrasound imaging.

PubMed

Mehta, Kunal S; Lee, Jake J; Taha, Ashraf G; Avgerinos, Efthymios; Chaer, Rabih A

2017-07-01

Contrast-enhanced ultrasound (CEUS) imaging is a powerful noninvasive modality offering numerous potential diagnostic and therapeutic applications in vascular medicine. CEUS imaging uses microbubble contrast agents composed of an encapsulating shell surrounding a gaseous core. These microbubbles act as nearly perfect intravascular reflectors of ultrasound energy and may be used to enhance the overall contrast and quality of ultrasound images. The purpose of this narrative review is to survey the current literature regarding CEUS imaging and discuss its diagnostic and therapeutic roles in current vascular and selected nonvascular applications. The PubMed, MEDLINE, and Embase databases were searched until July 2016 using the PubMed and Ovid Web-based search engines. The search terms used included contrast-enhanced, microbubble, ultrasound, carotid, aneurysm, and arterial. The diagnostic and therapeutic utility of CEUS imaging has grown exponentially, particularly in the realms of extracranial carotid arterial disease, aortic disease, and peripheral arterial disease. Studies have demonstrated that CEUS imaging is diagnostically superior to conventional ultrasound imaging in identifying vessel irregularities and measuring neovascularization to assess plaque vulnerability and end-muscle perfusion. Groups have begun to use microbubbles as agents in therapeutic applications for targeted drug and gene therapy delivery as well as for the enhancement of sonothrombolysis. The emerging technology of microbubbles and CEUS imaging holds considerable promise for cardiovascular medicine and cancer therapy given its diagnostic and therapeutic utility. Overall, with proper training and credentialing of technicians, the clinical implications are innumerable as microbubble technology is rapidly bursting onto the scene of cardiovascular medicine. Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Design concept of a cryogenic distillation column cascade for a ITER scale fusion reactor

NASA Astrophysics Data System (ADS)

Yamanishi, Toshihiko; Enoeda, Mikio; Okuno, Kenji

1994-07-01

A column cascade has been proposed for the fuel cycle of a ITER scale fusion reactor. The proposed cascade consists of three columns and has significant features: either top or bottom product is prior to the other for each column; it is avoided to withdraw side streams as products or feeds of down stream columns; and there is no recycle steam between the columns. In addition, the product purity of the cascade can be maintained against the changes of flow rates and compositions of feed streams just by adjusting the top and bottom flow rates. The control system has been designed for each column in the cascade. A key component in the prior product stream was selected, and the analysis method of this key component was proposed. The designed control system never brings instability as long as the concentration of the key component is measured with negligible time lag. The time lag for the measurement considerably affects the stability of the control system. A significant conclusion by the simulation in this work is that permissible time for the measurement is about 0.5 hour to obtain stable control. Hence, the analysis system using the gas chromatography is valid for control of the columns.

Stable Encapsulated Air Nanobubbles in Water.

PubMed

Wang, Yu; Liu, Guojun; Hu, Heng; Li, Terry Yantian; Johri, Amer M; Li, Xiaoyu; Wang, Jian

2015-11-23

The dispersion into water of nanocapsules bearing a highly hydrophobic fluorinated internal lining yielded encapsulated air nanobubbles. These bubbles, like their micrometer-sized counterparts (microbubbles), effectively reflected ultrasound. More importantly, the nanobubbles survived under ultrasonication 100-times longer than a commercial microbubble sample that is currently in clinical use. We justify this unprecedented stability theoretically. These nanobubbles, owing to their small size and potential ability to permeate the capillary networks of tissues, may expand the applications of microbubbles in diagnostic ultrasonography and find new applications in ultrasound-regulated drug delivery. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Modeling subharmonic response from contrast microbubbles as a function of ambient static pressure

PubMed Central

Katiyar, Amit; Sarkar, Kausik; Forsberg, Flemming

2011-01-01

Variation of subharmonic response from contrast microbubbles with ambient pressure is numerically investigated for non-invasive monitoring of organ-level blood pressure. Previously, several contrast microbubbles both in vitro and in vivo registered approximately linear (5–15 dB) subharmonic response reduction with 188 mm Hg change in ambient pressure. In contrast, simulated subharmonic response from a single microbubble is seen here to either increase or decrease with ambient pressure. This is shown using the code BUBBLESIM for encapsulated microbubbles, and then the underlying dynamics is investigated using a free bubble model. The ratio of the excitation frequency to the natural frequency of the bubble is the determining parameter—increasing ambient pressure increases natural frequency thereby changing this ratio. For frequency ratio below a lower critical value, increasing ambient pressure monotonically decreases subharmonic response. Above an upper critical value of the same ratio, increasing ambient pressure increases subharmonic response; in between, the subharmonic variation is non-monotonic. The precise values of frequency ratio for these three different trends depend on bubble radius and excitation amplitude. The modeled increase or decrease of subharmonic with ambient pressure, when one happens, is approximately linear only for certain range of excitation levels. Possible reasons for discrepancies between model and previous experiments are discussed. PMID:21476688

Effect of high intensity focused ultrasound (HIFU) in conjunction with a nanomedicines-microbubble complex for enhanced drug delivery.

PubMed

Han, Hyounkoo; Lee, Hohyeon; Kim, Kwangmeyung; Kim, Hyuncheol

2017-11-28

Although nanomedicines have been intensively investigated for cancer therapy in the past, poor accumulation of nanomedicines in tumor sites remains a serious problem. Therefore, a novel drug delivery system is required to enhance accumulation and penetration of nanomedicines at the tumor site. Recently, high-intensity focused ultrasound (HIFU) has been highlighted as a non-invasive therapeutic modality, and showed enhanced therapeutic efficacy in combination with nanomedicines. Cavitation effect induced by the combination of HIFU and microbubbles results in transiently enhanced cell membrane permeability, facilitating improved drug delivery efficiency into tumor sites. Therefore, we introduce the acoustic cavitation and thermal/mechanical effects of HIFU in conjunction with microbubble to overcome the limitation of conventional drug delivery. The cavitation effect maximized by the strong acoustic energy of HIFU induced the preferential accumulation of nanomedicine locally released from the nanomedicines-microbubble complex in the tumor. In addition, the mechanical effect of HIFU allowed the accumulated nanomedicines to penetrate into deeper tumor region. The preferential accumulation and deeper penetration of nanomedicines by HIFU showed enhanced therapeutic efficacy, compared to low frequency ultrasound (US). These overall results demonstrate that the strategy combined nanomedicines-microbubble complex with HIFU is a promising tools for cancer therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

Microbubble-assisted p53, RB, and p130 gene transfer in combination with radiation therapy in prostate cancer.

PubMed

Nande, Rounak; Greco, Adelaide; Gossman, Michael S; Lopez, Jeffrey P; Claudio, Luigi; Salvatore, Marco; Brunetti, Arturo; Denvir, James; Howard, Candace M; Claudio, Pier Paolo

2013-06-01

Combining radiation therapy and direct intratumoral (IT) injection of adenoviral vectors has been explored as a means to enhance the therapeutic potential of gene transfer. A major challenge for gene transfer is systemic delivery of nucleic acids directly into an affected tissue. Ultrasound (US) contrast agents (microbubbles) are viable candidates to enhance targeted delivery of systemically administered genes. Here we show that p53, pRB, and p130 gene transfer mediated by US cavitation of microbubbles at the tumor site resulted in targeted gene transduction and increased reduction in tumor growth compared to DU-145 prostate cancer cell xenografts treated intratumorally with adenovirus (Ad) or radiation alone. Microbubble-assisted/US-mediated Ad.p53 and Ad.RB treated tumors showed significant reduction in tumor volume compared to Ad.p130 treated tumors (p<0.05). Additionally, US mediated microbubble delivery of p53 and RB combined with external beam radiation resulted in the most profound tumor reduction in DU-145 xenografted nude mice (p<0.05) compared to radiation alone. These findings highlight the potential therapeutic applications of this novel image-guided gene transfer technology in combination with external beam radiation for prostate cancer patients with therapy resistant disease.

Modeling and Characterization of Encapsulated Microbubbles for Ultrasound Imaging and Drug Delivery

NASA Astrophysics Data System (ADS)

Sarkar, Kausik; Jain, Pankaj; Chatterjee, Dhiman

2008-07-01

Intravenously injected encapsulated microbubbles improve the contrast of an ultrasound image. Their destruction is used in measuring blood flow, stimulating arteriogenesis, and drug delivery. We measure attenuation and scattering of ultrasound through solution of commercial contrast agents such as Optison (GE Health Care, Princeton, NJ) and Definity (Bristol Meyer-Squibb Imaging, North Ballerina, MA). We have developed an interfacial rheology model for the encapsulation of such microbubbles. By matching with experimental data, we obtain the characteristic rheological parameters. We compare model predictions with other experiments. We also investigate microbubble destruction under acoustic excitation by measuring time-varying attenuation data. Three regions of acoustic pressure amplitudes are found: at low pressure, there is no destruction; at slightly higher pressure bubbles are destroyed, and the rate of destruction depends on a combination of PRF and amplitude. At a still higher pressure amplitude, the attenuation decreases catastrophically. The last two regimes correspond respectively to 1) slow destruction of bubbles due to increased gas diffusion and 2) complete bubble destruction leading to release of free bubbles. An analytical model for the bubble growth and dissolution will be presented. The effects of membrane permeability and elasticity on the stability of microbubbles are investigated. (Supported by DOD, NSF and NIH).

Influence of nesting shell size on brightness longevity and resistance to ultrasound-induced dissolution during enhanced B-mode contrast imaging.

PubMed

Wallace, N; Dicker, S; Lewin, P; Wrenn, S P

2014-12-01

This study aims to bridge the gap between transport mechanisms of an improved ultrasound contrast agent (UCA) and its resulting behavior in a clinical imaging study. Phospholipid-shelled microbubbles nested within the aqueous core of a polymer microcapsule are examined for their use and feasibility as an improved UCA. The nested formulation provides contrast comparable to traditional formulations, specifically an SF6 microbubble coated by a DSPC PEG-3000 monolayer, with the advantage that contrast persists at least nine times longer in a mock clinical, in vitro setting. The effectiveness of the sample was measured using a contrast ratio in units of decibels (dB) which compares the brightness of the nested microbubbles to a reference value of a phantom tissue mimic. During a 40min imaging study, six nesting formulations with average outer capsule diameters of 1.95, 2.53, 5.55, 9.95, 14.95, and 20.51μm reached final contrast ratio values of 0.25, 2.35, 3.68, 4.51, 5.93, and 8.00dB, respectively. The starting contrast ratio in each case was approximately 8dB and accounts for the brightness attributed to the nesting shell. As compared with empty microcapsules (no microbubbles nested within), enhancement of the initial contrast ratio increased systematically with decreasing microcapsule size. The time required to reach a steady state in the temporal contrast ratio profile also varied with microcapsule diameter and was found to be 420s for each of the four smallest shell diameters and 210s and 150s, respectively, for the largest two shell diameters. All nested formulations were longer-lived and gave higher final contrast ratios than a control sample comprising un-nested, but otherwise equivalent, microbubbles. Specifically, the contrast ratio of the un-nested microbubbles decreased to a negative value after 4min of continuous ultrasound exposure with complete disappearance of the microbubbles after 15min whereas all nested formulations maintained positive contrast ratio values for the duration of the 40min trial. The results are consistent with two distinct stages of gas transport: in the first stage, passive diffusion occurs under ambient conditions across the microbubble monolayer within the first few minutes after formulation until the aqueous interior of the microcapsule is saturated with gas; in the second stage ultrasound drives additional gas dissolution even further due to pressure modulation. It is important to understand the chemistry and transport mechanisms of this contrast agent under the influence of ultrasound to attain better perspicacity for enhanced applications in imaging. Results from this study will facilitate future preclinical studies and clinical applications of nested microbubbles for therapeutic and diagnostic imaging. Copyright © 2014 Elsevier B.V. All rights reserved.

Targeted Antiangiogenesis Gene Therapy Using Targeted Cationic Microbubbles Conjugated with CD105 Antibody Compared with Untargeted Cationic and Neutral Microbubbles

PubMed Central

Zhou, Yu; Gu, Haitao; Xu, Yan; Li, Fan; Kuang, Shaojing; Wang, Zhigang; Zhou, Xiyuan; Ma, Huafeng; Li, Pan; Zheng, Yuanyi; Ran, Haitao; Jian, Jia; Zhao, Yajing; Song, Weixiang; Wang, Qiushi; Wang, Dong

2015-01-01

Objective This study aimed to develop targeted cationic microbubbles conjugated with a CD105 antibody (CMB105) for use in targeted vascular endothelial cell gene therapy and ultrasound imaging. We compared the results with untargeted cationic microbubbles (CMB) and neutral microbubbles (NMB). Methods CMB105 were prepared and compared with untargeted CMB and NMB. First, the microbubbles were characterized in terms of size, zeta-potential, antibody binding ability and plasmid DNA loading capacity. A tumor model of subcutaneous breast cancer in nude mice was used for our experiments. The ability of different types of microbubbles to target HUVECs in vitro and tumor neovascularization in vivo was measured. The endostatin gene was selected for its outstanding antiangiogenesis effect. For in vitro experiments, the transfection efficiency and cell cycle were analyzed using flow cytometry, and the transcription and expression of endostatin were measured by qPCR and Western blotting, respectively. Vascular tube cavity formation and tumor cell invasion were used to evaluate the antiangiogenesis gene therapy efficiency in vitro. Tumors were exposed to ultrasound irradiation with different types of microbubbles, and the gene therapy effects were investigated by detecting apoptosis induction and changes in tumor volume. Results CMB105 and CMB differed significantly from NMB in terms of zeta-potential, and the DNA loading capacities were 16.76±1.75 μg, 18.21±1.22 μg, and 0.48±0.04 μg per 5×108 microbubbles, respectively. The charge coupling of plasmid DNA to CMB105 was not affected by the presence of the CD105 antibody. Both CMB105 and CMB could target to HUVECs in vitro, whereas only CMB105 could target to tumor neovascularization in vivo. In in vitro experiments, the transfection efficiency of CMB105 was 24.7-fold higher than the transfection efficiency of NMB and 1.47-fold higher than the transfection efficiency of CMB (P<0.05). With ultrasound-targeted microbubble destruction (UTMD)-mediated gene therapy, the transcription and expression of endostatin were the highest in the CMB105 group (P<0.001); the antiangiogenesis effect and inhibition of tumor cells invasion was better with CMB105 than CMB or NMB in vitro (P<0.01). After gene therapy, the tumor volumes of CMB105 group were significantly smaller than that of CMB and NMB, and many tumor cells had begun apoptosis in the CMB105 group, which had the highest apoptosis index (P<0.001). Conclusions As a contrast agent and plasmid carrier, CMB105 can be used not only for targeted ultrasound imaging but also for targeted gene therapy both in vitro and in vivo. The plasmid DNA binding ability of the CMB was not affected by conjugation of the CMB with the CD105 antibody, and because of its targeting ability, the gene transfection efficiency and therapeutic effect were better compared with the untargeted CMB and NMB. The advantages of targeted gene therapy with CMB105 in vivo were more prominent than with CMB or NMB because neither can target the endothelia in vivo. PMID:25699099

Targeted antiangiogenesis gene therapy using targeted cationic microbubbles conjugated with CD105 antibody compared with untargeted cationic and neutral microbubbles.

PubMed

Zhou, Yu; Gu, Haitao; Xu, Yan; Li, Fan; Kuang, Shaojing; Wang, Zhigang; Zhou, Xiyuan; Ma, Huafeng; Li, Pan; Zheng, Yuanyi; Ran, Haitao; Jian, Jia; Zhao, Yajing; Song, Weixiang; Wang, Qiushi; Wang, Dong

2015-01-01

This study aimed to develop targeted cationic microbubbles conjugated with a CD105 antibody (CMB105) for use in targeted vascular endothelial cell gene therapy and ultrasound imaging. We compared the results with untargeted cationic microbubbles (CMB) and neutral microbubbles (NMB). CMB105 were prepared and compared with untargeted CMB and NMB. First, the microbubbles were characterized in terms of size, zeta-potential, antibody binding ability and plasmid DNA loading capacity. A tumor model of subcutaneous breast cancer in nude mice was used for our experiments. The ability of different types of microbubbles to target HUVECs in vitro and tumor neovascularization in vivo was measured. The endostatin gene was selected for its outstanding antiangiogenesis effect. For in vitro experiments, the transfection efficiency and cell cycle were analyzed using flow cytometry, and the transcription and expression of endostatin were measured by qPCR and Western blotting, respectively. Vascular tube cavity formation and tumor cell invasion were used to evaluate the antiangiogenesis gene therapy efficiency in vitro. Tumors were exposed to ultrasound irradiation with different types of microbubbles, and the gene therapy effects were investigated by detecting apoptosis induction and changes in tumor volume. CMB105 and CMB differed significantly from NMB in terms of zeta-potential, and the DNA loading capacities were 16.76±1.75 μg, 18.21±1.22 μg, and 0.48±0.04 μg per 5×10(8) microbubbles, respectively. The charge coupling of plasmid DNA to CMB105 was not affected by the presence of the CD105 antibody. Both CMB105 and CMB could target to HUVECs in vitro, whereas only CMB105 could target to tumor neovascularization in vivo. In in vitro experiments, the transfection efficiency of CMB105 was 24.7-fold higher than the transfection efficiency of NMB and 1.47-fold higher than the transfection efficiency of CMB (P<0.05). With ultrasound-targeted microbubble destruction (UTMD)-mediated gene therapy, the transcription and expression of endostatin were the highest in the CMB105 group (P<0.001); the antiangiogenesis effect and inhibition of tumor cells invasion was better with CMB105 than CMB or NMB in vitro (P<0.01). After gene therapy, the tumor volumes of CMB105 group were significantly smaller than that of CMB and NMB, and many tumor cells had begun apoptosis in the CMB105 group, which had the highest apoptosis index (P<0.001). As a contrast agent and plasmid carrier, CMB105 can be used not only for targeted ultrasound imaging but also for targeted gene therapy both in vitro and in vivo. The plasmid DNA binding ability of the CMB was not affected by conjugation of the CMB with the CD105 antibody, and because of its targeting ability, the gene transfection efficiency and therapeutic effect were better compared with the untargeted CMB and NMB. The advantages of targeted gene therapy with CMB105 in vivo were more prominent than with CMB or NMB because neither can target the endothelia in vivo.

Lipid-shelled vehicles: engineering for ultrasound molecular imaging and drug delivery.

PubMed

Ferrara, Katherine W; Borden, Mark A; Zhang, Hua

2009-07-21

Ultrasound pressure waves can map the location of lipid-stabilized gas micro-bubbles after their intravenous administration in the body, facilitating an estimate of vascular density and microvascular flow rate. Microbubbles are currently approved by the Food and Drug Administration as ultrasound contrast agents for visualizing opacification of the left ventricle in echocardiography. However, the interaction of ultrasound waves with intravenously-injected lipid-shelled particles, including both liposomes and microbubbles, is a far richer field. Particles can be designed for molecular imaging and loaded with drugs or genes; the mechanical and thermal properties of ultrasound can then effect localized drug release. In this Account, we provide an overview of the engineering of lipid-shelled microbubbles (typical diameter 1000-10 000 nm) and liposomes (typical diameter 65-120 nm) for ultrasound-based applications in molecular imaging and drug delivery. The chemistries of the shell and core can be optimized to enhance stability, circulation persistence, drug loading and release, targeting to and fusion with the cell membrane, and therapeutic biological effects. To assess the biodistribution and pharmacokinetics of these particles, we incorporated positron emission tomography (PET) radioisotopes on the shell. The radionuclide (18)F (half-life approximately 2 h) was covalently coupled to a dipalmitoyl lipid, followed by integration of the labeled lipid into the shell, facilitating short-term analysis of particle pharmacokinetics and metabolism of the lipid molecule. Alternately, labeling a formed particle with (64)Cu (half-life 12.7 h), after prior covalent incorporation of a copper-chelating moiety onto the lipid shell, permits pharmacokinetic study of particles over several days. Stability and persistence in circulation of both liposomes and microbubbles are enhanced by long acyl chains and a poly(ethylene glycol) coating. Vascular targeting has been demonstrated with both nano- and microdiameter particles. Targeting affinity of the microbubble can be modulated by burying the ligand within a polymer brush layer; the application of ultrasound then reveals the ligand, enabling specific targeting of only the insonified region. Microbubbles and liposomes require different strategies for both drug loading and release. Microbubble loading is inhibited by the gas core and enhanced by layer-by-layer construction or conjugation of drug-entrapped particles to the surface. Liposome loading is typically internal and is enhanced by drug-specific loading techniques. Drug release from a microbubble results from the oscillation of the gas core diameter produced by the sound wave, whereas that from a liposome is enhanced by heat produced from the local absorption of acoustic energy within the tissue microenvironment. Biological effects induced by ultrasound, such as changes in cell membrane and vascular permeability, can enhance drug delivery. In particular, as microbubbles oscillate near a vessel wall, shock waves or liquid jets enhance drug transport. Mild heating induced by ultrasound, either before or after injection of the drug, facilitates the transport of liposomes from blood vessels to the tissue interstitium, thus increasing drug accumulation in the target region. Lipid-shelled vehicles offer many opportunities for chemists and engineers; ultrasound-based applications beyond the few currently in common use will undoubtedly soon multiply as molecular construction techniques are further refined.

A Targeting Microbubble for Ultrasound Molecular Imaging

PubMed Central

Yeh, James Shue-Min; Sennoga, Charles A.; McConnell, Ellen; Eckersley, Robert; Tang, Meng-Xing; Nourshargh, Sussan; Seddon, John M.; Haskard, Dorian O.; Nihoyannopoulos, Petros

2015-01-01

Rationale Microbubbles conjugated with targeting ligands are used as contrast agents for ultrasound molecular imaging. However, they often contain immunogenic (strept)avidin, which impedes application in humans. Although targeting bubbles not employing the biotin-(strept)avidin conjugation chemistry have been explored, only a few reached the stage of ultrasound imaging in vivo, none were reported/evaluated to show all three of the following properties desired for clinical applications: (i) low degree of non-specific bubble retention in more than one non-reticuloendothelial tissue; (ii) effective for real-time imaging; and (iii) effective for acoustic quantification of molecular targets to a high degree of quantification. Furthermore, disclosures of the compositions and methodologies enabling reproduction of the bubbles are often withheld. Objective To develop and evaluate a targeting microbubble based on maleimide-thiol conjugation chemistry for ultrasound molecular imaging. Methods and Results Microbubbles with a previously unreported generic (non-targeting components) composition were grafted with anti-E-selectin F(ab’)2 using maleimide-thiol conjugation, to produce E-selectin targeting microbubbles. The resulting targeting bubbles showed high specificity to E-selectin in vitro and in vivo. Non-specific bubble retention was minimal in at least three non-reticuloendothelial tissues with inflammation (mouse heart, kidneys, cremaster). The bubbles were effective for real-time ultrasound imaging of E-selectin expression in the inflamed mouse heart and kidneys, using a clinical ultrasound scanner. The acoustic signal intensity of the targeted bubbles retained in the heart correlated strongly with the level of E-selectin expression (|r|≥0.8), demonstrating a high degree of non-invasive molecular quantification. Conclusions Targeting microbubbles for ultrasound molecular imaging, based on maleimide-thiol conjugation chemistry and the generic composition described, may possess properties (i)–(iii) desired for clinical applications. PMID:26161541

Exploding microbubbles driving a simple electrochemical micropump

NASA Astrophysics Data System (ADS)

Uvarov, Ilia V.; Lemekhov, Sergey S.; Melenev, Artem E.; Svetovoy, Vitaly B.

2017-10-01

Electrochemical microactuators and micropumps are too slow for many applications. The use of the alternating polarity electrolysis can strongly reduce the response time of such devices. We investigate a powerful pumping regime of a simple valveless micropump made from polydimethylsiloxane on a glass substrate. Microsecond dynamics of the gas bubbles in the chamber is monitored with fast cameras. After an incubation period of 10-100 ms a microbubble filling the entire chamber pops up in less than 100~μ s and disappears in 10 ms. This bubble pushes liquid out and drives the pump. The phenomenon is interpreted as an explosion of the microbubble containing a mixture of H2 and O2 gases. For higher amplitude of the driving pulses the incubation time can be as short as 1-2 ms but many uncorrelated microbubbles are formed in the chamber, and disappear in 1 ms. As the result a less powerful but faster pumping is possible. A few principles allowing further improve the micropump characteristics are formulated.

Liquid core microbubble resonators for highly sensitive temperature sensing

NASA Astrophysics Data System (ADS)

Ward, Jonathan M.; Yang, Yong; Nic Chormaic, Sile

2014-03-01

It is experimentally shown that a large thermal blue shift of up to 100 GHz/K (0.2 nm/K at a wavelength of 775 nm) can be achieved with higher order radial modes in an ethanol-filled microbubble whispering gallery mode resonator (WGR). Q-factors for the most thermally sensitive modes are typically 105, equivalent to a measurement resolution of 8.5 mK. The thermal shift rate is determined for different modes when the core of the microbubble is filled with air, water, and ethanol. The measured shifts are compared against Finite Element Model (FEM) simulations. It is also shown that, if the microbubble is in the quasi-droplet regime, the fundamental TE mode in a bubble with a 500 nm wall is estimated to experience a shift of 35 GHz/K, while the effective index is still high enough to allow efficient coupling to a tapered optical fiber. Nonetheless, at a wall thickness of 1 μm, the most sensitive modes (n = 2) observed were still strongly coupled.

Dual-Frequency Piezoelectric Transducers for Contrast Enhanced Ultrasound Imaging

PubMed Central

Martin, K. Heath; Lindsey, Brooks D.; Ma, Jianguo; Lee, Mike; Li, Sibo; Foster, F. Stuart; Jiang, Xiaoning; Dayton, Paul A.

2014-01-01

For many years, ultrasound has provided clinicians with an affordable and effective imaging tool for applications ranging from cardiology to obstetrics. Development of microbubble contrast agents over the past several decades has enabled ultrasound to distinguish between blood flow and surrounding tissue. Current clinical practices using microbubble contrast agents rely heavily on user training to evaluate degree of localized perfusion. Advances in separating the signals produced from contrast agents versus surrounding tissue backscatter provide unique opportunities for specialized sensors designed to image microbubbles with higher signal to noise and resolution than previously possible. In this review article, we describe the background principles and recent developments of ultrasound transducer technology for receiving signals produced by contrast agents while rejecting signals arising from soft tissue. This approach relies on transmitting at a low-frequency and receiving microbubble harmonic signals at frequencies many times higher than the transmitted frequency. Design and fabrication of dual-frequency transducers and the extension of recent developments in transducer technology for dual-frequency harmonic imaging are discussed. PMID:25375755

Imaging of targeted lipid microbubbles to detect cancer cells using third harmonic generation microscopy

PubMed Central

Harpel, Kaitlin; Baker, Robert Dawson; Amirsolaimani, Babak; Mehravar, Soroush; Vagner, Josef; Matsunaga, Terry O.; Banerjee, Bhaskar; Kieu, Khanh

2016-01-01

The use of receptor-targeted lipid microbubbles imaged by ultrasound is an innovative method of detecting and localizing disease. However, since ultrasound requires a medium between the transducer and the object being imaged, it is impractical to apply to an exposed surface in a surgical setting where sterile fields need be maintained and ultrasound gel may cause the bubbles to collapse. Multiphoton microscopy (MPM) is an emerging tool for accurate, label-free imaging of tissues and cells with high resolution and contrast. We have recently determined a novel application of MPM to be used for detecting targeted microbubble adherence to the upregulated plectin-receptor on pancreatic tumor cells. Specifically, the third-harmonic generation response can be used to detect bound microbubbles to various cell types presenting MPM as an alternative and useful imaging method. This is an interesting technique that can potentially be translated as a diagnostic tool for the early detection of cancer and inflammatory disorders. PMID:27446711

On-chip generation of microbubbles as a practical technology for manufacturing contrast agents for ultrasonic imaging

PubMed Central

Hettiarachchi, Kanaka; Talu, Esra; Longo, Marjorie L.; Dayton, Paul A.; Lee, Abraham P.

2007-01-01

This paper presents a new manufacturing method to generate monodisperse microbubble contrast agents with polydispersity index (σ) values of <2% through microfluidic flow-focusing. Micron-sized lipid shell-based perfluorocarbon (PFC) gas microbubbles for use as ultrasound contrast agents were produced using this method. The poly(dimethylsiloxane) (PDMS)-based devices feature expanding nozzle geometry with a 7 μm orifice width, and are robust enough for consistent production of microbubbles with runtimes lasting several hours. With high-speed imaging, we characterized relationships between channel geometry, liquid flow rate Q, and gas pressure P in controlling bubble sizes. By a simple optimization of the channel geometry and Q and P, bubbles with a mean diameter of <5 μm can be obtained, ideal for various ultrasonic imaging applications. This method demonstrates the potential of microfluidics as an efficient means for custom-designing ultrasound contrast agents with precise size distributions, different gas compositions and new shell materials for stabilization, and for future targeted imaging and therapeutic applications. PMID:17389962

Dynamics of encapsulated microbubbles for contrast ultrasound imaging and drug delivery: from pressure dependent subharmonic to collapsing jet and acoustic streaming

NASA Astrophysics Data System (ADS)

Sarkar, Kausik

2016-11-01

Intravenously injected microbubbles used as ultrasound contrast enhancing agents are encapsulated by a nanometer-thick layer of lipids, proteins or polymers to stabilize them against premature dissolution. Over the years, we have developed interfacial rheological models for the encapsulation and used them to characterize several contrast agents by acoustic means. We will present an overview of our research emphasizing recent efforts in two directions. The first is on using subharmonic signals from the contrast microbubbles for non-invasive pressure estimation. Experimental measurement and modeling show that the subharmonic signal can both increase or decrease with pressure depending on frequency. Secondly, we will discuss boundary element (BEM) simulation of the collapse of an encapsulated microbubbles forming a jet near a blood vessel wall. Different rheology models of the encapsulation have been rigorously implemented in the BEM formulation. We will discuss the resulting stresses and the acoustic streaming near the wall leading to sonoporation and other bioeffects. Partially supported by Natinal Science Foundation.

Dual-frequency piezoelectric transducers for contrast enhanced ultrasound imaging.

PubMed

Martin, K Heath; Lindsey, Brooks D; Ma, Jianguo; Lee, Mike; Li, Sibo; Foster, F Stuart; Jiang, Xiaoning; Dayton, Paul A

2014-11-04

For many years, ultrasound has provided clinicians with an affordable and effective imaging tool for applications ranging from cardiology to obstetrics. Development of microbubble contrast agents over the past several decades has enabled ultrasound to distinguish between blood flow and surrounding tissue. Current clinical practices using microbubble contrast agents rely heavily on user training to evaluate degree of localized perfusion. Advances in separating the signals produced from contrast agents versus surrounding tissue backscatter provide unique opportunities for specialized sensors designed to image microbubbles with higher signal to noise and resolution than previously possible. In this review article, we describe the background principles and recent developments of ultrasound transducer technology for receiving signals produced by contrast agents while rejecting signals arising from soft tissue. This approach relies on transmitting at a low-frequency and receiving microbubble harmonic signals at frequencies many times higher than the transmitted frequency. Design and fabrication of dual-frequency transducers and the extension of recent developments in transducer technology for dual-frequency harmonic imaging are discussed.

Ablation of benign prostatic hyperplasia using microbubble-mediated ultrasound cavitation.

PubMed

Li, Tao; Liu, Zheng

2010-04-01

Benign prostatic hyperplasia (BPH) is a world-wide common disease in elderly male patients. A number of invasive physiotherapies have been used to replace prostatectomy. In this article we report our hypothesis of using microbubbles-mediated ultrasound cavitation effects to ablate prostatic tissues. Microbubble ultrasound contrast agent is widely used contrast media in ultrasonography, yet it is also found to act as cavitation nuclei or enhancer. Once excited by a high peak pressure ultrasound pulse, the mechanical effects, like shock wave and microstream, released from cavitation could produce a series of bioeffects, contributing to sonoporation, microvascular rupture and hematoma. BPH is known to have hyperplastic neovasculature and this make it possible to be disrupted by the physical effects of cavitation under existing microbubbles in circulation. Mechanical ablation of prostatic capillary or small vessels could result in pathological alterations such as thrombosis, micro-circulation blockage, prostatic necrosis and atrophia. Thereupon it could effectively treat BPH by nontraumatic ways. (c) 2009 Elsevier Ltd. All rights reserved.

Neuroprotective effect of combined ultrasound and microbubbles in a rat model of middle cerebral artery infarction

NASA Astrophysics Data System (ADS)

Fatar, M.; Griebe, M.; Stroick, M.; Kern, R.; Hennerici, M.; Meairs, S.

2005-03-01

Ultrasound-mediated microbubble thrombolysis (UMT) was performed in a middle cerebral artery occlusion model in rats to evaluate possible effects upon brain infarct volume, apoptosis, IL-6 and TNF-alpha levels, and disruption of the blood-brain barrier (BBB). The results show that infarct volume was significantly reduced (p<0.04) in the microbubble + ultrasound (MB + US) group as compared to control animals. The levels of IL-6 and TNF-alpha concentrations, as markers of tissue damage, were not significantly different. In trypan blue treated animals, no additional BBB disruption was observed for the UMT group. Likewise, there was no increase in apoptotic cell death outside the infarction area in animals treated with MB + US. The results demonstrate that UMT does not have a harmful effect upon ischemic stroke in a middle cerebral artery occlusion model of the rat. The significant reduction in brain infarction following insonation with ultrasound and microbubbles suggests a novel neuroprotective effect in ischemic stroke.

Localized Delivery of shRNA against PHD2 Protects the Heart from Acute Myocardial Infarction through Ultrasound-Targeted Cationic Microbubble Destruction.

PubMed

Zhang, Li; Sun, Zhenxing; Ren, Pingping; You, Manjie; Zhang, Jing; Fang, Lingyun; Wang, Jing; Chen, Yihan; Yan, Fei; Zheng, Hairong; Xie, Mingxing

2017-01-01

Hypoxia-inducible factor 1α (HIF-1α) plays a critical protective role in ischemic heart disease. Under normoxic conditions, HIF-1α was degraded by oxygen-dependent prolyl hydroxylase-2 (PHD2). Gene therapy has become a promising strategy to inhibit the degradation of HIF-1α and to improve cardiac function after ischemic injury. However, conventional gene delivery systems are difficult to achieve a targeted and localized gene delivery into the ischemic myocardia. Here, we report the localized myocardial delivery of shRNA against PHD2 through ultrasound-targeted microbubble destruction (UTMD) for protection the heart from acute myocardial infarction. In this study, a novel cationic microbubble was fabricated by using of the thin-film hydration and sonication method. The resulting microbubbles had a 28.2 ± 2.21 mV surface zeta potential and could greatly improve DNA binding performance, achieving 17.81 ± 1.46 μg of DNA loading capacity per 5 × 10 8 microbubbles. Combined with these cationic microbubbles, UTMD-mediated gene delivery was evaluated and the gene transfection efficiency was optimized in the H9C2 cardiac cells. Knockdown of PHD2 gene was successfully realized by UTMD-mediated shPHD2 transfection, resulting in HIF-1α-dependent protective effects on H9C2 cells through increasing the expression of HIF-1α, VEGF and bFGF. We further employed UTMD-mediated shPHD2 transfection into the localized ischemic myocardia in a rat ischemia model, demonstrating significantly reduced infarct size and greatly improved the heart function. The silencing of PHD2 and the up-regulation of its downstream genes in the treated myocardia were confirmed. Histological analysis further revealed numbers of HIF-1α- and VEGF-, and CD31-positive cells/mm 2 in the shPHD2-treated group were significantly greater than those in the sham or control vector groups (P < 0.05). In conclusion, our study provides a promising strategy to realize ultrasound-mediated localized myocardial shRNA delivery to protect the heart from acute myocardial infarction via cationic microbubbles.

Mechanical properties, microstructure, and specific adhesion of phospholipid monolayer-coated microbubbles

NASA Astrophysics Data System (ADS)

Kim, Dennis Heejong

1999-10-01

The objective of this study was to characterize properties of phospholipid monolayer shells formed on gas microbubbles, specifically (1)yield shear and shear viscosity as a function of the shell composition, (2)yield shear, shear viscosity, and microstructural domain density as a function of the quenching rate of the microbubbles following production, and (3)the adhesion of a lipid-coated microbubble to a colloidal substrate via receptor-ligand mediated specific interaction, either enhanced or inhibited by the presence of surface-grafted polymeric structures. The primary experimental technique employed was the micromanipulation method, wherein tapered fluid-filled pipets with bores on the order of 4-10 microns were used to (1)capture and maneuver individual micron scale bubbles in aqueous medium, and (2)apply suction pressures over the range of 1 dyn cm-2 to 10 5 dyn cm-2 (10-6 to 10 -1 atm) and track the corresponding deformation of the microbubble under applied pressure. The yield shear and shear viscosity increase with increasing acyl chain length of the lipid; an equivalent statement is that the yield shear and shear viscosity increase with reduced temperature of the shell material. Crystalline lipid domain sizes are dictated by the rate at which the system is (temperature) quenched in a manner predicted by classic materials science and metallurgy: rapidly cooled samples form the smallest grains and exhibit the lowest levels of yield shear and shear viscosity. Slowly cooled samples produce large grains and exhibit high levels of yield and viscosity. The success and strength of adhesion of a microbubble to a substrate is dictated by the identity of the adhesive molecules participating in the adhesion, as well as the surface architecture of the interfaces participating in adhesion. The term surface architecture is used to describe the physical arrangement of the full complement of steric stabilizers, spacers, and binding molecules present at the surface of a typical coated microbubble shell. Adhesion is successful for systems where the binding ligand is not impeded by the presence of surface-grafted poly(ethylene glycol) (PEG) moieties. Like the shell composition itself, the surface construct can be engineered to produce optimal performance in adhesion.

Localized Delivery of shRNA against PHD2 Protects the Heart from Acute Myocardial Infarction through Ultrasound-Targeted Cationic Microbubble Destruction

PubMed Central

Zhang, Li; Sun, Zhenxing; Ren, Pingping; You, Manjie; Zhang, Jing; Fang, Lingyun; Wang, Jing; Chen, Yihan; Yan, Fei; Zheng, Hairong; Xie, Mingxing

2017-01-01

Hypoxia-inducible factor 1α (HIF-1α) plays a critical protective role in ischemic heart disease. Under normoxic conditions, HIF-1α was degraded by oxygen-dependent prolyl hydroxylase-2 (PHD2). Gene therapy has become a promising strategy to inhibit the degradation of HIF-1α and to improve cardiac function after ischemic injury. However, conventional gene delivery systems are difficult to achieve a targeted and localized gene delivery into the ischemic myocardia. Here, we report the localized myocardial delivery of shRNA against PHD2 through ultrasound-targeted microbubble destruction (UTMD) for protection the heart from acute myocardial infarction. In this study, a novel cationic microbubble was fabricated by using of the thin-film hydration and sonication method. The resulting microbubbles had a 28.2 ± 2.21 mV surface zeta potential and could greatly improve DNA binding performance, achieving 17.81 ± 1.46 μg of DNA loading capacity per 5 × 108 microbubbles. Combined with these cationic microbubbles, UTMD-mediated gene delivery was evaluated and the gene transfection efficiency was optimized in the H9C2 cardiac cells. Knockdown of PHD2 gene was successfully realized by UTMD-mediated shPHD2 transfection, resulting in HIF-1α-dependent protective effects on H9C2 cells through increasing the expression of HIF-1α, VEGF and bFGF. We further employed UTMD-mediated shPHD2 transfection into the localized ischemic myocardia in a rat ischemia model, demonstrating significantly reduced infarct size and greatly improved the heart function. The silencing of PHD2 and the up-regulation of its downstream genes in the treated myocardia were confirmed. Histological analysis further revealed numbers of HIF-1α- and VEGF-, and CD31-positive cells/mm2 in the shPHD2-treated group were significantly greater than those in the sham or control vector groups (P < 0.05). In conclusion, our study provides a promising strategy to realize ultrasound-mediated localized myocardial shRNA delivery to protect the heart from acute myocardial infarction via cationic microbubbles. PMID:28042316

Measurement of the complex permittivity of microbubbles using a cavity perturbation technique for contrast enhanced ultra-wideband breast cancer detection.

PubMed

Ogunlade, Olumide; Chen, Yifan; Kosmas, Panagiotis

2010-01-01

Measurements of the complex permittivity of various concentrations of microbubbles in ethylene glycol liquid phantom have been carried out. A cavity perturbation technique using custom rectangular waveguide cavities, which are sensitive to small changes in the permittivity of the perturber, has been employed. Three different frequencies within the ultra-wideband (UWB) frequency spectrum have been used for the experiments. The results show that the concentration of the air filled microbubbles required to achieve a dielectric contrast as little as 2% exceeds the recommended dosage used in clinical ultrasound applications, by more than two orders of magnitude.

Experimental microbubble generation by sudden pressure drop and fluidics

NASA Astrophysics Data System (ADS)

Franco Gutierrez, Fernando; Figueroa Espinoza, Bernardo; Aguilar Corona, Alicia; Vargas Correa, Jesus; Solorio Diaz, Gildardo

2014-11-01

Mass and heat transfer, as well as chemical species in bubbly flow are of importance in environmental and industrial applications. Microbubbles are well suited to these applications due to the large interface contact area and residence time. The objective of this investigation is to build devices to produce microbubbles using two methods: pressure differences and fluidics. Some characteristics, advantages and drawbacks of both methods are briefly discussed, as well as the characterization of the bubbly suspensions in terms of parameters such as the pressure jump and bubble equivalent diameter distribution. The authors acknowledge the support of Consejo Nacional de Ciencia y Tecnología.

Properties of a Soybean Oil-based Surfactant and Its Application in Microbubble Preparation

USDA-ARS?s Scientific Manuscript database

Since microbubbles are thermodynamically unstable, surfactants are usually added to improve their stability. Demand for the use of vegetable oil-based surfactants has been increasing due to safety and environmental concerns. This work investigates a soybean oil-based surfactant and its application...

Ultrasonic Drug Delivery – A General Review

PubMed Central

Pitt, William G.; Husseini, Ghaleb A.; Staples, Bryant J.

2006-01-01

Ultrasound (US) has an ever-increasing role in the delivery of therapeutic agents including genetic material, proteins, and chemotherapeutic agents. Cavitating gas bodies such as microbubbles are the mediators through which the energy of relatively non-interactive pressure waves is concentrated to produce forces that permeabilize cell membranes and disrupt the vesicles that carry drugs. Thus the presence of microbubbles enormously enhances delivery of genetic material, proteins and smaller chemical agents. Delivery of genetic material is greatly enhanced by ultrasound in the presence of microbubbles. Attaching the DNA directly to the microbubbles or to gas-containing liposomes enhances gene uptake even further. US-enhanced gene delivery has been studied in various tissues including cardiac, vascular, skeletal muscle, tumor and even fetal tissue. US-enhanced delivery of proteins has found most application in transdermal delivery of insulin. Cavitation events reversibly disrupt the structure of the stratus corneum to allow transport of these large molecules. Other hormones and small proteins could also be delivered transdermally. Small chemotherapeutic molecules are delivered in research settings from micelles and liposomes exposed to ultrasound. Cavitation appears to play two roles: it disrupts the structure of the carrier vesicle and releases the drug; it also makes the cell membranes and capillaries more permeable to drugs. There remains a need to better understand the physics of cavitation of microbubbles and the impact that such cavitation has upon cells and drug-carrying vesicles. PMID:16296719

Modeling complicated rheological behaviors in encapsulating shells of lipid-coated microbubbles accounting for nonlinear changes of both shell viscosity and elasticity

NASA Astrophysics Data System (ADS)

Li, Qian; Matula, Thomas J.; Tu, Juan; Guo, Xiasheng; Zhang, Dong

2013-02-01

It has been accepted that the dynamic responses of ultrasound contrast agent (UCA) microbubbles will be significantly affected by the encapsulating shell properties (e.g., shell elasticity and viscosity). In this work, a new model is proposed to describe the complicated rheological behaviors in an encapsulating shell of UCA microbubbles by applying the nonlinear ‘Cross law’ to the shell viscous term in the Marmottant model. The proposed new model was verified by fitting the dynamic responses of UCAs measured with either a high-speed optical imaging system or a light scattering system. The comparison results between the measured radius-time curves and the numerical simulations demonstrate that the ‘compression-only’ behavior of UCAs can be successfully simulated with the new model. Then, the shell elastic and viscous coefficients of SonoVue microbubbles were evaluated based on the new model simulations, and compared to the results obtained from some existing UCA models. The results confirm the capability of the current model for reducing the dependence of bubble shell parameters on the initial bubble radius, which indicates that the current model might be more comprehensive to describe the complex rheological nature (e.g., ‘shear-thinning’ and ‘strain-softening’) in encapsulating shells of UCA microbubbles by taking into account the nonlinear changes of both shell elasticity and shell viscosity.

Ultrasound-mediated delivery and distribution of polymeric nanoparticles in the normal brain parenchyma of a metastatic brain tumour model

PubMed Central

Baghirov, Habib; Snipstad, Sofie; Sulheim, Einar; Berg, Sigrid; Hansen, Rune; Thorsen, Frits; Mørch, Yrr; Åslund, Andreas K. O.

2018-01-01

The treatment of brain diseases is hindered by the blood-brain barrier (BBB) preventing most drugs from entering the brain. Focused ultrasound (FUS) with microbubbles can open the BBB safely and reversibly. Systemic drug injection might induce toxicity, but encapsulation into nanoparticles reduces accumulation in normal tissue. Here we used a novel platform based on poly(2-ethyl-butyl cyanoacrylate) nanoparticle-stabilized microbubbles to permeabilize the BBB in a melanoma brain metastasis model. With a dual-frequency ultrasound transducer generating FUS at 1.1 MHz and 7.8 MHz, we opened the BBB using nanoparticle-microbubbles and low-frequency FUS, and applied high-frequency FUS to generate acoustic radiation force and push nanoparticles through the extracellular matrix. Using confocal microscopy and image analysis, we quantified nanoparticle extravasation and distribution in the brain parenchyma. We also evaluated haemorrhage, as well as the expression of P-glycoprotein, a key BBB component. FUS and microbubbles distributed nanoparticles in the brain parenchyma, and the distribution depended on the extent of BBB opening. The results from acoustic radiation force were not conclusive, but in a few animals some effect could be detected. P-glycoprotein was not significantly altered immediately after sonication. In summary, FUS with our nanoparticle-stabilized microbubbles can achieve accumulation and displacement of nanoparticles in the brain parenchyma. PMID:29338016

Modeling complicated rheological behaviors in encapsulating shells of lipid-coated microbubbles accounting for nonlinear changes of both shell viscosity and elasticity.

PubMed

Li, Qian; Matula, Thomas J; Tu, Juan; Guo, Xiasheng; Zhang, Dong

2013-02-21

It has been accepted that the dynamic responses of ultrasound contrast agent (UCA) microbubbles will be significantly affected by the encapsulating shell properties (e.g., shell elasticity and viscosity). In this work, a new model is proposed to describe the complicated rheological behaviors in an encapsulating shell of UCA microbubbles by applying the nonlinear 'Cross law' to the shell viscous term in the Marmottant model. The proposed new model was verified by fitting the dynamic responses of UCAs measured with either a high-speed optical imaging system or a light scattering system. The comparison results between the measured radius-time curves and the numerical simulations demonstrate that the 'compression-only' behavior of UCAs can be successfully simulated with the new model. Then, the shell elastic and viscous coefficients of SonoVue microbubbles were evaluated based on the new model simulations, and compared to the results obtained from some existing UCA models. The results confirm the capability of the current model for reducing the dependence of bubble shell parameters on the initial bubble radius, which indicates that the current model might be more comprehensive to describe the complex rheological nature (e.g., 'shear-thinning' and 'strain-softening') in encapsulating shells of UCA microbubbles by taking into account the nonlinear changes of both shell elasticity and shell viscosity.

[Destruction of synovial pannus of antigen-induced arthritis by ultrasonic cavitation in rabbits].

PubMed

Zhang, Ling-yan; Qiu, Li; Wang, Lei; Lin, Ling; Wen, Xiao-rong

2011-11-01

To optimize the conditions of ultrasonic irradiation and microbubble of ultrasound cavitation on destruction of synovial pannus of antigen-induced arthritis (AIA) in rabbits. Antigen-induced arthritis was successfully induced on bilateral knee joints of 85 rabbits. Each 10 AIA rabbits were divided into two groups to compare various peak negative pressures, different ultrasonic pulse durations, various pulse repetition frequencies, different irradiance duration, different dosages of microbubble contrast agents, different ultrasonic irradiance times. With intravenous infusion of Sonovue to the rabbits, ultrasonic irradiance was performed on the right knee joint using the above condition of ultrasound cavitation. At the day 1 after ultrasonic irradiance, MRI and pathological examination were employed to evaluate the optimal conditions. The optimal parameters and conditions for ultrasonic irradiance included intermittent ultrasonic application (in 6 s intervals), 0.6 mL/kg of microbubble contrast agent, 4.6 MPa of ultrasonic peak negative pressure, 100 cycles of pulse duration, 50 Hz of pulse repetition frequency, 5 min of ultrasonic duration, 0.6 mL/kg of dosages of microbubble contrast agents and multi-sessional ultrasonic irradiance. After the ultrasonic irradiance, the thickness of right knee synovium measured by MRI was thinner than that of left knee and synovial necrosis was confirmed by the pathological finding. Under optimal ultrasonic irradiation and microbubble conditions, ultrasonic cavitation could destroy synovial pannus of AIA in rabbits.

Effect of Anesthesia Carrier Gas on In-Vivo Circulation Times of Ultrasound Microbubble Contrast Agents in Rats

PubMed Central

Mullin, Lee; Gessner, Ryan; Kwan, James; Kaya, Mehmet; Borden, Mark A.; Dayton, Paul A.

2012-01-01

Purpose Microbubble contrast agents are currently implemented in a variety of both clinical and preclinical ultrasound imaging studies. The therapeutic and diagnostic capabilities of these contrast agents are limited by their short in-vivo lifetimes, and research to lengthen their circulation times is ongoing. In this manuscript, observations are presented from a controlled experiment performed to evaluate differences in circulation times for lipid shelled perfluorocarbon-filled contrast agents circulating within rodents as a function of inhaled anesthesia carrier gas. Methods The effects of two common anesthesia carrier gas selections - pure oxygen and medical air – were observed within five rats. Contrast agent persistence within the kidney was measured and compared for oxygen and air anesthesia carrier gas for six bolus contrast injections in each animal. Simulations were performed to examine microbubble behavior with changes in external environment gases. Results A statistically significant extension of contrast circulation time was observed for animals breathing medical air compared to breathing pure oxygen. Simulations support experimental observations and indicate that enhanced contrast persistence may be explained by reduced ventilation/perfusion mismatch and classical diffusion, in which nitrogen plays a key role by contributing to the volume and diluting other gas species in the microbubble gas core. Conclusion: Using medical air in place of oxygen as the carrier gas for isoflurane anesthesia can increase the circulation lifetime of ultrasound microbubble contrast agents. PMID:21246710

Predicting lake responses to phosphorus loading with measurement-based characterization of P recycling in sediments

NASA Astrophysics Data System (ADS)

Katsev, S.; Li, J.

2017-12-01

Predicting the time scales on which lake ecosystems respond to changes in anthropogenic phosphorus loadings is critical for devising efficient management strategies and setting regulatory limits on loading. Internal loading of phosphorus from sediments, however, can significantly contribute to the lake P budget and may delay recovery from eutrophication. The efficiency of mineralization and recycling of settled P in bottom sediments, which is ultimately responsible for this loading, is often poorly known and is surprisingly poorly characterized in the societally important systems such as the Great Lakes. We show that a simple mass-balance model that uses only a minimum number of parameters, all of which are measurable, can successfully predict the time scales over which the total phosphorus (TP) content of lakes responds to changes in external loadings, in a range of situations. The model also predicts the eventual TP levels attained under stable loading conditions. We characterize the efficiency of P recycling in Lake Superior based on a detailed characterization of sediments at 13 locations that includes chemical extractions for P and Fe fractions and characterization of sediment-water exchange fluxes of P. Despite the low efficiency of P remobilization in these deeply oxygenated sediments (only 12% of deposited P is recycled), effluxes of dissolved phosphorus (2.5-7.0 μmol m-2 d-1) still contribute 37% to total P inputs into the water column. In this oligotrophic large lake, phosphate effluxes are regulated by organic sedimentation rather than sediment redox conditions. By adjusting the recycling efficiency to conditions in other Laurentian Great Lakes, we show that the model reproduces the historical data for total phosphorus levels. Analysis further suggests that, in the Lower Lakes, the rate of P sequestration from water column into sediments has undergone a significant change in recent decades, possibly in response to their invasion by quagga mussels. Importantly, even for lakes where P budgets are dominated by internal loading, mass balance arguments show that, over multi-year time scales, lakes should respond to changes in external P inputs faster than their hydrological residence times.

Aromatic proteinaceous surfactants stabilize long-lived gas microbubbles from natural sources

NASA Technical Reports Server (NTRS)

Darrigo, J. S.

1981-01-01

Three different types of protein-specific chemical tests were performed on long-lived gas microbubbles derived from aqueous solutions of agarose powder and from filtered aqueous extracts of Hawaiian forest soil. The separate protein-specific tests involved use of either 0.3% (w/v) ninhydrin, 100 microM methylene blue dye, or 0.7-1.0 M 2-hydroxy-5-nitrobenzyl bromide. The chemical test results obtained with each of the two natural substances, i.e., agarose powder and Hawaiian forest soil, were very similar and indicate that the biological surfactants which surround and stabilize long-lived gas microbubbles are proteinaceous compounds that contain, and whose surface activity depends upon, aromatic amino acid residues, particularly tryptophan.

New plastic recycling technology | Science Inventory | US EPA

EPA Pesticide Factsheets

Greater than 60% of the total plastic content of municipal solid waste is comprised of polyolefins (high-density, low-density, and linear polyethylene and polypropylene. Polyethylene (PE) is the largest-volume component but presents a challenge due to the absence of low-energy degradation processes. This news column provides a digest of recent technical reports relating to clean technology and environmental policy,

Recovery oriented phosphorus adsorption process in decentralized advanced Johkasou.

PubMed

Ebie, Y; Kondo, T; Kadoya, N; Mouri, M; Maruyama, O; Noritake, S; Inamori, Y; Xu, K

2008-01-01

Decentralized advanced wastewater treatment using adsorption and desorption process for recovery and recycling oriented phosphorus removal was developed. Adsorbent particles made of zirconium were set in a column, and it was installed as subsequent stage of BOD and nitrogen removal type Johkasou, a household domestic wastewater treatment facility. The water quality of the effluent of adsorption column in a number of experimental sites was monitored. The effluent phosphorus concentration was kept below 1 mg l(-1) during 90 days at all the sites. Furthermore, over 80% of the sites achieved 1 mg l(-1) of T-P during 200 days. This adsorbent was durable, and deterioration of the particles was not observed over a long duration. The adsorbent collected from each site was immersed in alkali solution to desorb phosphorus. Then the adsorbent was reactivated by soaking in acid solution. The reactivated adsorbent was reused and showed almost the same phosphorus adsorption capacity as a new one. Meanwhile, the desorbed phosphorus was recovered with high purity as trisodium phosphate by crystallization. It is proposed as a new decentralized system for recycling phosphorus that paves the way to high-purity recovery of finite phosphorus. IWA Publishing 2008.

Efficient Enhancement of Blood-Brain Barrier Permeability Using Acoustic Cluster Therapy (ACT).

PubMed

Åslund, Andreas K O; Snipstad, Sofie; Healey, Andrew; Kvåle, Svein; Torp, Sverre H; Sontum, Per C; Davies, Catharina de Lange; van Wamel, Annemieke

2017-01-01

The blood-brain barrier (BBB) is a major obstacle in drug delivery for diseases of the brain, and today there is no standardized route to surpass it. One technique to locally and transiently disrupt the BBB, is focused ultrasound in combination with gas-filled microbubbles. However, the microbubbles used are typically developed for ultrasound imaging, not BBB disruption. Here we describe efficient opening of the BBB using the promising novel Acoustic Cluster Therapy (ACT), that recently has been used in combination with Abraxane® to successfully treat subcutaneous tumors of human prostate adenocarcinoma in mice. ACT is based on the conjugation of microbubbles to liquid oil microdroplets through electrostatic interactions. Upon activation in an ultrasound field, the microdroplet phase transfers to form a larger bubble that transiently lodges in the microvasculature. Further insonation induces volume oscillations of the activated bubble, which in turn induce biomechanical effects that increase the permeability of the BBB. ACT was able to safely and temporarily permeabilize the BBB, using an acoustic power 5-10 times lower than applied for conventional microbubbles, and successfully deliver small and large molecules into the brain.

Acoustic microstreaming due to an ultrasound contrast microbubble near a wall

NASA Astrophysics Data System (ADS)

Mobadersany, Nima; Sarkar, Kausik

2017-11-01

In an ultrasound field, in addition to the sinusoidal motion of fluid particles, particles experience a steady streaming velocity due to nonlinear second order effects. Here, we have simulated the microstreaming flow near a plane rigid wall caused by the pulsations of contrast microbubbles. Although these microbubbles were initially developed as a contrast enhancing agents for ultrasound imaging, they generate additional therapeutic effects that can be harnessed for targeted drug delivery or blood brain barrier (BBB) opening. The microbubbles have a gas core coated with a stabilizing layer of lipids or proteins. We use analytical models as well as boundary element (BEM) simulation to simulate the flow around these bubbles implementing interfacial rheology models for the coating. The microstreaming flow is characterized by two wall bounded vortices. The size of the vortices decreases with the decrease of the separation from the wall. The vortex-induced shear stress is simulated and analyzed as a function of excitation parameters and geometry. These microstreaming shear stress plays a critical role in increasing the membrane permeability facilitating drug delivery or rupturing biological tissues.

Enhancement and Passive Acoustic Mapping of Cavitation from Fluorescently Tagged Magnetic Resonance-Visible Magnetic Microbubbles In Vivo.

PubMed

Crake, Calum; Owen, Joshua; Smart, Sean; Coviello, Christian; Coussios, Constantin-C; Carlisle, Robert; Stride, Eleanor

2016-12-01

Previous work has indicated the potential of magnetically functionalized microbubbles to localize and enhance cavitation activity under focused ultrasound exposure in vitro. The aim of this study was to investigate magnetic targeting of microbubbles for promotion of cavitation in vivo. Fluorescently labelled magnetic microbubbles were administered intravenously in a murine xenograft model. Cavitation was induced using a 0.5-MHz focused ultrasound transducer at peak negative focal pressures of 1.2-2.0 MPa and monitored in real-time using B-mode imaging and passive acoustic mapping. Magnetic targeting was found to increase the amplitude of the cavitation signal by approximately 50% compared with untargeted bubbles. Post-exposure magnetic resonance imaging indicated deposition of magnetic nanoparticles in tumours. Magnetic targeting was similarly associated with increased fluorescence intensity in the tumours after the experiments. These results suggest that magnetic targeting could potentially be used to improve delivery of cavitation-mediated therapy and that passive acoustic mapping could be used for real-time monitoring of this process. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Time to detection of circulating microbubbles as a risk factor for symptoms of altitude decompression sickness

NASA Technical Reports Server (NTRS)

Kumar, K. V.; Calkins, Dick S.; Waligora, James M.; Gilbert, John H., III; Powell, Michael R.

1992-01-01

This study investigated the association between time at onset of circulating microbubbles (CMB) and symptoms of altitude decompression sickness (DCS), using Cox proportional hazard regression models. The study population consisted of 125 individuals who participated in direct ascent, simulated extravehicular activities profiles. Using individual CMB status as a time-dependent variable, we found that the hazard for symptoms increased significantly (at the end of 180 min at altitude) in the presence of CMB (Hazard Ratio = 29.59; 95 percent confidence interval (95 percent CI) = 7.66-114.27), compared to no CMB. Further examination was conducted on the subgroup of individuals who developed microbubbles during the test (n = 49), by using Cox regression. Individuals with late onset of CMB (greater than 60 min at altitude) showed a significantly reduced risk of symptoms (hazard ratio = 0.92; 95 percent CI = 0.89-0.95), compared to those with early onset (equal to or less than 60 min), while controlling for other risk factors. We conclude that time to detection of circulating microbubbles is an independent determinant of symptoms of DCS.

Characterization and destruction of Definity® microbubbles used for ultrasound imaging and drug delivery

NASA Astrophysics Data System (ADS)

Sarkar, Kausik; Chatterjee, Dhiman; Jain, Pankaj

2004-11-01

Intravenously injected encapsulated microbubbles improve the contrast of an ultrasound image. Their destruction is used in measuring blood flow, stimulating arteriogenesis, and drug delivery. We measure attenuation and scattering of ultrasound through solution of contrast agent Definity (Bristol Meyer-Squibb Imaging, North Ballerina, MA). We have developed an interfacial rheology model for the stabilizing encapsulation of such microbubbles. By matching with attenuation data, we obtain the characteristic rheological parameters for Definity. We compare model predictions with measured scattering. We investigate microbubble destruction under acoustic excitation by measuring time-varying attenuation data. Three regions of acoustic pressure amplitudes are found: at low pressure, there is no destruction; at slightly higher pressure bubbles are destroyed, and the rate of destruction depends on a combination of PRF and amplitude. At a still higher pressure amplitude, the attenuation decreases catastrophically. The last two regimes correspond respectively to 1) slow destruction of bubbles due to increased gas diffusion and 2) complete bubble destruction leading to release of free bubbles. (Supported by DOD, NSF and University of Delaware Research Foundation)

Integration of surface-active, periodically sequenced peptides into lipid-based microbubbles.

PubMed

Badami, Joseph V; Desir, Pierre; Tu, Raymond S

2014-07-29

The development of microbubbles toward functional, "theranostic" particles requires the incorporation of constituents with high binding specificity and therapeutic efficacy. Integrating peptides or proteins into the shell of lipid-based microbubbles can provide a means to access both receptor-ligand interactions and therapeutic properties. Simultaneously, peptides or proteins can define the characteristic monolayer mechanics of lipid bubbles and eliminate the need for post-bubble generation modification. The ability to engineer peptide sequences de novo that effectively partition into the bubble monolayer remains parametrically daunting. This work contributes to this effort using two simple amphipathic helical peptides that examine the role of local electrostatics and secondary structure. The two periodically sequenced peptides both have three positive charges, but peptide "K-2.5" spaces those charges 2.5 amino acids apart, while peptide "K-6.0" spaces the charges six amino acids apart. Size populations were determined for bubbles containing each peptide species using light scattering, and a quantitative method was developed to clearly define the fraction of peptides binding onto the microbubble monolayer. The impact of both the initial peptide concentration and the zwitterionic:anionic lipid ratio on peptide binding was also evaluated. Our results indicate that the lipid ratio affected only K-6.0 binding, which appears to be an outcome of the greater ensemble average α-helical population of the K-6.0. These findings provide further insights into the role of charge separation on peptide secondary structure, establishing a simple design metric for peptide binding onto microbubble systems.

Phase-shift perfluorocarbon agents enhance high intensity focused ultrasound thermal delivery with reduced near-field heating

PubMed Central

Phillips, Linsey C.; Puett, Connor; Sheeran, Paul S.; Dayton, Paul A.; Wilson Miller, G.; Matsunaga, Terry O.

2013-01-01

Ultrasound contrast agents are known to enhance high intensity focused ultrasound (HIFU) ablation, but these perfluorocarbon microbubbles are limited to the vasculature, have a short half-life in vivo, and may result in unintended heating away from the target site. Herein, a nano-sized (100–300 nm), dual perfluorocarbon (decafluorobutane/dodecafluoropentane) droplet that is stable, is sufficiently small to extravasate, and is convertible to micron-sized bubbles upon acoustic activation was investigated. Microbubbles and nanodroplets were incorporated into tissue-mimicking acrylamide-albumin phantoms. Microbubbles or nanodroplets at 0.1 × 106 per cm3 resulted in mean lesion volumes of 80.4 ± 33.1 mm3 and 52.8 ± 14.2 mm3 (mean ± s.e.), respectively, after 20 s of continuous 1 MHz HIFU at a peak negative pressure of 4 MPa, compared to a lesion volume of 1.0 ± 0.8 mm3 in agent-free control phantoms. Magnetic resonance thermometry mapping during HIFU confirmed undesired surface heating in phantoms containing microbubbles, whereas heating occurred at the acoustic focus of phantoms containing the nanodroplets. Maximal change in temperature at the target site was enhanced by 16.9% and 37.0% by microbubbles and nanodroplets, respectively. This perfluorocarbon nanodroplet has the potential to reduce the time to ablate tumors by one-third during focused ultrasound surgery while also safely enhancing thermal deposition at the target site. PMID:23927187

In vivo Sonothrombolysis of Ear Marginal Vein of Rabbits Monitored with High-frequency Ultrasound Needle Transducer.

PubMed

Chen, Ruimin; Paeng, Dong-Guk; Lam, Kwok Ho; Zhou, Qifa; Shung, K Kirk; Matsuoka, Naoki; Humayun, Mark S

2013-01-01

Ultrasound (US) is known to enhance thrombolysis when thrombolytic agents and/or microbubbles are injected into the targeted vessels. In this research, high-intensity US (1 MHz, 7 W/cm 2 , 30 % duty cycle) was applied in vivo to the ear marginal vein of three rabbits which was occluded by either laser photothrombosis or thrombin, right after the injection of 0.3~0.6 cc of microbubbles (13 × 10 8 bubbles/ml of concentration) through the other ear vein without using any thrombolytic agent. To determine the effect of the sonothrombolysis, the blood flow velocity near the occlusion site in the vein was measured by a custom-made 40-MHz US needle transducer and its corresponding Doppler US system. The Doppler spectra show that the blood flow velocity recovered from total occlusion after three 10-minute high-intensity US treatments. Fluorescein angiography was employed to confirm the opening of the vessel occlusion. A control study of three rabbits with only the microbubble injection showed no recovery on the occlusion in 3 hours. The results show that the sonothrombolysis in the rabbit ear marginal vein can be achieved with microbubbles only. The results of cavitation measurements indicate that the mechanism of sonothrombolysis is probably due to the cavitation induced by the microbubbles. Without the need of applying any thrombolytic agent, high-intensity US has high potential for therapies targeting on small blood vessels.

Contrast imaging in mouse embryos using high-frequency ultrasound.

PubMed

Denbeigh, Janet M; Nixon, Brian A; Puri, Mira C; Foster, F Stuart

2015-03-04

Ultrasound contrast-enhanced imaging can convey essential quantitative information regarding tissue vascularity and perfusion and, in targeted applications, facilitate the detection and measure of vascular biomarkers at the molecular level. Within the mouse embryo, this noninvasive technique may be used to uncover basic mechanisms underlying vascular development in the early mouse circulatory system and in genetic models of cardiovascular disease. The mouse embryo also presents as an excellent model for studying the adhesion of microbubbles to angiogenic targets (including vascular endothelial growth factor receptor 2 (VEGFR2) or αvβ3) and for assessing the quantitative nature of molecular ultrasound. We therefore developed a method to introduce ultrasound contrast agents into the vasculature of living, isolated embryos. This allows freedom in terms of injection control and positioning, reproducibility of the imaging plane without obstruction and motion, and simplified image analysis and quantification. Late gestational stage (embryonic day (E)16.6 and E17.5) murine embryos were isolated from the uterus, gently exteriorized from the yolk sac and microbubble contrast agents were injected into veins accessible on the chorionic surface of the placental disc. Nonlinear contrast ultrasound imaging was then employed to collect a number of basic perfusion parameters (peak enhancement, wash-in rate and time to peak) and quantify targeted microbubble binding in an endoglin mouse model. We show the successful circulation of microbubbles within living embryos and the utility of this approach in characterizing embryonic vasculature and microbubble behavior.

Spatial and temporal profile of cisplatin delivery by ultrasound-assisted intravesical chemotherapy in a bladder cancer model.

PubMed

Sasaki, Noboru; Ishi, Kazuhiro; Kudo, Nobuki; Nakayama, Shouta M M; Nakamura, Kensuke; Morishita, Keitaro; Ohta, Hiroshi; Ishizuka, Mayumi; Takiguchi, Mitsuyoshi

2017-01-01

Non-muscle invasive bladder cancer is one of the most common tumors of the urinary tract. Despite the current multimodal therapy, recurrence and progression of disease have been challenging problems. We hereby introduced a new approach, ultrasound-assisted intravesical chemotherapy, intravesical instillation of chemotherapeutic agents and microbubbles followed by ultrasound exposure. We investigated the feasibility of the treatment for non-muscle invasive bladder cancer. In order to evaluate intracellular delivery and cytotoxic effect as a function to the thickness, we performed all experiments using a bladder cancer mimicking 3D culture model. Ultrasound-triggered microbubble cavitation increased both the intracellular platinum concentration and the cytotoxic effect of cisplatin at the thickness of 70 and 122 μm of the culture model. The duration of enhanced cytotoxic effect of cisplatin by ultrasound-triggered microbubble cavitation was approximately 1 hr. Based on the distance and duration of delivery, we further tested the feasibility of repetition of the treatment. Triple treatment increased the effective distance by 1.6-fold. Our results clearly showed spatial and temporal profile of delivery by ultrasound-triggered microbubble cavitation in a tumor-mimicking structure. Furthermore, we demonstrated that the increase in intracellular concentration results in the enhancement of the cytotoxic effect in a structure with the certain thickness. Repetition of ultrasound exposure would be treatment of choice in future clinical application. Our results suggest ultrasound-triggered microbubble cavitation can be repeatable and is promising for the local control of non-muscle invasive bladder cancer.

A bridge column with superelastic NiTi SMA and replaceable rubber hinge for earthquake damage mitigation

NASA Astrophysics Data System (ADS)

Varela, Sebastian; ‘Saiid' Saiidi, M.

2016-07-01

This paper reports a unique concept for resilient bridge columns that can undergo intense earthquake loading and remain functional with minimal damage and residual drift. In this concept, the column is designed so that its components can be easily disassembled and reassembled to facilitate material recycling and component reuse. This is meant to foster sustainability of bridge systems while minimizing monetary losses from earthquakes. Self-centering and energy dissipation in the column were provided by unbonded superelastic nickel-titanium (NiTi) shape memory alloy bars placed inside a plastic hinge element made of rubber. This replaceable plastic hinge was in turn attached to a concrete-filled carbon fiber-reinforced polymer tube and a precast concrete footing that were designed to behave elastically. The proposed concept was evaluated experimentally by testing a ¼-scale column model under simulated near-fault earthquake motions on a shake table. After testing, the model was disassembled, reassembled and tested again. The seismic performance of the reassembled model was found to be comparable to that of the ‘virgin’ model. A relatively simple computational model of the column tested that was developed in OpenSees was able to match some of the key experimental response parameters.

ACOUSTIC CHARACTERIZATION AND PHARAMACOKINETIC ANALYSES OF NEW NANOBUBBLE ULTRASOUND CONTRAST AGENTS

PubMed Central

Wu, Hanping; Rognin, Nicolas G.; Krupka, Tianyi M.; Solorio, Luis; Yoshiara, Hiroki; Guenette, Gilles; Sanders, Christoher; Kamiyama, Naohisa; Exner, Agata A.

2013-01-01

In contrast to the clinically used microbubble ultrasound contrast agents, nanoscale bubbles (or nanobubbles) may potentially extravasate into tumors that exhibit more permeable vasculature, facilitating targeted molecular imaging and drug delivery. Our group recently presented a simple strategy using the non-ionic surfactant Pluronic as a size control excipient to produce nanobubbles with a mean diameter of 200 nm that exhibited stability and echogenicity on par with microbubbles. The objective of this study was to carry out an in-depth characterization of nanobubble properties as compared with Definity microbubbles, both in vitro and in vivo. Through use of a tissue-mimicking phantom, in vitro experiments measured the echogenicity of the contrast agent solutions and the contrast agent dissolution rate over time. Nanobubbles were found to be more echogenic than Definity microbubbles at three different harmonic frequencies (8, 6.2 and 3.5 MHz). Definity microbubbles also dissolved 1.67 times faster than nanobubbles. Pharmacokinetic studies were then performed in vivo in a subcutaneous human colorectal adenocarcinoma (LS174T) in mice. The peak enhancement and decay rates of contrast agents after bolus injection in the liver, kidney and tumor were analyzed. No significant differences were observed in peak enhancement between the nanobubble and Definity groups in the three tested regions (tumor, liver and kidney). However, the decay rates of nanobubbles in tumor and kidney were significantly slower than those of Definity in the first 200-s fast initial phase. There were no significant differences in the decay rate in the liver in the initial phase or in three regions of interest in the terminal phase. Our results suggest that the stability and acoustic properties of the new nanobubble contrast agents are superior to those of the clinically used Definity microbubbles. The slower washout of nanobubbles in tumors suggests potential entrapment of the bubbles within the tumor parenchyma. PMID:23932272

Acoustic characterization and pharmacokinetic analyses of new nanobubble ultrasound contrast agents.

PubMed

Wu, Hanping; Rognin, Nicolas G; Krupka, Tianyi M; Solorio, Luis; Yoshiara, Hiroki; Guenette, Gilles; Sanders, Christopher; Kamiyama, Naohisa; Exner, Agata A

2013-11-01

In contrast to the clinically used microbubble ultrasound contrast agents, nanoscale bubbles (or nanobubbles) may potentially extravasate into tumors that exhibit more permeable vasculature, facilitating targeted molecular imaging and drug delivery. Our group recently presented a simple strategy using the non-ionic surfactant Pluronic as a size control excipient to produce nanobubbles with a mean diameter of 200 nm that exhibited stability and echogenicity on par with microbubbles. The objective of this study was to carry out an in-depth characterization of nanobubble properties as compared with Definity microbubbles, both in vitro and in vivo. Through use of a tissue-mimicking phantom, in vitro experiments measured the echogenicity of the contrast agent solutions and the contrast agent dissolution rate over time. Nanobubbles were found to be more echogenic than Definity microbubbles at three different harmonic frequencies (8, 6.2 and 3.5 MHz). Definity microbubbles also dissolved 1.67 times faster than nanobubbles. Pharmacokinetic studies were then performed in vivo in a subcutaneous human colorectal adenocarcinoma (LS174T) in mice. The peak enhancement and decay rates of contrast agents after bolus injection in the liver, kidney and tumor were analyzed. No significant differences were observed in peak enhancement between the nanobubble and Definity groups in the three tested regions (tumor, liver and kidney). However, the decay rates of nanobubbles in tumor and kidney were significantly slower than those of Definity in the first 200-s fast initial phase. There were no significant differences in the decay rates in the liver in the initial phase or in three regions of interest in the terminal phase. Our results suggest that the stability and acoustic properties of the new nanobubble contrast agents are superior to those of the clinically used Definity microbubbles. The slower washout of nanobubbles in tumors suggests potential entrapment of the bubbles within the tumor parenchyma. Copyright © 2013 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Microbubble-mediated ultrasound therapy: a review of its potential in cancer treatment

PubMed Central

Ibsen, Stuart; Schutt, Carolyn E; Esener, Sadik

2013-01-01

The inherently toxic nature of chemotherapy drugs is essential for them to kill cancer cells but is also the source of the detrimental side effects experienced by patients. One strategy to reduce these side effects is to limit the healthy tissue exposure by encapsulating the drugs in a vehicle that demonstrates a very low leak rate in circulation while simultaneously having the potential for rapid release once inside the tumor. Designing a vehicle with these two opposing properties is the major challenge in the field of drug delivery. A triggering event is required to change the vehicle from its stable circulating state to its unstable release state. A unique mechanical actuation type trigger is possible by harnessing the size changes that occur when microbubbles interact with ultrasound. These mechanical actuations can burst liposomes and cell membranes alike allowing for rapid drug release and facilitating delivery into nearby cells. The tight focusing ability of the ultrasound to just a few cubic millimeters allows for precise control over the tissue location where the microbubbles destabilize the vehicles. This allows the ultrasound to highlight the tumor tissue and cause rapid drug release from any carrier present. Different vehicle designs have been demonstrated from carrying drug on just the surface of the microbubble itself to encapsulating the microbubble along with the drug within a liposome. In the future, nanoparticles may extend the circulation half-life of these ultrasound triggerable drug-delivery vehicles by acting as nucleation sites of ultrasound-induced mechanical actuation. In addition to the drug delivery capability, the microbubble size changes can also be used to create imaging contrast agents that could allow the internal chemical environment of a tumor to be studied to help improve the diagnosis and detection of cancer. The ability to attain truly tumor-specific release from circulating drug-delivery vehicles is an exciting future prospect to reduce chemotherapy side effects while increasing drug effectiveness. PMID:23667309

Quantitative ultrasound molecular imaging by modeling the binding kinetics of targeted contrast agent

NASA Astrophysics Data System (ADS)

Turco, Simona; Tardy, Isabelle; Frinking, Peter; Wijkstra, Hessel; Mischi, Massimo

2017-03-01

Ultrasound molecular imaging (USMI) is an emerging technique to monitor diseases at the molecular level by the use of novel targeted ultrasound contrast agents (tUCA). These consist of microbubbles functionalized with targeting ligands with high-affinity for molecular markers of specific disease processes, such as cancer-related angiogenesis. Among the molecular markers of angiogenesis, the vascular endothelial growth factor receptor 2 (VEGFR2) is recognized to play a major role. In response, the clinical-grade tUCA BR55 was recently developed, consisting of VEGFR2-targeting microbubbles which can flow through the entire circulation and accumulate where VEGFR2 is over-expressed, thus causing selective enhancement in areas of active angiogenesis. Discrimination between bound and free microbubbles is crucial to assess cancer angiogenesis. Currently, this is done non-quantitatively by looking at the late enhancement, about 10 min after injection, or by calculation of the differential targeted enhancement, requiring the application of a high-pressure ultrasound (US) burst to destroy all the microbubbles in the acoustic field and isolate the signal coming only from bound microbubbles. In this work, we propose a novel method based on mathematical modeling of the binding kinetics during the tUCA first pass, thus reducing the acquisition time and with no need for a destructive US burst. Fitting time-intensity curves measured with USMI by the proposed model enables the assessment of cancer angiogenesis at both the vascular and molecular levels. This is achieved by estimation of quantitative parameters related to the microvascular architecture and microbubble binding. The proposed method was tested in 11 prostate-tumor bearing rats by performing USMI after injection of BR55, and showed good agreement with current USMI methods. The novel information provided by the proposed method, possibly combined with the current non-quantitative methods, may bring deeper insight into cancer angiogenesis, and thus potentially improve cancer diagnosis and management.

Development of Microbubble Contrast Agents with Biochemical Recognition and Tunable Acoustic Response

NASA Astrophysics Data System (ADS)

Nakatsuka, Matthew Allan Masao

Microbubbles, consisting of gas-filled cores encapsulated within phospholipid or polymer shells, are the most widely used ultrasound contrast agents in the world. Because of their acoustic impedance mismatch with surrounding tissues and compressible gaseous interiors, they have high echogenicities that allow for efficient backscatter of ultrasound. They can also generate unique harmonic frequencies when insonated near their resonance frequency, depending on physical microbubble properties such as the stiffness and thickness of the encapsulating shell. Microbubbles are used to detect a number of cardiovascular diseases, but current methodologies lack the ability to detect and distinguish small, rapidly growing abnormalities that do not produce visible blockage or slowing of blood flow. This work describes the development, formulation, and validation of microbubbles with various polymer shell architectures designed to modulate their acoustic ability. We demonstrate that the addition of a thick disulfide crosslinked, poly(acrylic acid) encapsulating shell increases a bubble's resistance to cavitation and changes its resonance frequency. Modification of this shell architecture to use hybridized DNA strands to form crosslinks between the polymer chains allows for tuning of the bubble acoustic response. When the DNA crosslinks are in place, shell stiffness is increased so the bubbles do not oscillate and acoustic signal is muted. Subsequently, when these DNA strands are displaced, partial acoustic activity is restored. By using aptamer sequences with a specific affinity towards the biomolecule thrombin as the DNA crosslinking strand, this acoustic "ON/OFF" behavior can be specifically tailored towards the presence of a specific biomarker, and produces a change in acoustic signal at concentrations of thrombin consistent with acute deep venous thrombosis. Incorporation of the emulsifying agent poly(ethylene glycol) into the encapsulating shell improves microbubble yield and circulation half-life substantially, allowing for the in vivo detection of a blood clot in a rabbit model. The results presented here show a unique marriage of highly specific molecular imaging and sonography that could be tailored towards a wide variety of cardiovascular abnormalities.

Risk of decompression sickness in the presence of circulating microbubbles

NASA Technical Reports Server (NTRS)

Kumar, K. Vasantha; Powell, Michael R.

1993-01-01

In this study, we examined the association between microbubbles formed in the circulation from a free gas phase and symptoms of altitude decompression sickness (DCS). In a subgroup of 59 males of mean (S.D) age 31.2 (5.8) years who developed microbubbles during exposure to 26.59 kPa (4.3 psi) under simulated extravehicular activities (EVA), symptoms of DCS occurred in 24 (41 percent) individuals. Spencer grade 1 microbubbles occurred in 4 (7 percent), grade 2 in 9 (15 percent), grade 3 in 15 (25 percent), and grade 4 in 31 (53 percent) of subjects. Survival analysis using Cox proportional hazards regression showed that individuals with less than grade 3 CMB showed 2.46 times (95 percent confidence interval = 1.26 to 5.34) higher risk of symptoms. This information is crucial for defining the risk of DCS for inflight Doppler monitoring under space EVA. Altitude decompression sickness (DCS) occurs when there is acute reduction in ambient pressure. The symptoms of DCS are due to the formation of a free gas phase (in the form of gas microbubbles) in tissues during decompression. Musculo-skeletal pain of bends is the commonest form of DCS in altitude exposures. In the space flight environment, there is a risk of DCS when astronauts decompress from the normobaric shuttle pressure into the hypobaric space suit pressure (currently about 29.65 kPa (4.3 psi) for extra-vehicular activities (EVA). This risk is counterbalanced by a judicious combination of prior denitrogenation and staged decompression. Studies of DCS are limited by the duration of the test at reduced pressure. Since only a proportion of subjects tested develop symptoms, the information on DCS is generally incomplete or 'censored'. Many studies employ Doppler ultrasound monitoring of the precordial area for detecting circulating microbubbles (CMB). Although the association between CMB and bends pain is not causal, CMB are frequently monitored during decompression. In this paper, we examine the association between CMB and symptoms of DCS under simulated EVA profiles.

Enhancing laser thermal-therapy using ultrasound-microbubbles and gold nanorods: In vitro investigation

NASA Astrophysics Data System (ADS)

Tarapacki, Christine; Kumaradas, Carl; Karshafian, Raffi

2012-11-01

Gold nanorods (GNR) in laser-induced thermal therapy can significantly increase light absorption, leading to a local temperature increase and causing irreversible cell damage. One of the key challenges in using GNR as a thermal therapy agent is to deliver a concentration of GNR to generate sufficient heat and cause cell death. In this study, ultrasound and microbubble induced sonoporation is used to enhance intracellular uptake of GNR and improve the therapeutic outcome of laserinduced thermal therapy. Acute myeloid leukemia (AML) cells in suspension (0.6 mL) were treated with ultrasound and microbubbles (USMB) at 1 MHz frequency, 16 microseconds pulse duration, 1 kHz pulse repetition frequency, 1 minute insonation time, varying acoustic pressures (0, 1.26 and 1.73 MPa) and 10 μL Definity microbubble agent with and without GNR (12 nm × 48 nm) at varying concentration (1.0×1010 to 2.5×1011 GNR/mL). The GNR were manufactured through wet chemical synthesis process and measured using Transmission Electron Microscopy (TEM) and Atomic Absorption Spectroscopy (AAS) for size and concentration respectively. Following ultrasound and microbubble treatment, cells were centrifuged to remove excess gold nanorods and treated in suspension with an 810 nm laser (Diomed 60 NIR) at 4 W for 5 minutes. A thermal camera (FLIR Thermovision A40) was positioned to monitor the sample temperature throughout laser treatment and cell viability was assessed using flow cytometry with propidium iodide. Cell viability of 18±2% was achieved with GNR+USMB (1.26 MPa) compared to 72±3% with GNR alone (12 hour incubation) and 99±0.2% with USMB (1.26 MPa) alone. With increasing GNR concentration during ultrasound and microbubble treatment, laser induced sample temperature increased and consequently cell viability decreased. Cell viability decreased from 92±1% at 1.0×1011 GNR/mL to 29±5% at 1.5×1011 GNR/mL concentration with corresponding maximum temperatures of 50°C and 54°C, respectively. The combined treatment of ultrasound-microbubble and gold nanorod laser induced thermal-therapy showed a synergistic enhancement of cell death in vitro. This study shows promise for an enhanced therapeutic effect with the combined treatment in vivo.

Influence of ultrasound induced cavitation on magnetic resonance imaging contrast in the rat liver in the presence of macromolecular contrast agent.

PubMed

Frulio, Nora; Trillaud, Hervé; Deckers, Roel; Lepreux, Sébastien; Moonen, Chrit; Quesson, Bruno

2010-05-01

Local drug delivery by ultrasound (US)-induced cavitation is a promising strategy for increasing the drug concentration at the target location and for decreasing the systemic toxicity effects. The presence of microbubbles during sonication at the targeted location improves the likelihood for cavitation that can be exploited to increase the capillary permeability. The objective of this work was to evaluate the magnetic resonance imaging (MRI) contrast changes in hepatic tissue in vivo, induced by US-triggered cavitation and destruction of microbubbles (Sonovue), in the presence of a coinjected blood pool MRI contrast agent (Vistarem) used as a reporter macromolecule. The potential tissue damage induced by microbubbles destruction was also evaluated by histology. The change in the hepatic distribution of the macromolecular MRI contrast agent associated with cavitation was monitored at 1.5 T with a look-locker fast inversion recovery sequence to map the longitudinal relaxation rates, before and during 1 hour after intravenous administration of Vistarem and Sonovue. In 1 group of rats (n = 5), these microbubbles were immediately destroyed with a clinical echograph, using a high mechanical index (MI = 1.5) at low frequency (2 MHz). The control group (n = 7) received identical injections without application of US. The parametric relaxation rate images were computed, and the changes in time were analyzed to account for the potential effect of microbubble destruction by US on the permeability of the hepatic vessels. The animals were killed 1 day after the experiment for routine histology of the liver. For both groups of animals, after an initial increase, a transient decay of the longitudinal relaxation rate was observed, followed by a constant plateau after 20 minutes. The analysis of the mean relaxation rates in the liver showed significant (P < 0.01) higher values for the group with destruction of microbubbles as compared with the control group. The US-triggered cavitation and destruction of microbubble with the proposed protocol suggests an increased concentration of Vistarem of a factor 2 in the hepatic tissue. No tissue damage was observed at the microscopic analysis. The absence of tissue alterations indicates that the destruction of this US contrast agent could be safe in vivo under an appropriate choice of the sonication parameters. This approach opens new perspectives for translation toward clinical applications of local drug delivery. Ultrasound-mediated microbubble destruction may help in increasing the local concentration of a drug currently limited by the endothelial barrier. In addition, it may help in reducing the systemic toxicity to normal cells in standard chemotherapies, because the enhanced capillary permeability effect can be spatially adjusted by selecting the sonicated region.

Trypsin coatings on electrospun and alcohol-dispersed polymer nanofibers for trypsin digestion column

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jun, Seung-Hyun; Chang, Mun Seock; Kim, Byoung Chan

2010-09-15

The construction of a trypsin reactor in a chromatography column for rapid and efficient protein digestion in proteomics is described. Electrospun and alcohol-dispersed polymer nanofibers were used for the fabrication of highly stable trypsin coating, which was prepared by a two-step process of covalent attachment and enzyme crosslinking. In a comparative study with the trypsin coatings on asspun and non-dispersed nanofibers, it has been observed that a simple step of alcohol dispersion improved not only the enzyme loading but also the performance of protein digestion. In-column digestion of enolase was successfully performed in less than twenty minutes. By applying themore » alcohol dispersion of polymer nanofibers, the bypass of samples was reduced by filling up the column with well-dispersed nanofibers, and subsequently, interactions between the protein and the enzymes were improved yielding more complete and reproducible digestions. Regardless of alcohol-dispersion or not, trypsin coating showed better digestion performance and improved performance stability under recycled uses than covalently-attached trypsin. The combination of highly stable trypsin coating and alcoholdispersion of polymer nanofibers has opened up a new potential to develop a trypsin column for on-line and automated protein digestion.« less

Separation and characterization of polycyclic aromatic hydrocarbons and alkylphenols in coal derived solvents

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hurtubise, R.J.; Allen, T.W.; Hussain, A.

1981-03-29

Dry-column chromatography with an aluminum oxide stationary phase and a n-hexane-ether (19:1) mobile phase was used to separate polycyclic aromatic hydrocarbons (PAH) by ring size. Prior to the dry-column chromatography step, the coal derived solvents were added to an acid treated silica gel column and eluted with chloroform. This step removed pyridine-type nitrogen heterocycles. After separation of the individual ring fractions, the fractions were further separated by either thin layer chromatography (TLC) or high performance liquid chromatography (HPLC). If TLC was used, then after separation fluorescence profiles of each PAH ring fraction distributed on 30%-acetylated cellulose chromatoplates were obtained withmore » a spectrodensitometer. Measurement of fluorescence peak heights gave an approximate measure of the amount of the 3-, 4-, 5-, and 6- ring PAH. For HPLC separation, the 3- and 4- ring PAH fractions obtained from the dry-column chromatography step were separated with a ..mu..-Bondapak C/sub 18/ column and methanol:water (65:35) mobile phase. The HPLC separated PAH were characterized by chromatographic correlation factors and corrected fluorescence excitation spectra. Alkylphenols were identified in coal recycle solvent sample following separation by HPLC.« less

Microbubbles and ultrasound: a bird's eye view.

PubMed

Kaul, Sanjiv

2004-01-01

Gas-filled microbubbles were initially used as ultrasound contrast agent because of their intravascular rheology, which is similar to that of red blood cells. Their transit through tissue can thus be quantified with ultrasound. More recently, these bubbles have been successfully used for molecular imaging by incorporating ligands on their surfaces that will adhere to cellular and other components within the microvasculature and can be detected by ultrasound. These bubbles have also been used for delivery of genes and drugs which can be released locally by disruption of the bubbles with high-energy ultrasound. Finally, bioeffects produced by localized ultrasound disruption of microbubbles have been shown to induce angiogenesis. This brief review will provide a bird's eye view of these applications.

Further Examination of Biogeochemical Consequences of Mesoscale Eddies in the Sargasso Sea

NASA Astrophysics Data System (ADS)

Marquez, I. A., Jr.; Krause, J. W.; Lomas, M. W.

2016-02-01

The Bermuda Atlantic Time Series (BATS) is an ongoing 25-year biogeochemical record in the North Atlantic subtropical gyre. Contemporaneous data on the particulate phases of four major bioreactive elements, C, N, P, and Si only exist during two years and also for a companion project (Trophic BATS, i.e. TBATS). A combined dataset from BATS and TBATS was used to better understand the coupling of C, N, P, and Si in the Sargasso Sea by analyzing particulate phases of each element in the water column and exported material. Three conclusions are inferred: first, the effect of mesoscale eddies on standing stocks, export rates, and elemental coupling of C, N, P, and Si displays strong seasonality. Statistically significant differences between particulate water column and export ratios using internal and between site comparisons were robust in the summer only. Second, N, Si and particularly P were more efficiently recycled within the euphotic zones of eddies as elemental ratios in export material were greater than the corresponding ratios in the water column. This suggests that P may have a more critical biogeochemical role and its supply rate to the euphotic zone may control primary production in these closed systems. Third, the trends seen in these eddies do not support that export production was enhanced, instead these features had more efficient recycling of N, P, and Si relative to the BATS site. This decrease in export efficiency suggests a stimulation of export production above 'normal' BATS conditions within eddies would require significantly higher autotrophic standing stock and correspondingly high rates of organic matter production.

On the Vertical Distribution of Local and Remote Sources of Water for Precipitation

NASA Technical Reports Server (NTRS)

Bosilovich, Michael G.

2001-01-01

The vertical distribution of local and remote sources of water for precipitation and total column water over the United States are evaluated in a general circulation model simulation. The Goddard Earth Observing System (GEOS) general circulation model (GCM) includes passive constituent tracers to determine the geographical sources of the water in the column. Results show that the local percentage of precipitable water and local percentage of precipitation can be very different. The transport of water vapor from remote oceanic sources at mid and upper levels is important to the total water in the column over the central United States, while the access of locally evaporated water in convective precipitation processes is important to the local precipitation ratio. This result resembles the conceptual formulation of the convective parameterization. However, the formulations of simple models of precipitation recycling include the assumption that the ratio of the local water in the column is equal to the ratio of the local precipitation. The present results demonstrate the uncertainty in that assumption, as locally evaporated water is more concentrated near the surface.

Low-intensity focused ultrasound mediated localized drug delivery for liver tumors in rabbits.

PubMed

Gong, Yuping; Wang, Zhigang; Dong, Guifang; Sun, Yang; Wang, Xi; Rong, Yue; Li, Maoping; Wang, Dong; Ran, Haitao

2016-09-01

To explore the antitumor effects of low-intensity focused ultrasound (LIFU) mediated localized drug delivery of adriamycin-microbubble-PLGA nanoparticle complexes on rabbits VX2 liver tumor. ADM-NMCs were prepared by covalent linking of ADM-PLGA nanoparticles (ADM-NPs) to the shell of the microbubbles. A fixed water bag filled with microbubbles was subjected to LIFU and non-focused ultrasound respectively, and the ultrasound images of which were recorded before and after ultrasonication. A total of 54 VX2 liver tumor-burdened rabbits were divided into six groups randomly, including control, ADM-NPs combined with LIFU, microbubbles combined with LIFU, ADM-NPs and microbubbles combined with LIFU, ADM-NMCs combined with LIFU and ADM-NMCs combined with Non-FUS. The tumor volume and volume inhibition rate (VIR) of tumor progression were calculated and compared. Apoptotic cells were labeled by terminal deoxyuridine nick end. Proliferating cell nuclear antigen was detected by immunohistochemistry. The median survival time of the animals were recorded and compared. ADM-NMCs were successfully prepared with an average diameter of 1721 nm. The highest VIR and apoptotic index (AI) were found in the group of ADM-NMCs combined with LIFU while the lowest proliferating index (PI) was simultaneously observed in this group. The median survival time of the rabbits in the ADM-NMCs combined with LIFU group was the longest (71days) among all groups. ADM-NMCs combined with LIFU could inhibit the rabbits VX2 liver tumor progress by delaying the tumor proliferation and accelerating apoptosis, which presents a novel process for liver tumor targeting chemotherapy.

Fluidic oscillator-mediated microbubble generation to provide cost effective mass transfer and mixing efficiency to the wastewater treatment plants.

PubMed

Rehman, Fahad; Medley, Gareth J D; Bandulasena, Hemaka; Zimmerman, William B J

2015-02-01

Aeration is one of the most energy intensive processes in the waste water treatment plants and any improvement in it is likely to enhance the overall efficiency of the overall process. In the current study, a fluidic oscillator has been used to produce microbubbles in the order of 100 μm in diameter by oscillating the inlet gas stream to a pair of membrane diffusers. Volumetric mass transfer coefficient was measured for steady state flow and oscillatory flow in the range of 40-100l/min. The highest improvement of 55% was observed at the flow rates of 60, 90 and 100l/min respectively. Standard oxygen transfer rate and efficiency were also calculated. Both standard oxygen transfer rate and efficiency were found to be considerably higher under oscillatory air flow conditions compared to steady state airflow. The bubble size distributions and bubble densities were measured using an acoustic bubble spectrometer and confirmed production of monodisperse bubbles with approximately 100 μm diameters with fluidic oscillation. The higher number density of microbubbles under oscillatory flow indicated the effect of the fluidic oscillation in microbubble production. Visual observations and dissolved oxygen measurements suggested that the bubble cloud generated by the fluidic oscillator was sufficient enough to provide good mixing and to maintain uniform aerobic conditions. Overall, improved mass transfer coefficients, mixing efficiency and energy efficiency of the novel microbubble generation method could offer significant savings to the water treatment plants as well as reduction in the carbon footprint. Copyright © 2014 Elsevier Inc. All rights reserved.

Paradoxical Air Microembolism Induces Cerebral Bioelectrical Abnormalities and Occasionally Headache in Patent Foramen Ovale Patients With Migraine

PubMed Central

Sevgi, Eser Başak; Erdener, Sefik Evren; Demirci, Mehmet; Topcuoglu, Mehmet Akif; Dalkara, Turgay

2012-01-01

Background Although controversial, paradoxical embolism via patent foramen ovale (PFO) may account for some of the migraine attacks in a subset of migraine with aura (MA) patients. Induction of MA attacks with air bubble injection during transcranial Doppler ultrasound in MA patients with PFO supports this view. It is likely that cerebral embolism in patients with right-to-left shunt induces bioelectrical abnormalities to initiate MA under some conditions. Methods and Results We investigated changes in cerebral bioelectrical activity after intravenous microbubble injection in 10 MA patients with large PFO and right-to-left cardiac shunt. Eight PFO patients without migraine but with large right-to-left shunt and 12 MA patients without PFO served as controls. Four MA patients with PFO were reexamined with sham injections of saline without microbubbles. Bioelectrical activity was evaluated using spectral electroencephalography and, passage of microbubbles through cerebral arteries was monitored with transcranial Doppler ultrasound. Microbubble embolism caused significant electroencephalographic power increase in MA+PFO patients but not in control groups including the sham-injected MA+PFO patients. Headache developed in 2 MA with PFO patients after microbubble injection. Conclusions These findings demonstrate that air microembolism through large PFOs may cause cerebral bioelectrical disturbances and, occasionally, headache in MA patients, which may reflect an increased reactivity of their brain to transient subclinical hypoxia–ischemia, and suggest that paradoxical embolism is not a common cause of migraine but may induce headache in the presence of a large PFO and facilitating conditions. PMID:23316313

Nonlinear pulse compression in pulse-inversion fundamental imaging.

PubMed

Cheng, Yun-Chien; Shen, Che-Chou; Li, Pai-Chi

2007-04-01

Coded excitation can be applied in ultrasound contrast agent imaging to enhance the signal-to-noise ratio with minimal destruction of the microbubbles. Although the axial resolution is usually compromised by the requirement for a long coded transmit waveforms, this can be restored by using a compression filter to compress the received echo. However, nonlinear responses from microbubbles may cause difficulties in pulse compression and result in severe range side-lobe artifacts, particularly in pulse-inversion-based (PI) fundamental imaging. The efficacy of pulse compression in nonlinear contrast imaging was evaluated by investigating several factors relevant to PI fundamental generation using both in-vitro experiments and simulations. The results indicate that the acoustic pressure and the bubble size can alter the nonlinear characteristics of microbubbles and change the performance of the compression filter. When nonlinear responses from contrast agents are enhanced by using a higher acoustic pressure or when more microbubbles are near the resonance size of the transmit frequency, higher range side lobes are produced in both linear imaging and PI fundamental imaging. On the other hand, contrast detection in PI fundamental imaging significantly depends on the magnitude of the nonlinear responses of the bubbles and thus the resultant contrast-to-tissue ratio (CTR) still increases with acoustic pressure and the nonlinear resonance of microbubbles. It should be noted, however, that the CTR in PI fundamental imaging after compression is consistently lower than that before compression due to obvious side-lobe artifacts. Therefore, the use of coded excitation is not beneficial in PI fundamental contrast detection.

Microbubble signal and trial of org in acute stroke treatment (TOAST) classification in ischemic stroke.

PubMed

Lee, Chan-Hyuk; Kang, Hyun Goo; Lee, Ji Sung; Ryu, Han Uk; Jeong, Seul-Ki

2018-07-15

Right-to-left shunt (RLS) through a patent foramen ovale (PFO) is likely associated with ischemic stroke. Many studies have attempted to demonstrate the association between RLS and ischemic stroke. However, information on the association between the degree of RLS and the subtypes of ischemic stroke categorized by the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification is lacking. This was a retrospective study involving 508 patients with ischemic stroke who underwent a transcranial Doppler (TCD) microbubble test between 2013 and 2015. The degree of RLS was divided into 4 grades according to the microbubble signal (MBS) as follows: no MBS, grade 1; MBS < 20, grade 2; MBS > 20, grade 3; curtain sign, grade 4. The degree of RLS and the type of ischemic stroke as classified by TOAST were analyzed and compared with other clinical information and laboratory findings. The higher RLS grade was associated with the cardioembolism (CE) and stroke of undetermined etiology (SUE), and the microbubble signals were inversely related with small vessel disease (SVD). An MBS higher than grade 3 showed a 2.95-fold higher association with SUE than large artery atherosclerosis (LAA), while grade 4 MBS revealed an approximately 8-fold higher association with SUE than LAA. RLS identified by the TCD microbubble test was significantly and independently associated with cryptogenic ischemic stroke (negative evaluation). Subsequent studies are needed to determine the biologic relationship between RLS and ischemic stroke, particularly the cryptogenic subtype of ischemic stroke. Copyright © 2018 Elsevier B.V. All rights reserved.

Microvascular flow estimation by contrast-assisted ultrasound B-scan and statistical parametric images.

PubMed

Tsui, Po-Hsiang; Yeh, Chih-Kuang; Chang, Chien-Cheng

2009-05-01

The microbubbles destruction/replenishment technique has been previously applied to estimating blood flow in the microcirculation. The rate of increase of the time-intensity curve (TIC) due to microbubbles flowing into the region of interest (ROI), as measured from B-mode images, closely reflects the flow velocity. In previous studies, we proposed a new approach called the time-Nakagami-parameter curve (TNC) obtained from Nakagami images to monitor microbubble replenishment for quantifying the microvascular flow velocity. This study aimed to further explore some effects that may affect the TNC to estimate the microflow, including microbubble concentration, ultrasound transmitting energy, attenuation, intrinsic noise, and tissue clutter. In order to well control each effect production, we applied a typical simulation method to investigate the TIC and TNC. The rates of increase of the TIC and TNC were expressed by the rate constants beta(I) and beta(N), respectively, of a monoexponential model. The results show that beta(N) quantifies the microvascular flow velocity similarly to the conventional beta(I) . Moreover, the measures of beta(I) and beta(N) are not influenced by microbubble concentration, transducer excitation energy, and attenuation effect. Although the effect of intrinsic signals contributed by noise and blood would influence the TNC behavior, the TNC method has a better tolerance of tissue clutter than the TIC does, allowing the presence of some clutter components in the ROI. The results suggest that the TNC method can be used as a complementary tool for the conventional TIC to reduce the wall filter requirements for blood flow measurement in the microcirculation.

Disruption of tumor neovasculature by microbubble enhanced ultrasound: a potential new physical therapy of anti-angiogenesis.

PubMed

Liu, Zheng; Gao, Shunji; Zhao, Yang; Li, Peijing; Liu, Jia; Li, Peng; Tan, Kaibin; Xie, Feng

2012-02-01

Tumor angiogenesis is of vital importance to the growth and metastasis of solid tumors. The angiogenesis is featured with a defective, leaky and fragile vascular construction. Microbubble enhanced ultrasound (MEUS) cavitation is capable of mechanical disruption of small blood vessels depending on effective acoustic pressure amplitude. We hypothesized that acoustic cavitation combining high-pressure amplitude pulsed ultrasound (US) and circulating microbubble could potentially disrupt tumor vasculature. A high-pressure amplitude, pulsed ultrasound device was developed to induce inertial cavitation of circulating microbubbles. The tumor vasculature of rat Walker 256 was insonated percutaneously with two acoustic pressures, 2.6 MPa and 4.8 MPa, both with intravenous injection of a lipid microbubble. The controls were treated by the ultrasound only or sham ultrasound exposure. Contrast enhanced ultrasound (CEUS) and histology were performed to assess tumor circulation and pathological changes. The CEUS results showed that the circulation of Walker 256 tumors could be completely blocked off for 24 hours in 4.8 MPa treated tumors. The CEUS gray scale value (GSV) indicated that there was significant GSV drop-off in both of the two experimental groups but none in the controls. Histology showed that the tumor microvasculature was disrupted into diffuse hematomas accompanied by thrombosis, intercellular edema and multiple cysts formation. The 24 hours of tumor circulation blockage resulted in massive necrosis of the tumor. MEUS provides a new, simple physical method for anti-angiogenic therapy and may have great potential for clinical applications. Copyright © 2012 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Spontaneous echocardiographic contrast associated with portosystemic shunt due to persistent patent ductus venosus.

PubMed

Toib, Amir; Goldstein, Seth B; Khanna, Geetika; Canter, Charles E; Lee, Caroline K; Balzer, David T; Singh, Gautam K

2012-01-01

We describe a case of an infant with a single ventricle physiology, who presented with spontaneous microbubbles originating from her inferior vena cava. Imaging revealed a persistent patent ductus venosus, leading to a portosystemic shunt, streaming the microbubbles into the heart. We discuss the possible mechanisms for this rare phenomenon in a child. © 2011 Wiley Periodicals, Inc.

Sterilization of microorganisms by the supercritical carbon dioxide micro-bubble method.

PubMed

Ishikawa, H; Shimoda, M; Shiratsuchi, H; Osajima, Y

1995-10-01

Lactobacillus brevis and Saccharomyces cerevisiae were completely sterilized by the supercritical (SC) CO2 micro-bubble method. Gaseous (G) and liquid (LQ) CO2 were used in a similar manner to compare the sterilizing effect. Among the three treatments, the microorganisms were only effectively sterilized by the SC CO2 treatment at 25 MPa and 35 degrees C.

Dynamic behaviour of a two-microbubble system under ultrasonic wave excitation.

PubMed

Huang, Xiao; Wang, Qian-Xi; Zhang, A-Man; Su, Jian

2018-05-01

Acoustic bubbles have wide and important applications in ultrasonic cleaning, sonochemistry and medical ultrasonics. A two-microbubble system (TMS) under ultrasonic wave excitation is explored in the present study, by using the boundary element method (BEM) based on the potential flow theory. A parametric study of the behaviour of a TMS has been carried out in terms of the amplitude and direction of ultrasound as well as the sizes and separation distance of the two bubbles. Three regimes of the dynamic behaviour of the TMS have been identified in terms of the pressure amplitude of the ultrasonic wave. When subject to a strong wave with the pressure amplitude of 1 atm or larger, the two microbubbles become non-spherical during the first cycle of oscillation, with two counter liquid jets formed. When subject to a weak wave with the pressure amplitude of less than 0.5 atm, two microbubbles may be attracted, repelled, or translate along the wave direction with periodic stable separation distance, depending on their size ratio. However, for the TMS under moderate waves, bubbles undergo both non-spherical oscillation and translation as well as liquid jet rebounding. Copyright © 2018 Elsevier B.V. All rights reserved.

Laser vibrometry characterisation of a microfluidic lab-on-a-chip device: a preliminary investigation

NASA Astrophysics Data System (ADS)

Fury, C.; Gélat, P. N.; Jones, P. H.; Memoli, G.

2014-04-01

Since their original inception as ultrasound contrast agents, potential applications of microbubbles have evolved to encompass molecular imaging and targeted drug delivery. As these areas develop, so does the need to understand the mechanisms behind the interaction of microbubbles both with biological tissue and with other microbubbles. There is therefore a metrological requirement to develop a controlled environment in which to study these processes. Presented here is the design and characterisation of such a system, which consists of a microfluidic chip, specifically developed for manipulating microbubbles using both optical and acoustic trapping. A laser vibrometer is used to observe the coupling of acoustic energy into the chip from a piezoelectric transducer bonded to the surface. Measurement of the velocity of surface waves on the chip is investigated as a potential method for inferring the nature of the acoustic fields excited within the liquid medium of the device. Comparison of measured surface wavelengths with wave types suggests the observation of anti-symmetric Lamb or Love-Kirchhoff waves. Further visual confirmation of the acoustic fields through bubble aggregation highlights differences between the model and experimental results in predicting the position of acoustic pressure nodes in relation to excitation frequency.

Contrast-enhanced ultrasound imaging and in vivo circulatory kinetics with low-boiling-point nanoscale phase-change perfluorocarbon agents.

PubMed

Sheeran, Paul S; Rojas, Juan D; Puett, Connor; Hjelmquist, Jordan; Arena, Christopher B; Dayton, Paul A

2015-03-01

Many studies have explored phase-change contrast agents (PCCAs) that can be vaporized by an ultrasonic pulse to form microbubbles for ultrasound imaging and therapy. However, few investigations have been published on the utility and characteristics of PCCAs as contrast agents in vivo. In this study, we examine the properties of low-boiling-point nanoscale PCCAs evaluated in vivo and compare data with those for conventional microbubbles with respect to contrast generation and circulation properties. To do this, we develop a custom pulse sequence to vaporize and image PCCAs using the Verasonics research platform and a clinical array transducer. Results indicate that droplets can produce contrast enhancement similar to that of microbubbles (7.29 to 18.24 dB over baseline, depending on formulation) and can be designed to circulate for as much as 3.3 times longer than microbubbles. This study also reports for the first time the ability to capture contrast washout kinetics of the target organ as a measure of vascular perfusion. Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

CAVITATION THRESHOLD OF MICROBUBBLES IN GEL TUNNELS BY FOCUSED ULTRASOUND

PubMed Central

Sassaroli, E.; Hynynen, K.

2007-01-01

The investigation of inertial cavitation in micro-tunnels has significant implications for the development of therapeutic applications of ultrasound such as ultrasound-mediated drug and gene delivery. The threshold for inertial cavitation was investigated using a passive cavitation detector with a center frequency of 1 MHz. Micro-tunnels of various diameters (90 to 800 μm) embedded in gel were fabricated and injected with a solution of Optison™ contrast agent of concentrations 1.2% and 0.2% diluted in water. An ultrasound pulse of duration 500 ms and center frequency 1.736 MHz was used to insonate the microbubbles. The acoustic pressure was increased at one second intervals until broadband noise emission was detected. The pressure threshold at which broadband noise emission was observed was found to be dependent on the diameter of the micro-tunnels, with an average increase of 1.2 to 1.5 between the smallest and the largest tunnels, depending on the microbubble concentration. The evaluation of inertial cavitation in gel tunnels rather than tubes provides a novel opportunity to investigate microbubble collapse in a situation that simulates in vivo blood vessels better than tubes with solid walls do. PMID:17590501

Quantitation of MRI sensitivity to quasi-monodisperse microbubble contrast agents for spatially resolved manometry.

PubMed

Bencsik, Martin; Al-Rwaili, Amgad; Morris, Robert; Fairhurst, David J; Mundell, Victoria; Cave, Gareth; McKendry, Jonathan; Evans, Stephen

2013-11-01

The direct in-vivo measurement of fluid pressure cannot be achieved with MRI unless it is done with the contribution of a contrast agent. No such contrast agents are currently available commercially, whilst those demonstrated previously only produced qualitative results due to their broad size distribution. Our aim is to quantitate then model the MR sensitivity to the presence of quasi-monodisperse microbubble populations. Lipid stabilised microbubble populations with mean radius 1.2 ± 0.8 μm have been produced by mechanical agitation. Contrast agents with increasing volume fraction of bubbles up to 4% were formed and the contribution the bubbles bring to the relaxation rate was quantitated. A periodic pressure change was also continuously applied to the same contrast agent, until MR signal changes were only due to bubble radius change and not due to a change in bubble density. The MR data compared favourably with the prediction of an improved numerical simulation. An excellent MR sensitivity of 23 % bar(-1) has been demonstrated. This work opens up the possibility of generating microbubble preparations tailored to specific applications with optimised MR sensitivity, in particular MRI based in-vivo manometry. Copyright © 2012 Wiley Periodicals, Inc.

Renal Perfusion in Scleroderma Patients Assessed by Microbubble-Based Contrast-Enhanced Ultrasound

PubMed Central

Kleinert, Stefan; Roll, Petra; Baumgaertner, Christian; Himsel, Andrea; Mueller, Adelheid; Fleck, Martin; Feuchtenberger, Martin; Jenett, Manfred; Tony, Hans-Peter

2012-01-01

Objectives: Renal damage is common in scleroderma. It can occur acutely or chronically. Renal reserve might already be impaired before it can be detected by laboratory findings. Microbubble-based contrast-enhanced ultrasound has been demonstrated to improve blood perfusion imaging in organs. Therefore, we conducted a study to assess renal perfusion in scleroderma patients utilizing this novel technique. Materials and Methodology: Microbubble-based contrast agent was infused and destroyed by using high mechanical index by Siemens Sequoia (curved array, 4.5 MHz). Replenishment was recorded for 8 seconds. Regions of interests (ROI) were analyzed in renal parenchyma, interlobular artery and renal pyramid with quantitative contrast software (CUSQ 1.4, Siemens Acuson, Mountain View, California). Time to maximal Enhancement (TmE), maximal enhancement (mE) and maximal enhancement relative to maximal enhancement of the interlobular artery (mE%A) were calculated for different ROIs. Results: There was a linear correlation between the time to maximal enhancement in the parenchyma and the glomerular filtration rate. However, the other parameters did not reveal significant differences between scleroderma patients and healthy controls. Conclusion: Renal perfusion of scleroderma patients including the glomerular filtration rate can be assessed using microbubble-based contrast media. PMID:22670165

Optimization and characterization of stable lipid-based, oxygen-filled microbubbles by mixture design.

PubMed

Polizzotti, Brian D; Thomson, Lindsay M; O'Connell, Daniel W; McGowan, Francis X; Kheir, John N

2014-08-01

Tissue hypoxia is a final common pathway that leads to cellular injury and death in a number of critical illnesses. Intravenous injections of self-assembling, lipid-based oxygen microbubbles (LOMs) can be used to deliver oxygen gas, preventing organ injury and death from systemic hypoxemia. However, current formulations exhibit high polydispersity indices (which may lead to microvascular obstruction) and poor shelf-lives, limiting the translational capacity of LOMs. In this study, we report our efforts to optimize LOM formulations using a mixture response surface methodology (mRSM). We study the effect of changing excipient proportions (the independent variables) on microbubble diameter and product loss (the dependent variables). By using mRSM analysis, the experimental data were fit using a reduced Scheffé linear mixture model. We demonstrate that formulations manufactured from 1,2-distearoyl-sn-glycero-3-phosphocholine, corn syrup, and water produce micron-sized microbubbles with low polydispersity indices, and decreased product loss (relative to previously described formulations) when stored at room temperature over a 30-day period. Optimized LOMs were subsequently tested for their oxygen-releasing ability and found to have similar release kinetics as prior formulations. © 2014 Wiley Periodicals, Inc.

Development of the chemical and electrochemical coal cleaning process

NASA Astrophysics Data System (ADS)

Basilio, C. I.; Yoon, Roe-Hoan

The continuous testing of the Chemical and Electrochemical Coal Cleaning (CECC) was completed successfully using Middle Wyodak and Elkhorn No. 3 coal samples. The CECC unit was run under the optimum conditions established for these coal samples. For the Middle Wyodak coal, the ash content was reduced from 6.96 percent to as low 1.61 percent, corresponding to an ash rejection (by weight) of about 83 percent. The ash and sulfur contents of the Elkhorn No. 3 coal were reduced to as low as 1.8 percent and 0.9 percent. The average ash and sulfur rejections were calculated to be around 84 percent and 47 percent. The CECC continuous unit was used to treat -325 mesh Elkhorn No. 3 coal samples and gave ash and sulfur rejection values of as high as 77 percent and 66 percent. In these test, the clean -325 mesh coal particles were separated from the liberated mineral matter through microbubble column flotation, instead of wet-screening.

DO-increasing effects of a microscopic bubble generating system in a fish farm.

PubMed

Endo, Akira; Srithongouthai, Sarawut; Nashiki, Hisatsune; Teshiba, Ichiro; Iwasaki, Takaaki; Hama, Daigo; Tsutsumi, Hiroaki

2008-01-01

We have developed a "microscopic bubble generating system for the fish farm" and evaluated its ability to improve the quality of seawater and costs of it in marine cages of red sea bream (Pagrus major) in Kusuura Bay, Japan. Our results revealed that DO concentration of bubbling net pens increased and became significantly higher than the level outside the net pen (between 0.52 and 0.87 mg/L), and the whole water column was nearly saturated. Temperatures of the bubbling net pens decreased slightly between 0.08 and 0.12 degrees C in all the layers. Furthermore, micro-bubbles seemed to reach the deeper water due to the downward flow and diffusion. This study demonstrated that the microscopic bubble generating system developed in our research project could increase efficiently the dissolved oxygen concentration throughout all water layers of the fish farm. A capital and operation costs of the system is recoverable within a year.

State-of-the-Art Materials for Ultrasound-Triggered Drug Delivery

PubMed Central

Sirsi, Shashank; Borden, Mark

2014-01-01

Ultrasound is a unique and exciting theranostic modality that can be used to track drug carriers, trigger drug release and improve drug deposition with high spatial precision. In this review, we briefly describe the mechanisms of interaction between drug carriers and ultrasound waves, including cavitation, streaming and hyperthermia, and how those interactions can promote drug release and tissue uptake. We then discuss the rational design of some state-of-the-art materials for ultrasound-triggered drug delivery and review recent progress for each drug carrier, focusing on the delivery of chemotherapeutic agents such as doxorubicin. These materials include nanocarrier formulations, such as liposomes and micelles, designed specifically for ultrasound-triggered drug release, as well as microbubbles, microbubble-nanocarrier hybrids, microbubble-seeded hydrogels and phase-change agents. PMID:24389162

Micro-Bubble Experiments at the Van de Graaff Accelerator

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sun, Z. J.; Wardle, Kent E.; Quigley, K. J.

In order to test and verify the experimental designs at the linear accelerator (LINAC), several micro-scale bubble ("micro-bubble") experiments were conducted with the 3-MeV Van de Graaff (VDG) electron accelerator. The experimental setups included a square quartz tube, sodium bisulfate solution with different concentrations, cooling coils, gas chromatography (GC) system, raster magnets, and two high-resolution cameras that were controlled by a LabVIEW program. Different beam currents were applied in the VDG irradiation. Bubble generation (radiolysis), thermal expansion, thermal convection, and radiation damage were observed in the experiments. Photographs, videos, and gas formation (O 2 + H 2) data were collected.more » The micro-bubble experiments at VDG indicate that the design of the full-scale bubble experiments at the LINAC is reasonable.« less

Acoustic characterization of ultrasound contrast microbubbles and echogenic liposomes: Applications to imaging and drug-delivery

NASA Astrophysics Data System (ADS)

Paul, Shirshendu

Micron- to nanometer - sized ultrasound agents, like encapsulated microbubbles and echogenic liposomes (ELIPs), are being actively developed for possible clinical implementations in diagnostic imaging and ultrasound mediated drug/gene delivery. The primary objective of this thesis is to characterize the acoustic behavior of and the ultrasound-mediated contents release from these contrast agents for developing multi-functional ultrasound contrast agents. Subharmonic imaging using contrast microbubbles can improve image quality by providing a higher signal to noise ratio. However, the design and development of contrast microbubbles with favorable subharmonic behavior requires accurate mathematical models capable of predicting their nonlinear dynamics. To this goal, 'strain-softening' viscoelastic interfacial models of the encapsulation were developed and subsequently utilized to simulate the dynamics of encapsulated microbubbles. A hierarchical two-pronged approach of modeling --- a model is applied to one set of experimental data to obtain the model parameters (material characterization), and then the model is validated against a second independent experiment --- is demonstrated in this thesis for two lipid coated (SonazoidRTM and DefinityRTM) and a few polymer (polylactide) encapsulated microbubbles. The proposed models were successful in predicting several experimentally observed behaviors e.g., low subharmonic thresholds and "compression-only" radial oscillations. Results indicate that neglecting the polydisperse size distribution of contrast agent suspensions, a common practice in the literature, can lead to inaccurate results. In vitro experimental investigation of the dependence of subharmonic response from these microbubbles on the ambient pressure is also in conformity with the recent numerical investigations, showing both increase or decrease under appropriate excitation conditions. Experimental characterization of the ELIPs and polymersomes was performed with the goal of demonstrating their potential as ultrasound agents with simultaneous imaging and drug/gene delivery applications --- 'dual-purpose' contrast agents. Both in vitro acoustic studies and ultrasound imaging (performed in NDSU by our collaborators) showed the echogenicity of the various formulations studied. We believe that this echogenicity results from the larger diameter liposomes present in the polydisperse suspension obtained after reconstitution of the lyophilized powders. Although, ultrasound excitation (< 5 MHz) alone was incapable of causing optimal release of contents, a dual-triggering strategy (with enzymes or redox) proved successful, resulting in a total release of up to 80-90%. Considering these experimental results, it can be concluded that these novel formulations hold the potential of providing powerful treatment strategies for many diseases, including cardiovascular ones and various cancers.

Behaviour and fate of nine recycled water trace organics during managed aquifer recharge in an aerobic aquifer

NASA Astrophysics Data System (ADS)

Patterson, B. M.; Shackleton, M.; Furness, A. J.; Bekele, E.; Pearce, J.; Linge, K. L.; Busetti, F.; Spadek, T.; Toze, S.

2011-03-01

The fate of nine trace organic compounds was evaluated during a 12 month large-scale laboratory column experiment. The columns were packed with aquifer sediment and evaluated under natural aerobic and artificial anaerobic geochemical conditions, to assess the potential for natural attenuation of these compounds during aquifer passage associated with managed aquifer recharge (MAR). The nine trace organic compounds were bisphenol A (BPA), 17β-estradiol (E2), 17α-ethynylestradiol (EE2), N-nitrosodimethylamine (NDMA), N-nitrosomorpholine (NMOR), carbamazepine, oxazepam, iohexol and iodipamide. In the low organic carbon content Spearwood sediment, all trace organics were non-retarded with retardation coefficients between 1.0 and 1.2, indicating that these compounds would travel at near groundwater velocities within the aquifer. The natural aerobic geochemical conditions provided a suitable environment for the rapid degradation for BPA, E2, iohexol (half life < 1 day). Lag-times for the start of degradation of these compounds ranged from < 15 to 30 days. While iodipamide was persistent under aerobic conditions, artificial reductive geochemical conditions promoted via the addition of ethanol, resulted in rapid degradation (half life < 1 days). Pharmaceuticals (carbamazepine and oxazepam) and disinfection by-products (NDMA and NMOR) did not degrade under either aerobic or anaerobic aquifer geochemical conditions (half life > 50 days). Field-based validation experiments with carbamazepine and oxazepam also showed no degradation. If persistent trace organics are present in recycled waters at concentrations in excess of their intended use, natural attenuation during aquifer passage alone may not result in extracted water meeting regulatory requirements. Additional pre treatment of the recycled water would therefore be required.

Volatile Organic Carbon Emissions. Phase 2.

DTIC Science & Technology

1987-02-01

on sulfur (S IV) species *0. B. Nurmi, et al, "Sulfite Oxidation in Organic Acid Solutions," Flue Gas Desulfurization , American Chemical Society, 1982...in Organic Acid Solutions," Flue Gas Desulfurization , American Chemical Society, 1982, pp. 173-189. 8. Experimental Statistics; Handbook 91, United...Analysis of percentage solvent removal from absorber 49 inlet gas by Yates’ method 12. Analysis of weight percent solvent in recycle column 50 absorber

ELUTION OF URANIUM FROM RESIN

DOEpatents

McLEan, D.C.

1959-03-10

A method is described for eluting uranium from anion exchange resins so as to decrease vanadium and iron contamination and permit recycle of the major portion of the eluats after recovery of the uranium. Diminution of vanadium and iron contamination of the major portion of the uranium is accomplished by treating the anion exchange resin, which is saturated with uranium complex by adsorption from a sulfuric acid leach liquor from an ore bearing uranium, vanadium and iron, with one column volume of eluant prepared by passing chlorine into ammonium hydroxide until the chloride content is about 1 N and the pH is about 1. The resin is then eluted with 8 to 9 column volumes of 0.9 N ammonium chloride--0.1 N hydrochloric acid solution. The eluants are collected separately and treated with ammonia to precipitate ammonium diuranate which is filtered therefrom. The uranium salt from the first eluant is contaminated with the major portion of ths vanadium and iron and is reworked, while the uranium recovered from the second eluant is relatively free of the undesirable vanadium and irons. The filtrate from the first eluant portion is discarded. The filtrate from the second eluant portion may be recycled after adding hydrochloric acid to increase the chloride ion concentration and adjust the pH to about 1.

Targeted gene delivery to the synovial pannus in antigen-induced arthritis by ultrasound-targeted microbubble destruction in vivo.

PubMed

Xiang, Xi; Tang, Yuanjiao; Leng, Qianying; Zhang, Lingyan; Qiu, Li

2016-02-01

The purpose of this study was to optimize an ultrasound-targeted microbubble destruction (UTMD) technique to improve the in vivo transfection efficiency of the gene encoding enhanced green fluorescent protein (EGFP) in the synovial pannus in an antigen-induced arthritis rabbit model. A mixture of microbubbles and plasmids was locally injected into the knee joints of an antigen-induced arthritis (AIA) rabbits. The plasmid concentrations and ultrasound conditions were varied in the experiments. We also tested local articular and intravenous injections. The rabbits were divided into five groups: (1) ultrasound+microbubbles+plasmid; (2) ultrasound+plasmid; (3) microbubble+plasmid; (4) plasmid only; (5) untreated controls. EGFP expression was observed by fluorescent microscope and immunohistochemical staining in the synovial pannus of each group. The optimal plasmid dosage and ultrasound parameter were determined based on the results of EGFP expression and the present and absent of tissue damage under light microscopy. The irradiation procedure was performed to observe the duration of the EGFP expression in the synovial pannus and other tissues and organs, as well as the damage to the normal cells. The optimal condition was determined to be a 1-MHz ultrasound pulse applied for 5 min with a power output of 2 W/cm(2) and a 20% duty cycle along with 300 μg of plasmid. Under these conditions, the synovial pannus showed significant EGFP expression without significant damage to the surrounding normal tissue. The EGFP expression induced by the local intra-articular injection was significantly more increased than that induced by the intravenous injection. The EGFP expression in the synovial pannus of the ultrasound+microbubbles+plasmid group was significantly higher than that of the other four groups (P<0.05). The expression peaked on day 5, remained detectable on day 40 and disappeared on day 60. No EGFP expression was detected in the other tissues and organs. The UTMD technique can significantly enhance the in vivo gene transfection efficiency without significant tissue damage in the synovial pannus of an AIA model. Thus, this could become a safe and effective non-viral gene transfection procedure for arthritis therapy. Copyright © 2015 Elsevier B.V. All rights reserved.

Heat integrated ethanol dehydration flowsheets

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hutahaean, L.S.; Shen, W.H.; Brunt, V. Van

1995-04-01

zA theoretical evaluation of heat-integrated heterogeneous-azeotropic ethanol-water distillation flowsheets is presented. Simulations of two column flowsheets using several different hydrocarbon entrainers reveal a region of potential heat integration and substantial reduction in operating energy. In this paper, methods for comparing hydrocarbon entrainers are shown. Two aspects of entrainers are related to operating and capital costs. The binary azeotropic composition of the entrainer-ethanol mixture is related to the energy requirements of the flowsheet. A temperature difference in the azeotrophic column is related to the size of the column and overall process staging requirements. Although the hydrophobicity of an entrainer is essentialmore » for specification of staging in the dehydration column, no substantial increase in operating energy results from an entrainer that has a higher water content. Likewise, liquid-liquid equilibria between several entrainer-ethanol-water mixtures have no substantial effect on either staging or operation. Rather, increasing the alcohol content of the entrainer-ethanol azeotrope limits its recovery in the dehydration column, and increases the recycle and reflux streams. These effects both contribute to increasing the separation energy requirements and reducing the region of potential heat integration. A cost comparison with a multieffect extractive distillation flowsheet reveals that the costs are comparable; however, the extractive distillation flowsheet is more cost effective as operating costs increase.« less

Photothermolysis by laser-induced microbubbles generated around gold nanorod clusters selectively formed in leukemia cells

NASA Astrophysics Data System (ADS)

Lapotko, Dmitri; Lukianova-Hleb, Ekaterina; Zhdanok, Sergei; Rostro, Betty; Simonette, Rebecca; Hafner, Jason; Konopleva, Marina; Andreeff, Michael; Conjusteau, Andre; Oraevsky, Alexander

2008-02-01

In an effort of developing clinical LANTCET (laser-activated nano-thermolysis as cell elimination technology) we achieved selective destruction of individual tumor cells through laser generation of vapor microbubbles around clusters of light absorbing gold nanorods (GNR) selectively formed in target tumor cells. Among all gold nanoparticles, nanorods offer the highest optical absorption in the near-infrared. We applied covalent conjugates of gold nanorods with targeting vectors such as monoclonal antibodies CD33 (specific for Acute Myeloid Leukemia), while GNR conjugates with polyethylene-glycol (PEG) were used as nonspecific targeting control. GNR clusters were formed inside the tumor cells at 37 °C due to endocytosis of large concentration of nanorods accumulated on the surface of tumor cells targeted at 4 °C. Formation of GNR clusters significantly reduces the threshold of tumor cell damage making LANTCET safe for normal cells. Appearance of GNR clusters was verified directly with optical resonance scattering microscopy. LANTCET was performed in vitro with living cells of (1) model myeloid K562 cells (CD33 positive), (2) primary human bone marrow CD33-positive blast cells from patients diagnosed with acute myeloid leukemia. Laser-induced microbubbles were generated and detected with a photothermal microscope equipped with a tunable Ti-Sa pulsed laser. GNT cluster formation caused a 100-fold decrease in the threshold optical fluence for laser microbubble generation in tumor cells compared with that in normal cells under the same targeting and irradiation conditions. Combining imaging based on resonance optical scattering with photothermal imaging of microbubbles, we developed a method for detection, image-guided treatment and monitoring of LANTCET. Pilot experiments were performed in flow mode bringing LANTCET closer to reality of clinical procedure of purging tumor cells from bone marrow grafts.

Lipid shedding from single oscillating microbubbles.

PubMed

Luan, Ying; Lajoinie, Guillaume; Gelderblom, Erik; Skachkov, Ilya; van der Steen, Antonius F W; Vos, Hendrik J; Versluis, Michel; De Jong, Nico

2014-08-01

Lipid-coated microbubbles are used clinically as contrast agents for ultrasound imaging and are being developed for a variety of therapeutic applications. The lipid encapsulation and shedding of the lipids by acoustic driving of the microbubble has a crucial role in microbubble stability and in ultrasound-triggered drug delivery; however, little is known about the dynamics of lipid shedding under ultrasound excitation. Here we describe a study that optically characterized the lipid shedding behavior of individual microbubbles on a time scale of nanoseconds to microseconds. A single ultrasound burst of 20 to 1000 cycles, with a frequency of 1 MHz and an acoustic pressure varying from 50 to 425 kPa, was applied. In the first step, high-speed fluorescence imaging was performed at 150,000 frames per second to capture the instantaneous dynamics of lipid shedding. Lipid detachment was observed within the first few cycles of ultrasound. Subsequently, the detached lipids were transported by the surrounding flow field, either parallel to the focal plane (in-plane shedding) or in a trajectory perpendicular to the focal plane (out-of-plane shedding). In the second step, the onset of lipid shedding was studied as a function of the acoustic driving parameters, for example, pressure, number of cycles, bubble size and oscillation amplitude. The latter was recorded with an ultrafast framing camera running at 10 million frames per second. A threshold for lipid shedding under ultrasound excitation was found for a relative bubble oscillation amplitude >30%. Lipid shedding was found to be reproducible, indicating that the shedding event can be controlled. Copyright © 2014 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Estimation of Viscoelastic Properties of Cells Using Acoustic Tweezing Cytometry.

PubMed

Yang, Chunmei; Chen, Di; Hong, Xiaowei

2016-12-01

Recently developed acoustic tweezing cytometry uses ultrasound-responsive targeted microbubbles for biomechanical stimulation of live cells at the subcellular level. The purpose of this research was to estimate the viscoelastic characteristics of cells from the displacements of cell-bound microbubbles in response to ultrasound pulses on acoustic tweezing cytometry. Microbubbles were bound to NIH/3T3 fibroblasts and ATDC5 cells through an integrin-cytoskeleton linkage. The evolution of microbubble behaviors under irradiation by ultrasound pulses was captured by a high-speed camera and tracked by a customized algorithm. The total damping constant, stiffness, and rigidity of the cells were estimated by fitting the measured temporal displacement profiles to a Kelvin-Voigt-based model. The mean maximum displacement of the microbubbles attached to NIH/3T3 fibroblasts was much greater than that for ATDC5 cells. The mean fitted damping constant and stiffness ± SD for ATDC5 cells were 28.16 ± 7.08 mg/s and 0.5041 ± 0.1381 mN/m, respectively, and the values for NIH/3T3 fibroblasts were 13.12 ± 4.23 mg/s and 0.2591 ± 0.0715 mN/m. The rigidity for ATDC5 cells was 331.46 ± 106.50 MPa, whereas that for NIH/3T3 fibroblasts was 117.92 ± 34.83 MPa. The Arg-Gly-Asp-integrin-cytoskeleton system of NIH/3T3 fibroblasts appears to be softer than that of ATDC5 cells. The rigidity of ATDC5 cells was significantly greater than that of NIH/3T3 fibroblasts at the 95% confidence level. This strategy provides a novel way to determine the viscoelastic properties of the live cells. © 2016 by the American Institute of Ultrasound in Medicine.

Disruption of Prostate Microvasculature by Combining Microbubble-Enhanced Ultrasound and Prothrombin

PubMed Central

Liu, Yongliang; Qiao, Lu; Gao, Wenhong; Zhang, Weiguo; Liu, Zheng

2016-01-01

Previous studies have shown a unique method to disrupt tumor vasculature using pulsed, high-pressure amplitude therapeutic ultrasound combined with microbubbles. In this study, we attempted to destroy the prostate vasculature of canine prostates using microbubble-enhanced ultrasound (MEUS) and prothrombin. The prostates of 43 male mongrel canines were surgically exposed. Twenty-two prostates were treated using MEUS (n = 11) or MEUS and prothrombin (PMEUS, n = 11). The other 21 prostates, which were treated using microbubbles (n = 7), ultrasound (n = 7) or prothrombin (n = 7) only, served as the controls. Prothrombin was intravenously infused at 20 IU/kg. MEUS was induced using a therapeutic ultrasound device at a peak negative pressure of 4.47 MPa and a microbubble injection. Contrast-enhanced ultrasound was performed to assess the blood perfusion of the prostates. Then, the prostate tissue was harvested immediately after treatment and at 48 hours later for pathological examination. The contrast-enhanced ultrasound peak value of the prostate decreased significantly from 36.2 ± 5.6 to 27.1 ± 6.3 after treatment in the PMEUS group, but it remained unchanged in the other groups. Histological examination found severe microvascular rupture, hemorrhage and thrombosis in both MEUS- and PMEUS-treated prostates immediately after treatment, while disruption in the PMEUS group was more severe than in the MEUS group. Forty-eight hours after treatment, massive necrosis and infiltration of white blood cells occurred in the PMEUS group. This study demonstrated that PMEUS disrupted the normal microvasculature of canine prostates and induced massive necrosis. PMEUS could potentially become a new noninvasive method used for the treatment of benign prostatic hyperplasia. PMID:27643992

Surface phase behavior and microstructure of lipid/PEG-emulsifier monolayer-coated microbubbles.

PubMed

Borden, Mark A; Pu, Gang; Runner, Gabriel J; Longo, Marjorie L

2004-06-01

Langmuir trough methods and fluorescence microscopy were combined to investigate the phase behavior and microstructure of monolayer shells coating micron-scale bubbles (microbubbles) typically used in biomedical applications. The monolayer shell consisted of a homologous series of saturated acyl chain phospholipids and an emulsifier containing a single hydrophobic stearate chain and polyethylene glycol (PEG) head group. PEG-emulsifier was fully miscible with expanded phase lipids and phase separated from condensed phase lipids. Phase coexistence was observed in the form of dark condensed phase lipid domains surrounded by a sea of bright, emulsifier-rich expanded phase. A rich assortment of condensed phase area fractions and domain morphologies, including networks and other novel structures, were observed in each batch of microbubbles. Network domains were reproduced in Langmuir monolayers under conditions of heating-cooling followed by compression-expansion, as well as in microbubble shells that underwent surface flow with slight compression. Domain size decreased with increased cooling rate through the phase transition temperature, and domain branching increased with lipid acyl chain length at high cooling rates. Squeeze-out of the emulsifier at a surface pressure near 35 mN/m was indicated by a plateau in Langmuir isotherms and directly visualized with fluorescence microscopy, although collapse of the solid lipid domains occurred at much higher surface pressures. Compression of the monolayer past the PEG-emulsifier squeeze-out surface pressure resulted in a dark shell composed entirely of lipid. Under certain conditions, the PEG-emulsifier was reincorporated upon subsequent expansion. Factors that affect shell formation and evolution, as well as implications for the rational design of microbubbles in medical applications, are discussed.

Ultrasound-microbubble mediated cavitation of plant cells: effects on morphology and viability.

PubMed

Qin, Peng; Xu, Lin; Zhong, Wenjing; Yu, Alfred C H

2012-06-01

The interaction between ultrasound pulses and microbubbles is known to generate acoustic cavitation that may puncture biological cells. This work presents new experimental findings on the bioeffects of ultrasound-microbubble mediated cavitation in plant cells with emphasis on direct observations of morphological impact and analysis of viability trends in tobacco BY-2 cells that are widely studied in higher plant physiology. The tobacco cell suspensions were exposed to 1 MHz ultrasound pulses in the presence of 1% v/v microbubbles (10% duty cycle; 1 kHz pulse repetition frequency; 70 mm between probe and cells; 1-min exposure time). Few bioeffects were observed at low peak negative pressures (<0.4 MPa) where stable cavitation presumably occurred. In contrast, at 0.9 MPa peak negative pressure (with more inertial cavitation activities according to our passive cavitation detection results), random pores were found on tobacco cell wall (observed via scanning electron microscopy) and enhanced exogenous uptake into the cytoplasm was evident (noted in our fluorescein isothiocyanate dextran uptake analysis). Also, instant lysis was observed in 23.4% of cells (found using trypan blue staining) and programmed cell death was seen in 23.3% of population after 12 h (determined by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling [TUNEL]). These bioeffects generally correspond in trend with those for mammalian cells. This raises the possibility of developing ultrasound-microbubble mediated cavitation into a targeted gene transfection paradigm for plant cells and, conversely, adopting plant cells as experimental test-beds for sonoporation-based gene therapy in mammalian cells. Copyright © 2012 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Gene therapy for ocular diseases meditated by ultrasound and microbubbles (Review)

PubMed Central

WAN, CAIFENG; LI, FENGHUA; LI, HONGLI

2015-01-01

The eye is an ideal target organ for gene therapy as it is easily accessible and immune-privileged. With the increasing insight into the underlying molecular mechanisms of ocular diseases, gene therapy has been proposed as an effective approach. Successful gene therapy depends on efficient gene transfer to targeted cells to prove stable and prolonged gene expression with minimal toxicity. At present, the main hindrance regarding the clinical application of gene therapy is not the lack of an ideal gene, but rather the lack of a safe and efficient method to selectively deliver genes to target cells and tissues. Ultrasound-targeted microbubble destruction (UTMD), with the advantages of high safety, repetitive applicability and tissue targeting, has become a potential strategy for gene- and drug delivery. When gene-loaded microbubbles are injected, UTMD is able to enhance the transport of the gene to the targeted cells. High-amplitude oscillations of microbubbles act as cavitation nuclei which can effectively focus ultrasound energy, produce oscillations and disruptions that increase the permeability of the cell membrane and create transient pores in the cell membrane. Thereby, the efficiency of gene therapy can be significantly improved. The UTMD-mediated gene delivery system has been widely used in pre-clinical studies to enhance gene expression in a site-specific manner in a variety of organs. With reasonable application, the effects of sonoporation can be spatially and temporally controlled to improve localized tissue deposition of gene complexes for ocular gene therapy applications. In addition, appropriately powered, focused ultrasound combined with microbubbles can induce a reversible disruption of the blood-retinal barrier with no significant side effects. The present review discusses the current status of gene therapy of ocular diseases as well as studies on gene therapy of ocular diseases meditated by UTMD. PMID:26151686

Ultrasound Targeted Microbubble Destruction-Mediated Delivery of a Transcription Factor Decoy Inhibits STAT3 Signaling and Tumor Growth

PubMed Central

Kopechek, Jonathan A.; Carson, Andrew R.; McTiernan, Charles F.; Chen, Xucai; Hasjim, Bima; Lavery, Linda; Sen, Malabika; Grandis, Jennifer R.; Villanueva, Flordeliza S.

2015-01-01

Signal transducer and activator of transcription 3 (STAT3) is constitutively activated in many cancers where it acts to promote tumor progression. A STAT3-specific transcription factor decoy has been developed to suppress STAT3 downstream signaling, but a delivery strategy is needed to improve clinical translation. Ultrasound-targeted microbubble destruction (UTMD) has been shown to enhance image-guided local delivery of molecular therapeutics to a target site. The objective of this study was to deliver STAT3 decoy to squamous cell carcinoma (SCC) tumors using UTMD to disrupt STAT3 signaling and inhibit tumor growth. Studies performed demonstrated that UTMD treatment with STAT3 decoy-loaded microbubbles inhibited STAT3 signaling in SCC cells in vitro. Studies performed in vivo demonstrated that UTMD treatment with STAT3 decoy-loaded microbubbles induced significant tumor growth inhibition (31-51% reduced tumor volume vs. controls, p < 0.05) in mice bearing SCC tumors. Furthermore, expression of STAT3 downstream target genes (Bcl-xL and cyclin D1) was significantly reduced (34-39%, p < 0.05) in tumors receiving UTMD treatment with STAT3 decoy-loaded microbubbles compared to controls. In addition, the quantity of radiolabeled STAT3 decoy detected in tumors eight hours after treatment was significantly higher with UTMD treatment compared to controls (70-150%, p < 0.05). This study demonstrates that UTMD can increase delivery of a transcription factor decoy to tumors in vivo and that the decoy can inhibit STAT3 signaling and tumor growth. These results suggest that UTMD treatment holds potential for clinical use to increase the concentration of a transcription factor signaling inhibitor in the tumor. PMID:26681983

Combined ultrasound and MR imaging to guide focused ultrasound therapies in the brain

NASA Astrophysics Data System (ADS)

Arvanitis, Costas D.; Livingstone, Margaret S.; McDannold, Nathan

2013-07-01

Several emerging therapies with potential for use in the brain, harness effects produced by acoustic cavitation—the interaction between ultrasound and microbubbles either generated during sonication or introduced into the vasculature. Systems developed for transcranial MRI-guided focused ultrasound (MRgFUS) thermal ablation can enable their clinical translation, but methods for real-time monitoring and control are currently lacking. Acoustic emissions produced during sonication can provide information about the location, strength and type of the microbubble oscillations within the ultrasound field, and they can be mapped in real-time using passive imaging approaches. Here, we tested whether such mapping can be achieved transcranially within a clinical brain MRgFUS system. We integrated an ultrasound imaging array into the hemisphere transducer of the MRgFUS device. Passive cavitation maps were obtained during sonications combined with a circulating microbubble agent at 20 targets in the cingulate cortex in three macaques. The maps were compared with MRI-evident tissue effects. The system successfully mapped microbubble activity during both stable and inertial cavitation, which was correlated with MRI-evident transient blood-brain barrier disruption and vascular damage, respectively. The location of this activity was coincident with the resulting tissue changes within the expected resolution limits of the system. While preliminary, these data clearly demonstrate, for the first time, that it is possible to construct maps of stable and inertial cavitation transcranially, in a large animal model, and under clinically relevant conditions. Further, these results suggest that this hybrid ultrasound/MRI approach can provide comprehensive guidance for targeted drug delivery via blood-brain barrier disruption and other emerging ultrasound treatments, facilitating their clinical translation. We anticipate that it will also prove to be an important research tool that will further the development of a broad range of microbubble-enhanced therapies.

Assessment of the efficiency and economic viability of various methods of treatment of sanitary landfill leachate.

PubMed

Gupta, S K; Singh, Gurdeep

2007-12-01

This study assesses the efficiency of various physico-chemical, biological and other tertiary methods for treating leachate. An evaluation study on the treatability of the leachate from methane phase bed (MPB) reactor indicated that at an optimum hydraulic retention time of 6 days, the efficiency of the reactor in terms of biological oxygen demand (BOD) and chemical oxygen demand (COD) removal was 91.29 and 82.69%, respectively. Recycling of the treated leachate through the municipal solid waste layers in the leachate recycling unit (LRU) resulted in a significant increase in the biodegradation of organics present in the leachate. Optimum BOD and COD removal efficiencies were achieved at the third recycle; additional recycling of the leachate did not produce any significant improvement. Physico-chemical treatment of the leachate demonstrated that alum and lime (Option 2) were more economical than coagulants lime and MgCO(3). A cost analysis of the economics of the various treatments revealed that the alternative treatment consisting of a MPB bed followed by a LRU and aerated lagoon is the most cost-effective treatment. However, the alternative consisting of a MPB followed by the LRU and a soil column, which is slightly more costly, would be the most appropriate treatment when adequate land is readily available.

Creating Brain Lesions by Low Intensity Focused Ultrasound with Microbubbles: A Rat Study at Half MHz

PubMed Central

Huang, Yuexi; Vykhodtseva, Natalia I.; Hynynen, Kullervo

2014-01-01

Low intensity focused ultrasound was applied with microbubbles (Definity, 0.02 mL/kg) to produce brain lesions in 50 rats at 558 kHz. Burst sonications (burst length: 10 ms; pulse repetition frequency: 1 Hz; total exposure: 5 min; acoustic powers: 0.47-1.3W) generated ischemic or hemorrhagic lesions at the focal volume revealed by both MR imaging and histology. Shorter burst (2 ms) or shorter sonication time (1 min) reduced the probability of lesion production. Longer pulses (200ms, 500ms and continuous wave) caused significant near-field damages. Using microbubbles with focused ultrasound significantly reduced the acoustic power levels, therefore avoided skull heating issues and potentially can extend the treatable volume of transcranial focused ultrasound to the brain tissues close to the skull. PMID:23743099

Gene delivery systems by the combination of lipid bubbles and ultrasound.

PubMed

Negishi, Yoichi; Endo-Takahashi, Yoko; Maruyama, Kazuo

2016-11-28

Gene therapy is promising for the treatment of many diseases including cancers and genetic diseases. From the viewpoint of safety, ultrasound (US)-mediated gene delivery with nano/ microbubbles was recently developed as a novel non-viral vector system. US-mediated gene delivery using nano/microbubbles are able to produce transient changes in the permeability of the cell membrane after US-induced cavitation while reducing cellular damage and enables the tissue-specific or the site-specific intracellular delivery of gene both in vitro and in vivo. We have recently developed novel lipid nanobubbles (Lipid Bubbles). These nanobubbles can also be used to enhance the efficacy of the US-mediated genes (plasmid DNA, siRNA, and miRNA etc.) delivery. In this review, we describe US-mediated delivery systems combined with nano/microbubbles and discuss their feasibility as non-viral vector systems.

Complete penile corporeal septation: evaluation with contrast enhanced US.

PubMed

Bertolotto, Michele; Bucci, Stefano; Quaia, Emilio; Coss, Matteo; Liguori, Giovanni

2008-01-01

Complete penile corporeal septation is a rare malformation in which the corpora cavernosa are completely isolated. We describe a new method to reach the diagnosis of this malformation using contrast enhanced US. Two patients with complete penile corporeal septation underwent color Doppler and contrast enhanced US after bilateral cavernosal injection of 10 microg prostaglandin E1. Contrast enhanced US was performed using a contrast specific software (Contrast-Tuned imaging, EsaOte, Genoa, Italy) and a linear transducer designed to evaluate superficial structures. Microbubbles of SonoVue (Bracco, Milan, Italy) were injected in one corpus cavernosum. After cavernosal injection of microbubbles no adverse events were observed. Contrast enhanced US showed unilateral enhancement of the corpus cavernosum in which microbubbles were injected. Cavernosography confirmed unilateral corporeal opacification. Contrast enhanced US can be used effectively to diagnose complete penile corporeal septation.

Nanoparticles Formed by Acoustic Destruction of Microbubbles and Their Utilization for Imaging and Effects on Therapy by High Intensity Focused Ultrasound.

PubMed

Blum, Nicholas T; Yildirim, Adem; Chattaraj, Rajarshi; Goodwin, Andrew P

2017-01-01

This work reports that when PEG-lipid-shelled microbubbles with fluorocarbon interior (C 4 F 10 , C 5 F 12 , or C 6 F 14 ) are subjected to ultrasound pulses, they produce metastable, fluid-filled nanoparticles that can be re-imaged upon administration of HIFU. The nanoparticles produced by destruction of the microbubbles (MBNPs) are of 150 nm average diameter and can be re-imaged for up to an hour after creation for C 4 F 10 , and for at least one day for C 5 F 12 . The active species were found to be fluid (gas or liquid) filled nanoparticles rather than lipid debris. The acoustic droplet vaporization threshold of the nanoparticles was found to vary with the vapor pressure of the encapsulated fluorocarbon, and integrated image brightness was found to increase dramatically when the temperature was raised above the normal boiling point of the fluorocarbon. Finally, the vaporization threshold decreases in serum as compared to buffer, and administration of HIFU to the nanoparticles caused breast cancer cells to completely detach from their culture substrate. This work demonstrates a new functionality of microbubbles that could serve as a platform technology for ultrasound-based theranostics.

Preparation of monodisperse microbubbles using an integrated embedded capillary T-junction with electrohydrodynamic focusing.

PubMed

Parhizkar, Maryam; Stride, Eleanor; Edirisinghe, Mohan

2014-07-21

This work investigates the generation of monodisperse microbubbles using a microfluidic setup combined with electrohydrodynamic processing. A basic T-junction microfluidic device was modified by applying an electrical potential difference across the outlet channel. A model glycerol air system was selected for the experiments. In order to investigate the influence of the electric field strength on bubble formation, the applied voltage was increased systematically up to 21 kV. The effect of solution viscosity and electrical conductivity was also investigated. It was found that with increasing electrical potential difference, the size of the microbubbles reduced to ~25% of the capillary diameter whilst their size distribution remained narrow (polydispersity index ~1%). A critical value of 12 kV was found above which no further significant reduction in the size of the microbubbles was observed. The findings suggest that the size of the bubbles formed in the T-junction (i.e. in the absence of the electric field) is strongly influenced by the viscosity of the solution. The eventual size of bubbles produced by the composite device, however, was only weakly dependent upon viscosity. Further experiments, in which the solution electrical conductivity was varied by the addition of a salt indicated that this had a much stronger influence upon bubble size.

Formation and dissolution of microbubbles on highly-ordered plasmonic nanopillar arrays

PubMed Central

Liu, Xiumei; Bao, Lei; Dipalo, Michele; De Angelis, Francesco; Zhang, Xuehua

2015-01-01

Bubble formation from plasmonic heating of nanostructures is of great interest in many applications. In this work, we study experimentally the intrinsic effects of the number of three-dimensional plasmonic nanostructures on the dynamics of microbubbles, largely decoupled from the effects of dissolved air. The formation and dissolution of microbubbles is observed on exciting groups of 1, 4, and 9 nanopillars. Our results show that the power threshold for the bubble formation depends on the number density of the nanopillars in highly-ordered arrays. In the degassed water, both the growth rate and the maximal radius of the plasmonic microbubbles increase with an increase of the illuminated pillar number, due to the heat balance between the heat loss across the bubble and the collective heating generated from the nanopillars. Interestingly, our results show that the bubble dissolution is affected by the spatial arrangement of the underlying nanopillars, due to the pinning effect on the bubble boundary. The bubbles on nanopillar arrays dissolve in a jumping mode with step-wise features on the dissolution curves, prior to a smooth dissolution phase for the bubble pinned by a single pillar. The insight from this work may facilitate the design of nanostructures for efficient energy conversion. PMID:26687143

Selective accumulation of harmful compounds by the DNA-inorganic hybrid-immobilized glass bead.

PubMed

Yamada, Masanori; Hamai, Akari

2009-08-11

Previously, we reported the DNA-inorganic hybrid material including double-stranded DNA by mixing the aqueous DNA solution and silane coupling reagents. Here, we immobilized the DNA-inorganic hybrid material onto the glass bead and prepared the DNA-immobilized glass bead column. The DNA-immobilized glass beads were stable in water and the amount of eluted DNA from the DNA-glass beads did not change for more than 1 week. Additionally, this DNA-immobilized column selectively accumulated the harmful compounds with the planar structure, such as dioxin- and polychlorinated biphenyl (PCB)-derivatives, and these accumulation percentages were 50-70%. Furthermore, the DNA-immobilized glass bead was recycled nine times by the application of ethanol solution and the accumulative ratio was maintained at more than 60% and did not appear to be decreasing. Therefore, these DNA-columns might have a potential for the selective removal and separation of DNA-intercalating molecules and harmful compounds with the planar structure from experimental or industrial drainages.

Apparatus and method for two-stage oxidation of wastes

DOEpatents

Fleischman, Scott D.

1995-01-01

An apparatus and method for oxidizing wastes in a two-stage process. The apparatus includes an oxidation device, a gas-liquid contacting column and an electrocell. In the first stage of the process, wastes are heated in the presence of air to partially oxidize the wastes. The heated wastes produce an off-gas stream containing oxidizable materials. In the second stage, the off-gas stream is cooled and flowed through the contacting column, where the off-gas stream is contacted with an aqueous acid stream containing an oxidizing agent having at least two positive valence states. At least a portion of the oxidizable materials are transferred to the acid stream and destroyed by the oxidizing agent. During oxidation, the valence of the oxidizing agent is decreased from its higher state to its lower state. The acid stream is flowed to the electrocell, where an electric current is applied to the stream to restore the oxidizing agent to its higher valence state. The regenerated acid stream is recycled to the contacting column.

Separation of emulsified crude oil in saline water by flotation with micro- and nanobubbles generated by a multiphase pump.

PubMed

Oliveira, H A; Azevedo, A C; Etchepare, R; Rubio, J

2017-11-01

The flocculation-column flotation with hydraulic loading (HL, >10 m h -1 ) was studied for the treatment of oil-in-water emulsions containing 70-400 mg L -1 (turbidity = 70-226 NTU) of oil and salinity (30 and 100 g L -1 ). A polyacrylamide (Dismulgan, 20 mg L -1 ) flocculated the oil droplets, using two floc generator reactors, with rapid and slow mixing stages (head loss = 0.9 to 3.5 bar). Flotation was conducted in two cells (1.5 and 2.5 m) with microbubbles (MBs, 5-80 μm) and nanobubbles (NBs, 50-300 nm diameter, concentration of 10 8 NBs mL -1 ). Bubbles were formed using a centrifugal multiphase pump, with optimized parameters and a needle valve. The results showed higher efficiency with the taller column reducing the residual oil content to 4 mg L -1 and turbidity to 7 NTU. At high HL (27.5 m h -1 ), the residual oil concentrations were below the standard emission (29 mg L -1 ), reaching 18 mg L -1 . The best results were obtained with high concentration of NBs (apart from the bigger bubbles). Mechanisms involved appear to be attachment and entrapment of the NBs onto and inside the flocs. Thus, the aggregates were readily captured, by bigger bubbles (mostly MBs) aiding shear withstanding. Advantages are the small footprint of the cells, low residence time and high processing rate.

Light and ultrasound activated microbubbles around gold nanorods for photoacoustic microsurgery

NASA Astrophysics Data System (ADS)

Cavigli, Lucia; Centi, Sonia; Lai, Sarah; Borri, Claudia; Micheletti, Filippo; Tortoli, Paolo; Panettieri, Ilaria; Streit, Ingolf; Rossi, Francesca; Ratto, Fulvio; Pini, Roberto

2017-07-01

Photoacoustic imaging and microsurgery have recently attracted attention for applications in oncology. Here, we present a versatile set-up to trigger vapor microbubbles around plasmonic nanoparticles by a combined light-ultrasound excitation. This system enables the detection and parametrization of bubbles as a function of several variables, such us optical fluence, ultrasound intensity, nanoparticles concentration, thus providing useful directions to the development of new strategies for treatments based on optical cavitation.

Regimes of Micro-bubble Formation Using Gas Injection into Ladle Shroud

NASA Astrophysics Data System (ADS)

Chang, Sheng; Cao, Xiangkun; Zou, Zongshu

2018-03-01

Gas injection into a ladle shroud is a practical approach to produce micro-bubbles in tundishes, to promote inclusion removal from liquid steel. A semi-empirical model was established to characterize the bubble formation considering the effect of shearing action combined with the non-fully bubble break-up by turbulence. The model shows a good accuracy in predicting the size of bubbles formed in complex flow within the ladle shroud.

Regimes of Micro-bubble Formation Using Gas Injection into Ladle Shroud

NASA Astrophysics Data System (ADS)

Chang, Sheng; Cao, Xiangkun; Zou, Zongshu

2018-06-01

Gas injection into a ladle shroud is a practical approach to produce micro-bubbles in tundishes, to promote inclusion removal from liquid steel. A semi-empirical model was established to characterize the bubble formation considering the effect of shearing action combined with the non-fully bubble break-up by turbulence. The model shows a good accuracy in predicting the size of bubbles formed in complex flow within the ladle shroud.

A novel method to harvest Chlorella sp. by co-flocculation/air flotation.

PubMed

Zhang, Haiyang; Lin, Zhe; Tan, Daoyong; Liu, Chunhua; Kuang, Yali; Li, Zhu

2017-01-01

To develop a more effective dissolved air flotation process for harvesting microalgae biomass, a co-flocculation/air flotation (CAF) system was developed that uses an ejector followed by a helix tube flocculation reactor (HTFR) as a co-flocculation device to harvest Chlorella sp. 64.01. The optimal size distribution of micro-bubbles and an air release efficiency of 96 % were obtained when the flow ratio of inlet fluid (raw water) to motive fluid (saturated water) of the ejector was 0.14. With a reaction time of 24 s in the HTFR, microalgae cells and micro-bubbles were well flocculated, and these aerated flocs caused a fast rising velocity (96 m/h) and high harvesting efficiency (94 %). In a CAF process, micro-bubbles can be encapsulated into microalgae flocs, which makes aerated flocs more stable. CAF is an effective approach to harvesting microalgae.

Microbubbles and Ultrasound: A Bird's Eye View.

PubMed Central

Kaul, Sanjiv

2004-01-01

Gas-filled microbubbles were initially used as ultrasound contrast agent because of their intravascular rheology, which is similar to that of red blood cells. Their transit through tissue can thus be quantified with ultrasound. More recently, these bubbles have been successfully used for molecular imaging by incorporating ligands on their surfaces that will adhere to cellular and other components within the microvasculature and can be detected by ultrasound. These bubbles have also been used for delivery of genes and drugs which can be released locally by disruption of the bubbles with high-energy ultrasound. Finally, bioeffects produced by localized ultrasound disruption of microbubbles have been shown to induce angiogenesis. This brief review will provide a bird's eye view of these applications. Images Fig. 1 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 Fig. 11 Fig. 12 PMID:17060963

Inactivation of Bacillus spores by the supercritical carbon dioxide micro-bubble method.

PubMed

Ishikawa, H; Shimoda, M; Tamaya, K; Yonekura, A; Kawano, T; Osajima, Y

1997-06-01

Bacillus spores were effectively inactivated by the supercritical (SC) CO2 micro-bubble method. The micro-bubble SC CO2 treatment of B. cereus, B. subtilis, B. megaterium, B. polymyxa, and B. coagulans at 40 degrees C and 30 MPa for 30 min produced greater reduction (about 3 log cycles of reduction) than a similar treatment without a filter. The SC CO2 treatment of B. polymyxa, B. cereus, and B. subtilis spores at 45 degrees C, 50 degrees C, respectively, and 30 MPa for 60 min resulted in a 6-log cycle reduction of survival. The SC CO2 treatment under the foregoing conditions should offer higher efficiency than that of heat treatment at 100 degrees C for 60 min. In addition, the SC CO2 treatment (30 MPa, 60 degrees C, 30 min) of B. polymyxa and B. cereus spores also produced a 6-log cycle reduction.

Catalytic reactive separation system for energy-efficient production of cumene

DOEpatents

Buelna, Genoveva [Nuevo Laredo, MX; Nenoff, Tina M [Albuquerque, NM

2009-07-28

The present invention relates to an atmospheric pressure, reactive separation column packed with a solid acid zeolite catalyst for producing cumene from the reaction of benzene with propylene. Use of this un-pressurized column, where simultaneous reaction and partial separation occur during cumene production, allow separation of un-reacted, excess benzene from other products as they form. This high-yielding, energy-efficient system allows for one-step processing of cumene, with reduced need for product purification. Reacting propylene and benzene in the presence of beta zeolite catalysts generated a selectivity greater than 85% for catalytic separation reactions at a reaction temperature of 115 degrees C and at ambient pressure. Simultaneously, up to 76% of un-reacted benzene was separated from the product; which could be recycled back to the reactor for re-use.

Hemostatic mechanism underlying microbubble-enhanced non-focused ultrasound in the treatment of a rabbit liver trauma model

PubMed Central

Zhao, Da-wei; Tian, Meng; Yang, Jian-zheng; Du, Peng; Bi, Jie; Zhu, Xinjian

2016-01-01

The aim of our study was to investigate the hemostatic mechanism underlying microbubble-enhanced non-focused ultrasound treatment of liver trauma. Thirty rabbits with liver trauma were randomly divided into three groups—the microbubble-enhanced ultrasound (MEUS; further subdivided based on exposure intensity into MEUS1 [0.11 W/cm2], MEUS2 [0.55 W/cm2], and MEUS3 [1.1 W/cm2]), ultrasound without microbubbles (US), and microbubbles without ultrasound (MB) groups. The pre- and post-treatment bleeding weight and visual bleeding scores were evaluated. The serum liver enzyme concentrations as well as the blood perfusion level represented by mean peak contrast intensity (PI) ratio in the treatment area were analyzed. The hemostatic mechanism was evaluated by histological and transmission electron microscopic examination of liver tissue samples. The MEUS subgroups 1–3 (grade 0–1, grade 0–2, and grade 1–2, respectively) exhibited significantly lower post-treatment visual bleeding scores than the US and MB groups (both, grade 3–4; all, P < 0.05). Subgroups MEUS1 (0.346 ± 0.345 g) and MEUS2 (2.232 ± 2.256 g) exhibited significantly lower post-treatment bleeding weight than the US and MB groups (5.698 ± 1.938 and 5.688 ± 2.317 g, respectively; all, P < 0.05). Additionally, MEUS subgroups 1–3 exhibited significantly lower post-treatment blood perfusion levels (PI ratios, 0.64 ± 0.085, 0.73 ± 0.045, and 0.84 ± 0.034, respectively) than the US and MB groups (PI ratios, 1.00 ± 0.005 and 0.99 ± 0.005, respectively; all, P < 0.05). In the MEUS group, hepatic cells became edematous and compressed the hepatic sinus and associated blood vessels. However, the serum liver enzyme levels were not significantly altered. Microbubble-enhanced non-focused ultrasound does not significantly affect blood perfusion and liver function and can be used to induce rapid hemostasis in case of liver trauma. PMID:27633577

Ultrasound-guided drug delivery in cancer

PubMed Central

2017-01-01

Recent advancements in ultrasound and microbubble (USMB) mediated drug delivery technology has shown that this approach can improve spatially confined delivery of drugs and genes to target tissues while reducing systemic dose and toxicity. The mechanism behind enhanced delivery of therapeutics is sonoporation, the formation of openings in the vasculature, induced by ultrasound-triggered oscillations and destruction of microbubbles. In this review, progress and challenges of USMB mediated drug delivery are summarized, with special focus on cancer therapy. PMID:28607323

On the interplay of shell structure with low- and high-frequency mechanics of multifunctional magnetic microbubbles.

PubMed

Poehlmann, Melanie; Grishenkov, Dmitry; Kothapalli, Satya V V N; Härmark, Johan; Hebert, Hans; Philipp, Alexandra; Hoeller, Roland; Seuss, Maximilian; Kuttner, Christian; Margheritelli, Silvia; Paradossi, Gaio; Fery, Andreas

2014-01-07

Polymer-shelled magnetic microbubbles have great potential as hybrid contrast agents for ultrasound and magnetic resonance imaging. In this work, we studied US/MRI contrast agents based on air-filled poly(vinyl alcohol)-shelled microbubbles combined with superparamagnetic iron oxide nanoparticles (SPIONs). The SPIONs are integrated either physically or chemically into the polymeric shell of the microbubbles (MBs). As a result, two different designs of a hybrid contrast agent are obtained. With the physical approach, SPIONs are embedded inside the polymeric shell and with the chemical approach SPIONs are covalently linked to the shell surface. The structural design of hybrid probes is important, because it strongly determines the contrast agent's response in the considered imaging methods. In particular, we were interested how structural differences affect the shell's mechanical properties, which play a key role for the MBs' US imaging performance. Therefore, we thoroughly characterized the MBs' geometric features and investigated low-frequency mechanics by using atomic force microscopy (AFM) and high-frequency mechanics by using acoustic tests. Thus, we were able to quantify the impact of the used SPIONs integration method on the shell's elastic modulus, shear modulus and shear viscosity. In summary, the suggested approach contributes to an improved understanding of structure-property relations in US-active hybrid contrast agents and thus provides the basis for their sustainable development and optimization.

Numerical study on microbubble-enhanced heating for various parameters in EUS-FUS

NASA Astrophysics Data System (ADS)

Okita, Kohei; Maezawa, Miyuki; Takagi, Shu; Matsumoto, Yoichiro

2012-11-01

Endoscopic ultrasonography guided focused ultrasound surgery (EUS-FUS) have been developed as a less-invasive treatment for pancreatic cancer. In the present study, microbubble-enhanced heating for various parameters in EUS-FUS is investigated numerically. Mass and momentum equations for bubbly mixture are solved to reproduce the propagation of ultrasound of 4.8MHz through the gel containing microbubbles as Sonazoid®. The dynamics of bubble is governed by the equation which considers the elasticity of both shell and surrounding media. Additionally, the heat equation with the time averaged heat source is solved to obtain a temperature distribution. The basic equations are discretized by the 6th-order finite difference method and developed based on FDTD method. The mixture and bubbles are coupled by Euler-Lagrange method. As the results, the temperature around the target increased due to the microbubble oscillation with increasing the initial void fraction fG0 from 10-5 to 10-4%. However, at fG0=10-3%, ultrasounds were too attenuated to heat the target. The heating region moved from the target to the transducer side. By comparing the results with and without shell, the shell of bubble induced the heating around focus. This is because the decrease of the attenuation due to the elasticity of the shell and the increase of the viscous dissipation rate due to the viscosity of the shell.

Toward in vivo detection of hydrogen peroxide with ultrasound molecular imaging

PubMed Central

Olson, Emilia S.; Orozco, Jahir; Wu, Zhe; Malone, Christopher D.; Yi, Boemha; Gao, Wei; Eghtedari, Mohammad; Wang, Joseph; Mattrey, Robert F.

2013-01-01

We present a new class of ultrasound molecular imaging agents that extend upon the design of micromotors that are designed to move through fluids by catalyzing hydrogen peroxide (H2O2) and propelling forward by escaping oxygen microbubbles. Micromotor converters require 62 mm of H2O2 to move – 1000-fold higher than is expected in vivo. Here, we aim to prove that ultrasound can detect the expelled microbubbles, to determine the minimum H2O2 concentration needed for microbubble detection, explore alternate designs to detect the H2O2 produced by activated neutrophils and perform preliminary in vivo testing. Oxygen microbubbles were detected by ultrasound at 2.5 mm H2O2. Best results were achieved with a 400–500 nm spherical design with alternating surface coatings of catalase and PSS over a silica core. The lowest detection limit of 10–100 µm was achieved when assays were done in plasma. Using this design, we detected the H2O2 produced by freshly isolated PMA-activated neutrophils allowing their distinction from naïve neutrophils. Finally, we were also able to show that direct injection of these nanospheres into an abscess in vivo enhanced ultrasound signal only when they contained catalase, and only when injected into an abscess, likely because of the elevated levels of H2O2 produced by inflammatory mediators. PMID:23958028

Facilitation of Drug Transport across the Blood-Brain Barrier with Ultrasound and Microbubbles.

PubMed

Meairs, Stephen

2015-08-31

Medical treatment options for central nervous system (CNS) diseases are limited due to the inability of most therapeutic agents to penetrate the blood-brain barrier (BBB). Although a variety of approaches have been investigated to open the BBB for facilitation of drug delivery, none has achieved clinical applicability. Mounting evidence suggests that ultrasound in combination with microbubbles might be useful for delivery of drugs to the brain through transient opening of the BBB. This technique offers a unique non-invasive avenue to deliver a wide range of drugs to the brain and promises to provide treatments for CNS disorders with the advantage of being able to target specific brain regions without unnecessary drug exposure. If this method could be applied for a range of different drugs, new CNS therapeutic strategies could emerge at an accelerated pace that is not currently possible in the field of drug discovery and development. This article reviews both the merits and potential risks of this new approach. It assesses methods used to verify disruption of the BBB with MRI and examines the results of studies aimed at elucidating the mechanisms of opening the BBB with ultrasound and microbubbles. Possible interactions of this novel delivery method with brain disease, as well as safety aspects of BBB disruption with ultrasound and microbubbles are addressed. Initial translational research for treatment of brain tumors and Alzheimer's disease is presented.

Ultrasound-mediated drug delivery by gas bubbles generated from a chemical reaction.

PubMed

Lee, Sungmun; Al-Kaabi, Leena; Mawart, Aurélie; Khandoker, Ahsan; Alsafar, Habiba; Jelinek, Herbert F; Khalaf, Kinda; Park, Ji-Ho; Kim, Yeu-Chun

2018-02-01

Highly echogenic and ultrasound-responsive microbubbles such as nitrogen and perfluorocarbons have been exploited as ultrasound-mediated drug carriers. Here, we propose an innovative method for drug delivery using microbubbles generated from a chemical reaction. In a novel drug delivery system, luminol encapsulated in folate-conjugated bovine serum albumin nanoparticles (Fol-BSAN) can generate nitrogen gas (N 2 ) by chemical reaction when it reacts with hydrogen peroxide (H 2 O 2 ), one of reactive oxygen species (ROS). ROS plays an important role in the initiation and progression of cancer and elevated ROS have been observed in cancer cells both in vitro and in vivo. High-intensity focussed ultrasound (HIFU) is used to burst the N 2 microbubbles, causing site-specific delivery of anticancer drugs such as methotrexate. In this research, the drug delivery system was optimised by using water-soluble luminol and Mobil Composition of Matter-41 (MCM-41), a mesoporous material, so that the delivery system was sensitive to micromolar concentrations of H 2 O 2 . HIFU increased the drug release from Fol-BSAN by 52.9 ± 2.9% in 10 minutes. The cytotoxicity of methotrexate was enhanced when methotrexate is delivered to MDA-MB-231, a metastatic human breast cancer cell line, using Fol-BSAN with HIFU. We anticipate numerous applications of chemically generated microbubbles for ultrasound-mediated drug delivery.

A Preliminary Engineering Design of Intravascular Dual-Frequency Transducers for Contrast-Enhanced Acoustic Angiography and Molecular Imaging

PubMed Central

Ma, Jianguo; Martin, K. Heath; Dayton, Paul A.; Jiang, Xiaoning

2014-01-01

Current intravascular ultrasound (IVUS) probes are not optimized for contrast detection because of their design for high-frequency fundamental-mode imaging. However, data from transcutaneous contrast imaging suggests the possibility of utilizing contrast ultrasound for molecular imaging or vasa vasorum assessment to further elucidate atherosclerotic plaque deposition. This paper presents the design, fabrication, and characterization of a small-aperture (0.6 × 3 mm) IVUS probe optimized for high-frequency contrast imaging. The design utilizes a dual-frequency (6.5 MHz/30 MHz) transducer arrangement for exciting microbubbles at low frequencies (near their resonance) and detecting their broadband harmonics at high frequencies, minimizing detected tissue backscatter. The prototype probe is able to generate nonlinear microbubble response with more than 1.2 MPa of rarefractional pressure (mechanical index: 0.48) at 6.5 MHz, and is also able to detect microbubble response with a broadband receiving element (center frequency: 30 MHz, −6-dB fractional bandwidth: 58.6%). Nonlinear super-harmonics from microbubbles flowing through a 200-μm-diameter micro-tube were clearly detected with a signal-to-noise ratio higher than 12 dB. Preliminary phantom imaging at the fundamental frequency (30 MHz) and dual-frequency super-harmonic imaging results suggest the promise of small aperture, dual-frequency IVUS transducers for contrast-enhanced IVUS imaging. PMID:24801226

Localized Down-regulation of P-glycoprotein by Focused Ultrasound and Microbubbles induced Blood-Brain Barrier Disruption in Rat Brain

NASA Astrophysics Data System (ADS)

Cho, Hongseok; Lee, Hwa-Youn; Han, Mun; Choi, Jong-Ryul; Ahn, Sanghyun; Lee, Taekwan; Chang, Yongmin; Park, Juyoung

2016-08-01

Multi-drug resistant efflux transporters found in Blood-Brain Barrier (BBB) acts as a functional barrier, by pumping out most of the drugs into the blood. Previous studies showed focused ultrasound (FUS) induced microbubble oscillation can disrupt the BBB by loosening the tight junctions in the brain endothelial cells; however, no study was performed to investigate its impact on the functional barrier of the BBB. In this study, the BBB in rat brains were disrupted using the MRI guided FUS and microbubbles. The immunofluorescence study evaluated the expression of the P-glycoprotein (P-gp), the most dominant multi-drug resistant protein found in the BBB. Intensity of the P-gp expression at the BBB disruption (BBBD) regions was significantly reduced (63.2 ± 18.4%) compared to the control area. The magnitude of the BBBD and the level of the P-gp down-regulation were significantly correlated. Both the immunofluorescence and histologic analysis at the BBBD regions revealed no apparent damage in the brain endothelial cells. The results demonstrate that the FUS and microbubbles can induce a localized down-regulation of P-gp expression in rat brain. The study suggests a clinically translation of this method to treat neural diseases through targeted delivery of the wide ranges of brain disorder related drugs.

Cavitation and contrast: the use of bubbles in ultrasound imaging and therapy.

PubMed

Stride, E P; Coussios, C C

2010-01-01

Microbubbles and cavitation are playing an increasingly significant role in both diagnostic and therapeutic applications of ultrasound. Microbubble ultrasound contrast agents have been in clinical use now for more than two decades, stimulating the development of a range of new contrast-specific imaging techniques which offer substantial benefits in echocardiography, microcirculatory imaging, and more recently, quantitative and molecular imaging. In drug delivery and gene therapy, microbubbles are being investigated/developed as vehicles which can be loaded with the required therapeutic agent, traced to the target site using diagnostic ultrasound, and then destroyed with ultrasound of higher intensity energy burst to release the material locally, thus avoiding side effects associated with systemic administration, e.g. of toxic chemotherapy. It has moreover been shown that the motion of the microbubbles increases the permeability of both individual cell membranes and the endothelium, thus enhancing therapeutic uptake, and can locally increase the activity of drugs by enhancing their transport across biologically inaccessible interfaces such as blood clots or solid tumours. In high-intensity focused ultrasound (HIFU) surgery and lithotripsy, controlled cavitation is being investigated as a means of increasing the speed and efficacy of the treatment. The aim of this paper is both to describe the key features of the physical behaviour of acoustically driven bubbles which underlie their effectiveness in biomedical applications and to review the current state of the art.

Spatiotemporal evolution of cavitation dynamics exhibited by flowing microbubbles during ultrasound exposure.

PubMed

Choi, James J; Coussios, Constantin-C

2012-11-01

Ultrasound and microbubble-based therapies utilize cavitation to generate bioeffects, yet cavitation dynamics during individual pulses and across consecutive pulses remain poorly understood under physiologically relevant flow conditions. SonoVue(®) microbubbles were made to flow (fluid velocity: 10-40 mm/s) through a vessel in a tissue-mimicking material and were exposed to ultrasound [frequency: 0.5 MHz, peak-rarefactional pressure (PRP): 150-1200 kPa, pulse length: 1-100,000 cycles, pulse repetition frequency (PRF): 1-50 Hz, number of pulses: 10-250]. Radiated emissions were captured on a linear array, and passive acoustic mapping was used to spatiotemporally resolve cavitation events. At low PRPs, stable cavitation was maintained throughout several pulses, thus generating a steady rise in energy with low upstream spatial bias within the focal volume. At high PRPs, inertial cavitation was concentrated in the first 6.3 ± 1.3 ms of a pulse, followed by an energy reduction and high upstream bias. Multiple pulses at PRFs below a flow-dependent critical rate (PRF(crit)) produced predictable and consistent cavitation dynamics. Above the PRF(crit), energy generated was unpredictable and spatially biased. In conclusion, key parameters in microbubble-seeded flow conditions were matched with specific types, magnitudes, distributions, and durations of cavitation; this may help in understanding empirically observed in vivo phenomena and guide future pulse sequence designs.

Impacts of light shading and nutrient enrichment geo-engineering approaches on the productivity of a stratified, oligotrophic ocean ecosystem.

PubMed

Hardman-Mountford, Nick J; Polimene, Luca; Hirata, Takafumi; Brewin, Robert J W; Aiken, Jim

2013-12-06

Geo-engineering proposals to mitigate global warming have focused either on methods of carbon dioxide removal, particularly nutrient fertilization of plant growth, or on cooling the Earth's surface by reducing incoming solar radiation (shading). Marine phytoplankton contribute half the Earth's biological carbon fixation and carbon export in the ocean is modulated by the actions of microbes and grazing communities in recycling nutrients. Both nutrients and light are essential for photosynthesis, so understanding the relative influence of both these geo-engineering approaches on ocean ecosystem production and processes is critical to the evaluation of their effectiveness. In this paper, we investigate the relationship between light and nutrient availability on productivity in a stratified, oligotrophic subtropical ocean ecosystem using a one-dimensional water column model coupled to a multi-plankton ecosystem model, with the goal of elucidating potential impacts of these geo-engineering approaches on ecosystem production. We find that solar shading approaches can redistribute productivity in the water column but do not change total production. Macronutrient enrichment is able to enhance the export of carbon, although heterotrophic recycling reduces the efficiency of carbon export substantially over time. Our results highlight the requirement for a fuller consideration of marine ecosystem interactions and feedbacks, beyond simply the stimulation of surface blooms, in the evaluation of putative geo-engineering approaches.

Impacts of light shading and nutrient enrichment geo-engineering approaches on the productivity of a stratified, oligotrophic ocean ecosystem

PubMed Central

Hardman-Mountford, Nick J.; Polimene, Luca; Hirata, Takafumi; Brewin, Robert J. W.; Aiken, Jim

2013-01-01

Geo-engineering proposals to mitigate global warming have focused either on methods of carbon dioxide removal, particularly nutrient fertilization of plant growth, or on cooling the Earth's surface by reducing incoming solar radiation (shading). Marine phytoplankton contribute half the Earth's biological carbon fixation and carbon export in the ocean is modulated by the actions of microbes and grazing communities in recycling nutrients. Both nutrients and light are essential for photosynthesis, so understanding the relative influence of both these geo-engineering approaches on ocean ecosystem production and processes is critical to the evaluation of their effectiveness. In this paper, we investigate the relationship between light and nutrient availability on productivity in a stratified, oligotrophic subtropical ocean ecosystem using a one-dimensional water column model coupled to a multi-plankton ecosystem model, with the goal of elucidating potential impacts of these geo-engineering approaches on ecosystem production. We find that solar shading approaches can redistribute productivity in the water column but do not change total production. Macronutrient enrichment is able to enhance the export of carbon, although heterotrophic recycling reduces the efficiency of carbon export substantially over time. Our results highlight the requirement for a fuller consideration of marine ecosystem interactions and feedbacks, beyond simply the stimulation of surface blooms, in the evaluation of putative geo-engineering approaches. PMID:24132201

Organic compounds in concrete from demolition works.

PubMed

Van Praagh, M; Modin, H; Trygg, J

2015-11-01

This study aims to verify the effect of physically removing the outer surface of contaminated concrete on total contents and on potential mobility of pollutants by means of leaching tests. Reclaimed concrete from 3 industrial sites in Sweden were included: A tar impregnated military storage, a military tar track-depot, as well as concrete constructions used for disposing of pesticide production surplus and residues. Solid materials and leachates from batch and column leaching tests were analysed for metals, Cl, F, SO4, DOC and contents of suspected organic compounds (polycyclic aromatic hydrocarbons, PAH, and pesticides/substances for pesticide production such as phenoxy acids, chlorophenols and chlorocresols, respectively). In case of PAH contaminated concrete, results indicate that removing 1 or 5 mm of the surface lead to total concentrations below the Swedish guidelines for recycling of aggregates and soil in groundwork constructions. 3 out of 4 concrete samples contaminated with pesticides fulfilled Swedish guidelines for contaminated soil. Results from batch and column leaching tests indicated, however, that concentrations above environmental quality standards for certain PAH and phenoxy acids, respectively, might occur at site when the crushed concrete is recycled in groundwork constructions. As leaching tests engaged in the study deviated from leaching test standards with a limited number of samples, the potential impact of the leaching tests' equipment on measured PAH and pesticide leachate concentrations has to be evaluated in future work. Copyright © 2015. Published by Elsevier Ltd.

Biogeochemistry of silica in Devils Lake: Implications for diatom preservation

USGS Publications Warehouse

Lent, R.M.; Lyons, B.

2001-01-01

Diatom-salinity records from sediment cores have been used to construct climate records of saline-lake basins. In many cases, this has been done without thorough understanding of the preservation potential of the diatoms in the sediments through time. The purpose of this study was to determine the biogeochemistry of silica in Devils Lake and evaluate the potential effects of silica cycling on diatom preservation. During the period of record, 1867-1999, lake levels have fluctuated from 427 m above sea level in 1940 to 441.1 m above sea level in 1999. The biogeochemistry of silica in Devils Lake is dominated by internal cycling. During the early 1990s when lake levels were relatively high, about 94% of the biogenic silica (BSi) produced in Devils Lake was recycled in the water column before burial. About 42% of the BSi that was incorporated in bottom sediments was dissolved and diffused back into the lake, and the remaining 58% was buried. Therefore, the BSi accumulation rate was about 3% of the BSi assimilation rate. Generally, the results obtained from this study are similar to those obtained from studies of the biogeochemistry of silica in large oligotrophic lakes and the open ocean where most of the BSi produced is recycled in surface water. During the mid 1960s when lake levels were relatively low, BSi assimilation and water-column dissolution rates were much higher than when lake levels were high. The BSi assimilation rate was as much as three times higher during low lake levels. Even with the much higher BSi assimilation rate, the BSi accumulation rate was about three times lower because the BSi water-column dissolution rate was more than 99% of the BSi assimilation rate compared to 94% during high lake levels. Variations in the biogeochemistry of silica with lake level have important implications for paleolimnologic studies. Increased BSi water-column dissolution during decreasing lake levels may alter the diatom-salinity record by selectively removing the less resistant diatoms. Also, BSi accumulation may be proportional to the amount of silica input from tributary sources. Therefore, BSi accumulation chronologies from sediment cores may be effective records of tributary inflow.

Combined Ultrasound and MR Imaging to Guide Focused Ultrasound Therapies in the Brain

PubMed Central

Arvanitis, Costas D.; Livingstone, Margaret S.; McDannold, Nathan

2013-01-01

Purpose Several emerging therapies with potential for use in the brain harness effects produced by acoustic cavitation – the interaction between ultrasound and microbubbles either generated during sonication or introduced into the vasculature. Systems developed for transcranial MRI-guided focused ultrasound (MRgFUS) thermal ablation can enable their clinical translation, but methods for real-time monitoring and control are currently lacking. Acoustic emissions produced during sonication can provide information about the location, strength, and type of the microbubble oscillations within the ultrasound field, and they can be mapped in real-time using passive imaging approaches. Here, we tested whether such mapping can be achieved transcranially within a clinical brain MRgFUS system. Materials and Methods We integrated an ultrasound imaging array into the hemisphere transducer of the MRgFUS device. Passive cavitation maps were obtained during sonications combined with a circulating microbubble agent at 20 targets in the cingulate cortex in three macaques. The maps were compared with MRI-evident tissue effects. Results The system successfully mapped microbubble activity during both stable and inertial cavitation, which was correlated with MRI-evident transient blood-brain barrier disruption and vascular damage, respectively. The location of this activity was coincident with the resulting tissue changes within the expected resolution limits of the system. Conclusion While preliminary, these data clearly demonstrate, for the first time, that is possible to construct maps of stable and inertial cavitation transcranially, in a large animal model, and under clinically relevant conditions. Further, these results suggest that this hybrid ultrasound/MRI approach can provide comprehensive guidance for targeted drug delivery via blood-brain barrier disruption and other emerging ultrasound treatments, facilitating their clinical translation. We anticipate it will also prove to be an important research tool that will further the development of a broad range of microbubble-enhanced therapies. PMID:23788054

Unbinding of targeted ultrasound contrast agent microbubbles by secondary acoustic forces.

PubMed

Garbin, Valeria; Overvelde, Marlies; Dollet, Benjamin; de Jong, Nico; Lohse, Detlef; Versluis, Michel

2011-10-07

Targeted molecular imaging with ultrasound contrast agent microbubbles is achieved by incorporating targeting ligands on the bubble coating and allows for specific imaging of tissues affected by diseases. Improved understanding of the interplay between the acoustic forces acting on the bubbles during insonation with ultrasound and other forces (e.g. shear due to blood flow, binding of targeting ligands to receptors on cell membranes) can help improve the efficacy of this technique. This work focuses on the effects of the secondary acoustic radiation force, which causes bubbles to attract each other and may affect the adhesion of targeted bubbles. First, we examine the translational dynamics of ultrasound contrast agent microbubbles in contact with (but not adherent to) a semi-rigid membrane due to the secondary acoustic radiation force. An equation of motion that effectively accounts for the proximity of the membrane is developed, and the predictions of the model are compared with experimental data extracted from optical recordings at 15 million frames per second. A time-averaged model is also proposed and validated. In the second part of the paper, initial results on the translation due to the secondary acoustic radiation force of targeted, adherent bubbles are presented. Adherent bubbles are also found to move due to secondary acoustic radiation force, and a restoring force is observed that brings them back to their initial positions. For increasing magnitude of the secondary acoustic radiation force, a threshold is reached above which the adhesion of targeted microbubbles is disrupted. This points to the fact that secondary acoustic radiation forces can cause adherent bubbles to detach and alter the spatial distribution of targeted contrast agents bound to tissues during activation with ultrasound. While the details of the rupture of intermolecular bonds remain elusive, this work motivates the use of the secondary acoustic radiation force to measure the strength of adhesion of targeted microbubbles.

Photothermal and photoacoustic processes of laser activated nano-thermolysis of cells

NASA Astrophysics Data System (ADS)

Lapotko, Dmitri; Lukianova, Ekaterina; Mitskevich, Pavel; Smolnikova, Victoria; Potapnev, Michail; Konopleva, Marina; Andreeff, Michael; Oraevsky, Alexander

2007-02-01

Laser Activated Nano-Thermolysis was recently proposed for selective damage of individual target (cancer) cells by pulsed laser induced microbubbles around superheated clusters of optically absorbing nanoparticles (NP). One of the clinical applications of this technology is the elimination of residual tumor cells from human blood and bone marrow. Clinical standards for the safety and efficacy of such procedure require the development and verification of highly selective and controllable mechanisms of cell killing. Our previous experiments showed that laser-induced microbubble is the main damaging factor in the case cell irradiation by short laser pulses above the threshold. Our current aim was to study the cell damage mechanisms and analyze selectivity and efficacy of cell damage as a function of NP parameters, NP-cell interaction conditions, and conditions of bubble generation around NP and NP clusters in cells. Generation of laser-induced bubbles around gold NP with diameters 10-250 nm was studied in Acute Myeloblast Leukemia (AML) cultures, normal stem and model K562 human cells. Short laser pulses (10 ns, 532 nm) were applied to those cells in vitro and the processes in cells were investigated with photothermal, fluorescent and atomic force microscopies and also with fluorescence flow cytometry. We have found that the best selectivity of cell damage is achieved by (1) forming large clusters of optically absorbing NP in target cells and (2) irradiating the cells with single laser pulses with the lowest fluence that can generate microbubble only around large clusters but not around single NP. Laser microbubbles with the lifetime from 20 ns to 2000 ns generated in individual cells caused damage and lysis of the cellular membrane and consequently cell death. Laser microbubbles did not damage normal cells around the damaged target (tumor) cell. Laser irradiation with equal fluence did not cause any damage of cells without accumulated NP clusters.

MODELING MICROBUBBLE DYNAMICS IN BIOMEDICAL APPLICATIONS*

PubMed Central

CHAHINE, Georges L.; HSIAO, Chao-Tsung

2012-01-01

Controlling microbubble dynamics to produce desirable biomedical outcomes when and where necessary and avoid deleterious effects requires advanced knowledge, which can be achieved only through a combination of experimental and numerical/analytical techniques. The present communication presents a multi-physics approach to study the dynamics combining viscous- in-viscid effects, liquid and structure dynamics, and multi bubble interaction. While complex numerical tools are developed and used, the study aims at identifying the key parameters influencing the dynamics, which need to be included in simpler models. PMID:22833696

Ultrasound contrast agents: an overview.

PubMed

Cosgrove, David

2006-12-01

With the introduction of microbubble contrast agents, diagnostic ultrasound has entered a new era that allows the dynamic detection of tissue flow of both the macro and microvasculature. Underpinning this development is the fact that gases are compressible, and thus the microbubbles expand and contract in the alternating pressure waves of the ultrasound beam, while tissue is almost incompressible. Special software using multiple pulse sequences separates these signals from those of tissue and displays them as an overlay or on a split screen. This can be done at low acoustic pressures (MI<0.3) so that the microbubbles are not destroyed and scanning can continue in real time. The clinical roles of contrast enhanced ultrasound scanning are expanding rapidly. They are established in echocardiography to improve endocardial border detection and are being developed for myocardial perfusion. In radiology, the most important application is the liver, especially for focal disease. The approach parallels that of dynamic CT or MRI but ultrasound has the advantages of high spatial and temporal resolution. Thus, small lesions that can be indeterminate on CT can often be studied with ultrasound, and situations where the flow is very rapid (e.g., focal nodular hyperplasia where the first few seconds of arterial perfusion may be critical to making the diagnosis) are readily studied. Microbubbles linger in the extensive sinusoidal space of normal liver for several minutes whereas they wash out rapidly from metastases, which have a low vascular volume and thus appear as filling defects. The method has been shown to be as sensitive as three-phase CT. Microbubbles have clinical uses in many other applications where knowledge of the microcirculation is important (the macrocirculation can usually be assessed adequately using conventional Doppler though there are a few important situations where the signal boost given by microbubbles is useful, e.g., transcranial Doppler for evaluating vasospasm after subarachnoid haemorrhage). An important situation where demonstrating tissue devitalisation is important is in interstitial ablation of focal liver lesions: using microbubble contrast agents at the end of a procedure allows immediate evaluation of the adequacy of the ablation which can be extended if needed; this is much more convenient and cost-saving than moving the patient to CT and perhaps needing an additional ablation session at a later date. Similar considerations suggest that contrast-enhanced ultrasound might have a role in abdominal trauma: injury to the liver, spleen and kidneys can be assessed rapidly and repeatedly if necessary. Its role here alongside dynamic CT remains to be evaluated. Infarcts or ischaemia and regions of abnormal vascularity, especially in malignancies, in the kidneys and spleen seem to be useful and improved detection of the neovascularisation of ovarian carcinomas is promising. Similar benefits in the head-and-neck and in the skin while the demonstration of the neovascularisation of atheromatous plaques and of aggressive joint inflammation offer interesting potentials.

Interaction of a vortex ring and a bubble

NASA Astrophysics Data System (ADS)

Jha, Narsing K.; Govardhan, Raghuraman N.

2014-11-01

Micro-bubble injection in to boundary layers is one possible method for reducing frictional drag of ships. Although this has been studied for some time, the physical mechanisms responsible for drag reduction using microbubbles in turbulent boundary layers is not yet fully understood. Previous studies suggest that bubble-vortical structure interaction seems to be one of the important physical mechanisms for frictional drag reduction using microbubbles. In the present work, we study a simplification of this problem, namely, the interaction of a single vortical structure, in particular a vortex ring, with a single bubble for better understanding of the physics. The vortex ring is generated using a piston-cylinder arrangement and the bubble is generated by connecting a capillary to an air pump. The bubble dynamics is directly visualized using a high speed camera, while the vorticity modification is measured using time resolved PIV. The results show that significant deformations can occur of both the bubble and the vortex ring. Effect of different non-dimensional parameters on the interaction will be presented in the meeting.

Activation of microbubbles by low-intensity pulsed ultrasound enhances the cytotoxicity of curcumin involving apoptosis induction and cell motility inhibition in human breast cancer MDA-MB-231 cells.

PubMed

Li, Yixiang; Wang, Pan; Chen, Xiyang; Hu, Jianmin; Liu, Yichen; Wang, Xiaobing; Liu, Quanhong

2016-11-01

Ultrasound and microbubbles-mediated drug delivery has become a promising strategy to promote drug delivery and its therapeutic efficacy. The aim of this research was to assess the effects of microbubbles (MBs)-combined low-intensity pulsed ultrasound (LPUS) on the delivery and cytotoxicity of curcumin (Cur) to human breast cancer MDA-MB-231 cells. Under the experimental condition, MBs raised the level of acoustic cavitation and enhanced plasma membrane permeability; and cellular uptake of Cur was notably improved by LPUS-MBs treatment, aggravating Cur-induced MDA-MB-231 cells death. The combined treatment markedly caused more obvious changes of cell morphology, F-actin cytoskeleton damage and cell migration inhibition. Our results demonstrated that combination of MBs and LPUS may be an efficient strategy for improving anti-tumor effect of Cur, suggesting a potential effective method for antineoplastic therapy. Copyright © 2016 Elsevier B.V. All rights reserved.

Passive microlesion detection and mapping for treatment of hypertrophic cardiomyopathy

NASA Astrophysics Data System (ADS)

Zhu, Yiying I.; Miller, Douglas L.; Dou, Chunyan; Kripfgans, Oliver D.

2017-03-01

Intermittent high intensity ultrasound pulses with circulating contrast agent microbubbles can induce scattered microlesions of potential value for myocardial reduction therapy. This paper presents an in vitro setup imitating the treatment for monitoring development. A preclinical imaging system with a single element transducer, synchronization and receive-only imaging transducer array has been implemented on a research platform. Contrast agent microbubbles pumped in a dialysis tubing setup were exposed to high intensity focused ultrasound at 1.0/3.5 MHz center frequencies. Polystyrene spheres were employed as linear scatterers compared to contrast agents for system transfer function equalization. A cavitation mapping technique was employed to spatially locate and depict microbubble activity during treatment. For high acoustic pressure amplitudes a 5 dB difference between contrast agent and solid spheres was observed and spatially mapped. The in-plane resolution was 4.5 mm for axial and 1.5 mm laterally. In the future, this cavitation detection scheme will be applied to monitor in vivo microlesioning in real-time.

Mie scattering off coated microbubbles

NASA Astrophysics Data System (ADS)

Nelissen, Radboud; Koene, Elmer; Hilgenfeldt, Sascha; Versluis, Michel

2002-11-01

The acoustic behavior of coated microbubbles depends on parameters of the shell coating, which are in turn dependent on bubble size. More intimate knowledge of this size dependence is required for an improved modeling of a distribution of coated microbubbles such as found in ultrasound contrast agents (UCA). Here a setup is designed to simultaneously measure the optical and acoustic response of an ultrasound-driven single bubble contained in a capillary or levitated by the pressure field of a focused transducer. Optical detection is done by Mie scattering through an inverted microscope. Acoustical detection of the single bubble by a receiving transducer is made possible because of the large working distance of the microscope. For Mie scattering investigation of excited bubbles, two regimes can be distinguished, which require different detection techniques: Conventional wide-angle detection through the microscope objective is sufficient for bubbles of radius exceeding 10 mum. For smaller bubbles, two narrow-aperture detectors are used to reconstruct the bubble dynamics from the complex angle-dependence of the scattered light.

Coupled dynamics of translation and collapse of acoustically driven microbubbles.

PubMed

Reddy, Anil J; Szeri, Andrew J

2002-10-01

Pressure gradients drive the motion of microbubbles relative to liquids in which they are suspended. Examples include the hydrostatic pressure due to a gravitational field, and the pressure gradients in a sound field, useful for acoustic levitation. In this paper, the equations describing the coupled dynamics of radial oscillation and translation of a microbubble are given. The formulation is based on a recently derived expression for the hydrodynamic force on a bubble of changing size in an incompressible liquid [J. Magnaudet and D. Legendre, Phys. Fluids 10, 550-556 (1998)]. The complex interaction between radial and translation dynamics is best understood by examination of the added momentum associated with the liquid motion caused by the moving bubble. Translation is maximized when the bubble collapses violently. The new theory for coupled collapse and translation dynamics is compared to past experiments and to previous theories for decoupled translation dynamics. Special attention is paid to bubbles of relevance in biomedical applications.

Aggregate formation affects ultrasonic disruption of microalgal cells.

PubMed

Wang, Wei; Lee, Duu-Jong; Lai, Juin-Yih

2015-12-01

Ultrasonication is a cell disruption process of low energy efficiency. This study dosed K(+), Ca(2+) and Al(3+) to Chlorella vulgaris cultured in Bold's Basal Medium at 25°C and measured the degree of cell disruption under ultrasonication. Adding these metal ions yielded less negatively charged surfaces of cells, while with the latter two ions large and compact cell aggregates were formed. The degree of cell disruption followed: control=K(+)>Ca(2+)>Al(3+) samples. Surface charges of cells and microbubbles have minimal effects on the microbubble number in the proximity of the microalgal cells. Conversely, cell aggregates with large size and compact interior resist cell disruption under ultrasonication. Staining tests revealed high diffusional resistance of stains over the aggregate interior. Microbubbles may not be effective generated and collapsed inside the compact aggregates, hence leading to low cell disruption efficiencies. Effective coagulation/flocculation in cell harvesting may lead to adverse effect on subsequent cell disruption efficiency. Copyright © 2015 Elsevier Ltd. All rights reserved.

Targeted microbubbles with ultrasound irradiation and PD-1 inhibitor to increase antitumor activity in B-cell lymphoma.

PubMed

Zheng, Shiya; Song, Dan; Jin, Xiaoxiao; Zhang, Haijun; Aldarouish, Mohanad; Chen, Yan; Wang, Cailian

2018-02-01

Severe cardiac toxicity of doxorubicin and an immunosuppressive tumor micro-environment become main obstacles for the effective treatment of B-cell lymphoma. In this research, rituximab-conjugated and doxorubicin-loaded microbubbles (RDMs) were designed for exploring a combination approach of targeted microbubbles with ultrasound (US) irradiation and PD-1 inhibitor to overcome obstacles mentioned above. In vivo studies were performed on SU-DHL-4 cell-grafted mice and ex vivo studies were performed on CD20 + human SU-DHL-4 cells and human T cells. A greater therapeutic effect and higher expression of PD-L1 protein expression were obtained with RDMs with US irradiation in vivo. A significant inhibitory effect on SU-DHL-4 B-cell lymphoma cells was observed after treated by RDMs with US irradiation and PD-1 inhibitor ex vivo. Combination of RDMs with US irradiation and PD-1 inhibitor could be a promising therapeutic strategy for B-cell lymphoma.

The dynamic behavior of microbubbles during long ultrasound tone-burst excitation: mechanistic insights into ultrasound-microbubble mediated therapeutics using high-speed imaging and cavitation detection

PubMed Central

Pacella, John J.; Villanueva, Flordeliza S.

2015-01-01

Ultrasound (US)-microbubble (MB) mediated therapies have been shown to restore perfusion and enhance drug/gene delivery. Due to the presumption that MBs do not persist during long US exposure under high acoustic pressures, most schemes utilize short US pulses when a high US pressure is employed. However, we recently observed an enhanced thrombolytic effect using long US pulses at high acoustic pressures. Therefore we explored the fate of MBs during long tone-burst exposures (5 ms) at various acoustic pressures and MB concentrations via direct high-speed optical observation and passive cavitation detection. MBs first underwent stable or inertial cavitation depending on the acoustic pressure, and then formed gas-filled clusters that continued to oscillate, break up, and form new clusters. Cavitation detection confirmed continued, albeit diminishing acoustic activity throughout the 5-ms US excitation. These data suggest that persisting cavitation activity during long tone-bursts may confer additional therapeutic effects. PMID:26603628

Selective detection of cavitation bubbles by triplet pulse sequence in high-intensity focused ultrasound treatment

NASA Astrophysics Data System (ADS)

Iwasaki, Ryosuke; Nagaoka, Ryo; Yoshizawa, Shin; Umemura, Shin-ichiro

2018-07-01

Acoustic cavitation bubbles are known to enhance the heating effect in high-intensity focused ultrasound (HIFU) treatment. The detection of cavitation bubbles with high sensitivity and selectivity is required to predict the therapeutic and side effects of cavitation, and ensure the efficacy and safety of the treatment. A pulse inversion (PI) technique has been widely used for imaging microbubbles through enhancing the second-harmonic component of echo signals. However, it has difficulty in separating the nonlinear response of microbubbles from that due to nonlinear propagation. In this study, a triplet pulse (3P) method was investigated to specifically image cavitation bubbles by extracting the 1.5th fractional harmonic component. The proposed 3P method depicted cavitation bubbles with a contrast ratio significantly higher than those in conventional imaging methods with and without PI. The results suggest that the 3P method is effective for specifically detecting microbubbles in cavitation-enhanced HIFU treatment.

Apparatus for oil shale retorting

DOEpatents

Lewis, Arthur E.; Braun, Robert L.; Mallon, Richard G.; Walton, Otis R.

1986-01-01

A cascading bed retorting process and apparatus in which cold raw crushed shale enters at the middle of a retort column into a mixer stage where it is rapidly mixed with hot recycled shale and thereby heated to pyrolysis temperature. The heated mixture then passes through a pyrolyzer stage where it resides for a sufficient time for complete pyrolysis to occur. The spent shale from the pyrolyzer is recirculated through a burner stage where the residual char is burned to heat the shale which then enters the mixer stage.

Isolation of campesteryl ferulate and epi-campesteryl ferulate, two components of γ-oryzanol from rice bran.

PubMed

Bao, Yuhua; Yanase, Emiko; Nakatsuka, Shin-ichi

2013-01-01

Campesteryl ferulate (3a, 24R/α) and epi-campesteryl ferulate (3b, 24S/β), components of rice bran γ-oryzanol, were isolated by the preparative recycle HPLC system using a combination of ODS silica and cholester packed columns at over 99% purity. Their purities and structures of 3a and 3b thus obtained were confirmed by HPLC analysis and physical data (1H- and 13C-NMR, MS spectra, and X-ray crystallography).

Recycling used palm oil and used engine oil to produce white bio oil, bio petroleum diesel and heavy fuel

NASA Astrophysics Data System (ADS)

Al-abbas, Mustafa Hamid; Ibrahim, Wan Aini Wan; Sanagi, Mohd. Marsin

2012-09-01

Recycling waste materials produced in our daily life is considered as an additional resource of a wide range of materials and it conserves the environment. Used engine oil and used cooking oil are two oils disposed off in large quantities as a by-product of our daily life. This study aims at providing white bio oil, bio petroleum diesel and heavy fuel from the disposed oils. Toxic organic materials suspected to be present in the used engine oil were separated using vacuum column chromatography to reduce the time needed for the separation process and to avoid solvent usage. The compounds separated were detected by gas chromatography-mass spectrometry (GC-MS) and found to contain toxic aromatic carboxylic acids. Used cooking oils (thermally cracked from usage) were collected and separated by vacuum column chromatography. White bio oil produced was examined by GC-MS. The white bio oil consists of non-toxic hydrocarbons and is found to be a good alternative to white mineral oil which is significantly used in food industry, cosmetics and drugs with the risk of containing polycyclic aromatic compounds which are carcinogenic and toxic. Different portions of the used cooking oil and used engine were mixed to produce several blends for use as heavy oil fuels. White bio oil was used to produce bio petroleum diesel by blending it with petroleum diesel and kerosene. The bio petroleum diesel produced passed the PETRONAS flash point and viscosity specification test. The heat of combustion of the two blends of heavy fuel produced was measured and one of the blends was burned to demonstrate its burning ability. Higher heat of combustion was obtained from the blend containing greater proportion of used engine oil. This study has provided a successful recycled alternative for white bio oil, bio petroleum fuel and diesel which can be an energy source.

Fate and transport of selected estrogen compounds in Hawaii soils: effect of soil type and macropores.

PubMed

D'Alessio, Matteo; Vasudevan, Dharni; Lichwa, Joseph; Mohanty, Sanjay K; Ray, Chittaranjan

2014-10-01

The fate and transport of estrogen compounds in the environment is of increasing concern due to their potential impact on freshwater organisms, ecosystems and human health. The behavior of these compounds in batch experiments suggests low mobility, while field studies indicate the persistence of estrogen compounds in the soil with the possibility of migration to surface water as well as groundwater. To better understand the movement of these chemicals through soils, we examined their transport in three different Hawaiian soils and two aqueous matrices. The three different soils used were an Oxisol, a Mollisol and a cinder, characterized by different mineralogical properties and collected at depths of 60-90 cm and 210-240 cm. Two liquid matrices were used; deionized (DI) water containing calcium chloride (CaCl2), and recycled water collected from a wastewater treatment facility. The experiments were conducted in packed and structured columns. Non-equilibrium conditions were observed during the study, especially in the structured soil. This is believed to be primarily related to the presence of macropores in the soil. The presence of macropores resulted in reduced contact time between soil and estrogens, which facilitated their transport. We found that the organic carbon content and mineralogical composition of the soils had a profound effect on the transport of the estrogens. The mobility of estrone (E1) and 17β-estradiol (E2) was greater in cinder than in the other soils. In column experiments with recycled water, earlier breakthrough peaks and longer tails of estrogens were produced compared to those observed using DI water. The use of recycled water for agricultural purposes and the siting of septic tanks and cesspools should be critically reviewed in light of these findings, especially in areas where groundwater is the primary source of potable water, such as Hawaii. Copyright © 2014 Elsevier B.V. All rights reserved.

Fate and transport of selected estrogen compounds in Hawaii soils: Effect of soil type and macropores

NASA Astrophysics Data System (ADS)

D'Alessio, Matteo; Vasudevan, Dharni; Lichwa, Joseph; Mohanty, Sanjay K.; Ray, Chittaranjan

2014-10-01

The fate and transport of estrogen compounds in the environment is of increasing concern due to their potential impact on freshwater organisms, ecosystems and human health. The behavior of these compounds in batch experiments suggests low mobility, while field studies indicate the persistence of estrogen compounds in the soil with the possibility of migration to surface water as well as groundwater. To better understand the movement of these chemicals through soils, we examined their transport in three different Hawaiian soils and two aqueous matrices. The three different soils used were an Oxisol, a Mollisol and a cinder, characterized by different mineralogical properties and collected at depths of 60-90 cm and 210-240 cm. Two liquid matrices were used; deionized (DI) water containing calcium chloride (CaCl2), and recycled water collected from a wastewater treatment facility. The experiments were conducted in packed and structured columns. Non-equilibrium conditions were observed during the study, especially in the structured soil. This is believed to be primarily related to the presence of macropores in the soil. The presence of macropores resulted in reduced contact time between soil and estrogens, which facilitated their transport. We found that the organic carbon content and mineralogical composition of the soils had a profound effect on the transport of the estrogens. The mobility of estrone (E1) and 17β-estradiol (E2) was greater in cinder than in the other soils. In column experiments with recycled water, earlier breakthrough peaks and longer tails of estrogens were produced compared to those observed using DI water. The use of recycled water for agricultural purposes and the siting of septic tanks and cesspools should be critically reviewed in light of these findings, especially in areas where groundwater is the primary source of potable water, such as Hawaii.

Improving Sensitivity in Ultrasound Molecular Imaging by Tailoring Contrast Agent Size Distribution: In Vivo Studies

PubMed Central

Streeter, Jason E.; Gessner, Ryan; Miles, Iman; Dayton, Paul A.

2010-01-01

Molecular imaging with ultrasound relies on microbubble contrast agents (MCAs) selectively adhering to a ligand-specific target. Prior studies have shown that only small quantities of microbubbles are retained at their target sites, therefore, enhancing contrast sensitivity to low concentrations of microbubbles is essential to improve molecular imaging techniques. In order to assess the effect of MCA diameter on imaging sensitivity, perfusion and molecular imaging studies were performed with microbubbles of varying size distributions. To assess signal improvement and MCA circulation time as a function of size and concentration, blood perfusion was imaged in rat kidneys using nontargeted size-sorted MCAs with a Siemens Sequoia ultrasound system (Siemans, Mountain View, CA) in cadence pulse sequencing (CPS) mode. Molecular imaging sensitivity improvements were studied with size-sorted αvβ3-targeted bubbles in both fibrosarcoma and R3230 rat tumor models. In perfusion imaging studies, video intensity and contrast persistence was ≈8 times and ≈3 times greater respectively, for “sorted 3-micron” MCAs (diameter, 3.3 ± 1.95 μm) when compared to “unsorted” MCAs (diameter, 0.9 ± 0.45 μm) at low concentrations. In targeted experiments, application of sorted 3-micron MCAs resulted in a ≈20 times video intensity increase over unsorted populations. Tailoring size-distributions results in substantial imaging sensitivity improvement over unsorted populations, which is essential in maximizing sensitivity to small numbers of MCAs for molecular imaging. PMID:20236606

Delivery of Hydrogen Sulfide by Ultrasound Targeted Microbubble Destruction Attenuates Myocardial Ischemia-reperfusion Injury

PubMed Central

Chen, Gangbin; Yang, Li; Zhong, Lintao; Kutty, Shelby; Wang, Yuegang; Cui, Kai; Xiu, Jiancheng; Cao, Shiping; Huang, Qiaobing; Liao, Wangjun; Liao, Yulin; Wu, Juefei; Zhang, Wenzhu; Bin, Jianping

2016-01-01

Hydrogen sulfide (H2S) is an attractive agent for myocardial ischemia-reperfusion injury, however, systemic delivery of H2S may cause unwanted side effects. Ultrasound targeted microbubble destruction has become a promising tool for organ specific delivery of bioactive substance. We hypothesized that delivery of H2S by ultrasound targeted microbubble destruction attenuates myocardial ischemia-reperfusion injury and could avoid unwanted side effects. We prepared microbubbles carrying hydrogen sulfide (hs-MB) with different H2S/C3F8 ratios (4/0, 3/1, 2/2, 1/3, 0/4) and determined the optimal ratio. Release of H2S triggered by ultrasound was investigated. The cardioprotective effect of ultrasound targeted hs-MB destruction was investigated in a rodent model of myocardial ischemia-reperfusion injury. The H2S/C3F8 ratio of 2/2 was found to be an optimal ratio to prepare stable hs-MB with higher H2S loading capability. Ultrasound targeted hs-MB destruction triggered H2S release and increased the concentration of H2S in the myocardium and lung. Ultrasound targeted hs-MB destruction limited myocardial infarct size, preserved left ventricular function and had no influence on haemodynamics and respiratory. This cardioprotective effect was associated with alleviation of apoptosis and oxidative stress. Delivery of H2S to the myocardium by ultrasound targeted hs-MB destruction attenuates myocardial ischemia-reperfusion injury and may avoid unwanted side effects. PMID:27469291

The Effect of Short Duration Ultrasound Pulses on the Interaction Between Individual Microbubbles and Fibrin Clots.

PubMed

Acconcia, Christopher; Leung, Ben Y C; Manjunath, Anoop; Goertz, David E

2015-10-01

In previous work, we examined microscale interactions between microbubbles and fibrin clots under exposure to 1 ms ultrasound pulses. This provided direct evidence that microbubbles were capable of deforming clot boundaries and penetrating into clots, while also affecting fluid uptake and inducing fibrin network damage. Here, we investigate the effect of short duration (15 μs) pulses on microscale bubble-clot interactions as function of bubble diameter (3-9 μm) and pressure. Individual microbubbles (n = 45) were placed at the clot boundary with optical tweezers and exposed to 1 MHz ultrasound. High-speed (10 kfps) imaging and 2-photon microscopy were performed during and after exposure, respectively. While broadly similar phenomena were observed as in the 1 ms pulse case (i.e., bubble penetration, network damage and fluid uptake), substantial quantitative differences were present. The pressure threshold for bubble penetration was increased from 0.39 MPa to 0.6 MPa, and those bubbles that did enter clots had reduced penetration depths and were associated with less fibrin network damage and nanobead uptake. This appeared to be due in large part to increased bubble shrinkage relative to the 1 ms pulse case. Stroboscopic imaging was performed on a subset of bubbles (n = 11) and indicated that complex bubble oscillations can occur during this process. Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

In vivo ultrasound visualization of non-occlusive blood clots with thrombin-sensitive contrast agents.

PubMed

Nakatsuka, Matthew A; Barback, Christopher V; Fitch, Kirsten R; Farwell, Alexander R; Esener, Sadik C; Mattrey, Robert F; Cha, Jennifer N; Goodwin, Andrew P

2013-12-01

The use of microbubbles as ultrasound contrast agents is one of the primary methods to diagnose deep venous thrombosis. However, current microbubble imaging strategies require either a clot sufficiently large to produce a circulation filling defect or a clot with sufficient vascularization to allow for targeted accumulation of contrast agents. Previously, we reported the design of a microbubble formulation that modulated its ability to generate ultrasound contrast from interaction with thrombin through incorporation of aptamer-containing DNA crosslinks in the encapsulating shell, enabling the measurement of a local chemical environment by changes in acoustic activity. However, this contrast agent lacked sufficient stability and lifetime in blood to be used as a diagnostic tool. Here we describe a PEG-stabilized, thrombin-activated microbubble (PSTA-MB) with sufficient stability to be used in vivo in circulation with no change in biomarker sensitivity. In the presence of actively clotting blood, PSTA-MBs showed a 5-fold increase in acoustic activity. Specificity for the presence of thrombin and stability under constant shear flow were demonstrated in a home-built in vitro model. Finally, PSTA-MBs were able to detect the presence of an active clot within the vena cava of a rabbit sufficiently small as to not be visible by current non-specific contrast agents. By activating in non-occlusive environments, these contrast agents will be able to detect clots not diagnosable by current contrast agents. Copyright © 2013 Elsevier Ltd. All rights reserved.

Contrast Ultrasound Targeted Treatment of Gliomas in Mice via Drug-Bearing Nanoparticle Delivery and Microvascular Ablation

PubMed Central

Burke, Caitlin W.; Price, Richard J.

2010-01-01

We are developing minimally-invasive contrast agent microbubble based therapeutic approaches in which the permeabilization and/or ablation of the microvasculature are controlled by varying ultrasound pulsing parameters. Specifically, we are testing whether such approaches may be used to treat malignant brain tumors through drug delivery and microvascular ablation. Preliminary studies have been performed to determine whether targeted drug-bearing nanoparticle delivery can be facilitated by the ultrasound mediated destruction of "composite" delivery agents comprised of 100nm poly(lactide-co-glycolide) (PLAGA) nanoparticles that are adhered to albumin shelled microbubbles. We denote these agents as microbubble-nanoparticle composite agents (MNCAs). When targeted to subcutaneous C6 gliomas with ultrasound, we observed an immediate 4.6-fold increase in nanoparticle delivery in MNCA treated tumors over tumors treated with microbubbles co-administered with nanoparticles and a 8.5 fold increase over non-treated tumors. Furthermore, in many cancer applications, we believe it may be desirable to perform targeted drug delivery in conjunction with ablation of the tumor microcirculation, which will lead to tumor hypoxia and apoptosis. To this end, we have tested the efficacy of non-theramal cavitation-induced microvascular ablation, showing that this approach elicits tumor perfusion reduction, apoptosis, significant growth inhibition, and necrosis. Taken together, these results indicate that our ultrasound-targeted approach has the potential to increase therapeutic efficiency by creating tumor necrosis through microvascular ablation and/or simultaneously enhancing the drug payload in gliomas. PMID:21206463

Contrast ultrasound targeted treatment of gliomas in mice via drug-bearing nanoparticle delivery and microvascular ablation.

PubMed

Burke, Caitlin W; Price, Richard J

2010-12-15

We are developing minimally-invasive contrast agent microbubble based therapeutic approaches in which the permeabilization and/or ablation of the microvasculature are controlled by varying ultrasound pulsing parameters. Specifically, we are testing whether such approaches may be used to treat malignant brain tumors through drug delivery and microvascular ablation. Preliminary studies have been performed to determine whether targeted drug-bearing nanoparticle delivery can be facilitated by the ultrasound mediated destruction of "composite" delivery agents comprised of 100nm poly(lactide-co-glycolide) (PLAGA) nanoparticles that are adhered to albumin shelled microbubbles. We denote these agents as microbubble-nanoparticle composite agents (MNCAs). When targeted to subcutaneous C6 gliomas with ultrasound, we observed an immediate 4.6-fold increase in nanoparticle delivery in MNCA treated tumors over tumors treated with microbubbles co-administered with nanoparticles and a 8.5 fold increase over non-treated tumors. Furthermore, in many cancer applications, we believe it may be desirable to perform targeted drug delivery in conjunction with ablation of the tumor microcirculation, which will lead to tumor hypoxia and apoptosis. To this end, we have tested the efficacy of non-theramal cavitation-induced microvascular ablation, showing that this approach elicits tumor perfusion reduction, apoptosis, significant growth inhibition, and necrosis. Taken together, these results indicate that our ultrasound-targeted approach has the potential to increase therapeutic efficiency by creating tumor necrosis through microvascular ablation and/or simultaneously enhancing the drug payload in gliomas.

Real-time ultrasound angiography using superharmonic dual-frequency (2.25MHz/30MHz) cylindrical array: In vitro study.

PubMed

Wang, Zhuochen; Martin, K Heath; Dayton, Paul A; Jiang, Xiaoning

2018-01-01

Recent studies suggest that dual-frequency intravascular ultrasound (IVUS) transducers allow detection of superharmonic bubble signatures, enabling acoustic angiography for microvascular and molecular imaging. In this paper, a dual-frequency IVUS cylindrical array transducer was developed for real-time superharmonic imaging. A reduced form-factor lateral mode transmitter (2.25MHz) was used to excite microbubbles effectively at 782kPa with single-cycle excitation while still maintaining the small size and low profile (5Fr) (3Fr=1mm) for intravascular imaging applications. Superharmonic microbubble responses generated in simulated microvessels were captured by the high frequency receiver (30MHz). The axial and lateral full-width half-maximum of microbubbles in a 200-μm-diameter cellulose tube were measured to be 162μm and 1039μm, respectively, with a contrast-to-noise ratio (CNR) of 16.6dB. Compared to our previously reported single-element IVUS transducers, this IVUS array design achieves a higher CNR (16.6dBvs 11dB) and improved axial resolution (162μmvs 616μm). The results show that this dual-frequency IVUS array transducer with a lateral-mode transmitter can fulfill the native design requirement (∼3-5Fr) for acoustic angiography by generating nonlinear microbubble responses as well as detecting their superharmonic responses in a 5Fr form factor. Copyright © 2017 Elsevier B.V. All rights reserved.

Microbubble Cavitation Imaging

PubMed Central

Vignon, Francois; Shi, William T.; Powers, Jeffry E.; Everbach, E. Carr; Liu, Jinjin; Gao, Shunji; Xie, Feng; Porter, Thomas R.

2014-01-01

Ultrasound cavitation of microbubble contrast agents has a potential for therapeutic applications such as sonothrombolysis (STL) in acute ischemic stroke. For safety, efficacy, and reproducibility of treatment, it is critical to evaluate the cavitation state (moderate oscillations, stable cavitation, and inertial cavitation) and activity level in and around a treatment area. Acoustic passive cavitation detectors (PCDs) have been used to this end but do not provide spatial information. This paper presents a prototype of a 2-D cavitation imager capable of producing images of the dominant cavitation state and activity level in a region of interest. Similar to PCDs, the cavitation imaging described here is based on the spectral analysis of the acoustic signal radiated by the cavitating microbubbles: ultraharmonics of the excitation frequency indicate stable cavitation, whereas elevated noise bands indicate inertial cavitation; the absence of both indicates moderate oscillations. The prototype system is a modified commercially available ultrasound scanner with a sector imaging probe. The lateral resolution of the system is 1.5 mm at a focal depth of 3 cm, and the axial resolution is 3 cm for a therapy pulse length of 20 µs. The maximum frame rate of the prototype is 2 Hz. The system has been used for assessing and mapping the relative importance of the different cavitation states of a microbubble contrast agent. In vitro (tissue-mimicking flow phantom) and in vivo (heart, liver, and brain of two swine) results for cavitation states and their changes as a function of acoustic amplitude are presented. PMID:23549527

Temporal effect of inertial cavitation with and without microbubbles on surface deformation of agarose S gel in the presence of 1-MHz focused ultrasound.

PubMed

Tomita, Y; Matsuura, T; Kodama, T

2015-01-01

Sonoporation has the potential to deliver extraneous molecules into a target tissue non-invasively. There have been numerous investigations of cell membrane permeabilization induced by microbubbles, but very few studies have been carried out to investigate sonoporation by inertial cavitation, especially from a temporal perspective. In the present paper, we show the temporal variations in nano/micro-pit formations following the collapse of inertial cavitation bubbles, with and without Sonazoid® microbubbles. Using agarose S gel as a target material, erosion experiments were conducted in the presence of 1-MHz focused ultrasound applied for various exposure times, Tex (0.002-60 s). Conventional microscopy was used to measure temporal variations in micrometer-scale pit numbers, and atomic force microscopy utilized to detect surface roughness on a nanometer scale. The results demonstrated that nanometer-scale erosion was predominantly caused by Sonazoid® microbubbles and C4F10 gas bubbles for 0.002 s

Computational analysis of microbubble flows in bifurcating airways: role of gravity, inertia, and surface tension.

PubMed

Chen, Xiaodong; Zielinski, Rachel; Ghadiali, Samir N

2014-10-01

Although mechanical ventilation is a life-saving therapy for patients with severe lung disorders, the microbubble flows generated during ventilation generate hydrodynamic stresses, including pressure and shear stress gradients, which damage the pulmonary epithelium. In this study, we used computational fluid dynamics to investigate how gravity, inertia, and surface tension influence both microbubble flow patterns in bifurcating airways and the magnitude/distribution of hydrodynamic stresses on the airway wall. Direct interface tracking and finite element techniques were used to simulate bubble propagation in a two-dimensional (2D) liquid-filled bifurcating airway. Computational solutions of the full incompressible Navier-Stokes equation were used to investigate how inertia, gravity, and surface tension forces as characterized by the Reynolds (Re), Bond (Bo), and Capillary (Ca) numbers influence pressure and shear stress gradients at the airway wall. Gravity had a significant impact on flow patterns and hydrodynamic stress magnitudes where Bo > 1 led to dramatic changes in bubble shape and increased pressure and shear stress gradients in the upper daughter airway. Interestingly, increased pressure gradients near the bifurcation point (i.e., carina) were only elevated during asymmetric bubble splitting. Although changes in pressure gradient magnitudes were generally more sensitive to Ca, under large Re conditions, both Re and Ca significantly altered the pressure gradient magnitude. We conclude that inertia, gravity, and surface tension can all have a significant impact on microbubble flow patterns and hydrodynamic stresses in bifurcating airways.

Safety of Microbubbles and Transcranial Ultrasound in Rabbits

NASA Astrophysics Data System (ADS)

Culp, William C.; Brown, Aliza T.; Hennings, Leah; Lowery, John; Culp, Benjamin C.; Erdem, Eren; Roberson, Paula; Matsunaga, Terry O.

2007-05-01

The object of this study was to evaluate the safety of large doses of microbubbles and ultrasound administered to the head of rabbits as if they were receiving acute stroke therapy of a similar nature. Materials and Methods: Female New Zealand White rabbits were used, N=24, in three groups 1] n=4 control (no treatment), 2] n=10 bubble control (ultrasound plus aspirin), and 3] n=10 target group (ultrasound plus aspirin plus MRX-815 microbubbles). Group 3 was infused with IV bubbles over 1 hour at 0.16cc/kg. Ultrasound was delivered to the dehaired side of the head during bubble infusion and for 1 additional hour at 0.8 W/cm2 20% pulsed wave. Rabbits survived for 22 to 24 hours, were imaged with computerized tomography and 3 Tesla magnetic resonance imaging including contrast studies, and sacrificed. Tetrazolium (TTC) and Hematoxylin and Eosin (H&E) sections were made for pathological examination. Results: All 24 animals showed absence of bleeding, endothelial damage, EKG abnormalities, stroke, blood-brain-barrier breakdown, or other acute abnormalities. CT and MRI showed no bleeding or signs of stroke, but two animals had mild hydrocephalus. The EKGs showed normal variation in QTc. Rabbit behavior was normal in all. Minimal chronic inflammation unrelated to the study was seen in 5. Two animals were excluded because of protocol violations and replaced during the study. Conclusion: The administered dose of microbubbles and ultrasound demonstrated no detrimental effects on the healthy rabbit animal model.

Engineering brown fat into skeletal muscle using ultrasound-targeted microbubble destruction gene delivery in obese Zucker rats: Proof of concept design.

PubMed

Bastarrachea, Raul A; Chen, Jiaxi; Kent, Jack W; Nava-Gonzalez, Edna J; Rodriguez-Ayala, Ernesto; Daadi, Marcel M; Jorge, Barbara; Laviada-Molina, Hugo; Comuzzie, Anthony G; Chen, Shuyuan; Grayburn, Paul A

2017-09-01

Ultrasound-targeted microbubble destruction (UTMD) is a novel means of tissue-specific gene delivery. This approach systemically infuses transgenes precoupled to gas-filled lipid microbubbles that are burst within the microvasculature of target tissues via an ultrasound signal resulting in release of DNA and transfection of neighboring cells within the tissue. Previous work has shown that adenovirus containing cDNA of UCP-1, injected into the epididymal fat pads in mice, induced localized fat depletion, improving glucose tolerance, and decreasing food intake in obese diabetic mice. Our group recently demonstrated that gene therapy by UTMD achieved beta cell regeneration in streptozotocin (STZ)-treated mice and baboons. We hypothesized that gene therapy with BMP7/PRDM16/PPARGC1A in skeletal muscle (SKM) of obese Zucker diabetic fatty (fa/fa) rats using UTMD technology would produce a brown adipose tissue (BAT) phenotype with UCP-1 overexpression. This study was designed as a proof of concept (POC) project. Obese Zucker rats were administered plasmid cDNA contructs encoding a gene cocktail with BMP7/PRDM16/PPARGC1A incorporated within microbubbles and intravenously delivered into their left thigh. Controls received UTMD with plasmids driving a DsRed reporter gene. An ultrasound transducer was directed to the thigh to disrupt the microbubbles within the microcirculation. Blood samples were drawn at baseline, and after treatment to measure glucose, insulin, and free fatty acids levels. SKM was harvested for immunohistochemistry (IHC). Our IHC results showed a reliable pattern of effective UTMD-based gene delivery in enhancing SKM overexpression of the UCP-1 gene. This clearly indicates that our plasmid DNA construct encoding the gene combination of PRDM16, PPARGC1A, and BMP7 reprogrammed adult SKM tissue into brown adipose cells in vivo. Our pilot established POC showing that the administration of the gene cocktail to SKM in this rat model of genetic obesity using UTMD gene therapy, engineered a BAT phenotype with UCP-1 over-expression. © 2017 IUBMB Life, 69(9):745-755, 2017. © 2017 International Union of Biochemistry and Molecular Biology.

A multi-frequency sparse hemispherical ultrasound phased array for microbubble-mediated transcranial therapy and simultaneous cavitation mapping

NASA Astrophysics Data System (ADS)

Deng, Lulu; O'Reilly, Meaghan A.; Jones, Ryan M.; An, Ran; Hynynen, Kullervo

2016-12-01

Focused ultrasound (FUS) phased arrays show promise for non-invasive brain therapy. However, the majority of them are limited to a single transmit/receive frequency and therefore lack the versatility to expose and monitor the treatment volume. Multi-frequency arrays could offer variable transmit focal sizes under a fixed aperture, and detect different spectral content on receive for imaging purposes. Here, a three-frequency (306, 612, and 1224 kHz) sparse hemispherical ultrasound phased array (31.8 cm aperture; 128 transducer modules) was constructed and evaluated for microbubble-mediated transcranial therapy and simultaneous cavitation mapping. The array is able to perform effective electronic beam steering over a volume spanning (-40, 40) and (-30, 50) mm in the lateral and axial directions, respectively. The focal size at the geometric center is approximately 0.9 (2.1) mm, 1.7 (3.9) mm, and 3.1 (6.5) mm in lateral (axial) pressure full width at half maximum (FWHM) at 1224, 612, and 306 kHz, respectively. The array was also found capable of dual-frequency excitation and simultaneous multi-foci sonication, which enables the future exploration of more complex exposure strategies. Passive acoustic mapping of dilute microbubble clouds demonstrated that the point spread function of the receive array has a lateral (axial) intensity FWHM between 0.8-3.5 mm (1.7-11.7 mm) over a volume spanning (-25, 25) mm in both the lateral and axial directions, depending on the transmit/receive frequency combination and the imaging location. The device enabled both half and second harmonic imaging through the intact skull, which may be useful for improving the contrast-to-tissue ratio or imaging resolution, respectively. Preliminary in vivo experiments demonstrated the system’s ability to induce blood-brain barrier opening and simultaneously spatially map microbubble cavitation activity in a rat model. This work presents a tool to investigate optimal strategies for non-thermal FUS brain therapy and concurrent microbubble cavitation monitoring through the availability of multiple frequencies.

A multi-frequency sparse hemispherical ultrasound phased array for microbubble-mediated transcranial therapy and simultaneous cavitation mapping

PubMed Central

Deng, Lulu; O'Reilly, Meaghan A.; Jones, Ryan M.; An, Ran; Hynynen, Kullervo

2016-01-01

Focused ultrasound (FUS) phased arrays show promise for non-invasive brain therapy. However, the majority of them are limited to a single transmit/receive frequency and therefore lack the versatility to expose and monitor the treatment volume. Multi-frequency arrays could offer variable transmit focal sizes under a fixed aperture, and detect different spectral content on receive for imaging purposes. Here, a three-frequency (306, 612 and 1224 kHz) sparse hemispherical ultrasound phased array (31.8 cm aperture; 128 transducer modules) was constructed and evaluated for microbubble-mediated transcranial therapy and simultaneous cavitation mapping. The array is able to perform effective electronic beam steering over a volume spanning [−40, 40] and [−30, 50] mm in the lateral and axial directions, respectively. The focal size at the geometric center is approximately 0.9 (2.1) mm, 1.7 (3.9) mm, and 3.1 (6.5) mm in lateral (axial) pressure full width at half maximum (FWHM) at 1224, 612, and 306 kHz, respectively. The array was also found capable of dual-frequency excitation and simultaneous multi–foci sonication, which enables the future exploration of more complex exposure strategies. Passive acoustic mapping of dilute microbubble clouds demonstrated that the point spread function of the receive array has a lateral (axial) intensity FWHM between 0.8-3.5 mm (1.7-11.7 mm) over a volume spanning [−25, 25] mm in both the lateral and axial directions, depending on the transmit/receive frequency combination and the imaging location. The device enabled both half and second harmonic imaging through the intact skull, which may be useful for improving the contrast-to-tissue ratio or imaging resolution, respectively. Preliminary in-vivo experiments demonstrated the system's ability to induce blood-brain barrier opening and simultaneously spatially map microbubble cavitation activity in a rat model. This work presents a tool to investigate optimal strategies for non-thermal FUS brain therapy and concurrent microbubble cavitation monitoring through the availability of multiple frequencies. PMID:27845920

Assessment of Molecular Acoustic Angiography for Combined Microvascular and Molecular Imaging in Preclinical Tumor Models

PubMed Central

Lindsey, Brooks D.; Shelton, Sarah E.; Foster, F. Stuart; Dayton, Paul A.

2017-01-01

Purpose To evaluate a new ultrasound molecular imaging approach in its ability to image a preclinical tumor model and to investigate the capacity to visualize and quantify co-registered microvascular and molecular imaging volumes. Procedures Molecular imaging using the new technique was compared with a conventional ultrasound molecular imaging technique (multi-pulse imaging) by varying the injected microbubble dose and scanning each animal using both techniques. Each of the 14 animals was randomly assigned one of three doses; bolus dose was varied, and the animals were imaged for three consecutive days so that each animal received every dose. A microvascular scan was also acquired for each animal by administering an infusion of non-targeted microbubbles. These scans were paired with co-registered molecular images (VEGFR2-targeted microbubbles), the vessels were segmented, and the spatial relationships between vessels and VEGFR2 targeting locations were analyzed. In 5 animals, an additional scan was performed in which the animal received a bolus of microbubbles targeted to E- and P-selectin. Vessel tortuosity as a function of distance from VEGF and selectin targeting was analyzed in these animals. Results Although resulting differences in image intensity due to varying microbubble dose were not significant between the two lowest doses, superharmonic imaging had significantly higher contrast-to-tissue ratio (CTR) than multi-pulse imaging (mean across all doses: 13.98 dB for molecular acoustic angiography vs. 0.53 dB for multi-pulse imaging; p = 4.9 × 10−10). Analysis of registered microvascular and molecular imaging volumes indicated that vessel tortuosity decreases with increasing distance from both VEGFR2 and selectin targeting sites. Conclusions Molecular acoustic angiography (superharmonic molecular imaging) exhibited a significant increase in CTR at all doses tested due to superior rejection of tissue artifact signals. Due to the high resolution of acoustic angiography molecular imaging, it is possible to analyze spatial relationships in aligned microvascular and molecular superharmonic imaging volumes. Future studies are required to separate the effects of biomarker expression and blood flow kinetics in comparing local tortuosity differences between different endothelial markers such as VEGFR2, E-selectin and P-selectin. PMID:27519522

Time-lapse seismic waveform inversion for monitoring near-surface microbubble injection

NASA Astrophysics Data System (ADS)

Kamei, R.; Jang, U.; Lumley, D. E.; Mouri, T.; Nakatsukasa, M.; Takanashi, M.

2016-12-01

Seismic monitoring of the Earth provides valuable information regarding the time-varying changes in subsurface physical properties that are caused by natural or man-made processes. However, the resulting changes in subsurface properties are often small both in terms of magnitude and spatial extent, leading to seismic data differences that are difficult to detect at typical non-repeatable noise levels. In order to better extract information from the time-lapse data, exploiting the full seismic waveform information can be critical, since detected amplitude or traveltime changes may be minimal. We explore methods of waveform inversion that estimate an optimal model of time-varying elastic parameters at the wavelength scale to fit the observed time-lapse seismic data with modelled waveforms based on numerical solutions of the wave equation. We apply acoustic waveform inversion to time-lapse cross-well monitoring surveys of 64-m well intervals, and estimate the velocity changes that occur during the injection of microbubble water into shallow unconsolidated Quaternary sediments in the Kanto basin of Japan at a depth of 25 m below the surface. Microbubble water is comprised of water infused with air bubbles of a diameter less than 0.1mm, and may be useful to improve resistance to ground liquefaction during major earthquakes. Monitoring the space-time distribution and physical properties of microbubble injection is therefore important to understanding the full potential of the technique. Repeated monitoring surveys (>10) reveal transient behaviours in waveforms during microbubble injection. Time-lapse waveform inversion detects changes in P-wave velocity of less than 1 percent, initially as velocity increases and subsequently as velocity decreases. The velocity changes are mainly imaged within a thin (1 m) layer between the injection and the receiver well, inferring the fluid-flow influence of the fluvial sediment depositional environment. The resulting velocity models fit the observed waveforms very well, supporting the validity of the estimated velocity changes. In order to further improve the estimation of velocity changes, we investigate the limitations of acoustic waveform inversion, and apply elastic waveform inversion to the time-lapse data set.

A multi-frequency sparse hemispherical ultrasound phased array for microbubble-mediated transcranial therapy and simultaneous cavitation mapping.

PubMed

Deng, Lulu; O'Reilly, Meaghan A; Jones, Ryan M; An, Ran; Hynynen, Kullervo

2016-12-21

Focused ultrasound (FUS) phased arrays show promise for non-invasive brain therapy. However, the majority of them are limited to a single transmit/receive frequency and therefore lack the versatility to expose and monitor the treatment volume. Multi-frequency arrays could offer variable transmit focal sizes under a fixed aperture, and detect different spectral content on receive for imaging purposes. Here, a three-frequency (306, 612, and 1224 kHz) sparse hemispherical ultrasound phased array (31.8 cm aperture; 128 transducer modules) was constructed and evaluated for microbubble-mediated transcranial therapy and simultaneous cavitation mapping. The array is able to perform effective electronic beam steering over a volume spanning (-40, 40) and (-30, 50) mm in the lateral and axial directions, respectively. The focal size at the geometric center is approximately 0.9 (2.1) mm, 1.7 (3.9) mm, and 3.1 (6.5) mm in lateral (axial) pressure full width at half maximum (FWHM) at 1224, 612, and 306 kHz, respectively. The array was also found capable of dual-frequency excitation and simultaneous multi-foci sonication, which enables the future exploration of more complex exposure strategies. Passive acoustic mapping of dilute microbubble clouds demonstrated that the point spread function of the receive array has a lateral (axial) intensity FWHM between 0.8-3.5 mm (1.7-11.7 mm) over a volume spanning (-25, 25) mm in both the lateral and axial directions, depending on the transmit/receive frequency combination and the imaging location. The device enabled both half and second harmonic imaging through the intact skull, which may be useful for improving the contrast-to-tissue ratio or imaging resolution, respectively. Preliminary in vivo experiments demonstrated the system's ability to induce blood-brain barrier opening and simultaneously spatially map microbubble cavitation activity in a rat model. This work presents a tool to investigate optimal strategies for non-thermal FUS brain therapy and concurrent microbubble cavitation monitoring through the availability of multiple frequencies.

In vivo transcranial cavitation threshold detection during ultrasound-induced blood-brain barrier opening in mice.

PubMed

Tung, Yao-Sheng; Vlachos, Fotios; Choi, James J; Deffieux, Thomas; Selert, Kirsten; Konofagou, Elisa E

2010-10-21

The in vivo cavitation response associated with blood-brain barrier (BBB) opening as induced by transcranial focused ultrasound (FUS) in conjunction with microbubbles was studied in order to better identify the underlying mechanism in its noninvasive application. A cylindrically focused hydrophone, confocal with the FUS transducer, was used as a passive cavitation detector (PCD) to identify the threshold of inertial cavitation (IC) in the presence of Definity® microbubbles (mean diameter range: 1.1-3.3 µm, Lantheus Medical Imaging, MA, USA). A vessel phantom was first used to determine the reliability of the PCD prior to in vivo use. A cerebral blood vessel was simulated by generating a cylindrical channel of 610 µm in diameter inside a polyacrylamide gel and by saturating its volume with microbubbles. The microbubbles were sonicated through an excised mouse skull. Second, the same PCD setup was employed for in vivo noninvasive (i.e. transdermal and transcranial) cavitation detection during BBB opening. After the intravenous administration of Definity® microbubbles, pulsed FUS was applied (frequency: 1.525 or 1.5 MHz, peak-rarefactional pressure: 0.15-0.60 MPa, duty cycle: 20%, PRF: 10 Hz, duration: 1 min with a 30 s interval) to the right hippocampus of twenty-six (n = 26) mice in vivo through intact scalp and skull. T1 and T2-weighted MR images were used to verify the BBB opening. A spectrogram was generated at each pressure in order to detect the IC onset and duration. The threshold of BBB opening was found to be at a 0.30 MPa peak-rarefactional pressure in vivo. Both the phantom and in vivo studies indicated that the IC pressure threshold had a peak-rarefactional amplitude of 0.45 MPa. This indicated that BBB opening may not require IC at or near the threshold. Histological analysis showed that BBB opening could be induced without any cellular damage at 0.30 and 0.45 MPa. In conclusion, the cavitation response could be detected without craniotomy in mice and IC may not be required for BBB opening at relatively low pressures.

Nitrogen removal from landfill leachate using single or combined processes.

PubMed

He, P J; Shao, L M; Guo, H D; Li, G J; Lee, D J

2005-04-01

The municipal solids waste (MSW) collected at Shanghai includes a high proportion of food waste, which is easily hydrolyzed to generate ammonia-nitrogen in leachate. This study investigated the efficiency of nitrogen removal from landfill leachate employing four different treatment processes. The simulated rainfall and direct leachate recycling produced strong leachate with high ammonia-nitrogen content, and resulted in the removal of only a small amount of nitrogen. Although pretreating the leachate using an aerobic reactor removed some nitrogen, most of which was transformed to biomass because of the high organic loading applied. Using the three-compartment system, which comprises a landfill column with fresh MSW, a column with well-decomposed refuse layer as the methane generator, and a nitrifier, the ammonia-nitrogen was converted into nitrogen gas and hence removed. Experimental results demonstrated the feasibility of adopting the three-compartment system for managing nitrogen in landfill leachate generated from high-nitrogen-content MSW.

An algorithm for sensing venous oxygenation using ultrasound-modulated light enhanced by microbubbles

NASA Astrophysics Data System (ADS)

Honeysett, Jack E.; Stride, Eleanor; Deng, Jing; Leung, Terence S.

2012-02-01

Near-infrared spectroscopy (NIRS) can provide an estimate of the mean oxygen saturation in tissue. This technique is limited by optical scattering, which reduces the spatial resolution of the measurement, and by absorption, which makes the measurement insensitive to oxygenation changes in larger deep blood vessels relative to that in the superficial tissue. Acousto-optic (AO) techniques which combine focused ultrasound (US) with diffuse light have been shown to improve the spatial resolution as a result of US-modulation of the light signal, however this technique still suffers from low signal-to-noise when detecting a signal from regions of high optical absorption. Combining an US contrast agent with this hybrid technique has been proposed to amplify an AO signal. Microbubbles are a clinical contrast agent used in diagnostic US for their ability to resonate in a sound field: in this work we also make use of their optical scattering properties (modelled using Mie theory). A perturbation Monte Carlo (pMC) model of light transport in a highly absorbing blood vessel containing microbubbles surrounded by tissue is used to calculate the AO signal detected on the top surface of the tissue. An algorithm based on the modified Beer-Lambert law is derived which expresses intravenous oxygen saturation in terms of an AO signal. This is used to determine the oxygen saturation in the blood vessel from a dual wavelength microbubble-contrast AO measurement. Applying this algorithm to the simulation data shows that the venous oxygen saturation is accurately recovered, and this measurement is robust to changes in the oxygenation of the superficial tissue layer.

Ultrasound-microbubble-mediated intercellular adhesion molecule-1 small interfering ribonucleic acid transfection attenuates neointimal formation after arterial injury in mice.

PubMed

Suzuki, Jun-ichi; Ogawa, Masahito; Takayama, Kiyoshi; Taniyama, Yoshiaki; Morishita, Ryuichi; Hirata, Yasunobu; Nagai, Ryozo; Isobe, Mitsuaki

2010-03-02

The purpose of this study was to investigate the efficiency of small interfering ribonucleic acid (siRNA) in murine arteries. We transfected it using a nonviral ultrasound-microbubble-mediated in vivo gene delivery system. siRNA is an effective methodology to suppress gene function. The siRNA can be synthesized easily; however, a major obstacle in the use of siRNA as therapeutics is the difficulty involved in effective in vivo delivery. To investigate the efficiency of nonviral ultrasound-microbubble-mediated in vivo siRNA delivery, we used a fluorescein-labeled siRNA, green fluorescent protein (GFP) siRNA, and intercellular adhesion molecule (ICAM)-1 siRNA in murine arteries. Murine femoral arteries were injured using flexible wires to establish arterial injury. The fluorescein-labeled siRNA and GFP siRNA showed that this nonviral approach could deliver siRNA into target arteries effectively without any tissue damage and systemic adverse effects. ICAM-1 siRNA transfection into murine injured arteries significantly suppressed the development of neointimal formation in comparison to those in the control group. Immunohistochemistry revealed that accumulation of T cells and adhesion molecule positive cells was observed in nontreated injured arteries, whereas siRNA suppressed accumulation. The nonviral ultrasound-microbubble delivery of siRNA ensures effective transfection into target arteries. ICAM-1 siRNA has the potential to suppress arterial neointimal formation. Transfection of siRNA can be beneficial for the clinical treatment of cardiovascular and other inflammatory diseases. Copyright 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Hemostatic Effects of Microbubble-Enhanced Low-Intensity Ultrasound in a Liver Avulsion Injury Model

PubMed Central

Feng, Guiying; Liu, Jianhua; Zhao, Xiaochen; Wei, Jinglu; Ou, Wencai; Xiao, Shuyi; Hu, Zhiwen; Wei, Hongqin; Liu, Zheng

2014-01-01

Objectives Microbubble-enhanced therapeutic ultrasound (MEUS) can block the blood flow in the organs. The aim of this study was to evaluate the hemostatic effect of microbubble-enhanced pulsed, low-intensity ultrasound in a New Zealand White rabbit model of avulsion trauma of the liver. The therapeutic ultrasound (TUS) transducer was operated with the frequency of 1.2 MHz and an acoustic pressure of 3.4 MPa. Microbubble-(MB) enhanced ultrasound (MEUS) (n = 6) was delivered to the distal part of the liver where the avulsion was created. Livers were treated by TUS only (n = 4) or MB only (n = 4) which served as controls. Bleeding rates were measured and contrast enhanced ultrasound (CEUS) was performed to assess the hemostatic effect, and liver hemoperfusion before and after treatment. Generally, bleeding rates decreased more than 10-fold after the treatment with MEUS compared with those of the control group (P<0.05). CEUS showed significant declines in perfusion. The peak intensity value and the area under the curve also decreased after insonation compared with those of the control group (P<0.05). Histological examination showed cloudy and swollen hepatocytes, dilated hepatic sinusoids, perisinusoidal spaces with erythrocyte accumulation in small blood vessels, obvious hemorrhage around portal areas and scattered necrosis in liver tissues within the insonation area of MEUS Group. In addition, necrosis was found in liver tissue 48 h after insonation. We conclude that MEUS might provide an effective hemostatic therapy for serious organ trauma such as liver avulsion injury. PMID:24788757

Ultrasound-Induced Blood-Brain Barrier Opening

PubMed Central

Konofagou, Elisa E.; Tung, Yao-Sheng; Choi, James; Deffieux, Thomas; Baseri, Babak; Vlachos, Fotios

2014-01-01

Over 4 million U.S. men and women suffer from Alzheimer's disease; 1 million from Parkinson's disease; 350,000 from multiple sclerosis (MS); and 20,000 from amyotrophic lateral sclerosis (ALS). Worldwide, these four diseases account for more than 20 million patients. In addition, aging greatly increases the risk of neurodegenerative disease. Although great progress has been made in recent years toward understanding of these diseases, few effective treatments and no cures are currently available. This is mainly due to the impermeability of the blood-brain barrier (BBB) that allows only 5% of the 7000 small-molecule drugs available to treat only a tiny fraction of these diseases. On the other hand, safe and localized opening of the BBB has been proven to present a significant challenge. Of the methods used for BBB disruption shown to be effective, Focused Ultrasound (FUS), in conjunction with microbubbles, is the only technique that can induce localized BBB opening noninvasively and regionally. FUS may thus have a huge impact in trans-BBB brain drug delivery. The primary objective in this paper is to elucidate the interactions between ultrasound, microbubbles and the local microenvironment during BBB opening with FUS, which are responsible for inducing the BBB disruption. The mechanism of the BBB opening in vivo is monitored through the MRI and passive cavitation detection (PCD), and the safety of BBB disruption is assessed using H&E histology at distinct pressures, pulse lengths and microbubble diameters. It is hereby shown that the BBB can be disrupted safely and transiently under specific acoustic pressures (under 0.45 MPa) and microbubble (diameter under 8 μm) conditions. PMID:22201586

Quantitative evaluation of contrast-enhanced ultrasound after intravenous administration of a microbubble contrast agent for differentiation of benign and malignant thyroid nodules: assessment of diagnostic accuracy.

PubMed

Nemec, Ursula; Nemec, Stefan F; Novotny, Clemens; Weber, Michael; Czerny, Christian; Krestan, Christian R

2012-06-01

To investigate the diagnostic accuracy, through quantitative analysis, of contrast-enhanced ultrasound (CEUS), using a microbubble contrast agent, in the differentiation of thyroid nodules. This prospective study enrolled 46 patients with solitary, scintigraphically non-functional thyroid nodules. These patients were scheduled for surgery and underwent preoperative CEUS with pulse-inversion harmonic imaging after intravenous microbubble contrast medium administration. Using histology as a standard of reference, time-intensity curves of benign and malignant nodules were compared by means of peak enhancement and wash-out enhancement relative to the baseline intensity using a mixed model ANOVA. ROC analysis was performed to assess the diagnostic accuracy in the differentiation of benign and malignant nodules on CEUS. The complete CEUS data of 42 patients (31/42 [73.8%] benign and 11/42 [26.2%] malignant nodules) revealed a significant difference (P < 0.001) in enhancement between benign and malignant nodules. Furthermore, based on ROC analysis, CEUS demonstrated sensitivity of 76.9%, specificity of 84.8% and accuracy of 82.6%. Quantitative analysis of CEUS using a microbubble contrast agent allows the differentiation of benign and malignant thyroid nodules and may potentially serve, in addition to grey-scale and Doppler ultrasound, as an adjunctive tool in the assessment of patients with thyroid nodules. • Contrast-enhanced ultrasound (CEUS) helps differentiate between benign and malignant thyroid nodules. • Quantitative CEUS analysis yields sensitivity of 76.9% and specificity of 84.8%. • CEUS may be a potentially useful adjunct in assessing thyroid nodules.

Spatially Uniform Tumor Treatment and Drug Penetration by Regulating Ultrasound with Microbubbles.

PubMed

Ho, Yi-Ju; Wang, Tzu-Chia; Fan, Ching-Hsiang; Yeh, Chih-Kuang

2018-05-30

Tumor microenvironment has different morphologies of vessels in the core and rim regions, which influences the efficacy of tumor therapy. Our study proposed to improve the spatial uniformity of the antivascular effect and drug penetration within the tumor core and rim in combination therapies by regulating ultrasound-stimulated microbubble destruction (USMD). Focused ultrasound at 2 MHz and lipid-shell microbubbles (1.12 ± 0.08 μm, mean ± standard deviation) were used to perform USMD. The efficiency of the antivascular effect was evaluated by intravital imaging to determine the optimal USMD parameters. Tumor perfusion and histological alterations in the tumor core and rim were used to analyze the spatial uniformity of the antivascular effect and liposomal-doxorubicin (5 mg/kg) penetration in the combination therapy. Tumor vessels of specific sizes were disrupted by regulating USMD: vessels with sizes of 11 ± 3, 14 ± 5, 19 ± 7, and 23 ± 10 μm were disrupted by stimulation at acoustic pressures of 3, 5, 7, and 9 MPa, respectively (each p < 0.05). The effective treatment time of USMD (at 2 × 10 7 microbubbles/mouse, 7 MPa, and three cycles) was 60-120 min, which resulted in the disruption of 21-44% of vessels smaller than 50 μm. The reductions in perfusion and vascular density after combination therapy did not differ significantly between the tumor core and rim. This study found that regulating USMD can result in homogeneous antivascular effects and drug penetration within tumors and thereby improve the efficacy of combination therapies.

Fluorescent Microscope System to Monitor Real-Time Interactions between Focused Ultrasound, Echogenic Drug Delivery Vehicles, and Live Cell Membranes

PubMed Central

Ibsen, Stuart; Benchimol, Michael; Esener, Sadik

2012-01-01

Rapid development in the field of ultrasound triggered drug delivery has made it essential to study the real-time interaction between the membranes of live cells and the membranes of echogenic delivery vehicles under exposure to focused ultrasound. The objective of this work was to design an analysis system that combined fluorescent imagining, high speed videography, and definable pulse sequences of focused ultrasound to allow for real time observations of both cell and vehicle membranes. Documenting the behavior of the membranes themselves has not previously been possible due to limitations with existing optical systems used to understand the basic physics of microbubble/ultrasound interaction and the basic interaction between microbubbles and cells. The performance of this new system to monitor membrane behavior was demonstrated by documenting the modes of vehicle fragmentation at different ultrasound intensity levels. At 1.5 MPa the membranes were shown to completely fragment while at intensities below 1 MPa there is a popping and slow unfolding. The interaction between these vehicles and cell membranes was also documented by the removal of fluorescent particles from the surfaces of live cells out to 20 μm from the microbubble location. The fluid flow created by microstreaming around ensonated microbubbles was documented at video recording speeds from 60 to 18,000 frames per second. This information about membrane behavior allows the chemical and physical properties of the drug delivery vehicle to be designed along with the ultrasound pulse sequence to cause the most efficient drug delivery. PMID:22749476

Fluorescent microscope system to monitor real-time interactions between focused ultrasound, echogenic drug delivery vehicles, and live cell membranes.

PubMed

Ibsen, Stuart; Benchimol, Michael; Esener, Sadik

2013-01-01

Rapid development in the field of ultrasound triggered drug delivery has made it essential to study the real-time interaction between the membranes of live cells and the membranes of echogenic delivery vehicles under exposure to focused ultrasound. The objective of this work was to design an analysis system that combined fluorescent imagining, high speed videography, and definable pulse sequences of focused ultrasound to allow for real time observations of both cell and vehicle membranes. Documenting the behavior of the membranes themselves has not previously been possible due to limitations with existing optical systems used to understand the basic physics of microbubble/ultrasound interaction and the basic interaction between microbubbles and cells. The performance of this new system to monitor membrane behavior was demonstrated by documenting the modes of vehicle fragmentation at different ultrasound intensity levels. At 1.5MPa the membranes were shown to completely fragment while at intensities below 1MPa the membranes pop open and slowly unfold. The interaction between these vehicles and cell membranes was also documented by the removal of fluorescent particles from the surfaces of live cells out to 20μm from the microbubble location. The fluid flow created by microstreaming around ensonated microbubbles was documented at video recording speeds from 60 to 18,000 frames per second. This information about membrane behavior allows the chemical and physical properties of the drug delivery vehicle to be designed along with the ultrasound pulse sequence to cause the most efficient drug delivery. Copyright © 2012 Elsevier B.V. All rights reserved.

Enhanced shock wave generation via pre-breakdown acceleration using water electrolysis in negative streamer pulsed spark discharges

NASA Astrophysics Data System (ADS)

Lee, Kern; Chung, Kyoung-Jae; Hwang, Y. S.

2018-03-01

This paper presents a method for enhancement of shock waves generated from underwater pulsed spark discharges with negative (anode-directed) subsonic streamers, for which the pre-breakdown process is accelerated by preconditioning a gap with water electrolysis. Hydrogen microbubbles are produced at the cathode by the electrolysis and move towards the anode during the preconditioning phase. The numbers and spatial distributions of the microbubbles vary with the amplitude and duration of each preconditioning pulse. Under our experimental conditions, the optimum pulse duration is determined to be ˜250 ms at a pulse voltage of 400 V, where the buoyancy force overwhelms the electric force and causes the microbubbles to be swept out from the water gap. When a high-voltage pulse is applied to the gap just after the preconditioning pulse, the pre-breakdown process is significantly accelerated in the presence of the microbubbles. At the optimum preconditioning pulse duration, the average breakdown delay is reduced by 87% and, more importantly, the energy consumed during the pre-breakdown period decreases by 83%. This reduced energy consumption during the pre-breakdown period, when combined with the morphological advantages of negative streamers, such as thicker and longer stalks, leads to a significant improvement in the measured peak pressure (˜40%) generated by the underwater pulsed spark discharge. This acceleration of pre-breakdown using electrolysis overcomes the biggest drawback of negative subsonic discharges, which is slow vapor bubble formation due to screening effects, and thus enhances the efficiency of the shock wave generation process using pulsed spark discharges in water.

Hadamard-Encoded Multipulses for Contrast-Enhanced Ultrasound Imaging.

PubMed

Gong, Ping; Song, Pengfei; Chen, Shigao

2017-11-01

The development of contrast-enhanced ultrasound (CEUS) imaging offers great opportunities for new ultrasound clinical applications such as myocardial perfusion imaging and abdominal lesion characterization. In CEUS imaging, the contrast agents (i.e., microbubbles) are utilized to improve the contrast between blood and tissue based on their high nonlinearity under low ultrasound pressure. In this paper, we propose a new CEUS pulse sequence by combining Hadamard-encoded multipulses (HEM) with fundamental frequency bandpass filter (i.e., filter centered on transmit frequency). HEM consecutively emits multipulses encoded by a second-order Hadamard matrix in each of the two transmission events (i.e., pulse-echo events), as opposed to conventional CEUS methods which emit individual pulses in two separate transmission events (i.e., pulse inversion (PI), amplitude modulation (AM), and PIAM). In HEM imaging, the microbubble responses can be improved by the longer transmit pulse, and the tissue harmonics can be suppressed by the fundamental frequency filter, leading to significantly improved contrast-to-tissue ratio (CTR) and signal-to-noise ratio (SNR). In addition, the fast polarity change between consecutive coded pulse emissions excites strong nonlinear microbubble echoes, further enhancing the CEUS image quality. The spatial resolution of HEM image is compromised as compared to other microbubble imaging methods due to the longer transmit pulses and the lower imaging frequency (i.e., fundamental frequency). However, the resolution loss was shown to be negligible and could be offset by the significantly enhanced CTR, SNR, and penetration depth. These properties of HEM can potentially facilitate robust CEUS imaging for many clinical applications, especially for deep abdominal organs and heart.

Layered acoustofluidic resonators for the simultaneous optical and acoustic characterisation of cavitation dynamics, microstreaming, and biological effects.

PubMed

Pereno, V; Aron, M; Vince, O; Mannaris, C; Seth, A; de Saint Victor, M; Lajoinie, G; Versluis, M; Coussios, C; Carugo, D; Stride, E

2018-05-01

The study of the effects of ultrasound-induced acoustic cavitation on biological structures is an active field in biomedical research. Of particular interest for therapeutic applications is the ability of oscillating microbubbles to promote both cellular and tissue membrane permeabilisation and to improve the distribution of therapeutic agents in tissue through extravasation and convective transport. The mechanisms that underpin the interaction between cavitating agents and tissues are, however, still poorly understood. One challenge is the practical difficulty involved in performing optical microscopy and acoustic emissions monitoring simultaneously in a biologically compatible environment. Here we present and characterise a microfluidic layered acoustic resonator ( μ LAR) developed for simultaneous ultrasound exposure, acoustic emissions monitoring, and microscopy of biological samples. The μ LAR facilitates in vitro ultrasound experiments in which measurements of microbubble dynamics, microstreaming velocity fields, acoustic emissions, and cell-microbubble interactions can be performed simultaneously. The device and analyses presented provide a means of performing mechanistic in vitro studies that may benefit the design of predictable and effective cavitation-based ultrasound treatments.

Gaseous Microemboli and the Influence of Microporous Membrane Oxygenators

PubMed Central

Weitkemper, Heinz-H.; Oppermann, Bernd; Spilker, Andreas; Knobl, Hermann-J.; Körfer, Reiner

2005-01-01

Abstract: Gaseous microemboli (GME) are still an unsolved problem of extracorporeal circuits. They are associated with organ injury during cardiopulmonary bypass. Microbubbles of different sizes and number are generated in the blood as the result of different components of the extracorporeal circuit as well as surgical maneuvers. The aim of our study was to observe the behavior of microporous membrane oxygenators to GME in the daily use and in an in vitro model. For the detection of microbubbles, we used a two-channel ultrasonic bubble counter based on 2-MHz Doppler-System with special ultrasound probes. The amount and size of GME were monitored before and after membrane. In 28 scheduled cases with 3 different oxygenators and variability of surgical procedures, we observed the bubble activity in the extracorporeal circuit. In addition, we used an in-vitro model to study the ability of six different oxygenators by removing air in various tests. The oxygenators tested were manufactured with different membrane technologies. The results of our investigations showed varying membrane design lead to a partial removal of GME as well as a change in size and numbers of microbubbles. PMID:16350377

Perfectly monodisperse micro-bubble production by novel mechanical means. Scaling laws.

NASA Astrophysics Data System (ADS)

Ganan-Calvo, Alfonso M.; Gordillo, Jose M.; Ouarti, Nawel; Prevost, Thomas; Sampedro, Jose L.

2000-11-01

A continuous stream of controllable, perfectly homogeneous size micro-bubbles (of the order of some microns and larger) can be produced by a novel, extremely simple mechanical means that we call "Flow Focusing" (e.g. see Ganan-Calvo 1998, Phys. Rev. Lett. vol. 80, 285). Using this technique, a capillary gas micro-jet is formed ("focused") by a co-flowing stream of liquid forced through a sub-millimetric orifice. This gas micro-jet undergoes a rapid capillary breakup (e.g. Chandrasekhar 1961 "Hydrodynamic and Hydromagnetic Stability", p. 541) with a strong frequency "self-locking" effect. In this work we present a theoretical model which predicts the micro-bubble size as a function of the physical and geometrical parameters of the system. A complete experimental study is also provided, and the raw data are collapsed into a universal scaling law given by our theoretical model. This novel micro-fluidics phenomenon may have a wide variety of applications ranging from bio-medicine, pharmaceutical specialities, food industry, and even for the mesoscale micro-templating of micro-engineered materials (i.e. photonic crystals, smart materials, etc.).

Oxygen supersaturated fluid using fine micro/nanobubbles

PubMed Central

Matsuki, Noriaki; Ishikawa, Takuji; Ichiba, Shingo; Shiba, Naoki; Ujike, Yoshihito; Yamaguchi, Takami

2014-01-01

Microbubbles show peculiar properties, such as shrinking collapse, long lifetime, high gas solubility, negative electric charge, and free radical production. Fluids supersaturated with various gases can be easily generated using microbubbles. Oxygen microbubble fluid can be very useful for oxygen delivery to hypoxic tissues. However, there have been no reports of comparative investigations into adding fluids containing oxygen fine micro/nanobubbles (OFM-NBs) to common infusion solutions in daily medical care. In this study, it was demonstrated that OFMNBs can generate oxygen-supersaturated fluids, and they may be sufficiently small to infuse safely into blood vessels. It was found that normal saline solution is preferable for generating an oxygen-rich infusion fluid, which is best administered as a 30-minute intravenous infusion. It was also concluded that dextran solution is suitable for drug delivery substances packing oxygen gas over a 1-hour intravenous infusion. In addition, normal saline solution containing OFMNBs was effective for improving blood oxygenation. Thus, the use of OFMNB-containing fluids is a potentially effective novel method for improving blood oxygenation in cases involving hypoxia, ischemic diseases, infection control, and anticancer chemoradiation therapies. PMID:25285003

Oxygen supersaturated fluid using fine micro/nanobubbles.

PubMed

Matsuki, Noriaki; Ishikawa, Takuji; Ichiba, Shingo; Shiba, Naoki; Ujike, Yoshihito; Yamaguchi, Takami

2014-01-01

Microbubbles show peculiar properties, such as shrinking collapse, long lifetime, high gas solubility, negative electric charge, and free radical production. Fluids supersaturated with various gases can be easily generated using microbubbles. Oxygen microbubble fluid can be very useful for oxygen delivery to hypoxic tissues. However, there have been no reports of comparative investigations into adding fluids containing oxygen fine micro/nanobubbles (OFM-NBs) to common infusion solutions in daily medical care. In this study, it was demonstrated that OFMNBs can generate oxygen-supersaturated fluids, and they may be sufficiently small to infuse safely into blood vessels. It was found that normal saline solution is preferable for generating an oxygen-rich infusion fluid, which is best administered as a 30-minute intravenous infusion. It was also concluded that dextran solution is suitable for drug delivery substances packing oxygen gas over a 1-hour intravenous infusion. In addition, normal saline solution containing OFMNBs was effective for improving blood oxygenation. Thus, the use of OFMNB-containing fluids is a potentially effective novel method for improving blood oxygenation in cases involving hypoxia, ischemic diseases, infection control, and anticancer chemoradiation therapies.

Nonlinear oscillation and interfacial stability of an encapsulated microbubble under dual-frequency ultrasound

NASA Astrophysics Data System (ADS)

Calvisi, Michael; Liu, Yunqiao; Wang, Qianxi

2016-11-01

Encapsulated microbubbles (EMBs) are widely used in medical ultrasound imaging as contrast-enhanced agents. However, the potential damaging effects of violent, collapsing EMBs to cells and tissues in clinical practice have remained a concern. Dual-frequency ultrasound is a promising technique for improving the efficacy and safety of sonography. The EMB system modeled consists of the external liquid, membrane, and internal gases. The microbubble dynamics are simulated using a simple nonlinear interactive theory, considering the compressibility of the internal gas, viscosity of the liquid flow, and elasticity of the membrane. The radial oscillation and interfacial stability of an EMB under single and dual-frequency excitations are compared. The simulation results show that the dual-frequency technique produces larger backscatter pressure at higher harmonics of the primary driving frequency. This enriched acoustic spectrum can enhance blood-tissue contrast and improve sonographic image quality. The results further show that the acoustic pressure threshold associated with the onset of shape instability is greater for dual-frequency driving. This suggests that the dual-frequency technique stabilizes the EMB, thereby improving the efficacy and safety of contrast-enhanced agents.

Pre-breakdown phenomena and discharges in a gas-liquid system

NASA Astrophysics Data System (ADS)

Tereshonok, D. V.; Babaeva, N. Yu; Naidis, G. V.; Panov, V. A.; Smirnov, B. M.; Son, E. E.

2018-04-01

In this paper, we investigate pre-breakdown and breakdown phenomena in gas-liquid systems. Cavitation void formation and breakdown in bubbles immersed in liquids are studied numerically, while complete breakdown of bubbled water is studied in experiments. It is shown that taking into account the dependence of water dielectric constant on electric field strength plays the same important role for cavitation void appearance under the action of electrostriction forces as the voltage rise time. It is also shown that the initial stage of breakdown in deformed bubbles immersed in liquid strongly depends on spatial orientation of the bubbles relative to the external electric field. The effect of immersed microbubbles, distributed in bulk water, on breakdown time and voltage is studied experimentally. At the breakdown voltage, the slow ‘thermal’ mechanism is changed by the fast ‘streamer-leader’ showing a decrease in breakdown time by two orders of magnitude by introducing microbubbles (0.1% of volumetric gas content) into the water. In addition, the plasma channel is found to pass between nearby microbubbles, exhibiting some ‘guidance’ effect.

Revealing the physicochemical mechanism for ultrasonic separation of alcohol-water mixtures

NASA Astrophysics Data System (ADS)

Kirpalani, D. M.; Toll, F.

2002-08-01

The selective separation of ethanol from ethanol-water mixtures by ultrasonic atomization has been reported recently by Sato, Matsuura, and Fujii [J. Chem. Phys. 114, 2382 (2001)]. In that work, experimental data were reported that confirmed the generation of an ethanol-rich droplet mist and attempted to explain the selective separation in terms of parametric decay instability of the capillary wave formed during sonication. In the present work, an alternate mechanism based on the conjunction theory has been postulated for the process of ultrasonic atomization. This mechanism involves the formation of cavitating bubbles in the liquid during sonication and their eventual collapse at the liquid surface into a cloud of microbubbles that moves upwards in a capillary fountain jet. The selective separation of alcohols has been explained as a corollary effect of the physical mechanism resulting in a surface excess of alcohol molecules formed at the surface of the microbubbles. The alcohol molecules vaporize into the microbubbles and release an alcohol-rich mist on their collapse in regions of high accumulation of acoustic energy.

Focused Ultrasound-Induced Neurogenesis Requires an Increase in Blood-Brain Barrier Permeability.

PubMed

Mooney, Skyler J; Shah, Kairavi; Yeung, Sharon; Burgess, Alison; Aubert, Isabelle; Hynynen, Kullervo

2016-01-01

Transcranial focused ultrasound technology used to transiently open the blood-brain barrier, is capable of stimulating hippocampal neurogenesis; however, it is not yet known what aspects of the treatment are necessary for enhanced neurogenesis to occur. The present study set out to determine whether the opening of blood-brain barrier, the specific pressure amplitudes of focused ultrasound, and/or the intravenous administration of microbubbles (phospholipid microspheres) are necessary for the enhancement of neurogenesis. Specifically, mice were exposed to burst (10ms, 1Hz burst repetition frequency) focused ultrasound at the frequency of 1.68MHz and with 0.39, 0.78, 1.56 and 3.0MPa pressure amplitudes. These treatments were also conducted with or without microbubbles, at 0.39 + 0.78MPa or 1.56 + 3.0MPa, respectively. Only focused ultrasound at the ~0.78 MPa pressure amplitude with microbubbles promoted hippocampal neurogenesis and was associated with an increase in blood-brain barrier permeability. These results suggest that focused ultrasound -mediated neurogenesis is dependent upon the opening of the blood-brain barrier.

Photoacoustic/ultrasound dual-modality contrast agent and its application to thermotherapy.

PubMed

Wang, Yu-Hsin; Liao, Ai-Ho; Chen, Jui-Hao; Wang, Churng-Ren Chris; Li, Pai-Chi

2012-04-01

This study investigates a photoacoustic/ultrasound dual-modality contrast agent, including extending its applications from image-contrast enhancement to combined diagnosis and therapy with site-specific targeting. The contrast agent comprises albumin-shelled microbubbles with encapsulated gold nanorods (AuMBs). The gas-filled microbubbles, whose diameters range from submicrometer to several micrometers, are not only echogenic but also can serve as drug-delivery vehicles. The gold nanorods are used to enhance the generation of both photoacoustic and photothermal signals. The optical absorption peak of the gold nanorods is tuned to 760 nm and is invariant after microbubble encapsulation. Dual-modality contrast enhancement is first described here, and the applications to cellular targeting and laser-induced thermotherapy in a phantom are demonstrated. Photoacoustic imaging can be used to monitor temperature increases during the treatment. The targeting capability of AuMBs was verified, and the temperature increased by 26°C for a laser power of 980 mW, demonstrating the potential of combined diagnosis and therapy with the dual-modality agent. Targeted photo- or acoustic-mediated delivery is also possible.

Temperature-dependent differences in the nonlinear acoustic behavior of ultrasound contrast agents revealed by high-speed imaging and bulk acoustics.

PubMed

Mulvana, Helen; Stride, Eleanor; Tang, Mengxing; Hajnal, Jo V; Eckersley, Robert

2011-09-01

Previous work by the authors has established that increasing the temperature of the suspending liquid from 20°C to body temperature has a significant impact on the bulk acoustic properties and stability of an ultrasound contrast agent suspension (SonoVue, Bracco Suisse SA, Manno, Lugano, Switzerland). In this paper the influence of temperature on the nonlinear behavior of microbubbles is investigated, because this is one of the most important parameters in the context of diagnostic imaging. High-speed imaging showed that raising the temperature significantly influences the dynamic behavior of individual microbubbles. At body temperature, microbubbles exhibit greater radial excursion and oscillate less spherically, with a greater incidence of jetting and gas expulsion, and therefore collapse, than they do at room temperature. Bulk acoustics revealed an associated increase in the harmonic content of the scattered signals. These findings emphasize the importance of conducting laboratory studies at body temperature if the results are to be interpreted for in vivo applications. Copyright © 2011 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Three-Dimensional Phenomena in Microbubble Acoustic Streaming

NASA Astrophysics Data System (ADS)

Marin, Alvaro; Rossi, Massimiliano; Rallabandi, Bhargav; Wang, Cheng; Hilgenfeldt, Sascha; Kähler, Christian J.

2015-04-01

Ultrasound-driven oscillating microbubbles are used as active actuators in microfluidic devices to perform manifold tasks such as mixing, sorting, and manipulation of microparticles. A common configuration consists of side bubbles created by trapping air pockets in blind channels perpendicular to the main channel direction. This configuration consists of acoustically excited bubbles with a semicylindrical shape that generate significant streaming flow. Because of the geometry of the channels, such flows are generally considered as quasi-two-dimensional. Similar assumptions are often made in many other microfluidic systems based on flat microchannels. However, in this Letter we show that microparticle trajectories actually present a much richer behavior, with particularly strong out-of-plane dynamics in regions close to the microbubble interface. Using astigmatism particle-tracking velocimetry, we reveal that the apparent planar streamlines are actually projections of a stream surface with a pseudotoroidal shape. We, therefore, show that acoustic streaming cannot generally be assumed as a two-dimensional phenomenon in confined systems. The results have crucial consequences for most of the applications involving acoustic streaming such as particle trapping, sorting, and mixing.

Dynamic Behavior of Microbubbles during Long Ultrasound Tone-Burst Excitation: Mechanistic Insights into Ultrasound-Microbubble Mediated Therapeutics Using High-Speed Imaging and Cavitation Detection.

PubMed

Chen, Xucai; Wang, Jianjun; Pacella, John J; Villanueva, Flordeliza S

2016-02-01

Ultrasound (US)-microbubble (MB)-mediated therapies have been found to restore perfusion and enhance drug/gene delivery. On the presumption that MBs do not persist during long US exposure under high acoustic pressures, most schemes use short US pulses when a high US pressure is employed. However, we recently observed an enhanced thrombolytic effect using long US pulses at high acoustic pressures. Therefore, we explored the fate of MBs during long tone-burst exposures (5 ms) at various acoustic pressures and MB concentrations via direct high-speed optical observation and passive cavitation detection. MBs first underwent stable or inertial cavitation depending on the acoustic pressure and then formed gas-filled clusters that continued to oscillate, break up and form new clusters. Cavitation detection confirmed continued, albeit diminishing, acoustic activity throughout the 5-ms US excitation. These data suggest that persisting cavitation activity during long tone bursts may confer additional therapeutic effects. Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Cavitation-enhanced delivery of a replicating oncolytic adenovirus to tumors using focused ultrasound.

PubMed

Bazan-Peregrino, Miriam; Rifai, Bassel; Carlisle, Robert C; Choi, James; Arvanitis, Costas D; Seymour, Leonard W; Coussios, Constantin C

2013-07-10

Oncolytic viruses (OV) and ultrasound-enhanced drug delivery are powerful novel technologies. OV selectively self-amplify and kill cancer cells but their clinical use has been restricted by limited delivery from the bloodstream into the tumor. Ultrasound has been previously exploited for targeted release of OV in vivo, but its use to induce cavitation, microbubble oscillations, for enhanced OV tumor extravasation and delivery has not been previously reported. By identifying and optimizing the underlying physical mechanism, this work demonstrates that focused ultrasound significantly enhances the delivery and biodistribution of systemically administered OV co-injected with microbubbles. Up to a fiftyfold increase in tumor transgene expression was achieved, without any observable tissue damage. Ultrasound exposure parameters were optimized as a function of tumor reperfusion time to sustain inertial cavitation, a type of microbubble activity, throughout the exposure. Passive detection of acoustic emissions during treatment confirmed inertial cavitation as the mechanism responsible for enhanced delivery and enabled real-time monitoring of successful viral delivery. Copyright © 2013 Elsevier B.V. All rights reserved.

Investigation on the relationship between overpressure and sub-harmonic response from encapsulated microbubbles

NASA Astrophysics Data System (ADS)

Wu, Jun; Fan, Ting-Bo; Xu, Di; Zhang, Dong

2014-10-01

Sub-harmonic component generated from microbubbles is proven to be potentially used in noninvasive blood pressure measurement. Both theoretical and experimental studies are performed in the present work to investigate the dependence of the sub-harmonic generation on the overpressure with different excitation pressure amplitudes and pulse lengths. With 4-MHz ultrasound excitation at an applied acoustic pressure amplitude of 0.24 MPa, the measured sub-harmonic amplitude exhibits a decreasing change as overpressure increases; while non-monotonic change is observed for the applied acoustic pressures of 0.36 MPa and 0.48 MPa, and the peak position in the curve of the sub-harmonic response versus the overpressure shifts toward higher overpressure as the excitation pressure amplitude increases. Furthermore, the exciting pulse with long duration could lead to a better sensitivity of the sub-harmonic response to overpressure. The measured results are explained by the numerical simulations based on the Marmottant model. The numerical simulations qualitatively accord with the measured results. This work might provide a preliminary proof for the optimization of the noninvasive blood pressure measurement through using sub-harmonic generation from microbubbles.

Microbubble Enzyme-Linked Immunosorbent Assay for the Detection of Targeted Microbubbles in in Vitro Static Binding Assays.

PubMed

Wischhusen, Jennifer; Padilla, Frederic

2017-07-01

Targeted microbubbles (MBs) are ultrasound contrast agents that are functionalized with a ligand for ultrasound molecular imaging of endothelial markers. Novel targeted MBs are characterized in vitro by incubation in protein-coated wells, followed by binding quantification by microscopy or ultrasound imaging. Both methods provide operator-dependent results: Between 3 and 20 fields of view from a heterogeneous sample are typically selected for analysis by microscopy, and in ultrasound imaging, different acoustic settings affect signal intensities. This study proposes a new method to reproducibly quantify MB binding based on enzyme-linked immunosorbent assay (ELISA), in which bound MBs are revealed with an enzyme-linked antibody. MB-ELISA was adapted to in vitro static binding assays, incubating the MBs in inverted position or by agitation, and compared with microscopy. The specificity and sensitivity of MB-ELISA enable the reliable quantification of MB binding in a rapid, high-throughput and whole-well analysis, facilitating the characterization of new targeted contrast agents. Copyright © 2017 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Leaching of organic contaminants from storage of reclaimed asphalt pavement.

PubMed

Norin, Malin; Strömvall, A M

2004-03-01

Recycling of asphalt has been promoted by rapid increases in both the use and price of petroleum-based bitumen. Semi-volatile organic compounds in leachates from reclaimed asphalt pavement, measured in field samples and in laboratory column test, were analysed through a GC/MS screen-test methodology. Sixteen PAH (polyaromatic hydrocarbons) were also analysed in leachates from the column study. The highest concentrations of semi-volatile compounds, approximately 400 microg l(-1), were measured in field samples from the scarified stockpile. Naphthalene, butylated hydroxytoluene (BHT) and dibutyl phthalate (DBP) were the most dominant of the identified semi-volatiles. The occurrence of these compounds in urban groundwater, also indicate high emission rates and persistent structures of the compounds, making them potentially hazardous. Car exhausts, rubber tires and the asphalt material itself are all probable emission sources, determined from the organic contaminants released from the stockpiles. The major leaching mechanism indicated was dissolution of organic contaminants from the surface of the asphalt gravels. In the laboratory column test, the release of high-molecular weight and more toxic PAH was higher in the leachates after two years than at the commencement of storage. The concentrations of semi-volatiles in leachates, were also several times lower than those from the field stockpile. These results demonstrate the need to follow up laboratory column test with real field measurements.

Dynamics of acoustic droplet vaporization in gas embolotherapy

NASA Astrophysics Data System (ADS)

Qamar, Adnan; Wong, Zheng Z.; Fowlkes, J. Brian; Bull, Joseph L.

2010-04-01

Acoustic droplet vaporization is investigated in a theoretical model. This work is motivated by gas embolotherapy, a developmental cancer treatment involving tumor infarction with gas microbubbles that are selectively formed from liquid droplets. The results indicate that there exists a threshold value for initial droplet size below which the bubble evolution is oscillatory and above which it is smooth and asymptotic, and show that the vaporization process affects the subsequent microbubble expansion. Dampening of the bubble expansion is observed for higher viscosity and surface tension, with effects more pronounced for droplet size less than 6 μm in radius.

Rainbow glare by retinal imaging

NASA Astrophysics Data System (ADS)

Sun, Han-Ying; Chiang, Yao-Ting; Yeh, Shang-Min; Huang, Shuan-Yu; Horng, Chi-Ting; Wang, Hsiang-Chen

2016-07-01

This study aims to determine whether IntraLase surgery can cause rainbow glare. Monte-Carlo ray tracing method is used to study visual conditions of an ordered microstructure array on the cornea. A corneal flap in the simulated eye model can generate numerous microbubbles caused by IntraLase surgery. Moreover, this study evaluates the visual performance under different conditions such as the size and interval of the microbubble structure on the cornea with vary incident angles and diameters of light. The results of this study can help elucidate the real cause of rainbow glare as a side effect of IntraLase.

Stability analysis of ultrasound thick-shell contrast agents

PubMed Central

Lu, Xiaozhen; Chahine, Georges L.; Hsiao, Chao-Tsung

2012-01-01

The stability of thick shell encapsulated bubbles is studied analytically. 3-D small perturbations are introduced to the spherical oscillations of a contrast agent bubble in response to a sinusoidal acoustic field with different amplitudes of excitation. The equations of the perturbation amplitudes are derived using asymptotic expansions and linear stability analysis is then applied to the resulting differential equations. The stability of the encapsulated microbubbles to nonspherical small perturbations is examined by solving an eigenvalue problem. The approach then identifies the fastest growing perturbations which could lead to the breakup of the encapsulated microbubble or contrast agent. PMID:22280568

Precise and programmable manipulation of microbubbles by two-dimensional standing surface acoustic waves

NASA Astrophysics Data System (ADS)

Meng, Long; Cai, Feiyan; Chen, Juanjuan; Niu, Lili; Li, Yanming; Wu, Junru; Zheng, Hairong

2012-04-01

A microfluidic device is developed to transport microbubbles (MBs) along a desired trajectory in fluid by introducing the phase-shift to a planar standing surface acoustic wave (SSAW). The radiation force of SSAW due to the acoustic pressure gradient modulated by a phase-shift can move MBs to anticipated potential wells in a programmable manner. The resolution of the transportation is approximately 2.2 µm and the estimated radiation force on the MBs is on the order of 10-9 N. This device can be used for manipulation of bioparticles, cell sorting, tissue engineering, and other biomedical applications.

Virus elimination during the purification of monoclonal antibodies by column chromatography and additional steps.

PubMed

Roberts, Peter L

2014-01-01

The theoretical potential for virus transmission by monoclonal antibody based therapeutic products has led to the inclusion of appropriate virus reduction steps. In this study, virus elimination by the chromatographic steps used during the purification process for two (IgG-1 & -3) monoclonal antibodies (MAbs) have been investigated. Both the Protein G (>7log) and ion-exchange (5 log) chromatography steps were very effective for eliminating both enveloped and non-enveloped viruses over the life-time of the chromatographic gel. However, the contribution made by the final gel filtration step was more limited, i.e., 3 log. Because these chromatographic columns were recycled between uses, the effectiveness of the column sanitization procedures (guanidinium chloride for protein G or NaOH for ion-exchange) were tested. By evaluating standard column runs immediately after each virus spiked run, it was possible to directly confirm that there was no cross contamination with virus between column runs (guanidinium chloride or NaOH). To further ensure the virus safety of the product, two specific virus elimination steps have also been included in the process. A solvent/detergent step based on 1% triton X-100 rapidly inactivating a range of enveloped viruses by >6 log inactivation within 1 min of a 60 min treatment time. Virus removal by virus filtration step was also confirmed to be effective for those viruses of about 50 nm or greater. In conclusion, the combination of these multiple steps ensures a high margin of virus safety for this purification process. © 2014 American Institute of Chemical Engineers.

Design Through Simulation of a Molecular Sieve Column for Treatment of MON-3

NASA Technical Reports Server (NTRS)

Swartz, A. Ben; Wilson, D. B.

1999-01-01

The presence of water in propellant-grade MON-3 is a concern in the Aerospace Industry. NASA Johnson Space Center (JSC), White Sands Test Facility (WSTF) Propulsion Department has evaluated many types of molecular sieves for control of iron, the corrosion product of water in Mixed Oxides of Nitrogen (MON-3). In 1995, WSTF initiated laboratory and pilot-scale testing of molecular sieve type 3A for removal of water and iron. These tests showed sufficient promise that a series of continuous recycle tests were conducted at WSTF. Periodic samples of the circulating MON-3 solution were analyzed for water (wt %) and iron (ppm, wt). This test column was modeled as a series of transfer units; i. e., each unit represented the height equivalent of a theoretical plate. Such a model assumes there is equilibrium between the adsorbent material and the effluent stream from the unit. Operational and design parameters were derived based on the simulation results. These parameters were used to predict the design characteristics of a proposed molecular sieve column for removal of water and iron from MON-3 at the NASA Kennedy Space Center (KSC). In addition, these parameters were used to simulate a small, single-pass operation column at KSC currently used for treating MON-3. The results of this work indicated that molecular sieve type 3A in 1/16 in. diameter pellets, in a column 2.5 ft. in diameter, 18 ft. in height, and operated at 25 gpm is adequate for the required removal of water and iron from MON-3.

Anoxic monimolimnia: Nutrients devious feeders or bombs ready to explode?

NASA Astrophysics Data System (ADS)

Gianni, Areti; Zacharias, Ierotheos

2015-04-01

Coastal regions are under strong human influence and its environmental impact is reflected into their water quality. Oligotrophic estuaries and coastal systems have changed in mesotrophic and/or eutrophic, shown an increase in toxic algal blooms, hypoxic/anoxic events, and massive mortalities of many aquatic and benthic organisms. In strongly stratified and productive water basins, bottom water dissolved oxygen is depleted due to the excessive organic matter decomposition in these depths. Distribution and recycling of nutrients in their water column is inextricably dependent on oxygenation and redox conditions. Bottom water anoxia accelerates PO43-, NH4+ and H2S recycling and accumulation from organic matter decomposition. The anoxic, H2S, PO43- and NH4+ rich bottom water constitutes a toxic layer, threatening the balance of the entire ecosystem. In permanently stratified water basins, storm events could result in stratification destruction and water column total mixing. The turnover brings large amounts of H2S to the surface resulting in low levels of oxygen and massive fish kills. PO43- and NH4+ are released to the interface and surface waters promoting algal blooms. Μore organic matter is produced fueling anoxia. The arising question is, whether the balance of an anoxic water ecosystem is under the threat of its hypolimnetic nutrient and sulfide load, only in the case of storm events and water column total mixing. In polymictic water basins it is clear that the accumulated, in the bottom layer, nutrients will supply surface waters, after the pycnocline overturn. Besides this mechanism of basins' water quality degradation is nowadays recognized as one of the biggest obstacles in eutrophic environments management and restoration efforts. The role of internal load, in permanently stratified water basins, is not so clear. In the present study the impact of storm events on water column stability and bottom water anoxia of meromictic coastal basins, is investigated. The importance of internal load is emerged, presenting the disturbance on the main nutrients, dissolved oxygen, hydrogen sulfide and chlorophyll distribution, caused by the total water column mixing. Additionally, the relationship between temporal nutrients variations in surface layers, of permanent anoxic coastal basins with a) changes on the physicochemical characteristics of their water column, b) changes on the bottom water phosphorus and nitrogen concentration and c) their effect on the basin's primary productivity, is sought. In order to achieve the objectives of this study, two different sets of Aitoliko basin's (western Greece) data were used. The first one includes measurements of physicochemical parameters, nutrients, chlorophyll and hydrogen sulfide, four days after a storm event and the consequent anoxic crisis in Aitoliko basin on 4th of December 2008. The second one contains respective data obtained from a biennial (May 2006-May 2008) basin's monitoring. The changes in the physical, chemical and biological characteristics, of Aitoliko basin water column, after its total mixing, highlighted the importance of the accumulated nutrients and sulfides in the bottom layer. In addition, turned out that bottom layer can supply with nutrients the surface waters, even during periods of high water column stratification. Small scale, subtle, changes in physicochemical and hydrological basin's characteristics promoted this supply, affecting both quantitative and qualitative the ecosystem's primary productivity and shifting its quality character.

Xenon Recovery at Room Temperature using Metal-Organic Frameworks

DOE Office of Scientific and Technical Information (OSTI.GOV)

Elsaidi, Sameh K.; Ongari, Daniele; Xu, Wenqian

2017-07-24

Xenon is known to be a very efficient anesthetic gas but its cost prohibits the wider use in medical industry and other potential applications. It has been shown that Xe recovery and recycle from anesthetic gas mixture can significantly reduce its cost as anesthetic. The current technology uses series of adsorbent columns followed by low temperature distillation to recover Xe, which is expensive to use in medical facilities. Herein, we propose much efficient and simpler system to recover and recycle Xe from simulant exhale anesthetic gas mixture at room temperature using metal organic frameworks. Among the MOFs tested, PCN-12 exhibitsmore » unprecedented performance with high Xe capacity, Xe/O2, Xe/N2 and Xe/CO2 selectivity at room temperature. The in-situ synchrotron measurements suggest the Xe is occupied in the small pockets of PCN-12 compared to unsaturated metal centers (UMCs). Computational modeling of adsorption further supports our experimental observation of Xe binding sites in PCN-12.« less

Xenon Recovery at Room Temperature using Metal-Organic Frameworks

DOE Office of Scientific and Technical Information (OSTI.GOV)

Elsaidi, Sameh K.; Ongari, Daniele; Xu, Wenqian

2017-07-24

Xenon is known to be a very efficient anesthetic gas but its cost prohibits the wider use in medical industry and other potential applications. It has been shown that Xe recovery and recycle from anesthetic gas mixture can significantly reduce its cost as anesthetic. The current technology uses series of adsorbent columns followed by low temperature distillation to recover Xe, which is expensive to use in medical facilities. Herein, we propose much efficient and simpler system to recover and recycle Xe from simulant exhale anesthetic gas mixture at room temperature using metal organic frameworks. Among the MOFs tested, PCN-12 exhibitsmore » unprecedented performance with high Xe capacity, Xe/N2 and Xe/O2 selectivity at room temperature. The in-situ synchrotron measurements suggest the Xe is occupied in the small pockets of PCN-12 compared to unsaturated metal centers (UMCs). Computational modeling of adsorption further supports our experimental observation of Xe binding sites in PCN-12.« less

Cellulose nanocrystal-reinforced keratin bioadsorbent for effective removal of dyes from aqueous solution.

PubMed

Song, Kaili; Xu, Helan; Xu, Lan; Xie, Kongliang; Yang, Yiqi

2017-05-01

High-efficiency and recyclable three-dimensional bioadsorbents were prepared by incorporating cellulose nanocrystal (CNC) as reinforcements in keratin sponge matrix to remove dyes from aqueous solution. Adsorption performance of dyes by CNC-reinforced keratin bioadsorbent was improved significantly as a result of adding CNC as filler. Batch adsorption results showed that the adsorption capacities for Reactive Black 5 and Direct Red 80 by the bioadsorbent were 1201 and 1070mgg -1 , respectively. The isotherms and kinetics for adsorption of both dyes on bioadsorbent followed the Langmuir isotherm model and pseudo-second order model, respectively. Desorption and regeneration experiments showed that the removal efficiencies of the bioadsorbent for both dyes could remain above 80% at the fifth recycling cycles. Moreover, the bioadsorbent possessed excellent packed-bed column operation performance. Those results suggested that the adsorbent could be considered as a high-performance and promising candidate for dye wastewater treatment. Copyright © 2017 Elsevier Ltd. All rights reserved.

Separation and Recovery of Cobalt from Copper Leach Solutions

NASA Astrophysics Data System (ADS)

Jeffers, T. H.

1985-01-01

Significant amounts of cobalt, a strategic and critical metal, are present in readily accessible copper recycling leach solutions. However, cost-effective technology is not available to separate and recover the cobalt from this low-grade domestic source. The Bureau of Mines has developed a procedure using a chelating ion-exchange resin from Dow Chemical Co. to successfully extract cobalt from a pH 3.0 copper recycling solution containing only 30 mg/1 cobalt. Cyclic tests with the commercial resin XFS-4195 in 4-ft-high by 1-in.-diameter columns gave an average cobalt extraction of 95% when 65 bed volumes of solution were processed at a flow rate of 4 gpm/ft.2 Elution of the cobalt using a 50 g/l H2SO4 solution yielded an eluate containing 0.5 gli Co. Selective elution of the loaded resin and solvent extraction procedures using di-2-ethylhexyl phosphoric acid (D2EHPA) and Cyanex 272 removed the impurities and produced a cobalt sulfate solution containing 25 g/l Co.

Deformation Behavior of Recycled Concrete Aggregate during Cyclic and Dynamic Loading Laboratory Tests

PubMed Central

Sas, Wojciech; Głuchowski, Andrzej; Gabryś, Katarzyna; Soból, Emil; Szymański, Alojzy

2016-01-01

Recycled concrete aggregate (RCA) is a relatively new construction material, whose applications can replace natural aggregates. To do so, extensive studies on its mechanical behavior and deformation characteristics are still necessary. RCA is currently used as a subbase material in the construction of roads, which are subject to high settlements due to traffic loading. The deformation characteristics of RCA must, therefore, be established to find the possible fatigue and damage behavior for this new material. In this article, a series of triaxial cyclic loading and resonant column tests is used to characterize fatigue in RCA as a function of applied deviator stress after long-term cyclic loading. A description of the shakedown phenomenon occurring in the RCA and calculations of its resilient modulus (Mr) as a function of fatigue are also presented. Test result analysis with the stress-life method on the Wohler S-N diagram shows the RCA behavior in accordance with the Basquin law. PMID:28773905

Economic analysis of uricase production under uncertainty: Contrast of chromatographic purification and aqueous two-phase extraction (with and without PEG recycle).

PubMed

Torres-Acosta, Mario A; Aguilar-Yáñez, José M; Rito-Palomares, Marco; Titchener-Hooker, Nigel J

2016-01-01

Uricase is the enzyme responsible for the breakdown of uric acid, the key molecule leading to gout in humans, into allantoin, but it is absent in humans. It has been produced as a PEGylated pharmaceutical where the purification is performed through three sequential chromatographic columns. More recently an aqueous two-phase system (ATPS) was reported that could recover Uricase with high yield and purity. Although the use of ATPS can decrease cost and time, it also generates a large amount of waste. The ability, therefore, to recycle key components of ATPS is of interest. Economic modelling is a powerful tool that allows the bioprocess engineer to compare possible outcomes and find areas where further research or optimization might be required without recourse to extensive experiments and time. This research provides an economic analysis using the commercial software BioSolve of the strategies for Uricase production: chromatographic and ATPS, and includes a third bioprocess that uses material recycling. The key parameters that affect the process the most were located via a sensitivity analysis and evaluated with a Monte Carlo analysis. Results show that ATPS is far less expensive than chromatography, but that there is an area where the cost of production of both bioprocesses overlap. Furthermore, recycling does not impact the cost of production. This study serves to provide a framework for the economic analysis of Uricase production using alternative techniques. © 2015 The Authors Biotechnology Progress published by Wiley Periodicals, Inc. on behalf of American Institute of Chemical Engineers.

Economic analysis of uricase production under uncertainty: Contrast of chromatographic purification and aqueous two‐phase extraction (with and without PEG recycle)

PubMed Central

Torres‐Acosta, Mario A.; Aguilar‐Yáñez, José M.; Rito‐Palomares, Marco

2015-01-01

Uricase is the enzyme responsible for the breakdown of uric acid, the key molecule leading to gout in humans, into allantoin, but it is absent in humans. It has been produced as a PEGylated pharmaceutical where the purification is performed through three sequential chromatographic columns. More recently an aqueous two‐phase system (ATPS) was reported that could recover Uricase with high yield and purity. Although the use of ATPS can decrease cost and time, it also generates a large amount of waste. The ability, therefore, to recycle key components of ATPS is of interest. Economic modelling is a powerful tool that allows the bioprocess engineer to compare possible outcomes and find areas where further research or optimization might be required without recourse to extensive experiments and time. This research provides an economic analysis using the commercial software BioSolve of the strategies for Uricase production: chromatographic and ATPS, and includes a third bioprocess that uses material recycling. The key parameters that affect the process the most were located via a sensitivity analysis and evaluated with a Monte Carlo analysis. Results show that ATPS is far less expensive than chromatography, but that there is an area where the cost of production of both bioprocesses overlap. Furthermore, recycling does not impact the cost of production. This study serves to provide a framework for the economic analysis of Uricase production using alternative techniques. © 2015 American Institute of Chemical Engineers Biotechnol. Prog., 32:126–133, 2016 PMID:26561271

Doxorubicin loaded superparamagnetic PLGA-iron oxide multifunctional microbubbles for dual-mode US/MR imaging and therapy of metastasis in lymph nodes.

PubMed

Niu, Chengcheng; Wang, Zhigang; Lu, Guangming; Krupka, Tianyi M; Sun, Yang; You, Yufang; Song, Weixiang; Ran, Haitao; Li, Pan; Zheng, Yuanyi

2013-03-01

Current strategies for tumor-induced sentinel lymph node detection and metastasis therapy have limitations. In this work, we co-encapsulated iron oxide nanoparticles and chemotherapeutic drug into poly(lactic-co-glycolic acid) (PLGA) microbubbles to form multifunctional polymer microbubbles (MPMBs) for both tumor lymph node imaging and therapy. Fe(3)O(4) nanoparticles and doxorubicin (DOX) co-encapsulated PLGA microbubbles were prepared and filled with perfluorocarbon gas. Enhancement of ultrasound (US)/magnetic resonance (MR) imaging and US triggered drug delivery were evaluated both in vitro and in vivo. The MPMBs exhibited characters like narrow size distribution and smooth surface with a mean diameter of 868.0 ± 68.73 nm. In addition, varying the concentration of Fe(3)O(4) nanoparticles in the bubbles did not significantly influence the DOX encapsulation efficiency or drug loading efficiency. Our in vitro results demonstrated that these MPMBs could enhance both US and MR imaging which was further validated in vivo showing that these MPMBs enhanced tumor lymph nodes signals. The anti-tumor effect of MPMBs mediated chemotherapy was assessed in vivo using end markers like tumor proliferation index, micro blood vessel density and micro lymphatic vessel density, which were shown consistently the lowest after the MPMBs plus sonication treatment compared to controls. In line with these findings, the tumor cell apoptotic index was found the largest after the MPMBs plus sonication treatment. In conclusion, we have successfully developed a doxorubicin loaded superparamagnetic PLGA-Iron Oxide multifunctional theranostic agent for dual-mode US/MR Imaging of lymph node, and for low frequency US triggered therapy of metastasis in lymph nodes, which might provide a strategy for the imaging and chemotherapy of primary tumor and their metastases. Copyright © 2012 Elsevier Ltd. All rights reserved.

Production of microbubbles from axisymmetric flow focusing in the jetting regime for moderate Reynolds numbers.

PubMed

Vega, E J; Acero, A J; Montanero, J M; Herrada, M A; Gañán-Calvo, A M

2014-06-01

We analyze both experimentally and numerically the formation of microbubbles in the jetting regime reached when a moderately viscous liquid stream focuses a gaseous meniscus inside a converging micronozzle. If the total (stagnation) pressure of the injected gas current is fixed upstream, then there are certain conditions on which a quasisteady gas meniscus forms. The meniscus tip is sharpened by the liquid stream down to the gas molecular scale. On the other side, monodisperse collections of microbubbles can be steadily produced in the jetting regime if the feeding capillary is appropriately located inside the nozzle. In this case, the microbubble size depends on the feeding capillary position. The numerical simulations for an imposed gas flow rate show that a recirculation cell appears in the gaseous meniscus for low enough values of that parameter. The experiments allow one to conclude that the bubble pinch-off comprises two phases: (i) a stretching motion of the precursor jet where the neck radius versus the time before the pinch essentially follows a potential law, and (ii) a final stage where a very thin and slender gaseous thread forms and eventually breaks apart into a number of micron-sized bubbles. Because of the difference between the free surface and core velocities, the gaseous jet breakage differs substantially from that of liquid capillary jets and gives rise to bubbles with diameters much larger than those expected from the Rayleigh-type capillary instability. The dependency of the bubble diameter upon the flow-rate ratio agrees with the scaling law derived by A. M. Gañán-Calvo [Phys. Rev. E 69, 027301 (2004)], although a slight influence of the Reynolds number can be observed in our experiments.

Ultrasound-mediated gene delivery of naked plasmid DNA in skeletal muscles: a case for bolus injections.

PubMed

Sanches, Pedro Gomes; Mühlmeister, Mareike; Seip, Ralf; Kaijzel, Eric; Löwik, Clemens; Böhmer, Marcel; Tiemann, Klaus; Grüll, Holger

2014-12-10

Localized gene delivery has many potential clinical applications. However, the nucleic acids (e.g. pDNA and siRNA) are incapable of passively crossing the endothelium, cell membranes and other biological barriers which must be crossed to reach their intracellular targets. A possible solution is the use of ultrasound to burst circulating microbubbles inducing transient permeabilization of surrounding tissues which mediates nucleic acid extravasation and cellular uptake. In this study we report on an optimization of the ultrasound gene delivery technique. Naked pDNA (200 μg) encoding luciferase and SonoVue® microbubbles were co-injected intravenously in mice. The hindlimb skeletal muscles were exposed to ultrasound from a non-focused transducer (1 MHz, 1.25 MPa, PRI 30s) and injection protocols and total amounts as well as ultrasound parameters were systemically varied. Gene expression was quantified relative to a control using a bioluminescence camera system at day 7 after sonication. Bioluminescence ratios in sonicated/control muscles of up to 101× were obtained. In conclusion, we were able to specifically deliver genetic material to the selected skeletal muscles and overall, the use of bolus injections and high microbubble numbers resulted in increased gene expression reflected by stronger bioluminescence signals. Based on our data, bolus injections seem to be required in order to achieve transient highly concentrated levels of nucleic acids and microbubbles at the tissue of interest which upon ultrasound exposure should lead to increased levels of gene delivery. Thus, ultrasound mediated gene delivery is a promising technique for the clinical translation of localized drug delivery. Copyright © 2014 Elsevier B.V. All rights reserved.

Three-dimensional ultrasound molecular imaging of angiogenesis in colon cancer using a clinical matrix array ultrasound transducer.

PubMed

Wang, Huaijun; Kaneko, Osamu F; Tian, Lu; Hristov, Dimitre; Willmann, Jürgen K

2015-05-01

We sought to assess the feasibility and reproducibility of 3-dimensional ultrasound molecular imaging (USMI) of vascular endothelial growth factor receptor 2 (VEGFR2) expression in tumor angiogenesis using a clinical matrix array transducer and a clinical grade VEGFR2-targeted contrast agent in a murine model of human colon cancer. Animal studies were approved by the Institutional Administrative Panel on Laboratory Animal Care. Mice with human colon cancer xenografts (n = 33) were imaged with a clinical ultrasound system and transducer (Philips iU22; X6-1) after intravenous injection of either clinical grade VEGFR2-targeted microbubbles or nontargeted control microbubbles. Nineteen mice were scanned twice to assess imaging reproducibility. Fourteen mice were scanned both before and 24 hours after treatment with either bevacizumab (n = 7) or saline only (n = 7). Three-dimensional USMI data sets were retrospectively reconstructed into multiple consecutive 1-mm-thick USMI data sets to simulate 2-dimensional imaging. Vascular VEGFR2 expression was assessed ex vivo using immunofluorescence. Three-dimensional USMI was highly reproducible using both VEGFR2-targeted microbubbles and nontargeted control microbubbles (intraclass correlation coefficient, 0.83). The VEGFR2-targeted USMI signal significantly (P = 0.02) decreased by 57% after antiangiogenic treatment compared with the control group, which correlated well with ex vivo VEGFR2 expression on immunofluorescence (ρ = 0.93, P = 0.003). If only central 1-mm tumor planes were analyzed to assess antiangiogenic treatment response, the USMI signal change was significantly (P = 0.006) overestimated by an average of 27% (range, 2%-73%) compared with 3-dimensional USMI. Three-dimensional USMI is feasible and highly reproducible and allows accurate assessment and monitoring of VEGFR2 expression in tumor angiogenesis in a murine model of human colon cancer.

Sonophoresis Using Ultrasound Contrast Agents: Dependence on Concentration.

PubMed

Park, Donghee; Song, Gillsoo; Jo, Yongjun; Won, Jongho; Son, Taeyoon; Cha, Ohrum; Kim, Jinho; Jung, Byungjo; Park, Hyunjin; Kim, Chul-Woo; Seo, Jongbum

2016-01-01

Sonophoresis can increase skin permeability to various drugs in transdermal drug delivery. Cavitation is recognized as the predominant mechanism of sonophoresis. Recently, a new logical approach to enhance the efficiency of transdermal drug delivery was tried. It is to utilize the engineered microbubble and its resonant frequency for increase of cavitation activity. Actively-induced cavitation with low-intensity ultrasound (less than ~1 MPa) causes disordering of the lipid bilayers and the formation of aqueous channels by stable cavitation which indicates a continuous oscillation of bubbles. Furthermore, the mutual interactions of microbubble determined by concentration of added bubble are also thought to be an important factor for activity of stable cavitation, even in different characteristics of drug. In the present study, we addressed the dependence of ultrasound contrast agent concentration using two types of drug on the efficiency of transdermal drug delivery. Two types of experiment were designed to quantitatively evaluate the efficiency of transdermal drug delivery according to ultrasound contrast agent concentration. First, an experiment of optical clearing using a tissue optical clearing agent was designed to assess the efficiency of sonophoresis with ultrasound contrast agents. Second, a Franz diffusion cell with ferulic acid was used to quantitatively determine the amount of drug delivered to the skin sample by sonophoresis with ultrasound contrast agents. The maximum enhancement ratio of sonophoresis with a concentration of 1:1,000 was approximately 3.1 times greater than that in the ultrasound group without ultrasound contrast agent and approximately 7.5 times greater than that in the control group. These results support our hypothesis that sonophoresis becomes more effective in transdermal drug delivery due to the presence of engineered bubbles, and that the efficiency of transdermal drug delivery using sonophoresis with microbubbles depends on the concentration of microbubbles in case stable cavitation is predominant.

Improved Contrast-Enhanced Ultrasound Imaging With Multiplane-Wave Imaging.

PubMed

Gong, Ping; Song, Pengfei; Chen, Shigao

2018-02-01

Contrast-enhanced ultrasound (CEUS) imaging has great potential for use in new ultrasound clinical applications such as myocardial perfusion imaging and abdominal lesion characterization. In CEUS imaging, contrast agents (i.e., microbubbles) are used to improve contrast between blood and tissue because of their high nonlinearity under low ultrasound pressure. However, the quality of CEUS imaging sometimes suffers from a low signal-to-noise ratio (SNR) in deeper imaging regions when a low mechanical index (MI) is used to avoid microbubble disruption, especially for imaging at off-resonance transmit frequencies. In this paper, we propose a new strategy of combining CEUS sequences with the recently proposed multiplane-wave (MW) compounding method to improve the SNR of CEUS in deeper imaging regions without increasing MI or sacrificing frame rate. The MW-CEUS method emits multiple Hadamard-coded CEUS pulses in each transmission event (i.e., pulse-echo event). The received echo signals first undergo fundamental bandpass filtering (i.e., the filter is centered on the transmit frequency) to eliminate the microbubble's second-harmonic signals because they cannot be encoded by pulse inversion. The filtered signals are then Hadamard decoded and realigned in fast time to recover the signals as they would have been obtained using classic CEUS pulses, followed by designed recombination to cancel the linear tissue responses. The MW-CEUS method significantly improved contrast-to-tissue ratio and SNR of CEUS imaging by transmitting longer coded pulses. The image resolution was also preserved. The microbubble disruption ratio and motion artifacts in MW-CEUS were similar to those of classic CEUS imaging. In addition, the MW-CEUS sequence can be adapted to other transmission coding formats. These properties of MW-CEUS can potentially facilitate CEUS imaging for many clinical applications, especially assessing deep abdominal organs or the heart.

Targeted drug delivery with focused ultrasound-induced blood-brain barrier opening using acoustically-activated nanodroplets.

PubMed

Chen, Cherry C; Sheeran, Paul S; Wu, Shih-Ying; Olumolade, Oluyemi O; Dayton, Paul A; Konofagou, Elisa E

2013-12-28

Focused ultrasound (FUS) in the presence of systemically administered microbubbles has been shown to locally, transiently and reversibly increase the permeability of the blood-brain barrier (BBB), thus allowing targeted delivery of therapeutic agents in the brain for the treatment of central nervous system diseases. Currently, microbubbles are the only agents that have been used to facilitate the FUS-induced BBB opening. However, they are constrained within the intravascular space due to their micron-size diameters, limiting the delivery effect at or near the microvessels. In the present study, acoustically-activated nanodroplets were used as a new class of contrast agents to mediate FUS-induced BBB opening in order to study the feasibility of utilizing these nanoscale phase-shift particles for targeted drug delivery in the brain. Significant dextran delivery was achieved in the mouse hippocampus using nanodroplets at clinically relevant pressures. Passive cavitation detection was used in the attempt to establish a correlation between the amount of dextran delivered in the brain and the acoustic emission recorded during sonication. Conventional microbubbles with the same lipid shell composition and perfluorobutane core as the nanodroplets were also used to compare the efficiency of an FUS-induced dextran delivery. It was found that nanodroplets had a higher BBB opening pressure threshold but a lower stable cavitation threshold than microbubbles, suggesting that contrast agent-dependent acoustic emission monitoring was needed. A more homogeneous dextran delivery within the targeted hippocampus was achieved using nanodroplets without inducing inertial cavitation or compromising safety. Our results offered a new means of developing the FUS-induced BBB opening technology for potential extravascular targeted drug delivery in the brain, extending the potential drug delivery region beyond the cerebral vasculature. © 2013.

Select host cell proteins coelute with monoclonal antibodies in protein A chromatography.

PubMed

Nogal, Bartek; Chhiba, Krishan; Emery, Jefferson C

2012-01-01

The most significant factor contributing to the presence of host cell protein (HCP) impurities in Protein A chromatography eluates is their association with the product monoclonal antibodies (mAbs) has been reported previously, and it has been suggested that more efficacious column washes may be developed by targeting the disruption of the mAbs-HCP interaction. However, characterization of this interaction is not straight forward as it is likely to involve multiple proteins and/or types of interaction. This work is an attempt to begin to understand the contribution of HCP subpopulations and/or mAb interaction propensity to the variability in HCP levels in the Protein A eluate. We performed a flowthrough (FT) recycling study with product respiking using two antibody molecules of apparently different HCP interaction propensities. In each case, the ELISA assay showed depletion of select subpopulations of HCP in Protein A eluates in subsequent column runs, while the feedstock HCP in the FTs remained unchanged from its native harvested cell culture fluid (HCCF) levels. In a separate study, the final FT from each molecule's recycling study was cross-spiked with various mAbs. In this case, Protein A eluate levels remained low for all but two molecules which were known as having high apparent HCP interaction propensity. The results of these studies suggest that mAbs may preferentially bind to select subsets of HCPs, and the degree of interaction and/or identity of the associated HCPs may vary depending on the mAb. Copyright © 2012 American Institute of Chemical Engineers (AIChE).

Benthic-Pelagic Coupling in Biogeochemical and Climate Models: Existing Approaches, Recent developments and Roadblocks

NASA Astrophysics Data System (ADS)

Arndt, Sandra

2016-04-01

Marine sediments are key components in the Earth System. They host the largest carbon reservoir on Earth, provide the only long term sink for atmospheric CO2, recycle nutrients and represent the most important climate archive. Biogeochemical processes in marine sediments are thus essential for our understanding of the global biogeochemical cycles and climate. They are first and foremost, donor controlled and, thus, driven by the rain of particulate material from the euphotic zone and influenced by the overlying bottom water. Geochemical species may undergo several recycling loops (e.g. authigenic mineral precipitation/dissolution) before they are either buried or diffuse back to the water column. The tightly coupled and complex pelagic and benthic process interplay thus delays recycling flux, significantly modifies the depositional signal and controls the long-term removal of carbon from the ocean-atmosphere system. Despite the importance of this mutual interaction, coupled regional/global biogeochemical models and (paleo)climate models, which are designed to assess and quantify the transformations and fluxes of carbon and nutrients and evaluate their response to past and future perturbations of the climate system either completely neglect marine sediments or incorporate a highly simplified representation of benthic processes. On the other end of the spectrum, coupled, multi-component state-of-the-art early diagenetic models have been successfully developed and applied over the past decades to reproduce observations and quantify sediment-water exchange fluxes, but cannot easily be coupled to pelagic models. The primary constraint here is the high computation cost of simulating all of the essential redox and equilibrium reactions within marine sediments that control carbon burial and benthic recycling fluxes: a barrier that is easily exacerbated if a variety of benthic environments are to be spatially resolved. This presentation provides an integrative overview of the benthic-pelagic coupling that accounts for the complex process interplay from the euphotic ocean to the deep sediment. It explores the intensity of the benthic-pelagic coupling across different environments and from the seasonal to the geological timescale. Different modelling approaches of coupling sediment and water column dynamics in regional/global biogeochemical models and (paleo)climate models are critically evaluated and their most important limitations, as well as the implications for our ability to predict the response of the global carbon cycle to past or future perturbations is discussed. Finally, the presentation identifies major roadblocks to the development of new model approaches and highlights how new techniques, new observational and laboratory data, as well as a close interdisciplinary collaboration can overcome these roadblocks.

Stability analysis of ultrasound thick-shell contrast agents.

PubMed

Lu, Xiaozhen; Chahine, Georges L; Hsiao, Chao-Tsung

2012-01-01

The stability of thick shell encapsulated bubbles is studied analytically. 3-D small perturbations are introduced to the spherical oscillations of a contrast agent bubble in response to a sinusoidal acoustic field with different amplitudes of excitation. The equations of the perturbation amplitudes are derived using asymptotic expansions and linear stability analysis is then applied to the resulting differential equations. The stability of the encapsulated microbubbles to nonspherical small perturbations is examined by solving an eigenvalue problem. The approach then identifies the fastest growing perturbations which could lead to the breakup of the encapsulated microbubble or contrast agent. © 2012 Acoustical Society of America.

Mass production of monodisperse microbubbles for real applications avoiding microfluidics

NASA Astrophysics Data System (ADS)

Sanchez Quintero, Enrique Jesus; Evangelio, Alvaro; Gordillo, Jose Manuel

2017-11-01

In this presentation we report experiments showing the effect on the controlled generation of microbubbles of the pressure gradient imposed by the relative flow of a liquid stream around an airfoil-shaped solid. Taking advantage of the conclusions in, where the local pressure gradient was identified as the mechanism responsible of the generation of microbubbles in microfluidic devices and, with the purpose of overcoming the low production rates associated with these kind of microdevices, we have used the same physical principle but have applied it to a totally different geometry: a rectangular planar wing composed by symmetrical airfoils. The relative velocity field is imposed either submerging the static wing within a flowing hydraulic channel or by rotating the wings within a reservoir containing the otherwise quiescent liquid mass. We provide physical insight on the bubbling process and deduce a scaling law which expresses the diameters of the bubbles formed as a function of the gas flow rate, relative liquid velocity and the angle of attack of the incident flow. In spite of the geometry is totally different, we recover the same results obtained using microfluidic devices but with much higher production rates.

Nonlinear oscillation and interfacial stability of an encapsulated microbubble under dual-frequency ultrasound

NASA Astrophysics Data System (ADS)

Liu, Yunqiao; Calvisi, Michael L.; Wang, Qianxi

2017-04-01

Encapsulated microbubbles (EMBs) are widely used in medical ultrasound imaging as contrast-enhanced agents. However, the potential damaging effects of violent collapsing EMBs to cells and tissues in clinical settings have remained a concern. Dual-frequency ultrasound is a promising technique for improving the efficacy and safety of sonography. The system modeled consists of the external liquid, membrane and internal gases of an EMB. The microbubble dynamics are simulated using a simple nonlinear interactive theory, considering the compressibility of the internal gas, viscosity of the liquid flow and viscoelasticity of the membrane. The radial oscillation and interfacial stability of an EMB under single- and dual-frequency excitations are compared. The simulation results show that the dual-frequency technique produces larger backscatter pressure at higher harmonics of the primary driving frequency—this enriched acoustic spectrum can enhance blood-tissue contrast and improve the quality of sonographic images. The results further show that the acoustic pressure threshold associated with the onset of shape instability is greater for dual-frequency driving. This suggests that the dual-frequency technique stabilizes the encapsulated bubble, thereby improving the efficacy and safety of contrast-enhanced agents.

Quantifying activation of perfluorocarbon-based phase-change contrast agents using simultaneous acoustic and optical observation.

PubMed

Li, Sinan; Lin, Shengtao; Cheng, Yi; Matsunaga, Terry O; Eckersley, Robert J; Tang, Meng-Xing

2015-05-01

Phase-change contrast agents in the form of nanoscale droplets can be activated into microbubbles by ultrasound, extending the contrast beyond the vasculature. This article describes simultaneous optical and acoustical measurements for quantifying the ultrasound activation of phase-change contrast agents over a range of concentrations. In experiments, decafluorobutane-based nanodroplets of different dilutions were sonicated with a high-pressure activation pulse and two low-pressure interrogation pulses immediately before and after the activation pulse. The differences between the pre- and post-interrogation signals were calculated to quantify the acoustic power scattered by the microbubbles activated over a range of droplet concentrations. Optical observation occurred simultaneously with the acoustic measurement, and the pre- and post-microscopy images were processed to generate an independent quantitative indicator of the activated microbubble concentration. Both optical and acoustic measurements revealed linear relationships to the droplet concentration at a low concentration range <10(8)/mL when measured at body temperature. Further increases in droplet concentration resulted in saturation of the acoustic interrogation signal. Compared with body temperature, room temperature was found to produce much fewer and larger bubbles after ultrasound droplet activation. Copyright © 2015. Published by Elsevier Inc.

Pinched flow fractionation of microbubbles for ultrasound contrast agent enrichment

NASA Astrophysics Data System (ADS)

Versluis, Michel; Kok, Maarten; Segers, Tim

2014-11-01

An ultrasound contrast agent (UCA) suspension contains a wide size distribution of encapsulated microbubbles (typically 1-10 μm in diameter) that resonate to the driving ultrasound field by the intrinsic relationship between bubble size and ultrasound frequency. Medical transducers, however, operate in a narrow frequency range, which severely limits the number of bubbles that contribute to the echo signal. Thus, the sensitivity can be improved by narrowing down the size distribution of the bubble suspension. Here, we present a novel, low-cost, lab-on-a-chip method for the sorting of contrast microbubbles by size, based on a microfluidic separation technique known as pinched flow fractionation (PFF). We show by experimental and numerical investigation that the inclusion of particle rotation is essential for an accurate physical description of the sorting behavior of the larger bubbles. Successful sorting of a bubble suspension with a narrow size distribution (3.0 +/- 0.6 μm) has been achieved with a PFF microdevice. This sorting technique can be easily parallelized, and may lead to a significant improvement in the sensitivity of contrast-enhanced medical ultrasound. This work is supported by NanoNextNL, a micro and nanotechnology consortium of the Government of the Netherlands and 130 partners.

Formulating a subgrid-scale breakup model for microbubble generation from interfacial collisions

NASA Astrophysics Data System (ADS)

Chan, Wai Hong Ronald; Mirjalili, Shahab; Urzay, Javier; Mani, Ali; Moin, Parviz

2017-11-01

Multiphase flows often involve impact events that engender important effects like the generation of a myriad of tiny bubbles that are subsequently transported in large liquid bodies. These impact events are created by large-scale phenomena like breaking waves on ocean surfaces, and often involve the relative approach of liquid surfaces. This relative motion generates continuously shrinking length scales as the entrapped gas layer thins and eventually breaks up into microbubbles. The treatment of this disparity in length scales is computationally challenging. In this presentation, a framework is presented that addresses a subgrid-scale (SGS) model aimed at capturing the process of microbubble generation. This work sets up the components in an overarching volume-of-fluid (VoF) toolset and investigates the analytical foundations of an SGS model for describing the breakup of a thin air film trapped between two approaching water bodies in a physical regime corresponding to Mesler entrainment. Constituents of the SGS model, such as the identification of impact events and the accurate computation of the local characteristic curvature in a VoF-based architecture, and the treatment of the air layer breakup, are discussed and illustrated in simplified scenarios. Supported by Office of Naval Research (ONR)/A*STAR (Singapore).

Dual-Targeted Theranostic Delivery of miRs Arrests Abdominal Aortic Aneurysm Development.

PubMed

Wang, Xiaowei; Searle, Amy Kate; Hohmann, Jan David; Liu, Ao Leo; Abraham, Meike-Kristin; Palasubramaniam, Jathushan; Lim, Bock; Yao, Yu; Wallert, Maria; Yu, Eefang; Chen, Yung-Chih; Peter, Karlheinz

2018-04-04

Abdominal aortic aneurysm (AAA) is an often deadly disease without medical, non-invasive treatment options. The upregulation of vascular cell adhesion molecule-1 (VCAM-1) on aortic endothelium provides an early target epitope for a novel biotechnological theranostic approach. MicroRNA-126 was used as a therapeutic agent, based on its capability to downregulate VCAM-1 expression in endothelial cells and thereby reduces leukocyte adhesion and exerts anti-inflammatory effects. Ultrasound microbubbles were chosen as carriers, allowing both molecular imaging as well as targeted therapy of AAA. Microbubbles were coupled with a VCAM-1-targeted single-chain antibody (scFv mVCAM-1 ) and a microRNA-126 mimic (M 126 ) constituting theranostic microbubbles (Targ MB -M 126 ). Targ MB -M 126 downregulates VCAM-1 expression in vitro and in an in vivo acute inflammatory murine model. Most importantly, using Targ MB -M 126 and ultrasound-guided burst delivery of M 126 , the development of AAA in an angiotensin-II-induced mouse model can be prevented. Overall, we describe a unique biotechnological theranostic approach with the potential for early diagnosis and long-sought-after medical therapy of AAA. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Power cavitation-guided blood-brain barrier opening with focused ultrasound and microbubbles

NASA Astrophysics Data System (ADS)

Burgess, M. T.; Apostolakis, I.; Konofagou, E. E.

2018-03-01

Image-guided monitoring of microbubble-based focused ultrasound (FUS) therapies relies on the accurate localization of FUS-stimulated microbubble activity (i.e. acoustic cavitation). Passive cavitation imaging with ultrasound arrays can achieve this, but with insufficient spatial resolution. In this study, we address this limitation and perform high-resolution monitoring of acoustic cavitation-mediated blood-brain barrier (BBB) opening with a new technique called power cavitation imaging. By synchronizing the FUS transmit and passive receive acquisition, high-resolution passive cavitation imaging was achieved by using delay and sum beamforming with absolute time delays. Since the axial image resolution is now dependent on the duration of the received acoustic cavitation emission, short pulses of FUS were used to limit its duration. Image sets were acquired at high-frame rates for calculation of power cavitation images analogous to power Doppler imaging. Power cavitation imaging displays the mean intensity of acoustic cavitation over time and was correlated with areas of acoustic cavitation-induced BBB opening. Power cavitation-guided BBB opening with FUS could constitute a standalone system that may not require MRI guidance during the procedure. The same technique can be used for other acoustic cavitation-based FUS therapies, for both safety and guidance.

Power cavitation-guided blood-brain barrier opening with focused ultrasound and microbubbles.

PubMed

Burgess, M T; Apostolakis, I; Konofagou, E E

2018-03-15

Image-guided monitoring of microbubble-based focused ultrasound (FUS) therapies relies on the accurate localization of FUS-stimulated microbubble activity (i.e. acoustic cavitation). Passive cavitation imaging with ultrasound arrays can achieve this, but with insufficient spatial resolution. In this study, we address this limitation and perform high-resolution monitoring of acoustic cavitation-mediated blood-brain barrier (BBB) opening with a new technique called power cavitation imaging. By synchronizing the FUS transmit and passive receive acquisition, high-resolution passive cavitation imaging was achieved by using delay and sum beamforming with absolute time delays. Since the axial image resolution is now dependent on the duration of the received acoustic cavitation emission, short pulses of FUS were used to limit its duration. Image sets were acquired at high-frame rates for calculation of power cavitation images analogous to power Doppler imaging. Power cavitation imaging displays the mean intensity of acoustic cavitation over time and was correlated with areas of acoustic cavitation-induced BBB opening. Power cavitation-guided BBB opening with FUS could constitute a standalone system that may not require MRI guidance during the procedure. The same technique can be used for other acoustic cavitation-based FUS therapies, for both safety and guidance.

Improved survival in rats with glioma using MRI-guided focused ultrasound and microbubbles to disrupt the blood-brain barrier and deliver Doxil

NASA Astrophysics Data System (ADS)

Aryal, Muna; Zhi Zhang, Yong; Vykhodtseva, Natalia; Park, Juyoung; Power, Chanikarn; McDannold, Nathan

2012-02-01

Blood-brain-barrier (BBB) limits the transportation of most neuropeptides, proteins (enzymes, antibodies), chemotherapeutic agents, and genes that have therapeutic potential for the treatment of brain diseases. Different methods have been used to overcome this limitation, but they are invasive, non-targeted, or require the development of new drugs. We have developed a method that uses MRI-guided focused ultrasound (FUS) combined with circulating microbubbles to temporarily open BBB in and around brain tumors to deliver chemotherapy agents. Here, we tested whether this noninvasive technique could enhance the effectiveness of a chemotherapy agent (Doxil). Using 690 kHz FUS transducer and microbubble (Definity), we induced BBB disruption in intracranially-implanted 9L glioma tumors in rat's brain in three weekly sessions. Animals who received BBB disruption and Doxil had a median survival time of 34.5 days, which was significantly longer than that found in control animals which is 16, 18.5, 21 days who received no treatment, BBB disruption only and Doxil only respectively This work demonstrates that FUS technique has promise in overcoming barriers to drug delivery, which are particularly stark in the brain due to the BBB.